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Insulin-like peptide 3 (INSL3) as an indicator of leydig cell insufficiency (LCI) in Middle-aged and older men with hypogonadism: reference range and threshold
Anand-Ivell R, Heng K, Antonio L, Bartfai G, Casanueva FF, Maggi M, O'Neill TW, Punab M, Rastrelli G, Slowikowska-Hilczer J, Tournoy J, Vanderschueren D, Wu FC, Huhtaniemi IT and Ivell R
Insulin-like peptide 3 (INSL3) is a circulating biomarker for Leydig cell functional capacity in men, also indicating Leydig Cell Insufficiency (LCI) and potential primary hypogonadism. Using results from large cohort studies we explore sources of biological and technical variance, and establish a reference range for adult men. It is constitutively secreted with little within-individual variation and reflects testicular capacity to produce testosterone. The main INSL3 assays available indicate good concordance with low technical variance; there is no effect of ethnicity. INSL3 declines with age from 35 years at about 15% per decade. Like low calculated free testosterone, and to a lesser extent low total testosterone, reduced INSL3 is significantly associated with increasing age-related morbidity, including lower overall sexual function, reflecting LCI. Consequently, low INSL3 (≤0.4 ng/ml; ca. <2 SD from the population mean) might serve as an additional biochemical marker in the assessment of functional hypogonadism (late-onset hypogonadism, LOH) where testosterone is in the borderline low range. Excluding individuals with low LCI (INSL3 ≤ 0.4 ng/ml) leads to an age-independent (> 35 years) reference range (serum) for INSL3 in the eugonadal population of 0.4 - 2.3 ng/ml, with low INSL3 prospectively identifying individuals at risk of increased future morbidity.
Treatment patterns, clinical outcomes and gene mutation characteristics of hepatitis B virus-associated mantle cell lymphoma
Feng J, Fei Y, Gao M, Meng X, Zeng D, Zou D, Ye H, Liang Y, Sun X, Liang R, Zhou H, Wang X and Zhang H
Mantle cell lymphoma (MCL) is an uncommon and incurable B-cell lymphoma subtype that has an aggressive course. Hepatitis B virus (HBV) infection has been associated with an increased risk for B-cell lymphomas, and is characterized by distinct clinical and genetic features. Here, we showed that 9.5% of MCL Chinese patients were hepatitis B surface antigen positive (HBsAg). Compared to HBsAg-negative (HBsAg) patients, HBsAg MCL patients had a greater incidence of elevated lactate dehydrogenase (LDH), but no difference was observed in the other clinical characteristics, including sex, age, ECOG ps, Ann Arbor stage, MIPI, extranodal involvement and Ki-67. The HD-AraC (high-dose cytarabine) regimen was the main first-line induction regimen for younger HBsAg patients, and cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) were used for elderly patients. HBsAg seropositivity was associated with a significantly shorter PFS than HBsAg seronegativity when patients were treated with rituximab or CHOP-based regimens. Compared with CHOP, the HD-AraC regimen was associated with longer PFS in HBsAg patients. Treatment with a Bruton tyrosine kinase inhibitor (BTKi) alone can also cause HBV reactivation. Among the 74 patients who underwent targeted deep sequencing (TDS), the nonsynonymous mutation load of HBsAg MCL patients was greater than that of HBsAg MCL patients. HDAC1, TRAF5, FGFR4, SMAD2, JAK3, SMC1A, ZAP70, BLM, CDK12, PLCG2, SMO, TP63, NF1, PTPR, EPHA2, RPTOR and FIP1L1 were significantly enriched in HBsAg MCL patients.
Ensemble-based classification using microRNA expression identifies a breast cancer patient subgroup with an ultralow long-term risk of metastases
Block I, Burton M, Sørensen KP, Larsen MJ, Do TTN, Bak M, Cold S, Thomassen M, Tan Q and Kruse TA
Current clinical markers overestimate the recurrence risk in many lymph node negative (LNN) breast cancer (BC) patients such that a majority of these low-risk patients unnecessarily receive systemic treatments. We tested if differential microRNA expression in primary tumors allows reliable identification of indolent LNN BC patients to provide an improved classification tool for overtreatment reduction in this patient group.
A smoking cessation smartphone app that delivers real-time 'context aware' behavioural support: the Quit Sense feasibility RCT
Naughton F, Hope A, Siegele-Brown C, Grant K, Notley C, Colles A, West C, Mascolo C, Coleman T, Barton G, Shepstone L, Prevost T, Sutton S, Crane D, Greaves F and High J
During a quit attempt, cues from a smoker's environment are a major cause of brief smoking lapses, which increase the risk of relapse. Quit Sense is a theory-guided Just-In-Time Adaptive Intervention smartphone app, providing smokers with the means to learn about their environmental smoking cues and provides 'in the moment' support to help them manage these during a quit attempt.
Global Epidemiology and Geographic Variations of Pediatric-Onset Inflammatory Bowel Disease: A Comprehensive Analysis of the Global Burden of Disease Study 1990 to 2019
Wang Y, Pan CW, Huang Y, Zheng X, Li S, He M, Hashash JG, Farraye FA and Ehrlich AC
An increasing incidence of pediatric-onset inflammatory bowel disease (PIBD) has been reported in many countries. However, the global burden and distribution of this disease remain less understood. We aimed to examine the global epidemiology and trends of PIBD from 1990 to 2019.
The Functional Vision for Communication Questionnaire (FVC-Q): Exploring Parental Report of Non-Speaking Children's Fixation Skills Using a Structured History-Taking Approach
Sargent J, Griffiths T, Clarke MT, Bates K, Macleod K and Swettenham J
This paper explores whether a structured history-taking tool yields useful descriptions of children's looking skills. Parents of 32 children referred to a specialist communication clinic reported their child's looking skills using the Functional Vision for Communication Questionnaire (FVC-Q), providing descriptions of single object fixation, fixation shifts between objects and fixation shifts from object to person. Descriptions were compared with clinical assessment. 24/32 children were reported to have some limitation in fixation. Limitation was subsequently seen in 30/32 children. Parental report and assessment agreed fully in 23/32 (72%). The largest area of discrepancy was object-person fixation shifts, with five children not observed to show this behavior despite its being reported. Findings indicate a structured questionnaire yields description of fixations, which correspond well with clinical assessment. Descriptions supported discussion between parents and clinicians. It is proposed that the FVC-Q is a valuable tool in supporting clinicians in eliciting information about fixation skills.
Interindividual differences in mindfulness are linked to sleep-EEG characteristics
Wunderlin M, Studler M, Gianotti LRR, Züst MA and Knoch D
Mindfulness describes the ability to focus on the presence, including one's thoughts and feelings. Trait mindfulness - a person's inherent tendency to be mindful - has been connected to increased subjective sleep quality, but evidence from objective EEG-based sleep measures is lacking. Here, we investigate whether objective EEG-based sleep parameters explain interindividual differences in trait mindfulness.
Polysensitisation is associated with more severe symptoms: The reality of patients with allergy
Cacheiro-Llaguno C, Mösges R, Calzada D, González-de la Fuente S, Quintero E and Carnés J
Studying the sensitisation profiles of patients with allergies allows for a deeper understanding of the disease which may facilitate the selection of the best-personalised allergen immunotherapy. This observational, cross-sectional, multicentre study aimed to demonstrate the heterogeneity of the German population with allergies by analysing specific immunoglobulin E (sIgE) patterns towards aeroallergens and exploring the relationship between sensitisation and clinical symptoms.
"She's so pretty": The development of valuing personal attractiveness among young children
Halim MLD, Russo LN, Echave KN, Tawa S, Sakamoto DJ and Portillo MA
The current study sought to understand gender differences in how much children value personal attractiveness, whether age is associated with valuing personal attractiveness, and the role of gender identity development. Three- to five-year-olds (N = 170; 89 girls, 81 boys, 0 other genders; primarily Latiné, multiethnic, and non-Hispanic White American) were recruited from child centers across the Los Angeles and Orange County metropolitan areas. Across several indicators (e.g., self-report, preference for appearance-related female-typed occupations and fancy gender-typed outfits, memory for fancy gender-typed clothing, and spontaneous reasons for liking a media character), girls highly valued personal attractiveness. Girls also valued personal attractiveness and tied their gender to personal attractiveness to a greater extent than boys. We discuss implications for later well-being and health.
Establishing a research partnership to investigate functional loss and rehabilitation towards the end of life
Maddocks M, Brighton LJ, Connell L, Cowley A, Laird B, Peryer G, Petrasso C, Ziegler L and Harwood R
Functional loss, the inability to perform necessary or desired tasks, is a common consequence of life-limiting illnesses and associated symptoms (pain, fatigue, breathlessness, etc.) and causes suffering for patients and families. Rehabilitation, a set of interventions designed to address functional loss, is recognised as essential within palliative care, as it can improve quality of life and reduce care costs. However, not everyone has equal access to rehabilitation. Despite limited life expectancy or uncertain ability to benefit from interventions, palliative rehabilitation services are often absent. This is partly due to a lack of high-quality research around optimal models of rehabilitation. Research in this area is methodologically challenging and requires multidisciplinary and cross-speciality collaboration.
Optimizing lipid control in Taiwanese diabetic patients: A collaborative consensus by the Diabetes Association of the Republic of China (Taiwan) and the Taiwanese Association of Diabetes Educators
Shen FC, Chu CH, Chen JF, Kuo CS, Hsu CY, Lin CH, Sheen YJ, Su SC, Tien KJ, Lu CH, Lee CC, Yang YS, Tu ST, Chen PT, Chen CC, Chien MN, Li HY, Sheu WH, Huang CN, Wang CY and Ou HY
We present an in-depth analysis of dyslipidemia management strategies for patients with diabetes mellitus in Taiwan. It critically examines the disparity between established guideline recommendations and actual clinical practices, particularly in the context of evolving policies affecting statin prescriptions. The focus is on synthesizing the most recent findings concerning lipid management in patients with diabetes mellitus, with a special emphasis on establishing consensus regarding low-density lipoprotein cholesterol treatment targets. The article culminates in providing comprehensive, evidence-based recommendations tailored to the unique needs of those living with diabetes mellitus in Taiwan. It underscores the criticality of personalized care approaches, which incorporate multifaceted factors, and the integration of novel therapeutic options to enhance cardiovascular health outcomes.
Are "clean" products safe for children? An analysis of contact allergens in "clean" children's products from a popular retailer
Brumley C, Banks T, Arora P and Ophaug S
Considering consumer trends toward the use of "clean" personal care products and increasing recognition of childhood allergic contact dermatitis, we sought to characterize the allergen profile of such children's products.
Design and implementation of community consultation for research conducted under exception from informed consent regulations for the PreVent and the PreVent 2 trials: Changes over time and during the COVID-19 pandemic
Gugel T, Adams K, Baranoski M, Yanez ND, Kampp M, Johnson T, Aydin A, Fajardo EC, Sharp E, Potnis A, Johnson C and Treggiari MM
Emergency clinical research has played an important role in improving outcomes for acutely ill patients. This is due in part to regulatory measures that allow (EFIC) trials. The Food and Drug Administration (FDA) requires sponsor-investigators to engage in community consultation and public disclosure activities prior to initiating an trial. Various approaches to community consultation and public disclosure have been described and adapted to local contexts and Institutional Review Board (IRB) interpretations. The COVID-19 pandemic has precluded the ability to engage local communities through direct, in-person public venues, requiring research teams to find alternative ways to inform communities about emergency research.
Ubiquitous Gait Analysis through Footstep-Induced Floor Vibrations
Dong Y and Noh HY
Quantitative analysis of human gait is critical for the early discovery, progressive tracking, and rehabilitation of neurological and musculoskeletal disorders, such as Parkinson's disease, stroke, and cerebral palsy. Gait analysis typically involves estimating gait characteristics, such as spatiotemporal gait parameters and gait health indicators (e.g., step time, length, symmetry, and balance). Traditional methods of gait analysis involve the use of cameras, wearables, and force plates but are limited in operational requirements when applied in daily life, such as direct line-of-sight, carrying devices, and dense deployment. This paper introduces a novel approach for gait analysis by passively sensing floor vibrations generated by human footsteps using vibration sensors mounted on the floor surface. Our approach is low-cost, non-intrusive, and perceived as privacy-friendly, making it suitable for continuous gait health monitoring in daily life. Our algorithm estimates various gait parameters that are used as standard metrics in medical practices, including (), (), and extracts (). The main challenge we addressed in this paper is the effect of different floor types on the resultant vibrations. We develop floor-adaptive algorithms to extract features that are generalizable to various practical settings, including homes, hospitals, and eldercare facilities. We evaluate our approach through real-world walking experiments with 20 adults with 12,231 labeled gait cycles across concrete and wooden floors. Our results show 90.5% (RMSE 0.08s), 71.3% (RMSE 0.38m), and 92.3% (RMSPE 7.7%) accuracy in estimating temporal, spatial parameters, and gait health indicators, respectively.
Anti-Herpes Zoster Vaccination of Fragile Patients in Hospital Setting: A Nudge Intervention in Italy
De Caro F, Malatesta F, Pecoraro N, Capunzo M, Carpinelli L, Caruccio S, Cersosimo G, Costantino M, Giordano C, Longanella W, Patella V, Saggese Tozzi A, Savarese G, Sinopoli P, Vozzella EA and Moccia G
A nudge intervention against Herpes Zoster, created and implemented in Italy, is presented in order to administer the Shingrix vaccine on a sample of frail patients, as required by the National Prevention Plan. Individual and contextual factors associated with vaccine adherence were investigated.
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Van Asbroeck S, Köhler S, van Boxtel MPJ, Lipnicki DM, Crawford JD, Castro-Costa E, Lima-Costa MF, Blay SL, Shifu X, Wang T, Yue L, Lipton RB, Katz MJ, Derby CA, Guerchet M, Preux PM, Mbelesso P, Norton J, Ritchie K, Skoog I, Najar J, Sterner TR, Scarmeas N, Yannakoulia M, Dardiotis T, Rolandi E, Davin A, Rossi M, Gureje O, Ojagbemi A, Bello T, Kim KW, Han JW, Oh DJ, Trompet S, Gussekloo J, Riedel-Heller SG, Röhr S, Pabst A, Shahar S, Rivan NFM, Singh DKA, Jacobsen E, Ganguli M, Hughes T, Haan M, Aiello AE, Ding D, Zhao Q, Xiao Z, Narazaki K, Chen T, Chen S, Ng TP, Gwee X, Gao Q, Brodaty H, Trollor J, Kochan N, Lobo A, Santabárbara J, Gracia-Garcia P, Sachdev PS, Deckers K and
The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics.
Wearable Biosensor Technology in Education: A Systematic Review
Hernández-Mustieles MA, Lima-Carmona YE, Pacheco-Ramírez MA, Mendoza-Armenta AA, Romero-Gómez JE, Cruz-Gómez CF, Rodríguez-Alvarado DC, Arceo A, Cruz-Garza JG, Ramírez-Moreno MA and Lozoya-Santos JJ
Wearable Biosensor Technology (WBT) has emerged as a transformative tool in the educational system over the past decade. This systematic review encompasses a comprehensive analysis of WBT utilization in educational settings over a 10-year span (2012-2022), highlighting the evolution of this field to address challenges in education by integrating technology to solve specific educational challenges, such as enhancing student engagement, monitoring stress and cognitive load, improving learning experiences, and providing real-time feedback for both students and educators. By exploring these aspects, this review sheds light on the potential implications of WBT on the future of learning. A rigorous and systematic search of major academic databases, including Google Scholar and Scopus, was conducted in accordance with the PRISMA guidelines. Relevant studies were selected based on predefined inclusion and exclusion criteria. The articles selected were assessed for methodological quality and bias using established tools. The process of data extraction and synthesis followed a structured framework. Key findings include the shift from theoretical exploration to practical implementation, with EEG being the predominant measurement, aiming to explore mental states, physiological constructs, and teaching effectiveness. Wearable biosensors are significantly impacting the educational field, serving as an important resource for educators and a tool for students. Their application has the potential to transform and optimize academic practices through sensors that capture biometric data, enabling the implementation of metrics and models to understand the development and performance of students and professors in an academic environment, as well as to gain insights into the learning process.
