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A phase 2a study investigating the effects of ritlecitinib on brainstem auditory evoked potentials and intraepidermal nerve fiber histology in adults with alopecia areata
Anderson S, Cavaletti G, Hood LJ, Polydefkis M, Herrmann DN, Rance G, King B, McMichael AJ, Senna MM, Kim BS, Napatalung L, Wolk R, Zwillich SH, Schaefer G, Gong Y, Sisson M and Posner HB
Reversible axonal swelling and brainstem auditory evoked potential (BAEP) changes were observed in standard chronic (9-month) toxicology studies in dogs treated with ritlecitinib, an oral Janus kinase 3/tyrosine kinase expressed in hepatocellular carcinoma family kinase inhibitor, at exposures higher than the approved 50-mg human dose. To evaluate the clinical relevance of the dog toxicity finding, this phase 2a, double-blind study assessed BAEP changes and intraepidermal nerve fiber (IENF) histology in adults with alopecia areata treated with ritlecitinib. Patients were randomized to receive oral ritlecitinib 50 mg once daily (QD) with a 4-week loading dose of 200 mg QD or placebo for 9 months (placebo-controlled phase); they then entered the active-therapy extension and received ritlecitinib 50 mg QD (with a 4-week loading dose of 200 mg in patients switching from placebo). Among the 71 patients, no notable mean differences in change from baseline (CFB) in Waves I-V interwave latency (primary outcome) or Wave V amplitude on BAEP at a stimulus intensity of 80 dB nHL were observed in the ritlecitinib or placebo group at Month 9, with no notable differences in interwave latency or Wave V amplitude between groups. The CFB in mean or median IENF density and in percentage of IENFs with axonal swellings was minimal and similar between groups at Month 9. Ritlecitinib treatment was also not associated with an imbalanced incidence of neurological and audiological adverse events. These results provide evidence that the BAEP and axonal swelling finding in dogs are not clinically relevant in humans.
Primary health care utilisation and delivery in remote Australian clinics during the COVID-19 pandemic
Mathew S, Fitts MS, Liddle Z, Bourke L, Campbell N, Murakami-Gold L, Russell DJ, Humphreys JS, Rossingh B, Zhao Y, Jones MP, Boffa J, Ramjan M, Tangey A, Schultz R, Mulholland E and Wakerman J
The COVID-19 pandemic period (2020 to 2022) challenged and overstretched the capacity of primary health care services to deliver health care globally. The sector faced a highly uncertain and dynamic period that encompassed anticipation of a new, unknown, lethal and highly transmissible infection, the introduction of various travel restrictions, health workforce shortages, new government funding announcements and various policies to restrict the spread of the COVID-19 virus, then vaccination and treatments. This qualitative study aims to document and explore how the pandemic affected primary health care utilisation and delivery in remote and regional Aboriginal and Torres Strait Islander communities.
The impact of intraoperative hypotension on postoperative acute kidney injury, mortality and length of stay following off-pump coronary artery bypass grafting surgery: a single-center retrospective cohort study
Xiao C, Yang M, Cao L, Chen F, Jing S, Tan Y and Li H
Off-pump coronary artery bypass grafting (OPCABG) presents distinct hemodynamic characteristics, yet the relationship between intraoperative hypotension and short-term adverse outcomes remains clear. Our study aims to investigate association between intraoperative hypotension and postoperative acute kidney injury (AKI), mortality and length of stay in OPCABG patients.
Socioeconomic determinants and reasons for non-acceptance to vaccination recommendations during the 3 - 5 waves of the COVID-19 pandemic in Hungary
Ligeti AS, Oroszi B, Luca C, Bilics E, Ágoston J, Röst G and Koltai J
In Hungary, although six types of vaccines were widely available, the percentage of people receiving the primary series of COVID-19 vaccination remained below the EU average. This paper investigates the reasons for Hungary's lower vaccination coverage by exploring changing attitudes towards vaccination, socio-demographic determinants, and individual reasons for non-acceptance during the 3 - 5 pandemic waves of COVID-19.
Probabilistic prediction and context tree identification in the Goalkeeper game
Hernández N, Galves A, García JE, Gubitoso MD and Vargas CD
In this article we address two related issues on the learning of probabilistic sequences of events. First, which features make the sequence of events generated by a stochastic chain more difficult to predict. Second, how to model the procedures employed by different learners to identify the structure of sequences of events. Playing the role of a goalkeeper in a video game, participants were told to predict step by step the successive directions-left, center or right-to which the penalty kicker would send the ball. The sequence of kicks was driven by a stochastic chain with memory of variable length. Results showed that at least three features play a role in the first issue: (1) the shape of the context tree summarizing the dependencies between present and past directions; (2) the entropy of the stochastic chain used to generate the sequences of events; (3) the existence or not of a deterministic periodic sequence underlying the sequences of events. Moreover, evidence suggests that best learners rely less on their own past choices to identify the structure of the sequences of events.
Enhancing prostate cancer diagnosis and reducing unnecessary biopsies with [F]DCFPyL PET/CT imaging in PI-RADS 3/4 patients
Fu Y, Zhao M, Chen J, Wen Q and Chen B
For patients presenting with prostate imaging reporting and data system (PI-RADS) 3/4 findings on magnetic resonance imaging (MRI) examinations, the standard recommendation typically involves undergoing a biopsy for pathological assessment to ascertain the nature of the lesion. This course of action, though essential for accurate diagnosis, invariably amplifies the psychological distress experienced by patients and introduces a host of potential complications associated with the biopsy procedure. However, [F]DCFPyL PET/CT imaging emerges as a promising alternative, demonstrating considerable diagnostic efficacy in discerning benign prostate lesions from malignant ones. This study aims to explore the diagnostic value of [F]DCFPyL PET/CT imaging for prostate cancer in patients with PI-RADS 3/4 lesions, assisting in clinical decision-making to avoid unnecessary biopsies. 30 patients diagnosed with PI-RADS 3/4 lesions through mpMRI underwent [F]DCFPyL PET/CT imaging, with final biopsy pathology results as the "reference standard". Diagnostic performance was assessed through receiver operating characteristic (ROC) analysis, evaluating the diagnostic efficacy of molecular imaging PSMA (miPSMA) visual analysis and semi-quantitative analysis in [F]DCFPyL PET/CT imaging. Lesions were assigned miPSMA scores according to the prostate cancer molecular imaging standardized evaluation criteria. Among the 30 patients, 13 were pathologically confirmed to have prostate cancer. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of visual analysis in [F]DCFPyL PET/CT imaging for diagnosing PI-RADS 3/4 lesions were 61.5%, 88.2%, 80.0%, 75.0%, and 76.5%, respectively. Using SUVmax 4.17 as the optimal threshold, the sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for diagnosis were 92.3%, 88.2%, 85.7%, 93.8%, and 90.0%, respectively. The area under the ROC curve (AUC) for semi-quantitative analysis was 0.94, significantly higher than visual analysis at 0.80. [F]DCFPyL PET/CT imaging accurately diagnosed benign lesions in 15 (50%) of the PI-RADS 3/4 patients. For patients with PI-RADS 4 lesions, the positive predictive value of [F]DCFPyL PET/CT imaging reached 100%. [18F]DCFPyL PET/CT imaging provides potential preoperative prediction of lesion nature in mpMRI PI-RADS 3/4 patients, which may aid in treatment decision-making and reducing unnecessary biopsies.
Clinical and microbiological characteristics of persistent Staphylococcus aureus bacteremia, risk factors for mortality, and the role of CD4 T cells
Yang E, Cho YG, Kim E, Chang E, Bae S, Jung J, Kim MJ, Chong YP, Kim SH, Choi SH, Lee SO, Chung YS and Kim YS
This study evaluated the determinants of mortality and the T cell immune response in patients with persistent Staphylococcus aureus bacteremia (SAB). This was a prospective cohort study and patients with confirmed SAB were enrolled from 2008 to 2020. We compared clinical, microbiological, and genotypic features between surviving and deceased patients with persistent SAB. The concentrations of cytokines and the proportions of IFN-γ secreting CD4 T cells were measured serially during the bacteremia period. Of the 1760 patients, 242 had persistent bacteremia (PB), and 49 PB patients died within 30 days. In the multivariate analysis, the APACHE II score and female sex were independently associated with 30 days mortality. The level of IL-10 was significantly increased in the plasma of patients with a high Pitt bacteremia score and those who died within 12 weeks from the index day. The proportion of IFN-γ-secreting CD4 T cells were the highest just before the positive-to-negative conversion of blood cultures in patients with a low Pitt bacteremia score and those who survived for 12 weeks. The level of IL-10 is correlated with clinical outcomes in PB patients. IFN-γ secreting CD4 T cells might play a pivotal role in SAB PB.
Investigating the Bioavailability and Insulin-like Growth Factor-I Release of Two Different Strengths of Somapacitan: A Randomised, Double-Blind Crossover Trial
Dombernowsky SL, Damholt BB, Højby Rasmussen M, Sværke C and Kildemoes RJ
Randomised, double-blind, crossover trial to confirm bioequivalence of somapacitan, a long-acting growth hormone (GH), in 5 mg/1.5 mL and 10 mg/1.5 mL strengths in equimolar doses.
The meaning of culture in nursing at the end of life - an interview study with nurses in specialized palliative care
Mian R and Rejnö Å
The countries of the world are becoming increasingly multicultural and diverse, both as a result of growing migration, of people fleeing countries at war but also due to increased mobility related to labour immigration. Culture is a broad concept where the definitions focus on learned and shared values, traditions, and beliefs of a group of individuals. People's culture affects health and perceptions of illness as well as treatment, symptoms, and care. Moreover, people who are at the end of life, live and exist within all levels and contexts of care. Specialized palliative care requires that the nurse has sufficient knowledge and skills to be responsible for meeting the patient's nursing needs also on a cultural level, regardless of cultural affiliation. The aim of the study was to highlight nurses' experiences of the meaning of culture when caring for patients at the end of life in specialized palliative care.
Hidden blood loss and its risk factors after hip reconstruction in children
Yang J, Jiang H, Gu H, Du J, Zhuo Y, He K and Yu S
There were few reports in the literature regarding hidden blood loss following surgery for developmental dysplasia of the hip in children. This study aimed to evaluate the volume of hidden blood loss and its risk factors among children undergoing hip reconstruction for developmental dysplasia of the hip.
Novel online enfacement illusion for investigating self-perception in mental disorders: an experimental study protocol
Portingale J, Butler D and Krug I
Remote research methods and interventions for mental health disorders have become increasingly important, particularly for conditions like eating disorders (EDs). Embodiment illusions, which induce feelings of ownership over another person?s body or body parts, offer valuable insights into the mechanisms underlying self-perception issues in EDs and potential interventions. However, existing research using these illusions has been limited to face-to-face settings. We illustrate a novel online protocol to induce the enfacement illusion (embodiment illusion principles applied to one's face) in an ED-based sample.
Cost analysis of establishing and operating the first human milk bank at Da Nang Hospital for Women and Children in Vietnam: an activity-based costing ingredients study
Hoang MV, Nguyen TT, Tran AT, Luu TQ, Vu MQ, Tran HT, Nguyen OTX and Mathisen R
Breastfeeding is the biological norm for feeding infants and young children. When mothers' breastmilk is unavailable, donor human milk (DHM) from a human milk bank (HMB) becomes the next option for small vulnerable newborns. A comprehensive cost analysis is essential for understanding the investments needed to establish, operate, and scale up HMBs. This study aims to estimate and analyze such costs at the first facility established in Vietnam.
The intratumoral microbiota biomarkers for predicting survival and efficacy of immunotherapy in patients with ovarian serous cystadenocarcinoma
Qin H, Liu J, Qu Y, Li YY, Xu YL and Yan YF
Ovarian serous cystadenocarcinoma, accounting for about 90% of ovarian cancers, is frequently diagnosed at advanced stages, leading to suboptimal treatment outcomes. Given the malignant nature of the disease, effective biomarkers for accurate prediction and personalized treatment remain an urgent clinical need.
A multicenter, randomized, double-blind, placebo-controlled ascending dose study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamic (PD) effects of Posiphen in subjects with early Alzheimer's Disease
Galasko D, Farlow MR, Lucey BP, Honig LS, Elbert D, Bateman R, Momper J, Thomas RG, Rissman RA, Pa J, Aslanyan V, Balasubramanian A, West T, Maccecchini M and Feldman HH
Amyloid beta protein (Aβ) is a treatment target in Alzheimer's Disease (AD). Lowering production of its parent protein, APP, has benefits in preclinical models. Posiphen, an orally administered small molecule, binds to an iron-responsive element in APP mRNA and decreases translation of APP and Aβ. To augment human data for Posiphen, we evaluated safety, tolerability and pharmacokinetic and pharmacodynamic (PD) effects on Aβ metabolism using Stable Isotope Labeling Kinetic (SILK) analysis.
Determinants of mortality status and population attributable risk fractions of the North West Province, South African site of the international PURE study
Ricci C, Kruger IM, Kruger HS, Breet Y, Moss SJ, van Oort A, Bester P and Pieters M
Mortality data and comparative risk assessments from sub-Saharan Africa are limited. There is an urgent need for high quality population health surveys to be conducted, to improve the national health surveillance system. Our aim was to perform a comparative risk assesment and report on the mortality status and cause of death data of participants from a South African site of the international Prospective Urban Rural Epidemiology study.
The anesthetic management of a child with ohtahara syndrome and severe stridor: a case report
Patel N, Madi P, Monteiro I and Shah SP
Ohtahara syndrome is a progressive developmental and epileptic encephalopathy that manifests in the early infantile period. This rare condition is characterized by intractable seizures, psychomotor retardation, and poor prognosis. To date, there are a handful of case reports regarding the anesthetic management of children with Ohtahara syndrome. However, limited reports exist of patients with Ohtahara syndrome who present with difficult airways. This report describes our airway findings and general anesthetic management of a pediatric patient with Ohtahara syndrome undergoing diagnostic bronchoscopy for severe inspiratory stridor.