Measuring perceived utility of genomic sequencing: Development and validation of the GENEtic Utility (GENE-U) scale for pediatric diagnostic testing
Smith HS, Rubanovich CK, Robinson JO, Levchenko AN, Classen SA, Malek J, Biesecker B, Brothers KB, Wilfond BS, Rini C, Knight SJ, McGuire AL and Bloss CS
Measuring effects of genomic sequencing (GS) on patients and families is critical for translational research. We aimed to develop and validate an instrument to assess parents' perceived utility of pediatric diagnostic GS.
Enhancing X-Ray Sensitization with Multifunctional Nanoparticles
Liu J, Wu J, Chen T, Yang B, Liu X, Xi J, Zhang Z, Gao Y and Li Z
In the progression of X-ray-based radiotherapy for the treatment of cancer, the incorporation of nanoparticles (NPs) has a transformative impact. This study investigates the potential of NPs, particularly those comprised of high atomic number elements, as radiosensitizers. This aims to optimize localized radiation doses within tumors, thereby maximizing therapeutic efficacy while preserving surrounding tissues. The multifaceted applications of NPs in radiotherapy encompass collaborative interactions with chemotherapeutic, immunotherapeutic, and targeted pharmaceuticals, along with contributions to photodynamic/photothermal therapy, imaging enhancement, and the integration of artificial intelligence technology. Despite promising preclinical outcomes, the paper acknowledges challenges in the clinical translation of these findings. The conclusion maintains an optimistic stance, emphasizing ongoing trials and technological advancements that bolster personalized treatment approaches. The paper advocates for continuous research and clinical validation, envisioning the integration of NPs as a revolutionary paradigm in cancer therapy, ultimately enhancing patient outcomes.
The Effects of Hand Tremors on the Shooting Performance of Air Pistol Shooters with Different Skill Levels
Liu Y, Hu N, Sun M, Qu F and Zhou X
Physiologic hand tremors are a critical factor affecting the aim of air pistol shooters. However, the extent of the effect of hand tremors on shooting performance is unclear. In this study, we aim to explore the relationship between hand tremors and shooting performance scores as well as investigate potential links between muscle activation and hand tremors. In this study, 17 male air pistol shooters from China's national team and the Air Pistol Sports Center were divided into two groups: the elite group and the sub-elite group. Each participant completed 40 shots during the experiment, with shooters' hand tremors recorded using three-axis digital accelerometers affixed to their right hands. Muscle activation was recorded using surface electromyography on the right anterior deltoid, posterior deltoid, biceps brachii (short head), triceps brachii (long head), flexor carpi radialis, and extensor carpi radialis. Our analysis revealed weak correlations between shooting scores and hand tremor amplitude in multiple directions (middle-lateral, ML: r = -0.22, < 0.001; vertical, VT: r = -0.25, < 0.001), as well as between shooting scores and hand tremor complexity (ML: r = -0.26, < 0.001; VT: r = -0.28, < 0.001), across all participants. Notably, weak correlations between shooting scores and hand tremor amplitude (ML: r = -0.27, < 0.001; VT: r = -0.33, < 0.001) and complexity (ML: r = -0.31, < 0.001) were observed in the elite group but not in the sub-elite group. Moderate correlation were found between the biceps brachii (short head) RMS and hand tremor amplitude in the VT and ML directions (ML: r = 0.49, = 0.010; VT: r = 0.44, = 0.025) in all shooters, with a moderate correlation in the ML direction in elite shooters (ML: r = 0.49, = 0.034). Our results suggest that hand tremors in air pistol shooters are associated with the skill of the shooters, and muscle activation of the biceps brachii (long head) might be a factor affecting hand tremors. By balancing the agonist and antagonist muscles of the shoulder joint, shooters might potentially reduce hand tremors and improve their shooting scores.
The Stress of Measuring Plantar Tissue Stress in People with Diabetes-Related Foot Ulcers: Biomechanical and Feasibility Findings from Two Prospective Cohort Studies
Hulshof CM, Page M, van Baal SG, Bus SA, Fernando ME, van Gemert-Pijnen L, Kappert KDR, Lucadou-Wells S, Najafi B, van Netten JJ and Lazzarini PA
Reducing high mechanical stress is imperative to heal diabetes-related foot ulcers. We explored the association of cumulative plantar tissue stress (CPTS) and plantar foot ulcer healing, and the feasibility of measuring CPTS, in two prospective cohort studies (Australia (AU) and The Netherlands (NL)). Both studies used multiple sensors to measure factors to determine CPTS: plantar pressures, weight-bearing activities, and adherence to offloading treatments, with thermal stress response also measured to estimate shear stress in the AU-study. The primary outcome was ulcer healing at 12 weeks. Twenty-five participants were recruited: 13 in the AU-study and 12 in the NL-study. CPTS data were complete for five participants (38%) at baseline and one (8%) during follow-up in the AU-study, and one (8%) at baseline and zero (0%) during follow-up in the NL-study. Reasons for low completion at baseline were technical issues (AU-study: 31%, NL-study: 50%), non-adherent participants (15% and 8%) or combinations (15% and 33%); and at follow-up refusal of participants (62% and 25%). These underpowered findings showed that CPTS was non-significantly lower in people who healed compared with non-healed people (457 [117; 727], 679 [312; 1327] MPa·s/day). Current feasibility of CPTS seems low, given technical challenges and non-adherence, which may reflect the burden of treating diabetes-related foot ulcers.
Knowledge of and Attitudes Toward Clinical Trials: A Questionnaire-Based Study of 179 Male Third- and Fourth-Year PharmD Undergraduates from Riyadh, Saudi Arabia
Syed W, Al-Rawi MBA and Bashatah A
BACKGROUND Clinical Trials (CTs) are essential for the formation of a new medicine. This questionnaire-based study included 179 male third- and fourth-year PharmD undergraduate students from Riyadh, Saudi Arabia, between 18 and 23 years of age, was conducted in 2022, and aimed to evaluate student knowledge and attitudes toward CTs. MATERIAL AND METHODS A cross-sectional study was conducted using self-administered questionnaires. The data was collected using convenience sampling. Part 1 of the study collected demographics, with 6 items; part 2 measured knowledge about CTs (9 items); part 3 measured attitudes (5 items) measured on a 5-point Likert scale. A score of 1 was given for correct, and a score of 0 for each incorrect response. Multiple linear regression was used to evaluate the determinants of knowledge and attitudes about CTs. RESULTS A total of 108 (60.3%) undergraduates reported having heard about CTs, 15% of undergraduates had heard about institutional review boards, while 74.3% of the undergraduates believed that CTs have direct benefits to society. The mean knowledge score of the CTs among the students was 5.75±2.32 (median 6.00), while the mean attitude score of CTs was 16.45±4.56 (median 16.00). However, the results of the simple regression model revealed that age, year of study, and chronic disease status were not predictors of the knowledge and attitude score (P>0.05). CONCLUSIONS This study indicated that half of undergraduates were aware of CTs, were knowledgeable, and showed positive attitudes. Furthermore, the study identified potential misunderstandings about the benefits of CTs.
What's good for the gander is even better for the goose: Women buying commercial sex in China
Tsang EYH
Research about the commercial sex industry rarely examines the women who are the clients purchasing sexual services. Examining how this challenges gender stereotypes through the undoing gender framework reveals how gender norms can be reshaped through contextual changes. Based on 3 years of ethnographic data from a high-end bar in Tianjin, interviews with 27 female clients and 47 MSWs paint a complex picture of how some women adopted ungendered strategies regarding sexuality. As women take control of their own sexual behavior, they free themselves of some traditional societal expectations about their identity. Primarily motivated by pleasure and control, purchasing sex becomes a means for women to experience empowerment and self-confidence by breaking with traditional gender norms and expectations. Undoing gender involves expanding gendered repertoires, with women finding empowerment in adopting a masculine model of sexuality. However, social stigma and personal efficacy indicate that gender deconstruction is a gradual process. The research contributes to understanding complex gender dynamics and sexual behaviors within commercial sex transactions, shedding light on societal norms and individual agency.
A Rare Autochthonous Case of Hepatic Hydatid Cyst in the Non-Endemic Region of Taiwan
Chen MY and Chen TL
BACKGROUND Hepatic hydatid cyst disease, caused by the parasite Echinococcus granulosus, is endemic in certain rural areas of the world, but not in most of East Asia outside Mainland China. In Taiwan, only one autochthonous case has been reported over the past 40 years. We present the case of an urban 91-year-old female patient without international travel history for more than 40 years. CASE REPORT The 91-year-old woman who used a wheelchair came to the Emergency Department reporting melena for 2 days and 1 episode of coffee-grounds vomitus. Epigastric tenderness was present. An incidental finding of elevated liver enzymes along with the clinical picture prompted further survey. Computed tomography revealed a 14×10×12 cm homogeneous cystic lesion in the right hepatic lobe with a partially calcified wall. On sonograms, a similar lesion was found, and the pathognomic "water-lily" sign was visualized along with the isoechoic-to-hypoechoic internal septa, fulfilling the diagnosis despite the patient's refusal to undergo magnetic resonance imaging studies and invasive definite diagnostic procedures. Although anthelmintic chemotherapy and invasive therapeutic measures were also refused, her symptoms improved and was not recurrent under supportive measures. However, the cyst was still present 12 months after discharge. CONCLUSIONS The case highlights that in areas with few cases of hepatic hydatid disease, the accurate diagnosis could be missed in patients without a significant epidemiological history. However, once imaging findings, especially those that are pathognomic, are appropriately interpreted on at least 2 imaging modalities, such cases could be diagnosed without further definitive studies.
Respiration and Heart Rate Monitoring in Smart Homes: An Angular-Free Approach with an FMCW Radar
Mehrjouseresht P, Hail RE, Karsmakers P and Schreurs DMM
This paper proposes a new approach for wide angle monitoring of vital signs in smart home applications. The person is tracked using an indoor radar. Upon detecting the person to be static, the radar automatically focuses its beam on that location, and subsequently breathing and heart rates are extracted from the reflected signals using continuous wavelet transform (CWT) analysis. In this way, leveraging the radar's on-chip processor enables real-time monitoring of vital signs across varying angles. In our experiment, we employ a commercial multi-input multi-output (MIMO) millimeter-wave FMCW radar to monitor vital signs within a range of 1.15 to 2.3 m and an angular span of -44.8 to +44.8 deg. In the Bland-Altman plot, the measured results indicate the average difference of -1.5 and 0.06 beats per minute (BPM) relative to the reference for heart rate and breathing rate, respectively.
Thermal Imaging of the Tongue Surface as a Predictive Method in the Diagnosis of Type 2 Diabetes Mellitus
Wziątek-Kuczmik D, Świątkowski A, Cholewka A, Mrowiec A, Niedzielska I and Stanek A
Over the past 20 years, the high prevalence of diabetes has become a global public health problem.
Dynamic Stability, Symmetry, and Smoothness of Gait in People with Neurological Health Conditions
Tramontano M, Orejel Bustos AS, Montemurro R, Vasta S, Marangon G, Belluscio V, Morone G, Modugno N, Buzzi MG, Formisano R, Bergamini E and Vannozzi G
Neurological disorders such as stroke, Parkinson's disease (PD), and severe traumatic brain injury (sTBI) are leading global causes of disability and mortality. This study aimed to assess the ability to walk of patients with sTBI, stroke, and PD, identifying the differences in dynamic postural stability, symmetry, and smoothness during various dynamic motor tasks. Sixty people with neurological disorders and 20 healthy participants were recruited. Inertial measurement unit (IMU) sensors were employed to measure spatiotemporal parameters and gait quality indices during different motor tasks. The Mini-BESTest, Berg Balance Scale, and Dynamic Gait Index Scoring were also used to evaluate balance and gait. People with stroke exhibited the most compromised biomechanical patterns, with lower walking speed, increased stride duration, and decreased stride frequency. They also showed higher upper body instability and greater variability in gait stability indices, as well as less gait symmetry and smoothness. PD and sTBI patients displayed significantly different temporal parameters and differences in stability parameters only at the pelvis level and in the smoothness index during both linear and curved paths. This study provides a biomechanical characterization of dynamic stability, symmetry, and smoothness in people with stroke, sTBI, and PD using an IMU-based ecological assessment.
Comparison of Metabolic Power and Energy Cost of Submaximal and Sprint Running Efforts Using Different Methods in Elite Youth Soccer Players: A Novel Energetic Approach
Grassadonia G, Alcaraz PE and Freitas TT
Sprinting is a decisive action in soccer that is considerably taxing from a neuromuscular and energetic perspective. This study compared different calculation methods for the metabolic power (MP) and energy cost (EC) of sprinting using global positioning system (GPS) metrics and electromyography (EMG), with the aim of identifying potential differences in performance markers. Sixteen elite U17 male soccer players (age: 16.4 ± 0.5 years; body mass: 64.6 ± 4.4 kg; and height: 177.4 ± 4.3 cm) participated in the study and completed four different submaximal constant running efforts followed by sprinting actions while using portable GPS-IMU units and surface EMG. GPS-derived MP was determined based on GPS velocity, and the EMG-MP and EC were calculated based on individual profiles plotting the MP of the GPS and all EMG signals acquired. The goodness of fit of the linear regressions was assessed by the coefficient of determination (R), and a repeated measures ANOVA was used to detect changes. A linear trend was found in EMG activity during submaximal speed runs (R = 1), but when the sprint effort was considered, the trend became exponential (R = 0.89). The EMG/force ratio displayed two different trends: linear up to a 30 m sprint (R = 0.99) and polynomial up to a 50 m sprint (R = 0.96). Statistically significant differences between the GPS and EMG were observed for MP splits at 0-5 m, 5-10 m, 25-30 m, 30-35 m, and 35-40 m and for EC splits at 5-10 m, 25-30 m, 30-35 m, and 35-40 m ( ≤ 0.05). Therefore, the determination of the MP and EC based on GPS technology underestimated the neuromuscular and metabolic engagement during the sprinting efforts. Thus, the EMG-derived method seems to be more accurate for calculating the MP and EC in this type of action.
A Phosphenotron Device for Sensoric Spatial Resolution of Phosphenes within the Visual Field Using Non-Invasive Transcranial Alternating Current Stimulation
Sadrzadeh-Afsharazar F and Douplik A
This study presents phosphenotron, a device for enhancing the sensory spatial resolution of phosphenes in the visual field (VF). The phosphenotron employs a non-invasive transcranial alternating current stimulation (NITACS) to modulate brain activity by applying weak electrical currents to the scalp or face. NITACS's unique application induces phosphenes, a phenomenon where light is perceived without external stimuli. Unlike previous invasive methods, NITACS offers a non-invasive approach to create these effects. The study focused on assessing the spatial resolution of NITACS-induced phosphenes, crucial for advancements in visual aid technology and neuroscience. Eight participants were subjected to NITACS using a novel electrode arrangement around the eye orbits. Results showed that NITACS could generate spatially defined phosphene patterns in the VF, varying among individuals but consistently appearing within their VF and remaining stable through multiple stimulations. The study established optimal parameters for vibrant phosphene induction without discomfort and identified electrode positions that altered phosphene locations within different VF regions. Receiver Operating characteristics analysis indicated a specificity of 70.7%, sensitivity of 73.9%, and a control trial accuracy of 98.4%. These findings suggest that NITACS is a promising, reliable method for non-invasive visual perception modulation through phosphene generation.
A Multi-Modal Egocentric Activity Recognition Approach towards Video Domain Generalization
Papadakis A and Spyrou E
Egocentric activity recognition is a prominent computer vision task that is based on the use of wearable cameras. Since egocentric videos are captured through the perspective of the person wearing the camera, her/his body motions severely complicate the video content, imposing several challenges. In this work we propose a novel approach for domain-generalized egocentric human activity recognition. Typical approaches use a large amount of training data, aiming to cover all possible variants of each action. Moreover, several recent approaches have attempted to handle discrepancies between domains with a variety of costly and mostly unsupervised domain adaptation methods. In our approach we show that through simple manipulation of available source domain data and with minor involvement from the target domain, we are able to produce robust models, able to adequately predict human activity in egocentric video sequences. To this end, we introduce a novel three-stream deep neural network architecture combining elements of vision transformers and residual neural networks which are trained using multi-modal data. We evaluate the proposed approach using a challenging, egocentric video dataset and demonstrate its superiority over recent, state-of-the-art research works.
Ballistocardial Signal-Based Personal Identification Using Deep Learning for the Non-Invasive and Non-Restrictive Monitoring of Vital Signs
Takahashi K and Ueno H
Owing to accelerated societal aging, the prevalence of elderly individuals experiencing solitary or sudden death at home has increased. Therefore, herein, we aimed to develop a monitoring system that utilizes piezoelectric sensors for the non-invasive and non-restrictive monitoring of vital signs, including the heart rate and respiration, to detect changes in the health status of several elderly individuals. A ballistocardiogram with a piezoelectric sensor was tested using seven individuals. The frequency spectra of the biosignals acquired from the piezoelectric sensors exhibited multiple peaks corresponding to the harmonics originating from the heartbeat. We aimed for individual identification based on the shapes of these peaks as the recognition criteria. The results of individual identification using deep learning techniques revealed good identification proficiency. Altogether, the monitoring system integrated with piezoelectric sensors showed good potential as a personal identification system for identifying individuals with abnormal biological signals.
Experimental Evaluation of Pedestrian-Induced Multiaxial Gait Loads on Footbridges: Effects of the Structure-to-Human Interaction by Lateral Vibrating Platforms
Castillo B, Marulanda J and Thomson P
The introduction of resistant and lightweight materials in the construction industry has led to civil structures being vulnerable to excessive vibrations, particularly in footbridges exposed to human-induced gait loads. This interaction, known as Human-Structure Interaction (HSI), involves a complex interplay between structural vibrations and gait loads. Despite extensive research on HSI, the simultaneous effects of lateral structural vibrations with fundamental frequencies close to human gait frequency (around 1.0 Hz) and wide amplitudes (over 30.0 mm) remain inadequately understood, posing a contemporary structural challenge highlighted by incidents in iconic bridges like the Millennium Bridge in London, Solferino Bridge in Paris, and Premier Bridge in Cali, Colombia. This paper focuses on the experimental exploration of Structure-to-Human Interaction (S2HI) effects using the Human-Structure Interaction Multi-Axial Test Framework (HSI-MTF). The framework enables the simultaneous measurement of vertical and lateral loads induced by human gait on surfaces with diverse frequency ranges and wide-amplitude lateral harmonic motions. The study involved seven test subjects, evaluating gait loads on rigid and harmonic lateral surfaces with displacements ranging from 5.0 to 50.0 mm and frequency content from 0.70 to 1.30 Hz. A low-cost vision-based motion capture system with smartphones analyzed the support () and swing () periods of human gait. Results indicated substantial differences in and on lateral harmonic protocols, reaching up to 96.53% and 58.15%, respectively, compared to rigid surfaces. Normalized lateral loads () relative to the subject's weight () exhibited a linear growth proportional to lateral excitation frequency, with increased proportionality constants linked to higher vibration amplitudes. Linear regressions yielded an average R of 0.815. Regarding normalized vertical load () with respect to , a consistent behavior was observed for amplitudes up to 30.0 mm, beyond which a linear increase, directly proportional to frequency, resulted in a 28.3% increment compared to rigid surfaces. Correlation analyses using Pearson linear coefficients determined relationships between structural surface vibration and pedestrian lateral motion, providing valuable insights into Structure-to-Human Interaction dynamics.
Maximizing the Reliability and Precision of Measures of Prefrontal Cortical Oxygenation Using Frequency-Domain Near-Infrared Spectroscopy
Fletcher EKS, Burma JS, Javra RM, Friesen KB, Emery CA, Dunn JF and Smirl JD
Frequency-domain near-infrared spectroscopy (FD-NIRS) has been used for non-invasive assessment of cortical oxygenation since the late 1990s. However, there is limited research demonstrating clinical validity and general reproducibility. To address this limitation, recording duration for adequate validity and within- and between-day reproducibility of prefrontal cortical oxygenation was evaluated. To assess validity, a reverse analysis of 10-min-long measurements ( = 52) at different recording durations (1-10-min) was quantified via coefficients of variation and Bland-Altman plots. To assess within- and between-day within-subject reproducibility, participants ( = 15) completed 2-min measurements twice a day (morning/afternoon) for five consecutive days. While 1-min recordings demonstrated sufficient validity for the assessment of oxygen saturation (SO) and total hemoglobin concentration (THb), recordings ≥4 min revealed greater clinical utility for oxy- (HbO) and deoxyhemoglobin (HHb) concentration. Females had lower SO THb, HbO, and HHb values than males, but variability was approximately equal between sexes. Intraclass correlation coefficients ranged from 0.50-0.96. The minimal detectable change for SO was 1.15% (95% CI: 0.336-1.96%) and 3.12 µM for THb (95% CI: 0.915-5.33 µM) for females and 2.75% (95%CI: 0.807-4.70%) for SO and 5.51 µM (95%CI: 1.62-9.42 µM) for THb in males. Overall, FD-NIRS demonstrated good levels of between-day reliability. These findings support the application of FD-NIRS in field-based settings and indicate a recording duration of 1 min allows for valid measures; however, data recordings of ≥4 min are recommended when feasible.
Development and Evaluation of a Hybrid Measurement System to Determine the Kinematics of the Wrist
Dellai J, Gilles MA, Remy O, Claudon L and Dietrich G
Optical Motion Capture Systems (OMCSs) are considered the gold standard for kinematic measurement of human movements. However, in situations such as measuring wrist kinematics during a hairdressing activity, markers can be obscured, resulting in a loss of data. Other measurement methods based on non-optical data can be considered, such as magneto-inertial measurement units (MIMUs). Their accuracy is generally lower than that of an OMCS. In this context, it may be worth considering a hybrid system [MIMU + OMCS] to take advantage of OMCS accuracy while limiting occultation problems. The aim of this work was (1) to propose a methodology for coupling a low-cost MIMU (BNO055) to an OMCS in order to evaluate wrist kinematics, and then (2) to evaluate the accuracy of this hybrid system [MIMU + OMCS] during a simple hairdressing gesture. During hair cutting gestures, the root mean square error compared with the OMCS was 4.53° (1.45°) for flexion/extension, 5.07° (1.30°) for adduction/abduction, and 3.65° (1.19°) for pronation/supination. During combing gestures, they were significantly higher, but remained below 10°. In conclusion, this system allows for maintaining wrist kinematics in case of the loss of hand markers while preserving an acceptable level of precision (<10°) for ergonomic measurement or entertainment purposes.
COVID-19 Hierarchical Classification Using a Deep Learning Multi-Modal
Althenayan AS, AlSalamah SA, Aly S, Nouh T, Mahboub B, Salameh L, Alkubeyyer M and Mirza A
Coronavirus disease 2019 (COVID-19), originating in China, has rapidly spread worldwide. Physicians must examine infected patients and make timely decisions to isolate them. However, completing these processes is difficult due to limited time and availability of expert radiologists, as well as limitations of the reverse-transcription polymerase chain reaction (RT-PCR) method. Deep learning, a sophisticated machine learning technique, leverages radiological imaging modalities for disease diagnosis and image classification tasks. Previous research on COVID-19 classification has encountered several limitations, including binary classification methods, single-feature modalities, small public datasets, and reliance on CT diagnostic processes. Additionally, studies have often utilized a flat structure, disregarding the hierarchical structure of pneumonia classification. This study aims to overcome these limitations by identifying pneumonia caused by COVID-19, distinguishing it from other types of pneumonia and healthy lungs using chest X-ray (CXR) images and related tabular medical data, and demonstrate the value of incorporating tabular medical data in achieving more accurate diagnoses. Resnet-based and VGG-based pre-trained convolutional neural network (CNN) models were employed to extract features, which were then combined using early fusion for the classification of eight distinct classes. We leveraged the hierarchal structure of pneumonia classification within our approach to achieve improved classification outcomes. Since an imbalanced dataset is common in this field, a variety of versions of generative adversarial networks (GANs) were used to generate synthetic data. The proposed approach tested in our private datasets of 4523 patients achieved a macro-avg F1-score of 95.9% and an F1-score of 87.5% for COVID-19 identification using a Resnet-based structure. In conclusion, in this study, we were able to create an accurate deep learning multi-modal to diagnose COVID-19 and differentiate it from other kinds of pneumonia and normal lungs, which will enhance the radiological diagnostic process.
Assessing the Impact of COVID-19 on Amateur Runners' Performance: An Analysis through Monitoring Devices
García-Arrabé M, Giménez MJ, Moriceau J, Fevre A, Roy JS, González-de-la-Flor Á and de la Plaza San Frutos M
This retrospective study aimed to analyze the return to running of non-professional runners after experiencing asymptomatic or mild COVID-19. Participants aged 18-55 years who maintained a training load of ≥10 km/week for at least three months prior to diagnosis and utilized Garmin/Polar apps were included. From these devices, parameters such as pace, distance, total running time, cadence, and heart rate were collected at three intervals: pre-COVID, immediately post-COVID, and three months after diagnosis. The Wilcoxon signed rank test was used for analysis (significance was set at ≤0.05). Twenty-one participants (57.1% male; mean age 35.0 ± 9.8 years) were included. The results revealed a significant decrease in running duration and distance two weeks after diagnosis, without significant changes in other parameters. Three months after infection, no differences were observed compared to pre-infection data, indicating a return to the pre-disease training load. These findings underscore the transient impact of COVID-19 on training performance among non-professional runners with mild or asymptomatic symptoms, highlighting the importance of tailored strategies for resuming running after infection.
Personalized Machine Learning-Based Prediction of Wellbeing and Empathy in Healthcare Professionals
Nan J, Herbert MS, Purpura S, Henneken AN, Ramanathan D and Mishra J
Healthcare professionals are known to suffer from workplace stress and burnout, which can negatively affect their empathy for patients and quality of care. While existing research has identified factors associated with wellbeing and empathy in healthcare professionals, these efforts are typically focused on the group level, ignoring potentially important individual differences and implications for individualized intervention approaches. In the current study, we implemented N-of-1 personalized machine learning (PML) to predict wellbeing and empathy in healthcare professionals at the individual level, leveraging ecological momentary assessments (EMAs) and smartwatch wearable data. A total of 47 mood and lifestyle feature variables (relating to sleep, diet, exercise, and social connections) were collected daily for up to three months followed by applying eight supervised machine learning (ML) models in a PML pipeline to predict wellbeing and empathy separately. Predictive insight into the model architecture was obtained using Shapley statistics for each of the best-fit personalized models, ranking the importance of each feature for each participant. The best-fit model and top features varied across participants, with anxious mood (13/19) and depressed mood (10/19) being the top predictors in most models. Social connection was a top predictor for wellbeing in 9/12 participants but not for empathy models (1/7). Additionally, empathy and wellbeing were the top predictors of each other in 64% of cases. These findings highlight shared and individual features of wellbeing and empathy in healthcare professionals and suggest that a one-size-fits-all approach to addressing modifiable factors to improve wellbeing and empathy will likely be suboptimal. In the future, such personalized models may serve as actionable insights for healthcare professionals that lead to increased wellness and quality of patient care.
Characterization of Running Intensity in Canadian Football Based on Tactical Position
Zafar A, Guay S, Vinet SA, Apinis-Deshaies A, Creniault R, Martens G, Prince F and De Beaumont L
This study aimed to use a data-driven approach to identify individualized speed thresholds to characterize running demands and athlete workload during games and practices in skill and linemen football players. Data were recorded from wearable sensors over 28 sessions from 30 male Canadian varsity football athletes, resulting in a total of 287 performances analyzed, including 137 games and 150 practices, using a global positioning system. Speed zones were identified for each performance by fitting a 5-dimensional Gaussian mixture model (GMM) corresponding to 5 running intensity zones from minimal (zone 1) to maximal (zone 5). Skill players had significantly higher ( < 0.001) speed thresholds, percentage of time spent, and distance covered in maximal intensity zones compared to linemen. The distance covered in game settings was significantly higher ( < 0.001) compared to practices. This study highlighted the use of individualized speed thresholds to determine running intensity and athlete workloads for American and Canadian football athletes, as well as compare running performances between practice and game scenarios. This approach can be used to monitor physical workload in athletes with respect to their tactical positions during practices and games, and to ensure that athletes are adequately trained to meet in-game physical demands.
Exploring Human-Exoskeleton Interaction Dynamics: An In-Depth Analysis of Knee Flexion-Extension Performance across Varied Robot Assistance-Resistance Configurations
Mosconi D, Moreno Y and Siqueira A
Knee rehabilitation therapy after trauma or neuromotor diseases is fundamental to restore the joint functions as best as possible, exoskeleton robots being an important resource in this context, since they optimize therapy by applying tailored forces to assist or resist movements, contributing to improved patient outcomes and treatment efficiency. One of the points that must be taken into account when using robots in rehabilitation is their interaction with the patient, which must be safe for both and guarantee the effectiveness of the treatment. Therefore, the objective of this study was to assess the interaction between humans and an exoskeleton during the execution of knee flexion-extension movements under various configurations of robot assistance and resistance. The evaluation encompassed considerations of myoelectric activity, muscle recruitment, robot torque, and performed movement. To achieve this, an experimental protocol was implemented, involving an individual wearing the exoskeleton and executing knee flexion-extension motions while seated, with the robot configured in five distinct modes: passive (P), assistance on flexion (FA), assistance on extension (EA), assistance on flexion and extension (CA), and resistance on flexion and extension (CR). Results revealed distinctive patterns of movement and muscle recruitment for each mode, highlighting the complex interplay between human and robot; for example, the largest RMS tracking errors were for the EA mode (13.72 degrees) while the smallest for the CR mode (4.47 degrees), a non-obvious result; in addition, myoelectric activity was demonstrated to be greater for the completely assisted mode than without the robot (the maximum activation levels for the vastus medialis and vastus lateralis muscles were more than double those when the user had assistance from the robot). Tracking errors, muscle activations, and torque values varied across modes, emphasizing the need for careful consideration in configuring exoskeleton assistance and resistance to ensure effective and safe rehabilitation. Understanding these human-robot interactions is essential for developing precise rehabilitation programs, optimizing treatment effectiveness, and enhancing patient safety.
A Sensor-Based Upper Limb Treatment in Hemiplegic Patients: Results from a Randomized Pilot Study
Vanoglio F, Comini L, Gaiani M, Bonometti GP, Luisa A and Bernocchi P
In post-stroke patients, the disabling motor deficit mainly affects the upper limb. The focus of rehabilitation is improving upper limb function and reducing long-term disability. This study aims to evaluate the feasibility of using the Gloreha Aria (R-Lead), a sensor-based upper limb in-hospital rehabilitation, compared with conventional physiotherapist-led training in subacute hemiplegic patients. Twenty-one patients were recruited and randomised 1:1 to a sensor-based group (treatment group TG) or a conventional group (control group, CG). All patients performed 30 sessions of 30 min each of dedicated upper limb rehabilitation. The Fugl-Meyer Assessment for Upper Extremity (FMA-UE) was the primary evaluation., both as a motor score and as individual items. Secondary evaluations were Functional Independence Measure; global disability assessed with the Modified Barthel Index; Motor Evaluation Scale for UE in stroke; power grip; and arm, shoulder, and hand disability. All the enrolled patients, 10 in the TG and 11 in the CG, completed all hand rehabilitation sessions during their hospital stay without experiencing any adverse events. FMA-UE scores in upper limb motor function improved in both groups [delta change CG (11.8 ± 9.2) vs. TG (12.7 ± 8.6)]. The score at T1 for FMA joint pain (21.8 vs. 24 best score) suggests the use of the Gloreha Aria (R-Lead) as feasible in improving arm function abilities in post-stroke patients.