Distinct pattern of genomic breakpoints in CML and BCR::ABL1-positive ALL: analysis of 971 patients
Hovorkova L, Winkowska L, Skorepova J, Krumbholz M, Benesova A, Polivkova V, Alten J, Bardini M, Meyer C, Kim R, Trahair TN, Clappier E, Chiaretti S, Henderson M, Sutton R, Sramkova L, Stary J, Polakova KM, Marschalek R, Metzler M, Cazzaniga G, Cario G, Trka J, Zaliova M and Zuna J
The BCR::ABL1 is a hallmark of chronic myeloid leukemia (CML) and is also found in acute lymphoblastic leukemia (ALL). Most genomic breaks on the BCR side occur in two regions - Major and minor - leading to p210 and p190 fusion proteins, respectively.
Association between the adherence to Mediterranean diet and depression in rheumatoid arthritis patients: a cross-sectional study from the NHANES database
Ma L, Yuan J, Yang X, Yan M, Li Y and Niu M
Rheumatoid arthritis (RA) is a systemic autoimmune disease, and depression is a most frequent comorbid condition associated with RA. Studies have shown that inflammation plays a vital role in the pathophysiology of depression and RA. Mediterranean diet (MED) has been proved to be a healthy anti-inflammatory dietary pattern. This study aims to explore the association between the adherence to Mediterranean diet (aMED) and depression in RA patients.
Gastrointestinal toxicities of proteasome inhibitor therapy
Shah J, Devalaraju S, Baerman E, Lee IJ, Takigawa K, Machado AP, Catinis C, Shatila M, Varatharajalu K, Shafi M, Lee HC, Strati P, Thomas A and Wang Y
Proteasome inhibitors (PIs), which cause cell death via tumor suppressor and pro-apoptotic proteins, are integral to treatment of many hematologic malignancies but are limited by their gastrointestinal adverse effects. Evidence regarding these PI-related adverse effects is scant. In this study, we evaluated gastrointestinal adverse events caused by PIs and compared gastrointestinal toxicities between bortezomib, carfilzomib, and ixazomib.
Exploring the shift in newborn care practices among mothers and grandmothers in rural Odisha, India - a qualitative study
Thomas L, Arun S, Varughese DT, Soreng CK, Manjari BP, Khosla PS and Pani DK
This study delves into newborn care and infant-feeding practices in rural Odisha, specifically focusing on the rural KBK + region of Odisha (Kalahandi-Bolangir-Koraput region), inhabited predominantly by Schedule Tribes and Schedule Castes individuals. There has been an improvement in the health indicators in these areas in recent times. In the background of improved health indicators in these areas, this research explores the current and changing newborn care practices and attempts to gain insight into people's perceptions of the factors that brought about the changes.
Sexually dimorphic oxytocin circuits drive intragroup social conflict and aggression in wild house mice
Sofer Y, Zilkha N, Gimpel E, Wagner S, Chuartzman SG and Kimchi T
In nature, both males and females engage in competitive aggressive interactions to resolve social conflicts, yet the behavioral principles guiding such interactions and their underlying neural mechanisms remain poorly understood. Through circuit manipulations in wild mice, we unveil oxytocin-expressing (OT) neurons in the hypothalamic paraventricular nucleus (PVN) as a neural hub governing behavior in dyadic and intragroup social conflicts, influencing the degree of behavioral sexual dimorphism. We demonstrate that OT PVN neurons are essential and sufficient in promoting aggression and dominance hierarchies, predominantly in females. Furthermore, pharmacogenetic activation of these neurons induces a change in the 'personality' traits of the mice within groups, in a sex-dependent manner. Finally, we identify an innervation from these OT neurons to the ventral tegmental area that drives dyadic aggression, in a sex-specific manner. Our data suggest that competitive aggression in naturalistic settings is mediated by a sexually dimorphic OT network connected with reward-related circuitry.
International medical learners and their adjustment after returning to their countries of origin: a qualitative study
Wongprom I, Ruangsomboon O, Huang J and Ghavam-Rassoul A
International medical trainees, including residents and fellows, must cope with many challenges, such as differences in cultural hierarchical systems, languages, and acceptance. Nonetheless, the need for adjustment perpetuates even after training is completed abroad. When some international trainees return to their countries of origin, they continue to face adjustment challenges due to reverse culture shock. Others must make many further readjustments. This study presents an exploration of the adjustment and coping strategies of international medical learners after returning to their countries of origin upon completion of their programs.
A three-dimensional quantitative assessment on bony growth and symmetrical recovery of mandible after decompression for unicystic ameloblastoma
Bao T, Yu D, Zheng J, Zhu W, Wei D and Wang H
Unicystic ameloblastoma (UAM) of the jaw can be effectively reduced in volume through decompression, which promotes bone regeneration and restores jaw symmetry. This study quantitatively evaluated changes in mandible volume and symmetry following decompression of mandibular UAM. This study included 17 patients who underwent surgical decompression followed by second-stage curettage for mandibular UAM. Preoperative and postoperative three-dimensional computed tomography (CT) images were collected. Bone volume and the area of cortical perforation were measured to assess bone growth during decompression. Mandibular volumetric symmetry was analyzed by calculating the volumetric ratio of the two sides of the mandible. Twelve pairs of landmarks were identified on the surface of the lesion regions, and their coordinates were used to calculate the mean asymmetry index (AI) of the mandible. Paired t-tests and the Mann-Whitney U test were used for statistical analysis, with p < 0.05 considered indicative of statistical significance. The mean duration of decompression was 9.41 ± 3.28 months. The mean bone volume increased by 8.07 ± 2.41%, and cortical perforation recovery was 71.97 ± 14.99%. The volumetric symmetry of the mandible improved significantly (p < 0.05), and a statistically significant decrease in AI was observed (p < 0.05). In conclusion, UAM decompression enhances bone growth and symmetry recovery of the mandible. The present evaluation technique is clinically useful for quantitatively assessing mandibular asymmetry.
Predicting progression from subjective cognitive decline to mild cognitive impairment or dementia based on brain atrophy patterns
Lerch O, Ferreira D, Stomrud E, van Westen D, Tideman P, Palmqvist S, Mattsson-Carlgren N, Hort J, Hansson O and Westman E
Alzheimer's disease (AD) is a progressive neurodegenerative disorder where pathophysiological changes begin decades before the onset of clinical symptoms. Analysis of brain atrophy patterns using structural MRI and multivariate data analysis are an effective tool in identifying patients with subjective cognitive decline (SCD) at higher risk of progression to AD dementia. Atrophy patterns obtained from models trained to classify advanced AD versus normal subjects, may not be optimal for subjects at an early stage, like SCD. In this study, we compared the accuracy of the SCD progression prediction using the 'severity index' generated using a standard classification model trained on patients with AD dementia versus a new model trained on β-amyloid (Aβ) positive patients with amnestic mild cognitive impairment (aMCI).