Identification of the Biomechanical Response of the Muscles That Contract the Most during Disfluencies in Stuttered Speech
Marin E, Unsihuay N, Abarca VE and Elias DA
Stuttering, affecting approximately 1% of the global population, is a complex speech disorder significantly impacting individuals' quality of life. Prior studies using electromyography (EMG) to examine orofacial muscle activity in stuttering have presented mixed results, highlighting the variability in neuromuscular responses during stuttering episodes. Fifty-five participants with stuttering and 30 individuals without stuttering, aged between 18 and 40, participated in the study. EMG signals from five facial and cervical muscles were recorded during speech tasks and analyzed for mean amplitude and frequency activity in the 5-15 Hz range to identify significant differences. Upon analysis of the 5-15 Hz frequency range, a higher average amplitude was observed in the zygomaticus major muscle for participants while stuttering ( < 0.05). Additionally, when assessing the overall EMG signal amplitude, a higher average amplitude was observed in samples obtained from disfluencies in participants who did not stutter, particularly in the depressor anguli oris muscle ( < 0.05). Significant differences in muscle activity were observed between the two groups, particularly in the depressor anguli oris and zygomaticus major muscles. These results suggest that the underlying neuromuscular mechanisms of stuttering might involve subtle aspects of timing and coordination in muscle activation. Therefore, these findings may contribute to the field of biosensors by providing valuable perspectives on neuromuscular mechanisms and the relevance of electromyography in stuttering research. Further research in this area has the potential to advance the development of biosensor technology for language-related applications and therapeutic interventions in stuttering.
Pupil Response in Visual Tracking Tasks: The Impacts of Task Load, Familiarity, and Gaze Position
Wu Y, Zhang Z, Zhang Y, Zheng B and Aghazadeh F
Pupil size is a significant biosignal for human behavior monitoring and can reveal much underlying information. This study explored the effects of task load, task familiarity, and gaze position on pupil response during learning a visual tracking task. We hypothesized that pupil size would increase with task load, up to a certain level before decreasing, decrease with task familiarity, and increase more when focusing on areas preceding the target than other areas. Fifteen participants were recruited for an arrow tracking learning task with incremental task load. Pupil size data were collected using a Tobii Pro Nano eye tracker. A 2 × 3 × 5 three-way factorial repeated measures ANOVA was conducted using R (version 4.2.1) to evaluate the main and interactive effects of key variables on adjusted pupil size. The association between individuals' cognitive load, assessed by NASA-TLX, and pupil size was further analyzed using a linear mixed-effect model. We found that task repetition resulted in a reduction in pupil size; however, this effect was found to diminish as the task load increased. The main effect of task load approached statistical significance, but different trends were observed in trial 1 and trial 2. No significant difference in pupil size was detected among the three gaze positions. The relationship between pupil size and cognitive load overall followed an inverted U curve. Our study showed how pupil size changes as a function of task load, task familiarity, and gaze scanning. This finding provides sensory evidence that could improve educational outcomes.
Association of Visual-Based Signals with Electroencephalography Patterns in Enhancing the Drowsiness Detection in Drivers with Obstructive Sleep Apnea
Minhas R, Peker NY, Hakkoz MA, Arbatli S, Celik Y, Erdem CE, Semiz B and Peker Y
Individuals with obstructive sleep apnea (OSA) face increased accident risks due to excessive daytime sleepiness. PERCLOS, a recognized drowsiness detection method, encounters challenges from image quality, eyewear interference, and lighting variations, impacting its performance, and requiring validation through physiological signals. We propose visual-based scoring using adaptive thresholding for eye aspect ratio with OpenCV for face detection and Dlib for eye detection from video recordings. This technique identified 453 drowsiness (PERCLOS ≥ 0.3 || CLOSDUR ≥ 2 s) and 474 wakefulness episodes (PERCLOS < 0.3 and CLOSDUR < 2 s) among fifty OSA drivers in a 50 min driving simulation while wearing six-channel EEG electrodes. Applying discrete wavelet transform, we derived ten EEG features, correlated them with visual-based episodes using various criteria, and assessed the sensitivity of brain regions and individual EEG channels. Among these features, theta-alpha-ratio exhibited robust mapping (94.7%) with visual-based scoring, followed by delta-alpha-ratio (87.2%) and delta-theta-ratio (86.7%). Frontal area (86.4%) and channel F4 (75.4%) aligned most episodes with theta-alpha-ratio, while frontal, and occipital regions, particularly channels F4 and O2, displayed superior alignment across multiple features. Adding frontal or occipital channels could correlate all episodes with EEG patterns, reducing hardware needs. Our work could potentially enhance real-time drowsiness detection reliability and assess fitness to drive in OSA drivers.
Detecting Leadership Opportunities in Group Discussions Using Off-the-Shelf VR Headsets
Gu C, Chen J, Zhang J, Yang T, Liu Z and Konomi S
The absence of some forms of non-verbal communication in virtual reality (VR) can make VR-based group discussions difficult even when a leader is assigned to each group to facilitate discussions. In this paper, we discuss if the sensor data from off-the-shelf VR devices can be used to detect opportunities for facilitating engaging discussions and support leaders in VR-based group discussions. To this end, we focus on the detection of suppressed speaking intention in VR-based group discussions by using personalized and general models. Our extensive analysis of experimental data reveals some factors that should be considered to enable effective feedback to leaders. In particular, our results show the benefits of combining the sensor data from leaders and low-engagement participants, and the usefulness of specific HMD sensor features.
Call to Action: Investigating Interaction Delay in Smartphone Notifications
Stach M, Mulansky L, Reichert M, Pryss R and Beierle F
Notifications are an essential part of the user experience on smart mobile devices. While some apps have to notify users immediately after an event occurs, others can schedule notifications strategically to notify them only on opportune moments. This tailoring allows apps to shorten the users' interaction delay. In this paper, we present the results of a comprehensive study that identified the factors that influence users' interaction delay to their smartphone notifications. We analyzed almost 10 million notifications collected in-the-wild from 922 users and computed their response times with regard to their demographics, their Big Five personality trait scores and the device's charging state. Depending on the app category, the following tendencies can be identified over the course of the day: Most notifications were logged in late morning and late afternoon. This number decreases in the evening, between 8 p.m. and 11 p.m., and at the same time exhibits the lowest average interaction delays at daytime. We also found that the user's sex and age is significantly associated with the response time. Based on the results of our study, we encourage developers to incorporate more information on the user and the executing device in their notification strategy to notify users more effectively.
Energy Expenditure Prediction from Accelerometry Data Using Long Short-Term Memory Recurrent Neural Networks
Vibæk M, Peimankar A, Wiil UK, Arvidsson D and Brønd JC
The accurate estimation of energy expenditure from simple objective accelerometry measurements provides a valuable method for investigating the effect of physical activity (PA) interventions or population surveillance. Methods have been evaluated previously, but none utilize the temporal aspects of the accelerometry data. In this study, we investigated the energy expenditure prediction from acceleration measured at the subjects' hip, wrist, thigh, and back using recurrent neural networks utilizing temporal elements of the data. The acceleration was measured in children (N = 33) performing a standardized activity protocol in their natural environment. The energy expenditure was modelled using Multiple Linear Regression (MLR), stacked long short-term memory (LSTM) networks, and combined convolutional neural networks (CNN) and LSTM. The correlation and mean absolute percentage error (MAPE) were 0.76 and 19.9% for the MLR, 0.882 and 0.879 and 14.22% for the LSTM, and, with the combined LSTM-CNN, the best performance of 0.883 and 13.9% was achieved. The prediction error for vigorous intensities was significantly different ( < 0.01) from those of the other intensity domains: sedentary, light, and moderate. Utilizing the temporal elements of movement significantly improves energy expenditure prediction accuracy compared to other conventional approaches, but the prediction error for vigorous intensities requires further investigation.
Personal Air-Quality Monitoring with Sensor-Based Wireless Internet-of-Things Electronics Embedded in Protective Face Masks
Kuglics L, Géczy A, Dusek K, Busek D and Illés B
In this paper, the design and research of a sensor-based personal air-quality monitoring device are presented, which is retrofitted into different personal protective face masks. Due to its small size and low power consumption, the device can be integrated into and applied in practical urban usage. We present our research and the development of the sensor node based on a BME680-type environmental sensor cluster with a wireless IoT (Internet of Things)-capable central unit and overall low power consumption. The integration of the sensor node was investigated with traditional medical masks and a professional FFP2-type mask. The filtering efficiency after embedding was validated with a head model and a particle counter. We found that the professional mask withstood the embedding without losing the protective filtering aspect. We compared the inner and outer sensor data and investigated the temperature, pressure, humidity, and AQI (Air Quality Index) relations with possible sensor data-fusion options. The novelty is increased with the dual-sensor layout (inward and outward). It was found that efficient respiration monitoring is achievable with the device. With the analysis of the recorded data, characteristic signals were identified in an urban environment, enabling urban altimetry and urban zone detection. The results promote smart city concepts and help in endeavors related to SDGs (Sustainable Development Goals) 3 and 11.
Validity Verification of Human Pose-Tracking Algorithms for Gait Analysis Capability
Matsuda T, Fujino Y, Makabe H, Morisawa T, Takahashi T, Kakegawa K, Matsumoto T, Kiyohara T, Torimoto Y, Miwa M, Fujiwara T and Daida H
Two-dimensional (2D) clinical gait analysis systems are more affordable and portable than contemporary three-dimensional (3D) clinical models. Using the Vicon 3D motion capture system as the standard, we evaluated the internal statistics of the Imasen and open-source OpenPose gait measurement systems, both designed for 2D input, to validate their output based on the similarity of results and the legitimacy of their inner statistical processes. We measured time factors, distance factors, and joint angles of the hip and knee joints in the sagittal plane while varying speeds and gaits during level walking in three in-person walking experiments under normal, maximum-speed, and tandem scenarios. The intraclass correlation coefficients of the 2D models were greater than 0.769 for all gait parameters compared with those of Vicon, except for some knee joint angles. The relative agreement was excellent for the time-distance gait parameter and moderate-to-excellent for each gait motion contraction range, except for hip joint angles. The time-distance gait parameter was high for Cronbach's alpha coefficients of 0.899-0.993 but low for 0.298-0.971. Correlation coefficients were greater than 0.571 for time-distance gait parameters but lower for joint angle parameters, particularly hip joint angles. Our study elucidates areas in which to improve 2D models for their widespread clinical application.
ST-TGR: Spatio-Temporal Representation Learning for Skeleton-Based Teaching Gesture Recognition
Chen Z, Huang W, Liu H, Wang Z, Wen Y and Wang S
Teaching gesture recognition is a technique used to recognize the hand movements of teachers in classroom teaching scenarios. This technology is widely used in education, including for classroom teaching evaluation, enhancing online teaching, and assisting special education. However, current research on gesture recognition in teaching mainly focuses on detecting the static gestures of individual students and analyzing their classroom behavior. To analyze the teacher's gestures and mitigate the difficulty of single-target dynamic gesture recognition in multi-person teaching scenarios, this paper proposes skeleton-based teaching gesture recognition (ST-TGR), which learns through spatio-temporal representation. This method mainly uses the human pose estimation technique RTMPose to extract the coordinates of the keypoints of the teacher's skeleton and then inputs the recognized sequence of the teacher's skeleton into the MoGRU action recognition network for classifying gesture actions. The MoGRU action recognition module mainly learns the spatio-temporal representation of target actions by stacking a multi-scale bidirectional gated recurrent unit (BiGRU) and using improved attention mechanism modules. To validate the generalization of the action recognition network model, we conducted comparative experiments on datasets including NTU RGB+D 60, UT-Kinect Action3D, SBU Kinect Interaction, and Florence 3D. The results indicate that, compared with most existing baseline models, the model proposed in this article exhibits better performance in recognition accuracy and speed.
Associations between pathological features and risk of metachronous colorectal cancer
Zhang Y, Win AK, Makalic E, Buchanan DD, Pai RK, Phipps AI, Rosty C, Boussioutas A, Karahalios A and Jenkins MA
Survivors of colorectal cancer (CRC) are at risk of developing another primary colorectal cancer - metachronous CRC. Understanding which pathological features of the first tumour are associated with risk of metachronous CRC might help tailor existing surveillance guidelines. Population-based CRC cases were recruited from the United States, Canada and Australia between 1997 and 2012 and followed prospectively until 2022 by the Colon Cancer Family Registry. Metachronous CRC was defined as a new primary CRC diagnosed at least 1 year after the initial CRC. Those with the genetic cancer predisposition Lynch syndrome or MUTYH mutation carriers were excluded. Cox regression models were fitted to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for the associations. Of 6085 CRC cases, 138 (2.3%) were diagnosed with a metachronous CRC over a median follow-up time of 12 years (incidence: 2.0 per 1000 person-years). CRC cases with a synchronous CRC were 3.4-fold more likely to develop a metachronous CRC (adjusted HR: 3.36, 95% CI: 1.89-5.98) than those without a synchronous tumour. CRC cases with MMR-deficient tumours had a 72% increased risk of metachronous CRC (adjusted HR: 1.72, 95% CI: 1.11-2.64) compared to those with MMR-proficient tumours. Compared to cases who had an adenocarcinoma histologic type, those with an undifferentiated histologic type were 77% less likely to develop a metachronous CRC (adjusted HR: 0.23, 95% CI: 0.06-0.94). Existing surveillance guidelines for CRC survivors could be updated to include increased surveillance for those whose first CRC was diagnosed with a synchronous CRC or was MMR-deficient.
Potential Prodromal Digital Postural Sway Markers for Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Detected via Dual-Tasking and Sensory Manipulation
Timm EC, Purcell NL, Ouyang B, Berry-Kravis E, Hall DA and O'Keefe JA
FXTAS is a neurodegenerative disorder occurring in some Fragile X Messenger Ribonucleoprotein 1 () gene premutation carriers (PMCs) and is characterized by cerebellar ataxia, tremor, and cognitive deficits that negatively impact balance and gait and increase fall risk. Dual-tasking (DT) cognitive-motor paradigms and challenging balance conditions may have the capacity to reveal markers of FXTAS onset. Our objectives were to determine the impact of dual-tasking and sensory and stance manipulation on balance in FXTAS and potentially detect subtle postural sway deficits in PMCs who are asymptomatic for signs of FXTAS on clinical exam. Participants with FXTAS, PMCs without FXTAS, and controls underwent balance testing using an inertial sensor system. Stance, vision, surface stability, and cognitive demand were manipulated in 30 s trials. FXTAS participants had significantly greater total sway area, jerk, and RMS sway than controls under almost all balance conditions but were most impaired in those requiring vestibular control. PMCs without FXTAS had significantly greater RMS sway compared with controls in the feet apart, firm, single task conditions both with eyes open and closed (EC) and the feet together, firm, EC, DT condition. Postural sway deficits in the RMS postural sway variability domain in asymptomatic PMCs might represent prodromal signs of FXTAS. This information may be useful in providing sensitive biomarkers of FXTAS onset and as quantitative balance measures in future interventional trials and longitudinal natural history studies.
Effect of Rule Modifications on Kinematic Parameters Using Maturity Stage as a Moderating Variable in U-10 Football Players
García-Angulo FJ, Palao JM, Giménez-Egido JM and Ortega-Toro E
The aim of the present study was to analyse the effects of regulatory modifications in competitive situations on cinematic variables, considering maturity stage as a moderating factor, in youth football players. A quasi-experimental study was conducted in which 45 players with a mean age of 9.47 ± 0.54 participated. The independent variable analysed was the modification of rules (playing time, scoring, and specific rules). The dependent variables analysed were cinematic variables. These variables were recorded with Wimu. The maturity stage was considered a moderating factor in this effect. The main results indicate that the modified competition reduced the total distance covered, maximum acceleration speed, and distance covered in acceleration and deceleration in different speed zones. In addition, the maturity stage was found to moderate the effect of the intervention on the total distance covered, distance covered by accelerating in zone 3, and distance covered by decelerating in zone 3. Thus, the proposed modification appeared to reduce the physical demand for competition. Furthermore, it reduced the differences between players with early maturational development and those with late maturational development.
Immunogenicity of Two Doses of BNT162b2 mRNA COVID-19 Vaccine with a ChAdOx1-S Booster Dose among Navy Personnel in Mexico
Ventura-Enríquez Y, Cortina-De la Rosa E, Díaz-Padilla E, Murrieta S, Segundo-Martínez S, Fernández-Sánchez V and Vargas-De-León C
Booster doses of the SARS-CoV-2 vaccine have been recommended to improve and prolong immunity, address waning immunity over time, and contribute to the control of the COVID-19 pandemic. A heterologous booster vaccine strategy may offer advantages over a homologous approach. To compare the immunogenicity of two doses of BNT162b2 mRNA COVID-19 vaccine with a ChAdOx1-S booster dose, immunoglobulin G (IgG) anti-spike (anti-S) and anti-nucleocapsid (anti-N) antibody titers (Ab) were compared over 1 year and post-booster vaccination. Results showed that, at 3- to 9-month assessments in vaccinated subjects, an-ti-N Ab were undetectable in participants with no history of COVID-19. In contrast, anti-S Ab measurements were lower than those with COVID-19, and a decrease was observed during the 9 months of observation. After booster vaccination, no differences were found in anti-S between participants who reported a history of COVID-19 and those who did not. Anti-S levels were higher after booster vaccination measurement vs. at 9 months in participants with COVID-19 and without COVID-19, i.e., independent of an infection history. Vaccine administration elicited a response of higher anti-S IgG levels in those infected before vaccination, although levels decreased during the first nine months. IgG anti-N titers were higher in participants with a history of declared infection and who were asymptomatic. The ChAdOx1-S booster increased anti-S Ab levels in participants regardless of whether they had been infected or not to a significantly higher value than with the first two vaccines. These findings underscore the importance of booster vaccination in eliciting a robust and sustained immune response against COVID-19, regardless of the prior infection status.
Predictive capacity of the Integrated Care for Older People (ICOPE) screening tool for intrinsic capacity impairments: results from the INSPIRE-T cohort
Giudici KV, de Souto Barreto P, Guyonnet S, Beard JR, Takeda C, Cantet C, Andrieu S, Vellas B and
The Integrated Care for Older People (ICOPE) approach was developed by the World Health Organization (WHO) aiming to shift the traditional focus of care based on diseases to a function- and person-centered approach, focused on maintaining and monitoring intrinsic capacity (IC). This study aimed to investigate the ability of the ICOPE screening tool to identify older people with clinically meaningful impairments in IC domains.
Sosuga Virus Detected in Egyptian Rousette Bats () in Sierra Leone
Amman BR, Koroma AH, Schuh AJ, Conteh I, Sealy TK, Foday I, Johnny J, Bakarr IA, Whitmer SLM, Wright EA, Gbakima AA, Graziano J, Bangura C, Kamanda E, Osborne A, Saidu E, Musa JA, Bangura DF, Williams SMT, Fefegula GM, Sumaila C, Jabaty J, James FH, Jambai A, Garnett K, Kamara TF, Towner JS and Lebbie A
Sosuga virus (SOSV), a rare human pathogenic paramyxovirus, was first discovered in 2012 when a person became ill after working in South Sudan and Uganda. During an ecological investigation, several species of bats were sampled and tested for SOSV RNA and only one species, the Egyptian rousette bat (ERBs; ), tested positive. Since that time, multiple other species have been sampled and ERBs in Uganda have continued to be the only species of bat positive for SOSV infection. Subsequent studies of ERBs with SOSV demonstrated that ERBs are a competent host for SOSV and shed this infectious virus while exhibiting only minor infection-associated pathology. Following the 2014 Ebola outbreak in West Africa, surveillance efforts focused on discovering reservoirs for zoonotic pathogens resulted in the capture and testing of many bat species. Here, SOSV RNA was detected by qRT-PCR only in ERBs captured in the Moyamba District of Sierra Leone in the central region of the country. These findings represent a substantial range extension from East Africa to West Africa for SOSV, suggesting that this paramyxovirus may occur in ERB populations throughout its sub-Saharan African range.
Achievement of Primary Prevention Cardiometabolic Targets in Women with HIV: An Urgent Call to Action to Pursue Cardiovascular Health
Mazzitelli M, Scaglione V, Cozzolino C, Zuin M, Putaggio C, Bragato B, Vania E, Sasset L, Leoni D, Baldo V and Cattelan A
Cardiometabolic health has become crucial, especially for women with HIV (WWH). We assessed the achievement of targets for hypertension, dyslipidemia, and diabetes (H/Dy/DT) in primary prevention in a WWH cohort.
Identification of Bacteria and Viruses Associated with Patients with Acute Febrile Illness in Khon Kaen Province, Thailand
Jitvaropas R, Sawaswong V, Poovorawan Y, Auysawasdi N, Vuthitanachot V, Wongwairot S, Rodkvamtook W, Lindroth E, Payungporn S and Linsuwanon P
The majority of cases of undifferentiated acute febrile illness (AFI) in the tropics have an undefined etiology. In Thailand, AFI accounts for two-thirds of illnesses reported to the Ministry of Public Health. To characterize the bacterial and viral causes of these AFIs, we conducted molecular pathogen screening and serological analyses in patients who sought treatment in Chum Phae Hospital, Khon Kaen province, during the period from 2015 to 2016. Through integrated approaches, we successfully identified the etiology in 25.5% of cases, with dengue virus infection being the most common cause, noted in 17% of the study population, followed by scrub typhus in 3.8% and rickettsioses in 6.8%. Further investigations targeting viruses in patients revealed the presence of Guadeloupe mosquito virus (GMV) in four patients without other pathogen co-infections. The characterization of four complete genome sequences of GMV amplified from AFI patients showed a 93-97% nucleotide sequence identity with GMV previously reported in mosquitoes. Nucleotide substitutions resulted in amino acid differences between GMV amplified from AFI patients and mosquitoes, observed in 37 positions. However, these changes had undergone purifying selection pressure and potentially had a minimal impact on protein function. Our study suggests that the GMV strains identified in the AFI patients are relatively similar to those previously reported in mosquitoes, highlighting their potential role associated with febrile illness.
Implementing Gait Kinematic Trajectory Forecasting Models on an Embedded System
Shayne M, Molina LA, Hu B and Chomiak T
Smart algorithms for gait kinematic motion prediction in wearable assistive devices including prostheses, bionics, and exoskeletons can ensure safer and more effective device functionality. Although embedded systems can support the use of smart algorithms, there are important limitations associated with computational load. This poses a tangible barrier for models with increased complexity that demand substantial computational resources for superior performance. Forecasting through Recurrent Topology (FReT) represents a computationally lightweight time-series data forecasting algorithm with the ability to update and adapt to the input data structure that can predict complex dynamics. Here, we deployed FReT on an embedded system and evaluated its accuracy, computational time, and precision to forecast gait kinematics from lower-limb motion sensor data from fifteen subjects. FReT was compared to pretrained hyperparameter-optimized NNET and deep-NNET (D-NNET) model architectures, both with static model weight parameters and iteratively updated model weight parameters to enable adaptability to evolving data structures. We found that FReT was not only more accurate than all the network models, reducing the normalized root-mean-square error by almost half on average, but that it also provided the best balance between accuracy, computational time, and precision when considering the combination of these performance variables. The proposed FReT framework on an embedded system, with its improved performance, represents an important step towards the development of new sensor-aided technologies for assistive ambulatory devices.
Vitamin D Levels and SARS-CoV-2 Infection among Medically Underserved Populations in the Minority and Rural Coronavirus Insights Study
Coudray MS, Hansel S, Alesci S, Meyer WA, Christenson RH, Landry LG, Edwards C, Puckrein G, Forney DJ and Akinboboye O
Extant literature presents contradictory findings on the role of vitamin D on SARS-CoV-2 infection. Our study included an examination of the relationship between vitamin D levels and SARS-CoV-2 infection among the Minority and Rural Coronavirus Insights Study (MRCIS) cohort, a diverse population of medically underserved persons presenting at five Federally qualified health centers in the United States.
High Prevalence of Hepatitis B Virus Drug Resistance Mutations to Lamivudine among People with HIV/HBV Coinfection in Rural and Peri-Urban Communities in Botswana
Phinius BB, Anderson M, Gobe I, Mokomane M, Choga WT, Phakedi B, Ratsoma T, Mpebe G, Makhema J, Shapiro R, Lockman S, Musonda R, Moyo S and Gaseitsiwe S
(1) Background: We aimed to determine the prevalence of hepatitis B virus (HBV) resistance-associated mutations (RAMs) in people with HBV and human immunodeficiency virus (HBV/HIV) in Botswana. (2) Methods: We sequenced HBV deoxyribonucleic acid (DNA) from participants with HBV/HIV from the Botswana Combination Prevention Project study (2013-2018) using the Oxford Nanopore GridION platform. Consensus sequences were analyzed for genotypic and mutational profiles. (3) Results: Overall, 98 HBV sequences had evaluable reverse transcriptase region coverage. The median participant age was 43 years (IQR: 37, 49) and 66/98 (67.4%) were female. Most participants, i.e., 86/98 (87.8%) had suppressed HIV viral load (VL). HBV RAMs were identified in 61/98 (62.2%) participants. Most RAMs were in positions 204 (60.3%), 180 (50.5%), and 173 (33.3%), mostly associated with lamivudine resistance. The triple mutations rtM204V/L180M/V173L were the most predominant (17/61 [27.9%]). Most participants (96.7%) with RAMs were on antiretroviral therapy for a median duration of 7.5 years (IQR: 4.8, 10.5). Approximately 27.9% (17/61) of participants with RAMs had undetectable HBV VL, 50.8% (31/61) had VL < 2000 IU/mL, and 13/61 (21.3%) had VL ≥ 2000 IU/mL. (4) Conclusions: The high prevalence of lamivudine RAMs discourages the use of ART regimens with 3TC as the only HBV-active drug in people with HIV/HBV.
Plasma Lipidomic Profiles in cART-Treated Adolescents with Perinatally Acquired HIV Compared to Matched Controls
van der Post J, Guerra TEJ, van den Hof M, Vaz FM, Pajkrt D and van Genderen JG
Children with perinatally acquired human immunodeficiency virus (PHIV) are growing into adulthood with HIV and treatment-associated comorbidities, such as dyslipidemia and insulin resistance. HIV is identified as independent risk factor for cardiovascular disease (CVD). The hypothesis behind increased CVD risk associated with HIV includes vascular inflammation, dyslipidemia and combination antiretroviral therapy (cART) metabolomic toxicity. To investigate differences in lipid profiles and pathophysiological mechanisms of CVD risk in adolescents with PHIV, we compared the plasma lipidome of PHIV adolescents and HIV-negative controls. We additionally investigated the influence of current cART regimens and increased lipoprotein(a) (Lp(a)) levels on the plasma lipidome. We included 20 PHIV-infected adolescents and 20 HIV-negative controls matched for age, sex, ethnic origin and socio-economic status. Plasma lipidome was measured using Thermo Scientific Ultimate 3000 binary high-performance liquid chromatography (HPLC)-mass spectrometry. We evaluated the plasma lipidome in PHIV adolescents using different cART regimens (including those known to be associated with lipid alterations). The median age was 17.5 years (15.5-20.7) and 16.5 years (15.7-19.8) for PHIV adolescents and controls, respectively. Of PHIV adolescents, 45% used a non-nucleotide reverse transcriptase inhibitor (NNRTI)-based (25%) or protease inhibitor (PI)-based (20%) cART regimen. In this pilot study, we observed no significant differences between lipidomic profiles between PHIV adolescents and controls. We observed no differences in the plasma lipidome in participants with increased versus normal Lp(a) levels. Different cART regimens appear to influence chain length differences in the plasma lipidome of PHIV adolescents; however, the significance and causality of this observation remains undetermined. Further research on the influence of cART on lipid composition could further identify these alterations.
Applying Next-Generation Sequencing to Track HIV-1 Drug Resistance Mutations Circulating in Portugal
Pimentel V, Pingarilho M, Sebastião CS, Miranda M, Gonçalves F, Cabanas J, Costa I, Diogo I, Fernandes S, Costa O, Corte-Real R, Martins MRO, Seabra SG, Abecasis AB and Gomes P
The global scale-up of antiretroviral treatment (ART) offers significant health benefits by suppressing HIV-1 replication and increasing CD4 cell counts. However, incomplete viral suppression poses a potential threat for the emergence of drug resistance mutations (DRMs), limiting ART options, and increasing HIV transmission.
Risk of Cardiovascular Events in People with HIV (PWH) Treated with Integrase Strand-Transfer Inhibitors: The Debate Is Not Over; Results of the SCOLTA Study
Corti N, Menzaghi B, Orofino G, Guastavigna M, Lagi F, Di Biagio A, Taramasso L, De Socio GV, Molteni C, Madeddu G, Salomoni E, Pellicanò GF, Pontali E, Bellagamba R, Celesia BM, Cascio A, Sarchi E, Gulminetti R, Calza L, Maggi P, Cenderello G, Bandera A, Carleo MA, Falasca K, Ferrara S, Martini S, Guadagnino G, Angioni G, Bargiacchi O, Ricci ED, Squillace N and Bonfanti P
Cardiovascular disease (CVD) is common in people with HIV (PWH), and has great impact in terms of morbidity and mortality. Several intertwined mechanisms are believed to play a role in determining the increased risk of CVD, including the effect of certain antiretrovirals; among these, the role of integrase strand-transfer inhibitors (INSTIs) is yet to be fully elucidated. We conducted a multicenter, observational study comprising 4984 PWH evaluating the antiretroviral therapy (ART)-related nature of CVD in real life settings, both in naïve vs. treatment-experienced people. A comparison was conducted between INSTIs vs. either protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) considering demographic, baseline clinical characteristics, incidence of CVD in both 2-year and complete follow-up periods. Among 2357 PWH exposed to INSTIs, 24 people experienced CVD; the corresponding figure was 12 cases out of 2599 PWH exposed to other ART classes. At univariate and multivariate analysis, a tendency towards an increased risk of CVD was observed in the 2-year follow-up period in PWH exposed to INSTIs in the absence, however, of statistical significance. These findings leave open the hypothesis that INSTIs may play a role, albeit minimal, in determining an increased risk of CVD in PWH.
Scented Solutions: Examining the Efficacy of Scent Interventions in Mitigating Driving Fatigue
Jiang X, Muthusamy K, Chen J and Fang X
Fatigued driving threatens the safety of people's lives and property. Scent countermeasures offer minimal disruption and high efficacy, making them a promising approach. The aim of this study was to explore the application of scent countermeasures in alleviating fatigued driving. This study explored changes in EEG frequency bands (alpha, beta, theta, and gamma) and the activity of EEG metrics (, and ) in the temporal lobe during driving tasks, selected fatigued driving identifiers, and aided validation by investigating subjective fatigue with the Karolinska Sleepiness Scale (KSS). The EEG indicators all increased, with a significant increase in . was combined with the KSS to explore the effects of three scents, peppermint, grapefruit, and lavender, on driving fatigue. The subjective questionnaire results indicated that all three scents significantly improved driving fatigue, with significantly lower levels of driving fatigue compared to the control group. The analysis of EEG signals revealed a significant decrease in after the implementation of scent countermeasures. Moreover, was found to be lower in all three odor intervention groups compared to the control group. All three scents were found to significantly alleviate driving fatigue. The grapefruit scent had a better timely effect in relieving driving fatigue and the lavender scent had a longer effectiveness. This study provides further exploration for the application of odor interventions to alleviate driving fatigue. This study provides a practical reference for drivers to use odors to avoid fatigue in order to improve road safety.
Evaluation of Hand Action Classification Performance Using Machine Learning Based on Signals from Two sEMG Electrodes
Shaw HO, Devin KM, Tang J and Jiang L
Classification-based myoelectric control has attracted significant interest in recent years, leading to prosthetic hands with advanced functionality, such as multi-grip hands. Thus far, high classification accuracies have been achieved by increasing the number of surface electromyography (sEMG) electrodes or adding other sensing mechanisms. While many prescribed myoelectric hands still adopt two-electrode sEMG systems, detailed studies on signal processing and classification performance are still lacking. In this study, nine able-bodied participants were recruited to perform six typical hand actions, from which sEMG signals from two electrodes were acquired using a Delsys Trigno Research+ acquisition system. Signal processing and machine learning algorithms, specifically, linear discriminant analysis (LDA), k-nearest neighbors (KNN), and support vector machines (SVM), were used to study classification accuracies. Overall classification accuracy of 93 ± 2%, action-specific accuracy of 97 ± 2%, and F1-score of 87 ± 7% were achieved, which are comparable with those reported from multi-electrode systems. The highest accuracies were achieved using SVM algorithm compared to LDA and KNN algorithms. A logarithmic relationship between classification accuracy and number of features was revealed, which plateaued at five features. These comprehensive findings may potentially contribute to signal processing and machine learning strategies for commonly prescribed myoelectric hand systems with two sEMG electrodes to further improve functionality.