Impact of high-altitude hypoxia on Helicobacter pylori-induced gastritis pathological manifestations and inflammatory responses
Li C, Wang X and Cui S
Chronic gastritis caused by Helicobacter pylori (Hp) infection is a common gastrointestinal disorder. Despite the high prevalence of Hp infection and chronic gastritis in the Tibetan Plateau, there is a lack of studies elucidating the influence of plateau hypoxia on Hp-induced gastritis. This study aimed to investigate the impact of high-altitude hypoxia on Hp-induced gastritis, particularly focusing on pathological manifestations and inflammatory responses.
Impact on pregnancy outcomes of intermittent preventive treatment with sulfadoxine-pyrimethamine in urban and peri-urban Papua New Guinea: a retrospective cohort study
Cellich P, Unger HW, Rogerson SJ and Mola GDL
Intermittent preventive treatment in pregnancy with sulfadoxine-pyrimethamine (IPTp-SP) reduces malaria-attributable adverse pregnancy outcomes and may also prevent low birth weight (< 2,500 g) through mechanisms independent of malaria. Malaria transmission in Papua New Guinea (PNG) is highly heterogeneous. The impact of IPTp-SP on adverse birth outcomes in settings with little or no malaria transmission, such as PNG's capital city Port Moresby, is unknown.
Impact of neighborhood context on self-rated health among very old adults living in Germany: a cross-sectional representative study
Zimmermann J
Increasingly, evidence has shown that different aspects of neighborhood context play a significant role in self-rated health, one of the key health indicators in advanced age. Nevertheless, very old adults are often under represented or excluded from such research. Therefore, the first aim of this study was to examine whether social, socioeconomic, and physical neighborhood context is associated with self-rated health in the very old population of Germany. The second objective was to explore whether the link of socioeconomic and physical neighborhood context with self-rated health is moderated by availability of social resources in neighborhoods.
Therapeutic effect of induction therapy including nab-paclitaxel followed by surgical resection for the patients with locally advanced non-small-cell lung cancer
Uramoto H, Motono N and Iwai S
Lung cancer is associated with a high mortality rate worldwide. Non-small-cell lung cancer (NSCLC) is a major subtype of lung cancer. Carboplatin (CBDCA) plus nab-paclitaxel (PTX) has become a standard treatment for advanced unresectable NSCLC. However, treatment with nab-PTX has not been established as a standard therapy for resectable locally advanced (LA)-NSCLC.
Interpersonal violence against people with intellectual disabilities in São Paulo, Brazil: characteristics of victims, perpetrators and referrals
Silva MTD, Fontoura AVB, Pires ANG, Carvalheira APP, Hino P, Okuno MFP, Taminato M, Caldas JMP and Fernandes H
Interpersonal violence is a phenomenon that can occur with different people and conditions. However, people with intellectual disabilities have increased vulnerability to this problem, with potential risks to their health and well-being. The aim of this study was to identify the sociodemographic characteristics of people with disabilities who have been victims of interpersonal violence, the profile of the perpetrators and the measures taken after the victims have been cared for.
M2-type tumor-associated macrophages upregulated PD-L1 expression in cervical cancer via the PI3K/AKT pathway
Guo F, Kong W, Li D, Zhao G, Anwar M, Xia F, Zhang Y, Ma C and Ma X
PD-1/PD-L1 inhibitors have become a promising therapy. However, the response rate is lower than 30% in patients with cervical cancer (CC), which is related to immunosuppressive components in tumor microenvironment (TME). Tumor-associated macrophages (TAMs), as one of the most important immune cells, are involved in the formation of tumor suppressive microenvironment. Therefore, it will provide a theoretical basis for curative effect improvement about the regulatory mechanism of TAMs on PD-L1 expression.
Association and temporal sequence of pneumonia and gastrointestinal bleeding after acute ischemic stroke
Zhang R, Hou H, Zhao X, Liu L, Wang Y, Liu G, Wang Y and Ji R
Stroke-associated pneumonia (SAP) and gastrointestinal bleeding (GIB) are common medical complications after stroke. The previous study suggested a strong association between SAP and GIB after stroke. However, little is known about the time sequence of SAP and GIB. In the present study, we aimed to verify the association and clarify the temporal sequence of SAP and GIB after ischemic stroke.
Effect of the data-informed platform for health intervention on the culture of data use for decision-making among district health office staff in North Shewa Zone, Ethiopia: a cluster-randomised controlled trial
Zeleke GT, Avan BI, Dubale MA and Schellenberg J
Similar to other low and middle-income countries, Ethiopia faces limitations in using local health data for decision-making.We aimed to assess the effect of an intervention, namely the data-informed platform for health, on the culture of data-based decision making as perceived by district health office staff in Ethiopia's North Shewa Zone.
Rate of abnormalities in quantitative MR neuroimaging of persons with chronic traumatic brain injury
Rahmani F, Batson RD, Zimmerman A, Reddigari S, Bigler ED, Lanning SC, Ilasa E, Grafman JH, Lu H, Lin AP and Raji CA
Mild traumatic brain injury (mTBI) can result in lasting brain damage that is often too subtle to detect by qualitative visual inspection on conventional MR imaging. Although a number of FDA-cleared MR neuroimaging tools have demonstrated changes associated with mTBI, they are still under-utilized in clinical practice.
Molecular alterations and prognosis of breast cancer with cutaneous metastasis
Xu Y, Ding L, Li C, Hua B, Wang S, Zhang J, Liu C, Guo R and Zhang Y
Cutaneous metastasis (CM) accounts for 5-30% of patients with breast cancer (BC) and presents unfavorable response to treatment and poor prognosis. A better understanding of the molecular alterations involved in metastasis is essential, which would help identify diagnostic and efficacy biomarkers for CM.
Critical Self-reflection on Racism by Hospital Physicians in Large German Cities. A Qualitative Reconstructive Study Using Episodic Interviews
Nassal T and Tezcan-Güntekin H
Racism permeates healthcare institutions and interpersonal interactions, impacting both staff and patients. The role of doctors, given their influential position in the healthcare system, is particularly crucial in this context. Despite this, there is a scarcity of evidence regarding the manifestation of racism among healthcare professionals in Germany. Critical whiteness studies emphasize the importance of white* individuals engaging in critical self-reflection to mitigate racism. This study aimed to explore the attitudes of white* physicians in hospitals in major German cities towards racism and their critical reflection on personal attitudes and actions concerning racism in interactions with staff members and patients. Data was collected through six episodic interviews with physicians, analyzed using the reconstructive qualitative procedure of the documentary method, leading to a sense-genetic typology. The sense-genetic typology revealed three distinct attitudes towards racism: acknowledging, individualistic, and ignoring. Four types emerged concerning the self-reflection of white doctors: self-critical, socially critical, worried, and defensive. The most promising potential for interventions to reduce racism lies within the self-critical and socially critical types, both demonstrating an acknowledging attitude. Conversely, the worrying and defensive types may present challenges in deconstruction. This suggests that interventions aimed at reducing racism should be tailored and implemented with a nuanced approach.
Assessing the value and knowledge gains from an online tick identification and tick-borne disease management course for the Southeastern United States
Lippi CA, Gaff HD, White AL and Ryan SJ
Tick-borne diseases are a growing public health threat in the United States. Despite the prevalence and rising burden of tick-borne diseases, there are major gaps in baseline knowledge and surveillance efforts for tick vectors, even among vector control districts and public health agencies. To address this issue, an online tick training course (OTTC) was developed through the Southeastern Center of Excellence in Vector-Borne Diseases (SECOEVBD) to provide a comprehensive knowledge base on ticks, tick-borne diseases, and their management.