Physical Activity Detection for Diabetes Mellitus Patients Using Recurrent Neural Networks
Dénes-Fazakas L, Simon B, Hartvég Á, Kovács L, Dulf ÉH, Szilágyi L and Eigner G
Diabetes mellitus (DM) is a persistent metabolic disorder associated with the hormone insulin. The two main types of DM are type 1 (T1DM) and type 2 (T2DM). Physical activity plays a crucial role in the therapy of diabetes, benefiting both types of patients. The detection, recognition, and subsequent classification of physical activity based on type and intensity are integral components of DM treatment. The continuous glucose monitoring system (CGMS) signal provides the blood glucose (BG) level, and the combination of CGMS and heart rate (HR) signals are potential targets for detecting relevant physical activity from the BG variation point of view. The main objective of the present research is the developing of an artificial intelligence (AI) algorithm capable of detecting physical activity using these signals. Using multiple recurrent models, the best-achieved performance of the different classifiers is a 0.99 area under the receiver operating characteristic curve. The application of recurrent neural networks (RNNs) is shown to be a powerful and efficient solution for accurate detection and analysis of physical activity in patients with DM. This approach has great potential to improve our understanding of individual activity patterns, thus contributing to a more personalized and effective management of DM.
IMU-Based Real-Time Estimation of Gait Phase Using Multi-Resolution Neural Networks
Tang L, Shushtari M and Arami A
This work presents a real-time gait phase estimator using thigh- and shank-mounted inertial measurement units (IMUs). A multi-rate convolutional neural network (CNN) was trained to estimate gait phase for a dataset of 16 participants walking on an instrumented treadmill with speeds varying between 0.1 to 1.9 m/s, and conditions such as asymmetric walking, stop-start, and sudden speed changes. One-subject-out cross-validation was used to assess the robustness of the estimator to the gait patterns of new individuals. The proposed model had a spatial root mean square error of 5.00±1.65%, and a temporal mean absolute error of 2.78±0.97% evaluated at the heel strike. A second cross-validation was performed to show that leaving out any of the walking conditions from the training dataset did not result in significant performance degradation. A 2-sample Kolmogorov-Smirnov test showed that there was no significant increase in spatial or temporal error when testing on the abnormal walking conditions left out of the training set. The results of the two cross-validations demonstrate that the proposed model generalizes well across new participants, various walking speeds, and gait patterns, showcasing its potential for use in investigating patient populations with pathological gaits and facilitating robot-assisted walking.
The Analytical Validity of Stride Detection and Gait Parameters Reconstruction Using the Ankle-Mounted Inertial Measurement Unit Syde
Michaud M, Guérin A, Dejean de La Bâtie M, Bancel L, Oudre L and Tricot A
The increasing use of inertial measurement units (IMU) in biomedical sciences brings new possibilities for clinical research. The aim of this paper is to demonstrate the accuracy of the IMU-based wearable Syde device, which allows day-long and remote continuous gait recording in comparison to a reference motion capture system. Twelve healthy subjects (age: 23.17 ± 2.04, height: 174.17 ± 6.46 cm) participated in a controlled environment data collection and performed a series of gait tasks with both systems attached to each ankle. A total of 2820 strides were analyzed. The results show a median absolute stride length error of 1.86 cm between the IMU-based wearable device reconstruction and the motion capture ground truth, with the 75th percentile at 3.24 cm. The median absolute stride horizontal velocity error was 1.56 cm/s, with the 75th percentile at 2.63 cm/s. With a measurement error to the reference system of less than 3 cm, we conclude that there is a valid physical recovery of stride length and horizontal velocity from data collected with the IMU-based wearable Syde device.
Trail making test - black & white (TMT B&W): Normative study for the Chilean population
Carvallo C and Ramos-Henderson M
The trailmaking test (TMT) has an educational bias that makes it inapplicable to people with low levels of education due to its dependence on the alphabet. The TMT standardization is the only one available in Chile, and there is a need for alternative ways of using the TMT that do not depend on the level of education for its applicability. To determine the normative scores of the TMT - black & white (TMT B&W), considering sociodemographic factors in adult and elderly Chilean population. A total sample of 227 participants (133 healthy, 94 cognitively impaired) from the Ageing Mets cohort were recruited from three areas in Chile (Antofagasta, Santiago, and Puerto Montt). The TMT B&W was administered to all participants. A multiple regression model was used to generate normative data only in the cognitively healthy group, considering the effect of age, education and sex. A significant effect of age was found in the score of the TMT B&W Parts A and B. The level of education influenced the part B of the test; however, the completion rate of the TMT B&W parts A and B was over 90% in cognitively healthy people. Norms for the number of errors were obtained, and differences between groups were found after controlling for the effect of age and education. This study is the first to provide normative data for the Chilean version of the TMT B&W and will benefit clinical neuropsychologists by improving the procedures for more accurately assessing executive functions and its impairments.
OPTORER: A Dynamic Routing and Touring Service for Indoors and Outdoor Tours
Vassilakis C, Polychronaki M, Margaritis D, Kogias DG and Leligou HC
This paper introduces a new routing and touring service both for outdoor and indoor places of touristic and cultural interest designed to be used in the wider area of Attica, Greece. This service is the result of the work performed in OPTORER (OPTORER: OPtimal rouTing and explOration of touRistic and cultural arEas of interest within Attica given personalized adaptive preferences, promoted underlying purpose, and interactive experience), project, and it aspires to offer a range of innovative and thematic routes to several specified points of interest in the selected area of Attica, encouraging the combination of indoor and outdoor routes in a single tour. The aim is to optimize the user experience while promoting specific, user-centric features, with safety and social welfare being a priority for every designed tour, resulting in enhancing the touristic experience in the area. Using a common smartphone device, as well as common wearable devices (i.e., smartwatches), the OPTORER service will provide an end-to-end solution by developing the algorithms and end-user applications, together with an orchestration platform responsible for managing, operating, and executing the service that produces and presents to the end user results derived from solving dynamically complex optimization problems.
Dismantling Barriers to Hepatitis B and Delta Screening, Prevention, and Linkage to Care among the PWUD Community in Philadelphia
Zovich B, Freeland C, Moore H, Sapp K, Qureshi A, Holbert R, Zambrano J, Bhangoo D, Cohen C, Hass RW and Jessop A
The prevalence of hepatitis B and delta viruses (HBV/HDV) among people who use drugs (PWUD) remains largely unknown. In the context of one Philadelphia-based harm reduction organization (HRO), this study aimed to assess HBV/HDV prevalence and facilitate linkage to care. Participants completed a demographic HBV/HDV risk factor survey and were screened for HBV and reflexively for HDV if positive for HBV surface antigen or isolated core antibody. Fisher's exact tests and regression were used to understand relationships between risks and HBV blood markers. Of the 498 participants, 126 (25.3%) did not have hepatitis B immunity, 52.6% had been vaccinated against HBV, and 17.9% had recovered from a past infection. Eleven (2.2%) participants tested positive for isolated HBV core antibody, 10 (2.0%) for HBV surface antigen, and one (0.2%) for HDV antibody. History of incarceration was associated with current HBV infection, while transactional sex and experience of homelessness were predictive of previous exposure. This study found high rates of current and past HBV infection, and a 10% HBV/HDV co-infection rate. Despite availability of vaccine, one quarter of participants remained vulnerable to infection. Findings demonstrate the need to improve low-threshold HBV/HDV screening, vaccination, and linkage to care among PWUD. The study also identified gaps in the HBV/HDV care cascade, including lack of point-of-care diagnostics and lack of support for HROs to provide HBV services.
Epidemiological Features of Human Norovirus Genotypes before and after COVID-19 Countermeasures in Osaka, Japan
Shirai T, Phadungsombat J, Ushikai Y, Yoshikaie K, Shioda T and Sakon N
We investigated the molecular epidemiology of human norovirus (HuNoV) in all age groups using samples from April 2019 to March 2023, before and after the COVID-19 countermeasures were implemented. GII.2[P16] and GII.4[P31], the prevalent strains in Japan before COVID-19 countermeasures, remained prevalent during the COVID-19 pandemic, except from April to November 2020; in 2021, the prevalence of GII.2[P16] increased among children. Furthermore, there was an increase in the prevalence of GII.4[P16] after December 2022. Phylogenetic analysis of GII.P31 RdRp showed that some strains detected in 2022 belonged to a different cluster of other strains obtained during the present study period, suggesting that HuNoV strains will evolve differently even if they have the same type of RdRp. An analysis of the amino acid sequence of VP1 showed that some antigenic sites of GII.4[P16] were different from those of GII.4[P31]. The present study showed high infectivity of HuNoV despite the COVID-19 countermeasures and revealed changes in the prevalent genotypes and mutations of each genotype. In the future, we will investigate whether GII.4[P16] becomes more prevalent, providing new insights by comparing the new data with those analyzed in the present study.
Trends in and Risk Factors for Drug Resistance in in HIV-Infected Patients
Le X, Qian X, Liu L, Sun J, Song W, Qi T, Wang Z, Tang Y, Xu S, Yang J, Wang J, Chen J, Zhang R, Zhu Z and Shen Y
Trends in and risk factors for drug resistance in () in human immunodeficiency virus (HIV)-infected patients with active tuberculosis were analyzed. The clinical data of and HIV-coinfected patients treated at the Shanghai Public Health Clinical Center between 2010 and 2022 were collected. The diagnosis of tuberculosis was confirmed by solid or liquid culture. The phenotypic drug susceptibility test was carried out via the proportional method, and the resistance to first-line and second-line drugs was analyzed. Logistic regression analysis was performed to identify associated risk factors for drug resistance in . Of the 304 patients with a -positive culture and first-line drug susceptibility test results, 114 (37.5%) were resistant to at least one first-line anti-tuberculosis drug. Of the 93 patients with first-line and second-line drug susceptibility test results, 40 (43%) were resistant to at least one anti-tuberculosis drug, and 20 (21.5%), 27 (29.0%), 19 (20.4%), 16 (17.2%), and 14 (15.1%) were resistant to rifampicin, streptomycin, ofloxacin, levofloxacin, and moxifloxacin, respectively; 17 patients (18.3%) had multidrug-resistant tuberculosis (MDR-TB). Between 2010 and 2021, the rate of resistance to streptomycin and rifampicin ranged from 14.3% to 40.0% and from 8.0% to 26.3%, respectively, showing an increasing trend year by year. From 2016 to 2021, the rate of resistance to quinolones fluctuated between 7.7% and 27.8%, exhibiting an overall upward trend. Logistic regression analysis showed that being aged <60 years old was a risk factor for streptomycin resistance, mono-drug resistance, and any-drug resistance (RR 4.139, = 0.023; RR 7.734, = 0.047; RR 3.733, = 0.009). Retreatment tuberculosis was a risk factor for resistance to rifampicin, ofloxacin, of levofloxacin (RR 2.984, = 0.047; RR 4.517, = 0.038; RR 6.277, = 0.014). The drug resistance rates of to rifampicin and to quinolones in HIV/AIDS patients were high and have been increasing year by year. Age and a history of previous anti-tuberculosis treatment were the main factors associated with the development of drug resistance in HIV/AIDS patients with tuberculosis.
Association of the +874T/A Polymorphism with Symptomatic COVID-19 Susceptibility
Sarges KML, Póvoa da Costa F, Santos EFD, Cantanhede MHD, da Silva R, Veríssimo AOL, Viana MNDSA, Rodrigues FBB, Leite MM, Torres MKDS, Bentes da Silva C, Brito MTFM, Silva ALSD, Henriques DF, Vallinoto IMVC, Viana GMR, Queiroz MAF, Vallinoto ACR and Santos EJMD
Tumor necrosis factor (TNF) and interferon-gamma (IFNγ) are important inflammatory mediators in the development of cytokine storm syndrome (CSS). Single nucleotide polymorphisms (SNPs) regulate the expression of these cytokines, making host genetics a key factor in the prognosis of COVID-19. In this study, we investigated the associations of the -308G/A and +874T/A polymorphisms with COVID-19. We analyzed the frequencies of the two polymorphisms in the control groups (CG: -308G/A, = 497; +874T/A, = 397), a group of patients with COVID-19 (CoV, = 222) and among the subgroups of patients with nonsevere ( = 150) and severe ( = 72) COVID-19. We found no significant difference between the genotypic and allelic frequencies of -308G/A in the groups analyzed; however, both the frequencies of the high expression genotype (TT) (CoV: 13.51% vs. CG: 6.30%; = 0.003) and the *T allele (CoV: 33.56% vs. CG: 24. 81%; = 0.001) of the +874T/A polymorphism were higher in the COVID-19 group than in the control group, with no differences between the subgroups of patients with nonsevere and severe COVID-19. The *T allele of +874T/A (rs2430561) is associated with susceptibility to symptomatic COVID-19. These SNPs provided valuables clues about the potential mechanism involved in the susceptibility to developing symptomatic COVID-19.
Antibodies Induced by Smallpox Vaccination after at Least 45 Years Cross-React with and In Vitro Neutralize Mpox Virus: A Role for Polyclonal B Cell Activation?
Mariotti S, Venturi G, Chiantore MV, Teloni R, De Santis R, Amendola A, Fortuna C, Marsili G, Grilli G, Lia MS, Kiros ST, Lagi F, Bartoloni A, Iacobino A, Cresta R, Lastilla M, Biselli R, Di Bonito P, Lista F and Nisini R
To evaluate whether antibodies specific for the vaccinia virus (VV) are still detectable after at least 45 years from immunization. To confirm that VV-specific antibodies are endowed with the capacity to neutralize Mpox virus (MPXV) in vitro. To test a possible role of polyclonal non-specific activation in the maintenance of immunologic memory.
Characterizing Infections in Two Epidemic Waves of SARS-CoV-2 Omicron Variants: A Cohort Study in Guangzhou, China
Qu L, Xie C, Qiu M, Yi L, Liu Z, Zou L, Hu P, Jiang H, Lian H, Yang M, Yang H, Zeng H, Chen H, Zhao J, Xiao J, He J, Yang Y, Chen L, Li B, Sun J and Lu J
After the adjustment of COVID-19 epidemic policy, mainland China experienced two consecutive waves of Omicron variants within a seven-month period. In Guangzhou city, as one of the most populous regions, the viral infection characteristics, molecular epidemiology, and the dynamic of population immunity are still elusive.
Molecular and Entomological Characterization of 2023 Dengue Outbreak in Dhading District, Central Nepal
Rimal S, Shrestha S, Paudel SW, Shah Y, Bhandari G, Pandey K, Kharbuja A, Kapandji M, Gautam I, Bhujel R, Takamatsu Y, Bhandari R, Klungthong C, Shrestha SK, Fernandez S, Malavige GN, Pandey BD, Urano T, Morita K, Ngwe Tun MM and Dumre SP
In 2023, Nepal faced its second largest dengue outbreak ever, following a record-breaking number of dengue cases in 2022, characterized by the expansion of infections into areas of higher altitudes. However, the characteristics of the 2023 circulating dengue virus (DENV) and the vector density remain poorly understood. Therefore, we performed DENV serotyping, clinical and laboratory assessment, and entomological analysis of the 2023 outbreak in central Nepal. A total of 396 fever cases in Dhading hospital suspected of being DENV positive were enrolled, and blood samples were collected and tested by different techniques including PCR. Of these, 278 (70.2%) had confirmed DENV infection. Multiple serotypes (DENV-1, -2, and -3) were detected. DENV-2 (97.5%) re-emerged after six years in Dhading while DENV-3 was identified for the first time. Dengue inpatients had significantly higher frequency of anorexia, myalgia, rash, diarrhea, nausea, vomiting, abdominal pain, and thrombocytopenia ( < 0.05). In this area, mosquitoes largely predominated (90.7%) with the majority being (60.7%). We also found high levels of index (20.0%) and container index (16.7%). We confirmed multiple DENV serotype circulation with serotype re-emergence and new serotype introduction, and high vector density in 2023. These findings call for the urgent initiation and scaling up of DENV molecular surveillance in human and mosquito populations for dengue control and prevention in Nepal.