Extracellular Matrix Structure and Interaction with Immune Cells in Adult Astrocytic Tumors
Di Vito A, Donato A, Bria J, Conforti F, La Torre D, Malara N and Donato G
The extracellular matrix (ECM) is a dynamic set of molecules produced by the cellular component of normal and pathological tissues of the embryo and adult. ECM acts as critical regulator in various biological processes such as differentiation, cell proliferation, angiogenesis, and immune control. The most frequent primary brain tumors are gliomas and by far the majority are adult astrocytic tumors (AATs). The prognosis for patients with these neoplasms is poor and the treatments modestly improves survival. In the literature, there is a fair number of studies concerning the composition of the ECM in AATs, while the number of studies relating the composition of the ECM with the immune regulation is smaller. Circulating ECM proteins have emerged as a promising biomarker that reflect the general immune landscape of tumor microenvironment and may represent a useful tool in assessing disease activity. Given the importance it can have for therapeutic and prognostic purposes, the aim of our study is to summarize the biological properties of ECM components and their effects on the tumor microenvironment and to provide an overview of the interactions between major ECM proteins and immune cells in AATs. As the field of immunotherapy in glioma is quickly expanding, we retain that current data together with future studies on ECM organization and functions in glioma will provide important insights into the tuning of immunotherapeutic approaches.
Calcium supplementation during trauma resuscitation: a propensity score-matched analysis from the TraumaRegister DGU
Helsloot D, Fitzgerald M, Lefering R, Groombridge C, Becaus N, Verelst S, Missant C and
In major trauma patients, hypocalcemia is associated with increased mortality. Despite the absence of strong evidence on causality, early calcium supplementation has been recommended. This study investigates whether calcium supplementation during trauma resuscitation provides a survival benefit.
Evaluation of the effectiveness of picosecond KTP and fractional thulium lasers on pigmented-type periorbital dark circles
AlRamthan A, Shaban M, AlSaqer F, Alkhazi H, Shamsaldeen O and Ashour L
To determine the effectiveness of picosecond KTP in reducing peri-ocular dark circles caused mainly by excessive pigmentation and to compare Picosecond KTP with Thulium laser ability in reducing the intensity and extent of peri-ocular dark circles.
Effect of body mass index on 30-day complication rate and implant survival rate after simultaneous bilateral unicompartmental knee arthroplasty: a multicentre retrospective study
Xu K, Wang T, Yu T, Zhao X, Zhang Y and Zhang L
The practice of simultaneous bilateral unicompartmental knee arthroplasty (SBUKA) remains a topic of debate, particularly in patients with obesity. Thus, the purpose of this study was to assess the impact of body mass index (BMI) on the 30-day complication rate and the survival rate of the implant following SBUKA.
The postoperative renal function of persistent cloaca patients treated by posterior sagittal anorecto-urethro-vaginopalsty: results of a nationwide survey in Japan
Sugita K, Harumatsu T, Nagano A, Yano K, Onishi S, Kawano T, Ieiri S and Kubota M
We investigated the postoperative renal function in persistent cloaca (PC) patients who underwent posterior sagittal anorecto-urethro-vaginopalsty (PSARUVP) and factors influencing the renal functional outcomes.
Receiving home care forms and the risk for emergency department visits in community-dwelling Dutch older adults, a retrospective cohort study using national data
Smeekes OS, De Boer TR, Van Der Mei RD, Buurman BM and Willems HC
Older adults receiving home care have a higher risk of visiting the emergency department (ED) than community-dwelling older adults not receiving home care. This may result from a higher incidence of comorbidities and reduced functional autonomy in home care recipients. Since people receive different types of home care because of their different comorbidities and autonomy profiles, it is possible that distinguishing between the form of home care can help identify subpopulations with different risks for ED visits and help develop targeted interventions. This study aimed to compare the risk of visiting the ED in older adults receiving different forms of home care with those living at home without receiving home care in a national cohort in one year.
Anatolian genetic ancestry in North Lebanese populations
Platt DE, Henschel A, Taleb NN and Zalloua P
Lebanon's rich history as a cultural crossroad spanning millennia has significantly impacted the genetic composition of its population through successive waves of migration and conquests from surrounding regions. Within modern-day Lebanon, the Koura district stands out with its unique cultural foundations, primarily characterized by a notably high concentration of Greek Orthodox Christians compared to the rest of the country. This study investigates whether the prevalence of Greek Orthodoxy in Koura can be attributed to modern Greek heritage or continuous blending resulting from the ongoing influx of refugees and trade interactions with Greece and Anatolia. We analyzed both ancient and modern DNA data from various populations in the region which could have played a role in shaping the current population of Koura using our own and published data. Our findings indicate that the genetic influence stemming directly from modern Greek immigration into the area appears to be limited. While the historical presence of Greek colonies has left its mark on the region's past, the distinctive character of Koura seems to have been primarily shaped by cultural and political factors, displaying a stronger genetic connection mostly with Anatolia, with affinity to ancient but not modern Greeks.
Associations between different triglyceride glucose index-related obesity indices and periodontitis: results from NHANES 2009-2014
Yang L, Fang S, Zhang R and Xia R
This study aimed to explore the associations between triglyceride glucose (TyG) index-related obesity indices and periodontitis within the American population.
Oil painting teaching design based on the mobile platform in higher art education
Yi G
To improve the current oil painting teaching mode in Chinese universities, this study combines deep learning technology and artificial intelligence technology to explore oil painting teaching. Firstly, the research status of individualized education and related research on image classification based on brush features are analyzed. Secondly, based on a convolutional neural network, mathematical morphology, and support vector machine, the oil painting classification model is constructed, in which the extracted features include color and brush features. Moreover, based on artificial intelligence technology and individualized education theory, a personalized intelligent oil painting teaching framework is built. Finally, the performance of the intelligent oil painting classification model is evaluated, and the content of the personalized intelligent oil painting teaching framework is explained. The results show that the average classification accuracy of oil painting is 90.25% when only brush features are extracted. When only color features are extracted, the average classification accuracy is over 89%. When the two features are extracted, the average accuracy of the oil painting classification model reaches 94.03%. Iterative Dichotomiser3, decision tree C4.5, and support vector machines have an average classification accuracy of 82.24%, 83.57%, and 94.03%. The training speed of epochs data with size 50 is faster than that of epochs original data with size 100, but the accuracy is slightly decreased. The personalized oil painting teaching system helps students adjust their learning plans according to their conditions, avoid learning repetitive content, and ultimately improve students' learning efficiency. Compared with other studies, this study obtains a good oil painting classification model and a personalized oil painting education system that plays a positive role in oil painting teaching. This study has laid the foundation for the development of higher art education.
Prescription medication use in the 10 years prior to diagnosis of young onset Alzheimer's disease: a nationwide nested case-control study
Damsgaard L, Janbek J, Laursen TM, Vestergaard K, Gottrup H, Jensen-Dahm C and Waldemar G
Patients with young onset Alzheimer's disease (YOAD) face long diagnostic delays. Prescription medication use may provide insights into early signs and symptoms, which may help facilitate timely diagnosis.
Retrospective analysis of pathological changes in the maxillary sinus with CBCT
Dogan ME, Uluısık N and Yuvarlakbaş SD
The aim of this study is to examine the frequency of maxillary sinus pathologies and their relationship with each other using cone beam computed tomography (CBCT) and to make a new grade according to the number of affected walls. 1000 maxillary sinuses of 500 patients with CBCT images were included in the study. Anatomical variations and pathological formations of the maxillary sinuses were examined. Images were evaluated for the presence of flat, polypoidal, partial and generalized mucosal thickening, partial and total opacification, polyps and mucous retention cysts. Maxillary sinus pathologies were graded according to the number of walls affected. In the examined CBCT images, no pathology was found in 54.2% of the maxillary sinuses, while pathology was observed in 45.8%. The most common sinus pathologies were mucous retention cyst (12.3%) and polypoidal thickening (12.2%). While pneumatization, ostium obstruction, and the presence of sinus-related roots were associated with sinus pathology, no relationship was found with nasal septum deviation and the presence of septa. Before dental implant and sinus surgery applications, the presence of sinus pathologies and their relationship with anatomical variations can be evaluated with CBCT, a three-dimensional technique, and complications such as sinus membrane perforation, infection, failure to break the bone window due to the presence of antral septa, graft loss and oroantral fistula formation can be reduced.
Highly extensile approach for comminuted ulna coronoid process fractures with mini-plate fixation: a case series of 31 patients
Zhou SC, Jin SY, Wang QY, Ren GK, Peng CG, Wang YB and Wu DK
For the treatment of coronoid process fractures, medial, lateral, anterior, anteromedial, and posterior approaches have been increasingly reported; however, there is no general consensus on the method of fixation of coronal fractures. Here, we present a highly-extensile minimally invasive approach to treat coronoid process fractures using a mini-plate that can achieve anatomic reduction, stable fixation, and anterior capsular repair. Further, the study aimed to determine the complication rate of the anterior minimally invasive approach and to evaluate functional and clinical patient-reported outcomes during follow-up.
SLPI overexpression in hMSCs could be implicated in the HSC gene expression profile in AML
Azevedo PL, Maradei S, de Sá Bigni R, Santos Ramires Aragao J, Abdelhay E and Binato R
Acute myeloid leukaemia (AML) is a severe haematological neoplasm that originates from the transformation of haematopoietic stem cells (HSCs) into leukaemic stem cells (LSCs). The bone marrow (BM) microenvironment, particularly that of mesenchymal stromal cells (hMSCs), plays a crucial role in the maintenance of HSCs. In this context, we explored whether alterations in the secretome of hMSCs derived from AML patients (hMSC-AML) could impact HSC gene expression. Proteomic analysis revealed that the secretome of coculture assays with hMSC-AMLs and HSC from healthy donor is altered, with increased levels of secretory leukocyte protease inhibitor (SLPI), a protein associated with important processes for maintenance of the haematopoietic niche that has already been described to be altered in several tumours. Increased SLPI expression was also observed in the BM plasma of AML patients. Transcriptome analysis of HSCs cocultured with hMSC-AML in comparison with HSCs cocultured with hMSC-HD revealed altered expression of SLPI target genes associated with the cell cycle, proliferation, and apoptosis. Important changes were identified, such as increased expression levels of CCNA2, CCNE2, CCND2, CD133 and CDK1 and decreased levels of CDKN2A and IGFBP3, among others. Overall, these findings suggest that the altered secretome of coculture assays with hMSC-AMLs and HSC from healthy donor, particularly increased SLPI expression, can contribute to gene expression changes in HSCs, potentially influencing important molecular mechanisms related to AML development and progression.
Benchmarking for healthy food stores: protocol for a randomised controlled trial with remote Aboriginal and Torres Strait Islander communities in Australia to enhance adoption of health-enabling store policy and practice
Brimblecombe J, Ferguson M, McMahon E, Fredericks B, Turner N, Pollard C, Maple-Brown L, Batstone J, McCarthy L, Miles E, De Silva K, Barnes A, Chatfield M, Hill A, Christian M, van Burgel E, Fairweather M, Murison A, Lukose D, Gaikwad S, Lewis M, Clancy R, Santos C, Uhlmann K, Funston S, Baddeley L, Tsekouras S, Ananthapavan J, Sacks G and Lee A
Aboriginal and Torres Strait Islander communities in remote Australia have initiated bold policies for health-enabling stores. Benchmarking, a data-driven and facilitated 'audit and feedback' with action planning process, provides a potential strategy to strengthen and scale health-enabling best-practice adoption by remote community store directors/owners. We aim to co-design a benchmarking model with five partner organisations and test its effectiveness with Aboriginal and Torres Strait Islander community stores in remote Australia.
Dental complications as a potential indicator of Redondovirus infection: a cross-sectional study
Mohebbi A, Kiani SJ, Khanaliha K, Donyavi T, Emtiazi N, Sharifian K, Mohebbi M, Gholami A, Behnezhad F, Abbasi-Kolli M, Dehghani-Dehej F and Bokharaei-Salim F
Redondoviridae is a newly discovered virus family linked to oral and respiratory conditions in people, while there is still debate about whether it is also coinfected with other respiratory viruses. This study aimed to determine the frequency of Redondovirus (ReDoV) in nasopharyngeal samples and to investigate any possible links to SARS-CoV-2 infections.
Measuring electronic health literacy in the context of diabetes care: psychometric evaluation of a Persian version of the condition-specific eHealth literacy scale for diabetes
Peimani M, Tanhapour M, Bandarian F, Nasli-Esfahani E and Ostovar A
The rise of the internet and social media has led to increased interest among diabetes patients in using technology for information gathering and disease management. However, adequate eHealth literacy is crucial for protecting patients from unreliable diabetes-related information online.
Differentiation of glioma and solitary brain metastasis: a multi-parameter magnetic resonance imaging study using histogram analysis
Su Y, Cheng R, Guo J, Zhang M, Wang J, Ji H, Wang C, Hao L, He Y and Xu C
Differentiation of glioma and solitary brain metastasis (SBM), which requires biopsy or multi-disciplinary diagnosis, remains sophisticated clinically. Histogram analysis of MR diffusion or molecular imaging hasn't been fully investigated for the differentiation and may have the potential to improve it.