Factors Associated with Neutralizing Antibody Responses following 2-Dose and 3rd Booster Monovalent COVID-19 Vaccination in Japanese People Living with HIV
Ngare I, Tan TS, Toyoda M, Kuwata T, Takahama S, Nakashima E, Yamasaki N, Motozono C, Fujii T, Minami R, Barabona G and Ueno T
People living with HIV (PLWH) could be at risk of blunted immune responses to COVID-19 vaccination. We investigated factors associated with neutralizing antibody (NAb) responses against SARS-CoV-2 and variants of concern (VOCs), following two-dose and third booster monovalent COVID-19 mRNA vaccination in Japanese PLWH. NAb titers were assessed in polyclonal IgG fractions by lentiviral-based pseudovirus assays. Overall, NAb titers against Wuhan, following two-dose vaccination, were assessed in 82 PLWH on treatment, whereby 17/82 (20.73%) were classified as low-NAb participants. Within the low-NAb participants, the third booster vaccination enhanced NAb titers against Wuhan and VOCs, albeit to a significantly lower magnitude than the rest. In the multivariate analysis, NAb titers against Wuhan after two-dose vaccination correlated with age and days since vaccination, but not with CD4 count, CD4/CD8 ratio, and plasma high-sensitivity C-Reactive protein (hsCRP). Interestingly, an extended analysis within age subgroups revealed NAb titers to correlate positively with the CD4 count and negatively with plasma hsCRP in younger, but not older, participants. In conclusion, a third booster vaccination substantially enhances NAb titers, but the benefit may be suboptimal in subpopulations of PLWH exhibiting low titers at baseline. Considering clinical and immune parameters could provide a nuanced understanding of factors associated with vaccine responses in PLWH.
Cardiometabolic Differences in People Living with HIV Receiving Integrase Strand Transfer Inhibitors Compared to Non-nucleoside Reverse Transcriptase Inhibitors: Implications for Current ART Strategies
Vos WAJW, Vadaq N, Matzaraki V, Otten T, Groenendijk AL, Blaauw MJT, van Eekeren LE, Brinkman K, de Mast Q, Riksen NP, Stalenhoef AFH, van Lunzen J, van der Ven AJAM, Blok WL and Stalenhoef JE
In people living with HIV (PLHIV), integrase strand transfer inhibitors (INSTIs) are part of the first-line combination antiretroviral therapy (cART), while non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens are alternatives. Distinct cART regimens may variably influence the risk for non-AIDS comorbidities. We aimed to compare the metabolome and lipidome of INSTI and NNRTI-based regimens. The 2000HIV study includes asymptomatic PLHIV (n = 1646) on long-term cART, separated into a discovery cohort with 730 INSTI and 617 NNRTI users, and a validation cohort encompassing 209 INSTI and 90 NNRTI users. Baseline plasma samples from INSTI and NNRTI users were compared using mass spectrometry-based untargeted metabolomic (n = 500) analysis. Perturbed metabolic pathways were identified using MetaboAnalyst software. Subsequently, nuclear magnetic resonance spectroscopy was used for targeted lipoprotein and lipid (n = 141) analysis. Metabolome homogeneity was observed between the different types of INSTI and NNRTI. In contrast, higher and lower levels of 59 and 45 metabolites, respectively, were found in the INSTI group compared to NNRTI users, of which 77.9% (81/104) had consistent directionality in the validation cohort. Annotated metabolites belonged mainly to 'lipid and lipid-like molecules', 'organic acids and derivatives' and 'organoheterocyclic compounds'. In pathway analysis, perturbed 'vitamin B1 (thiamin) metabolism', 'de novo fatty acid biosynthesis', 'bile acid biosynthesis' and 'pentose phosphate pathway' were detected, among others. Lipoprotein and lipid levels in NNRTIs were heterogeneous and could not be compared as a group. INSTIs compared to individual NNRTI types showed that HDL cholesterol was lower in INSTIs compared to nevirapine but higher in INSTIs compared to doravirine. In addition, LDL size was lower in INSTIs and nevirapine compared to doravirine. NNRTIs show more heterogeneous cardiometabolic effects than INSTIs, which hampers the comparison between these two classes of drugs. Targeted lipoproteomic and lipid NMR spectroscopy showed that INSTI use was associated with a more unfavorable lipid profile compared to nevirapine, which was shifted to a more favorable profile for INSTI when substituting nevirapine for doravirine, with evidently higher fold changes. The cardiovascular disease risk profile seems more favorable in INSTIs compared to NNRTIs in untargeted metabolomic analysis using mass-spectrometry.
Monitoring HPV Prevalence and Risk Cofactors for Abnormal Cytology in the Post-Vaccination Period among Croatian Women
Pešut E, Šimić I, Fureš R, Milutin Gašperov N, Lež C, Feratović F, Kukina Žvigač T, Grce M, Erceg Ivkošić I and Sabol I
The incidence and mortality rate of cervical cancer in Croatia remains a health challenge despite screening efforts. Besides the persistent infection with HPV, the development of cancer is also associated with some cofactors. The goal of this study was to assess circulating HPV genotypes and risk factors for the development of cervical precancer after almost 16 years from the onset of HPV vaccination in Croatia. In this study, a total of 321 women attending gynecological care were evaluated. Relevant medical and demographic information, including cytology, were collected. HPV genotyping was performed by PCR. Comparing the HPV types found in circulation in the pre-vaccination (1999-2015) and post-vaccination periods (2020-2023), a statistically significant reduction in HPV 31 was noted, while the overall prevalence increased in the post-vaccination period. Besides the expected HPV positivity as a risk factor, the history of smoking was associated with LSIL or worse cytology at enrollment. For the first time, this population study revealed a statistically significant shift in the HPV genotype in the post-vaccination period, as well as the confirmation of risk factors for the development of abnormal cytology among Croatian women.
No Remdesivir Resistance Observed in the Phase 3 Severe and Moderate COVID-19 SIMPLE Trials
Hedskog C, Spinner CD, Protzer U, Hoffmann D, Ko C, Gottlieb RL, Askar M, Roestenberg M, de Vries JJC, Carbo EC, Martin R, Li J, Han D, Rodriguez L, Parvangada A, Perry JK, Ferrer R, Antón A, Andrés C, Casares V, Günthard HF, Huber M, McComsey GA, Sadri N, Aberg JA, van Bakel H and Porter DP
Remdesivir (RDV) is a broad-spectrum nucleotide analog prodrug approved for the treatment of COVID-19 in hospitalized and non-hospitalized patients with clinical benefit demonstrated in multiple Phase 3 trials. Here we present SARS-CoV-2 resistance analyses from the Phase 3 SIMPLE clinical studies evaluating RDV in hospitalized participants with severe or moderate COVID-19 disease. The severe and moderate studies enrolled participants with radiologic evidence of pneumonia and a room-air oxygen saturation of ≤94% or >94%, respectively. Virology sample collection was optional in the study protocols. Sequencing and related viral load data were obtained retrospectively from participants at a subset of study sites with local sequencing capabilities (10 of 183 sites) at timepoints with detectable viral load. Among participants with both baseline and post-baseline sequencing data treated with RDV, emergent Nsp12 substitutions were observed in 4 of 19 (21%) participants in the severe study and none of the 2 participants in the moderate study. The following 5 substitutions emerged: T76I, A526V, A554V, E665K, and C697F. The substitutions T76I, A526V, A554V, and C697F had an EC fold change of ≤1.5 relative to the wildtype reference using a SARS-CoV-2 subgenomic replicon system, indicating no significant change in the susceptibility to RDV. The phenotyping of E665K could not be determined due to a lack of replication. These data reveal no evidence of relevant resistance emergence and further confirm the established efficacy profile of RDV with a high resistance barrier in COVID-19 patients.
De-Escalated Therapy and Early Treatment of Recurrences in HPV-Associated Head and Neck Cancer: The Potential for Biomarkers to Revolutionize Personalized Therapy
Yarbrough WG, Schrank TP, Burtness BA and Issaeva N
Human papillomavirus-associated (HPV+) head and neck squamous cell carcinoma (HNSCC) is the most common HPV-associated cancer in the United States, with a rapid increase in incidence over the last two decades. The burden of HPV+ HNSCC is likely to continue to rise, and given the long latency between infection and the development of HPV+ HNSCC, it is estimated that the effect of the HPV vaccine will not be reflected in HNSCC prevalence until 2060. Efforts have begun to decrease morbidity of standard therapies for this disease, and its improved characterization is being leveraged to identify and target molecular vulnerabilities. Companion biomarkers for new therapies will identify responsive tumors. A more basic understanding of two mechanisms of HPV carcinogenesis in the head and neck has identified subtypes of HPV+ HNSCC that correlate with different carcinogenic programs and that identify tumors with good or poor prognosis. Current development of biomarkers that reliably identify these two subtypes, as well as biomarkers that can detect recurrent disease at an earlier time, will have immediate clinical application.
Peripheral Neuropathy in Patients with Hepatitis C Infection-Reversibility after HCV Eradication: A Single Center Study
Androutsakos T, Tsantzali I, Karagiannakis DS, Flevari P, Iakovou D, Pouliakis A, Kykalos S, Doris S and Xyla V
Chronic hepatitis C virus (HCV) infection is characterized by a variety of extra-hepatic manifestations; peripheral neuropathy (PN) is one of the most common, especially when mixed cryoglobulinemia (MCG) is present. The prevalence and risk factors of HCV-related PN in the absence of MCG are largely unknown. We conducted a prospective, single-center study, examining the prevalence and reversibility of HCV-associated neuropathy in the absence of MCG. Nerve fiber density in the epidermis was evaluated through skin biopsy and electroneurography (ENG) before HCV-treatment initiation and 1 year post sustained virological remission (SVR). Forty HCV-infected individuals (nine HIV co-infected) with no other neuron-harming factors were included; four other HCV mono- and three HIV co-infected individuals were excluded due to presence of diabetes, B12 insufficiency, or neurotoxic drugs. Twelve consecutive controls with no neuron-harming conditions were also recruited; eight more were excluded due to meeting exclusion criteria. Four patients had ENG signs of polyneuropathy (two with HCV mono- and two with HIV co-infection), while seven more (five with HCV mono- and two with HIV co-infection) had signs of mono-neuropathy, leading to PN prevalences of 22.5% and 44% for mono- and co-infection, respectively ( value 0.179). The two patients with HCV mono-infection and polyneuropathy and the one with ulnar nerve damage showed ENG improvement 1 year post SVR. Regarding intraepidermal nerve density, HCV infection, irrespective of HIV co-infection, was correlated with a lower intraepidermal neuron density that improved 1 year post SVR ( value 0.0002 for HCV and 0.0326 for HCV/HIV co-infected patients). PN is common in HCV infection; successful eradication of HCV leads to PN improvement.
From Forgotten Pathogen to Target for New Vaccines: What Clinicians Need to Know about Respiratory Syncytial Virus Infection in Older Adults
Boattini M, Almeida A, Comini S, Bianco G, Cavallo R and Costa C
Respiratory syncytial virus (RSV) is increasingly recognized as being implicated in acute illness in older adults, with a significant weight in hospitalizations for respiratory illness and death. By means of a best-evidence review, this paper aims to investigate whether RSV can be considered a forgotten pathogen in older patients, looking at trends in the literature volume and exploring possible epidemiological and clinical features underlying the focus given to it. We then present an assessment of its disease burden and present and future strategies for its reduction, particularly in light of the recent availability of new vaccines.
Molecular Epidemiology and Clinical Characteristics of an Outbreak on Respiratory Virus Coinfection in Gansu, China
Liu W, Zhang H, Zhao T, Cai X, Yang L, Gao G, Che X, Zhu Z, Zeng T and Cui F
This study aims to analyze the epidemiological and pathogenic characteristics of an outbreak primarily caused by respiratory syncytial virus (RSV), human rhinovirus (HRV), and human metapneumovirus (HMPV) in a kindergarten and primary school. The outbreak was investigated by field epidemiological investigation, and the common respiratory pathogens were screened by RT-PCR detection technology. The attack rate of this outbreak was 63.95% (110/172). Main symptoms included cough (85.45%), sore throat (60.91%), and sneezing (60.00%). Multifactorial logistic regression analysis revealed that continuous handwashing and mouth and nose covering when sneezing were protective factors. All 15 collected throat swab specimens tested positive for viruses, with HMPV as the predominant pathogen (80.00%), followed by HRV (53.33%), and two cases of positive respiratory syncytial virus (13.33%). Among them, six samples showed coinfections of HMPV and HRV, and one had coinfections of HMPV and RSV, resulting in a coinfection rate of 46.67%. Genetic sequencing indicated that the HMPV genotype in this outbreak was A2c, and the HRV genotype was type A, resulting in a coinfection outbreak of HMPV, HRV, and RSV in schools and kindergartens, suggesting that multi-pathogen surveillance of respiratory tract infections should be strengthened.
Quantitative and Qualitative Distinctions between HIV-1 and SIV Reservoirs: Implications for HIV-1 Cure-Related Studies
Mudd JC
The persistence of the latent viral reservoir is the main hurdle to curing HIV-1 infection. SIV infection of non-human primates (NHPs), namely Indian-origin rhesus macaques, is the most relevant and widely used animal model to evaluate therapies that seek to eradicate HIV-1. The utility of a model ultimately rests on how accurately it can recapitulate human disease, and while reservoirs in the NHP model behave quantitatively very similar to those of long-term suppressed persons with HIV-1 (PWH) in the most salient aspects, recent studies have uncovered key nuances at the clonotypic level that differentiate the two in qualitative terms. In this review, we will highlight differences relating to proviral intactness, clonotypic structure, and decay rate during ART between HIV-1 and SIV reservoirs and discuss the relevance of these distinctions in the interpretation of HIV-1 cure strategies. While these, to some degree, may reflect a unique biology of the virus or host, distinctions among the proviral landscape in SIV are likely to be shaped significantly by the condensed timeframe of NHP studies. ART is generally initiated earlier in the disease course, and animals are virologically suppressed for shorter periods before receiving interventions. Because these are experimental variables dictated by the investigator, we offer guidance on study design for cure-related studies performed in the NHP model. Finally, we highlight the case of GS-9620 (Vesatolimod), an antiviral TLR7 agonist tested in multiple independent pre-clinical studies in which virological outcomes may have been influenced by study-related variables.
Prevalence of Respiratory Viral Infections in Deceased Persons during the COVID-19 Pandemic Season 2021-2022: A Population-Based Observational Study
Trobajo-Sanmartín C, Navascués A, Fernández-Huerta M, Martínez-Baz I, Casado I, Ezpeleta C and Castilla J
Although the omicron variant of SARS-CoV-2 circulated intensely during the 2021-2022 season, many patients with severe acute respiratory disease tested negative for COVID-19. The aim of this study was to assess the presence of different respiratory viruses in deceased persons. The proportion of deceased persons with respiratory viral infections in the 2021-2022 season in Navarre, Spain, was estimated considering all deaths caused by confirmed COVID-19 according to the epidemiological surveillance and the results of multiplex PCR tests for respiratory viruses performed in a sample of deceased persons with a cause of death other than COVID-19. Of 3578 deaths, 324 (9.1%) were initially reported as caused by pre-mortem confirmed COVID-19. A sample of 242 persons who died by causes other than COVID-19 were tested post-mortem; 64 (26.4%) of them were positive for any respiratory virus: 11.2% for SARS-CoV-2, 5.8% for rhinovirus, 3.7% for human coronavirus, 2.5% for metapneumovirus, 1.7% for respiratory syncytial virus, 1.7% for parainfluenza, 1.2% for influenza, and less than 1% each for adenovirus and bocavirus. Combining both approaches, we estimated that 34.4% of all deceased persons during the study period had a respiratory viral infection and 19.2% had SARS-CoV-2. Only 33.3% (9/27) of SARS-CoV-2 and 5.0% (2/40) of other viruses detected post-mortem had previously been confirmed pre-mortem. In a period with very intense circulation of SARS-CoV-2 during the pandemic, other respiratory viruses were also frequently present in deceased persons. Some SARS-CoV-2 infections and most other viral infections were not diagnosed pre-mortem. Several respiratory viruses may contribute to excess mortality in winter.