Role of central endpoint adjudication and challenges in trials on neonatal sepsis-a case of ProSPoNS trial
Sinha AP, Raja D, Mahajan KS, Sharma P, Gupta SS, Poluru R, Kawade AS, Dayma G, Sazawal S, Bavdekar A, Parida S, Nangia S, Raut AV, Bethou A, Devi P, Gorpade M, Fatima T, Nayak R, Kapil A, Azam M, Khan PA, Pandey RM, Arora NK and
Despite progress in reducing the infant mortality in India, the neonatal mortality decline has been slower, necessitating concerted efforts to achieve Sustainable Development Goal-3. A promising strategy aiming to prevent neonatal sepsis in high-risk, vulnerable, low birth weight neonates through an innovative intervention includes probiotic supplementation. This article communicates the decision by the ProSPoNS trial investigators to establish a Central Endpoint Adjudication Committee (CEAC) as an addendum to the protocol published in Trials in 2021 for the purpose of clarifying the primary outcome. In the published protocol, the study hypothesis and primary objective are based on "sepsis," the primary outcome has been specified as sepsis/PSBI, whereas the sample size estimation was performed based on the "physician diagnosed sepsis." To align all the three above, the investigators meeting, held on 17th-18th August 2023, at MGIMS Sevagram, Wardha, deliberated and unanimously agreed that "physician diagnosed sepsis" is the primary study outcome which includes sepsis/PSBI. The CEAC, chaired by an external subject expert and members including trial statistician, a microbiologist, and all site principal investigators will employ four criteria to determine "physician diagnosed sepsis": (1) blood culture status, (2) sepsis screen status, (3) PSBI/non-PSBI signs and symptoms, and (4) the clinical course for each sickness event. Importantly, this clarification maintains consistency with the approved study protocol (Protocol No. 5/7/915/2012 version 3.1 dated 14 Feb 2020), emphasizing the commitment to methodological transparency and adherence to predefined standards. The decision to utilize the guidance of a CEAC is recommended as the gold standard in multicentric complex clinical trials to achieve consistency and accuracy in assessment of outcomes.Trial registrationClinical Trial Registry of India (CTRI) CTRI/2019/05/019197. Registered on 16 May 2019.
Strategic use of resources to enhance colorectal cancer screening for patients with diabetes (SURE: CRC4D) in federally qualified health centers: a protocol for hybrid type ii effectiveness-implementation trial
O'Malley DM, Crabtree BF, Kaloth S, Ohman-Strickland P, Ferrante J, Hudson SV and Kinney AY
Persons with diabetes have 27% elevated risk of developing colorectal cancer (CRC) and are disproportionately from priority health disparities populations. Federally qualified health centers (FQHCs) struggle to implement CRC screening programs for average risk patients. Strategies to effectively prioritize and optimize CRC screening for patients with diabetes in the primary care safety-net are needed.
Associations of different combinations of moderate-vigorous physical activity and muscle-strengthening activity with mortality among US lung cancer survivors
Song W, Zou M, Zheng W, Hu X, Gao H and Cheng Z
To investigate the associations of different combinations of moderate to vigorous physical activity (MVPA) and muscle strengthening activity (MSA) with all-cause and cancer mortality among lung cancer survivors.
Comparison of the clinical efficacy and prognosis of the two techniques for treating partial articular-sided supraspinatus tendon tears under arthroscopy
Zhang L, Fang Z, Zhang Y, Wang X and Hong Z
At present, shoulder arthroscopy is usually used for treatment of rotator cuff injuries. There is still debate over the precise technique of using shoulder arthroscopy to treat partial articular-sided supraspinatus tendon injuries.
A taxonomy of demand-driven questions for use by evidence producers, intermediaries and decision-makers: results from a cross-sectional survey
Mansilla C, Sweetman A, Guyatt G and Lavis JN
Globally, a growing number of calls to formalize and strengthen evidence-support systems have been released, all of which emphasize the importance of evidence-informed decision making. To achieve this, it is critical that evidence producers and decision-makers interact, and that decision-makers' evidence needs can be efficiently translated into questions to which evidence producers can respond. This paper aims to create a taxonomy of demand-driven questions for use by evidence producers, intermediaries (i.e., people working in between researchers and decision-makers) and decision-makers.
Participants' perspectives of being recruited into a randomised trial of a weight loss intervention before colorectal cancer surgery: a qualitative interview study
Talbot A, Jebb SA, Foster C, Realpe AX, Wheatstone P, Buczacki S and Koutoukidis DA
The period between cancer diagnosis and surgery presents an opportunity for trials to assess the feasibility of behaviour change interventions. However, this can be a worrying time for patients and may hinder recruitment. We describe the perspectives of patients with excess weight awaiting colorectal cancer surgery about their recruitment into a randomised trial of a prehabilitation weight loss intervention.
A biobehavioral observational study to understand the multilevel determinants of cardiovascular health in Black women: the BLOOM Study protocol
Liao Y, Brothers RM, Brown KK and Lee RE
The racial/ethnic and gender disparities in cardiovascular disease (CVD) morbidity and mortality in the United States are evident. Across nearly every metric, non-Hispanic Black women have poorer overall cardiovascular health. Emerging evidence shows a disproportionately high burden of increased CVD risk factors in Black women of childbearing age, which has a far-reaching impact on both maternal and child outcomes, resulting in premature onset of CVD and further widens the racial disparities in CVD. There is growing recognition that the fundamental driver of persistent racial/ethnic disparities in CVD, as well as disparities in behavioral risk factors such as physical activity and sleep, is structural racism. Further, the lived personal experience of racial discrimination not only has a negative impact on health behaviors, but also links to various physiological pathways to CVD risks, such as internalized stress resulting in a pro-inflammatory state. Limited research, however, has examined the interaction between daily experience and health behaviors, which are influenced by upstream social determinants of health, and the downstream effect on biological/physiological indicators of cardiovascular health in non-pregnant Black women of childbearing age.
Phenogrouping heart failure with preserved or mildly reduced ejection fraction using electronic health record data
Soltani F, Jenkins DA, Kaura A, Bradley J, Black N, Farrant JP, Williams SG, Mulla A, Glampson B, Davies J, Papadimitriou D, Woods K, Shah AD, Thursz MR, Williams B, Asselbergs FW, Mayer EK, Herbert C, Grant S, Curzen N, Squire I, Johnson T, O'Gallagher K, Shah AM, Perera D, Kharbanda R, Patel RS, Channon KM, Lee R, Peek N, Mayet J and Miller CA
Heart failure (HF) with preserved or mildly reduced ejection fraction includes a heterogenous group of patients. Reclassification into distinct phenogroups to enable targeted interventions is a priority. This study aimed to identify distinct phenogroups, and compare phenogroup characteristics and outcomes, from electronic health record data.
Spinal fusion surgery use among adults with low back pain enrolled in a digital musculoskeletal program: an observational study
Yadav S, Gold LS, Zaidi QH, Hwang R, Lu L and Wang G
To compare 12-month spinal fusion surgery rates in the setting of low back pain among digital musculoskeletal (MSK) program participants versus a comparison cohort who only received usual care.
Multiparametric mri-based radiomics nomogram for predicting lymph-vascular space invasion in cervical cancer
Liu FH, Zhao XR, Zhang XL, Zhao M and Lu S
To develop and validate a multiparametric magnetic resonance imaging (mpMRI)-based radiomics model for predicting lymph-vascular space invasion (LVSI) of cervical cancer (CC).