Suspected North Carolina Counterfeit Pill-Involved Deaths, 2020-2022
Friederich LW, Cox ME, Hyson BE and Bishop-Freeman SC
The North Carolina Office of the Chief Medical Examiner regularly assumes jurisdiction over deaths that are suspicious, unusual, or unattended by a medical professional. In recent years, the presence of counterfeit pills is occasionally suggested by investigatory notes and/or scene findings that document reported consumption of prescription drugs, or prescription drugs on scene, which are not reflected in the final autopsy findings after toxicological analysis of the decedent's blood samples. Counterfeit pill consumption is a major public health hazard worthy of attention from the forensic toxicology community. Seventy-five cases from January 2020 to December 2022 serve as a convenience sample of cases where prescription pills including formulations of alprazolam, oxycodone, and hydrocodone were specifically referenced during the death scene investigation as recently consumed, yet an unexpected substance was found during toxicological analysis rather than the expected pharmaceutical drug. Of note, novel benzodiazepines detected included flualprazolam, etizolam, clonazolam metabolite (8-aminoclonazolam), bromazolam, flubromazolam, and desalkylflurazepam. Decedents' ages ranged from 16 to 69, across 33 different North Carolina counties. Case notes indicated that eight of the decedents obtained pills through direct personal relationships, six decedents obtained them from "the street", and one decedent likely purchased pills online. Pills were largely consumed orally or through insufflation. Seven case reports contained indication that decedents knew or suspected the counterfeit nature of their pills. This study describes the context and characteristics of 2020-2022 suspected counterfeit pill-involved deaths in North Carolina to further the understanding of the forensic science community, law enforcement partners, public health stakeholders, and those potentially at risk through the consumption of counterfeit pills.
Hepatitis E Virus Infection in Voluntary Blood Donors in the Russian Federation
Potemkin IA, Kyuregyan KK, Karlsen AA, Isaeva OV, Kichatova VS, Lopatukhina MA, Asadi Mobarkhan FA, Zlobina AG, Zheltobriukh AV, Bocharova KA, Belyakova VV, Rassolova SV, Ivanova NV, Solonin SA, Bazhenov AI, Godkov MA and Mikhailov MI
Transfusion-transmitted hepatitis E virus (HEV) infection is an increasing concern in many countries. We investigated the detection rate of HEV viremia in blood donors in Russia. A total of 20,405 regular repetitive voluntary non-renumerated blood donors from two regions (Moscow and Belgorod) were screened for HEV RNA using the cobas HEV test in mini-pools of six plasma samples. Samples from each reactive pool were tested individually. The average HEV RNA prevalence was 0.024% (95% CI: 0.01-0.05%), or 1 case per 4081 donations. No statistically significant differences in HEV RNA prevalence were observed between the two study regions. The PCR threshold cycle (Ct) values ranged from 25.0 to 40.5 in reactive pools, and from 20.9 to 41.4 in reactive plasma samples when tested individually. The HEV viremic donors had different antibody patterns. Two donor samples were reactive for both anti-HEV IgM and IgG antibodies, one sample was reactive for anti-HEV IgM and negative for anti-HEV IgG, and two samples were seronegative. At follow-up testing 6 months later, on average, four donors available for follow-up had become negative for HEV RNA and positive for anti-HEV IgG. The HEV ORF2 sequence belonging to HEV-3 sub-genotype 3a was obtained from one donor sample. The sequencing failed in the other four samples from viremic donors, presumably due to the low viral load. In conclusion, the HEV RNA detection rate in blood donors in Russia corresponds with data from other European countries, including those that implemented universal donor HEV screening. These data support the implementation of HEV RNA donor screening to reduce the risk of transfusion-transmitted HEV infection in Russia.
Scoping Review of Clinical Presentations and Outcomes in Patients with Concomitant COVID-19 Infection and Acute Mesenteric Ischaemia
Cai W, Zhao Y and Mallappa S
COVID-19 infection confers an increased risk of coagulation dysfunction (1) predisposing to thromboembolism in many anatomical sites including the gastrointestinal tract (GIT) (2). This study investigates the clinical presentation and outcome in patients presenting with concurrent COVID-19 infection and gastrointestinal tract ischaemia. Furthermore, differentiation and comparisons are drawn between those with arterial and venous aetiology for mesenteric ischaemia.
Sudden Infant Death Associated with Rhinovirus Infection
Auvray C, Perez-Martin S, Schuffenecker I, Pitoiset C, Tarris G, Ambert-Balay K, Martin L, Dullier-Taillefumier N, Bour JB and Manoha C
A less than one-month-old infant with symptoms of rhinitis died unexpectedly in his sleep. He was not born prematurely and had no known underlying disease. Cerebrospinal fluid, nasopharyngeal and lung samples, and rectal swab were found to be positive for subgroup A rhinovirus, while the blood was negative. This case highlights the important finding that the rhinovirus, a common pathogen associated with upper respiratory tract infections, can sometimes, as the only pathogen, lead to complications such as a cerebrospinal infection and be involved in the sudden infant death syndrome (SIDS). Vigilance is necessary in case of viral infections in the infant's environment, and measures of hygiene and protection must be encouraged in order to reduce the risk of the SIDS.
The Glycan Ectodomain of SARS-CoV-2 Spike Protein Modulates Cytokine Production and Expression of CD206 Mannose Receptor in PBMC Cultures of Pre-COVID-19 Healthy Subjects
Barbati C, Bromuro C, Vendetti S, Torosantucci A, Cauda R, Cassone A and Palma C
The ability of recombinant, SARS-CoV-2 Spike (S) protein to modulate the production of two COVID-19 relevant, pro-inflammatory cytokines (IL-6 and IFN-γ) in PBMC cultures of healthy, pre-COVID-19 subjects was investigated. We observed that cytokine production was largely and diversely modulated by the S protein depending on antigen or mitogen stimulation, as well as on the protein source, insect (S-in) or human (S-hu) cells. While both proteins co-stimulated cytokine production by polyclonally CD3-activated T cells, PBMC activation by the mitogenic lectin Concanavalin A (Con A) was up-modulated by S-hu protein and down-modulated by S-in protein. These modulatory effects were likely mediated by the S glycans, as demonstrated by direct Con A-S binding experiments and use of yeast mannan as Con A binder. While being ineffective in modulating memory antigenic T cell responses, the S proteins and mannan were able to induce IL-6 production in unstimulated PBMC cultures and upregulate the expression of the mannose receptor (CD206), a marker of anti-inflammatory M2 macrophage. Our data point to a relevant role of N-glycans, particularly N-mannosidic chains, decorating the S protein in the immunomodulatory effects here reported. These novel biological activities of the S glycan ectodomain may add to the comprehension of COVID-19 pathology and immunity to SARS-CoV-2.
Disease Burden and Inpatient Management of Children with Acute Respiratory Viral Infections during the Pre-COVID Era in Germany: A Cost-of-Illness Study
Alchikh M, Conrad TOF, Obermeier PE, Ma X, Schweiger B, Opota O and Rath BA
Respiratory viral infections (RVIs) are common reasons for healthcare consultations. The inpatient management of RVIs consumes significant resources. From 2009 to 2014, we assessed the costs of RVI management in 4776 hospitalized children aged 0-18 years participating in a quality improvement program, where all ILI patients underwent virologic testing at the National Reference Centre followed by detailed recording of their clinical course. The direct (medical or non-medical) and indirect costs of inpatient management outside the ICU ('non-ICU') versus management requiring ICU care ('ICU') added up to EUR 2767.14 (non-ICU) vs. EUR 29,941.71 (ICU) for influenza, EUR 2713.14 (non-ICU) vs. EUR 16,951.06 (ICU) for RSV infections, and EUR 2767.33 (non-ICU) vs. EUR 14,394.02 (ICU) for human rhinovirus (hRV) infections, respectively. Non-ICU inpatient costs were similar for all eight RVIs studied: influenza, RSV, hRV, adenovirus (hAdV), metapneumovirus (hMPV), parainfluenza virus (hPIV), bocavirus (hBoV), and seasonal coronavirus (hCoV) infections. ICU costs for influenza, however, exceeded all other RVIs. At the time of the study, influenza was the only RVI with antiviral treatment options available for children, but only 9.8% of influenza patients (non-ICU) and 1.5% of ICU patients with influenza received antivirals; only 2.9% were vaccinated. Future studies should investigate the economic impact of treatment and prevention of influenza, COVID-19, and RSV post vaccine introduction.
Intensive Care Unit Mortality Trends during the First Two Years of the COVID-19 Pandemic in Greece: A Multi-Center Retrospective Study
Fragkou PC, Karagiannis SP, Dimopoulou D, Kefala S, Fligou F, Gallos P, Jahaj E, Bellou A, Koukaki E, Magira E, Orfanos P, Papathanakos G, Papathanasiou A, Pediaditis E, Pontikis K, Rovina N, Vaporidi K, Xenikakis M, Theodorakopoulou M and Kotanidou A
Data on COVID-19 mortality among patients in intensive care units (ICUs) from Eastern and/or Southern European countries, including Greece, are limited. The purpose of this study was to evaluate the ICU mortality trends among critically ill COVID-19 patients during the first two years of the pandemic in Greece and to further investigate if certain patients' clinical characteristics contributed to this outcome. We conducted a multi-center retrospective observational study among five large university hospitals in Greece, between February 2020 and January 2022. All adult critically ill patients with confirmed COVID-19 disease who required ICU admission for at least 24 h were eligible. In total, 1462 patients (66.35% males) were included in this study. The mean age of this cohort was 64.9 (±13.27) years old. The 28-day mortality rate was 35.99% ( = 528), while the overall in-hospital mortality was 50.96% ( = 745). Cox regression analysis demonstrated that older age (≥65 years old), a body mass index within the normal range, and a delay in ICU admission from symptom onset, as well as worse baseline clinical severity scores upon ICU admission, were associated with a greater risk of death. Mortality of critically ill COVID-19 patients was high during the first two years of the pandemic in Greece but comparable to other countries. Risk factors for death presented in this study are not different from those that have already been described for COVID-19 in other studies.
The Expression Levels of and IFN-α Are Associated with Immune Reconstitution in HIV-1-Infected Individuals
Queiroz MAF, Oliveira AQT, Moura TCF, Brito WRDS, Santana EGM, Lima LLP, Lopes FT, Bichara CDA, Amoras EDSG, Ishak R, Vallinoto IMVC and Vallinoto ACR
TREX1 acts in the initial prevention of an autoimmune response, but it may contribute to the permissiveness of retrovirus infections. This study investigated the association between the levels of gene expression with the polymorphisms rs3135941 (T/C) and rs3135945 (G/A), and the presence of antinuclear antibodies (ANA) in antiretroviral therapy (ART)-naïve individuals and after 1 year of treatment. Blood samples from 119 individuals with HIV-1 were subjected to genotyping of polymorphisms and quantification of gene expression and HIV-1 viral load by qPCR. The concentration of IFN-α and the number of CD4/CD8 T lymphocytes were determined by ELISA and flow cytometry, respectively; ANA was investigated by immunofluorescence. A control group of 167 seronegative individuals was used for the comparison of genotypic frequencies. The frequency of the polymorphisms were not associated with HIV infection or with variations in the expression of and IFN-α ( > 0.05). ART-naïve individuals exhibited higher TREX1 expression and lower IFN-α expression. After 1 year of ART, levels were reduced, while IFN-α and CD4 T lymphocytes were elevated ( < 0.05). Some individuals on ART presented ANA. These results suggest that ART-mediated restoration of immune competence is associated with a reduction in expression, which may induce the development of ANA, regardless of the polymorphism investigated.
Human and Viral microRNA Expression in Acute and Chronic HIV Infections
Lazzari E, Rozera G, Gagliardini R, Esvan R, Mondi A, Mazzotta V, Camici M, Girardi E, Antinori A, Maggi F and Abbate I
Human and viral microRNAs (miRNAs) are involved in the regulation of gene transcription, and the establishment of their profiles in acute (AHI) and chronic (CHI) HIV infections may shed light on the pathogenetic events related to different phases of HIV disease. Next-generation sequencing (NGS) of miRNA libraries was performed, and the reads were used to analyze miRNA differential expression in the plasma with AHI and CHI. Functional analysis was then undertaken to investigate the biological processes characterizing the two phases of HIV infection. Except for hsa-miR-122-5p, which was found in 3.39% AHI vs. 0.18% CHI, the most represented human miRNAs were similarly represented in AHI and CHI. However, when considering the overall detected miRNAs in AHI and CHI, 15 displayed differential expression (FDR < 0.05). Functional analysis identified 163 target mRNAs involved in promoting angiogenesis activation in AHI versus CHI through the action of hsa-miR10b-5p, hsa-miR1290, hsa-miR1-3p, and hsa-miR296-5p. The viral miRNAs detected, all belonging to herpesviruses, accounted for only 0.014% of total reads. The present data suggest that AHI patients exhibit strong innate immune activation through the upregulation of hsa-miR-122-5p and early activation of angiogenesis. More specific investigations are needed to study the role of viral miRNAs in HIV pathogenesis.
Differential impact of prenatal PTSD symptoms and preconception trauma exposure on placental and methylation
Stroud LR, Jao NC, Ward LG, Lee SY and Marsit CJ
Perinatal stress is associated with altered placental methylation, which plays a critical role in fetal development and infant outcomes. This proof-of-concept pilot study investigated the impact of lifetime trauma exposure and perinatal PTSD symptoms on epigenetic regulation of placenta glucocorticoid signaling genes ( and Lifetime trauma exposure and PTSD symptoms during pregnancy were assessed in a racially/ethnically diverse sample of pregnant women ( = 198). Participants were categorized into three groups: (1) No Trauma (-T); (2) Trauma, No Symptoms (T - S); and (3) Trauma and Symptoms (T + S). Placental tissue was analyzed via bisulfite pyrosequencing for degree of methylation at the promoter and regulatory regions. Analyses of covariance were used to test group differences in percentages of and methylation overall and at each CpG site. We found a significant impact of PTSD symptoms on placental methylation. Compared to the -T group, the T + S group had greater methylation overall and at CpG6, CpG8, CpG9, and CpG13, but lower methylation at CpG5. The T + S group had significantly higher N methylation overall and at CpG8 compared to the T - S group. There were no differences between the T - S group and - T group. Additionally, no group differences emerged for methylation. Pregnant trauma survivors with PTSD symptoms exhibited differential patterns of placental methylation compared to trauma survivors without PTSD symptoms and pregnant women unexposed to trauma. Results highlight the critical importance of interventions to address the mental health of pregnant trauma survivors.
On the Feasibility of Using Behavioral Listening Effort Test Methods to Evaluate Auditory Performance in Cochlear Implant Users
Hendrikse MME, Dingemanse G and Goedegebure A
Realistic outcome measures that reflect everyday hearing challenges are needed to assess hearing aid and cochlear implant (CI) fitting. Literature suggests that listening effort measures may be more sensitive to differences between hearing-device settings than established speech intelligibility measures when speech intelligibility is near maximum. Which method provides the most effective measurement of listening effort for this purpose is currently unclear. This study aimed to investigate the feasibility of two tests for measuring changes in listening effort in CI users due to signal-to-noise ratio (SNR) differences, as would arise from different hearing-device settings. By comparing the effect size of SNR differences on listening effort measures with test-retest differences, the study evaluated the suitability of these tests for clinical use. Nineteen CI users underwent two listening effort tests at two SNRs (+4 and +8 dB relative to individuals' 50% speech perception threshold). We employed dual-task paradigms-a sentence-final word identification and recall test (SWIRT) and a sentence verification test (SVT)-to assess listening effort at these two SNRs. Our results show a significant difference in listening effort between the SNRs for both test methods, although the effect size was comparable to the test-retest difference, and the sensitivity was not superior to speech intelligibility measures. Thus, the implementations of SVT and SWIRT used in this study are not suitable for clinical use to measure listening effort differences of this magnitude in individual CI users. However, they can be used in research involving CI users to analyze group data.
Family physicians and menstrual care: An analysis of CERA 2023
Casola AR, Rea O and Ho T
Menstrual health is an important indicator of overall health and has large impacts on quality of life. Despite number and impact, discussion of menstruation remains largely taboo within health care. Patients and physicians are not engaging in regular, meaningful discussions on menstruation. Family physicians, as primary care providers, can facilitate these important conversations.
Impression life with pulmonary hypertension: clinically relevant characteristics and quality of life among patients in Gansu, China
Zhang J, Wen Y, Yin Y, Zhang Y, Zhang R, Zhang X, Ye J, Feng Y and Meng H
The adverse effects of pulmonary arterial hypertension (PAH) on physical, emotional, and health-related quality of life (HRQoL) remain primarily unrecognized, especially in resource-limited settings.
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