Sexual and reproductive health in young women with ADHD from the view of health care professionals
Wallin K, Alehagen S, Hanberger L, Lundell IW and Hultsjö S
Sexual risk-taking and struggles in managing romantic relationships may put young women with Attention Deficit Hyperactivity Disorder (ADHD) at risk of sexually transmitted diseases, unplanned pregnancies, and low relational satisfaction. To gain understanding of sexual behaviors and intimate relationships, this study aimed to identify and describe health care professionals' (HCPs) perceptions and experiences of sexual and reproductive health (SRH) in young women with ADHD.
Detection of spatial, temporal and spatiotemporal distribution of diarrhea incidence among under-five children in Central Gondar zone, Northwest Ethiopia: a time-series study (2019-2022)
Yitageasu G, Feleke H, Andualem Z, Demoze L, Asrat K and Gizaw Z
Under-five children's diarrhea is a significant public health threat and the World Health Organization (WHO) reported it as the second leading cause of children's death worldwide. In this study area, little is known about the spatiotemporal distribution of under-5 diarrhea incidence. This study was therefore, conducted among all districts in the Central Gondar zone to assess the spatial, temporal, and spatiotemporal variation in diarrhea incidence among under-five children in the Central Gondar zone. The data for children under 5 years of age with diarrhea was obtained from Central Gondar Zone Health Department diarrhea reports from January 2019 to December 2022. All districts were included and geo-coded. The spatial data were created in ArcGIS 10.8.1. Global and local spatial autocorrelation were used to detect hot spots and cold spots. The Poisson model was generated by applying the Kulldorff method in SaTScan™9.6 to analyse the the purely temporal, spatial, and space-time clusters. The study revealed spatial variation of under-5 diarrhea where Gondar City, Gondar Zuria, East Dembia, and Lay Armacho districts were the high-rate spatial clusters during the study period. A year search window for temporal scan statistic identified 01 January 2020-30 December 2021 as risk periods across all districts. Spatiotemporal scan statistics detected high-rate clusters at Gondar City, Gondar Zuria, East Dembia, Lay Armacho, and Alefa between 2019 and 2022. In conclusion, there has been a spatial, temporal, and spatiotemporal variability of under-5 children's diarrhea in the Central Gondar Zone. Interventional and preventive strategies should be developed and given priority to the areas that has been detected as a hotspot in this study to reduce the mortality and morbidity of under 5 children.
An improved 3D-UNet-based brain hippocampus segmentation model based on MR images
Yang Q, Wang C, Pan K, Xia B, Xie R and Shi J
Accurate delineation of the hippocampal region via magnetic resonance imaging (MRI) is crucial for the prevention and early diagnosis of neurosystemic diseases. Determining how to accurately and quickly delineate the hippocampus from MRI results has become a serious issue. In this study, a pixel-level semantic segmentation method using 3D-UNet is proposed to realize the automatic segmentation of the brain hippocampus from MRI results.
Bundle care approach to reduce device associated infections in post-living-donor-liver transplantation in a tertiary care hospital, Egypt
Wassef MA, Ghaith DM, Hussien MM, El-Shazly MA and Yousef RHA
Device-associated infections (DAIs) are a significant cause of morbidity following living donor liver transplantation (LDLT). We aimed to assess the impact of bundled care on reducing rates of device-associated infections.
Retrospective multicenter study of elderly patients with platinum-sensitive relapsed ovarian cancer treated with trabectedin and pegylated liposomal doxorubicin (pld) in a real-world setting: a geico study
Rubio MJ, Manzano A, de Sande LM, Estévez-García P, Gordon MDM, de Prado DS, de Aranguiz BHF, Guerra-Alia EM, Carbó-Bagué A, Romero I, Corbellas M, González-Haba A, Robles-Barraza CE, Martínez-García J and González-Martín A
Trabectedin in combination with pegylated liposomal doxorubicin (PLD) is approved for the treatment of patients with platinum-sensitive relapsed ovarian cancer. Nevertheless, there is currently limited information regarding this treatment in elderly patients with ovarian cancer in a real-world setting.
Homoharringtonine may help improve the outcomes of venetoclax and azacitidine in AML1-ETO positive acute myeloid leukemia
Yin Z, Yao Z, Chen D, Zhang Y, Weng G, Du X, Lin D, Xiao J, Sun Z, Zhang H, Liang X, Guo Z, Zhao W, Xuan L, Jiang X, Shi P, Liu Q, Ping B and Yu G
T(8;21)(q22;q22.1)/AML1-ETO positive acute myeloid leukemia (AE-AML) is sensitive to conventional chemotherapy with a favorable prognosis. However, recent small case reports suggest the limited effectiveness of venetoclax (VEN) and hypomethylating agents (HMA) in treating AE-AML. The aim of this retrospective study was to evaluate the effectiveness of VEN plus AZA (VA) in AE-AML and explore whether adding homoharringtonine (HHT) to VA (VAH) could improve the response.
Mentoring as a complex adaptive system - a systematic scoping review of prevailing mentoring theories in medical education
Teo MYK, Ibrahim H, Lin CKR, Hamid NABA, Govindasamy R, Somasundaram N, Lim C, Goh JL, Zhou Y, Tay KT, Ong RRS, Tan V, Toh Y, Pisupati A, Raveendran V, Chua KZY, Quah ELY, Sivakumar J, Senthilkumar SD, Suresh K, Loo WTW, Wong RSM, Pei Y, Sng JH, Quek SQM, Owyong JLJ, Yeoh TT, Ong EK, Phua GLG, Mason S, Hill R, Chowdhury AR, Ong SYK and Krishna LKR
Effective mentorship is an important component of medical education with benefits to all stakeholders. In recent years, conceptualization of mentorship has gone beyond the traditional dyadic experienced mentor-novice mentee relationship to include group and peer mentoring. Existing theories of mentorship do not recognize mentoring's personalized, evolving, goal-driven, and context-specific nature. Evidencing the limitations of traditional cause-and-effect concepts, the purpose of this review was to systematically search the literature to determine if mentoring can be viewed as a complex adaptive system (CAS).
Psychometric Properties of the EQ-5D-5L in Patients with Alopecia Areata
Lloyd A, Aggio D, Dixon C, Law EH and Price T
For many decision makers in Health Technology Assessment the EQ-5D-5L is the standard measure of health-related quality of life (HRQL). However, evidence has shown the limitations of the measure in certain disease areas, including dermatology. Alopecia areata (AA) is associated with a significant HRQL impact, partly due to the emotional impact of hair loss.
Interplay between WNT/PI3K-mTOR axis and the microbiota in APC-driven colorectal carcinogenesis: data from a pilot study and possible implications for CRC prevention
Di Paola FJ, Alquati C, Conti G, Calafato G, Turroni S, D'Amico F, Ceccarelli C, Buttitta F, Bernardi A, Cuicchi D, Poggioli G, Turchetti D, Ferrari S, Cannizzaro R, Realdon S, Brigidi P and Ricciardiello L
Wnt/β-catenin signalling impairment accounts for 85% of colorectal cancers (CRCs), including sporadic and familial adenomatous polyposis (FAP) settings. An altered PI3K/mTOR pathway and gut microbiota also contribute to CRC carcinogenesis. We studied the interplay between the two pathways and the microbiota composition within each step of CRC carcinogenesis.
Efficacy of adjuvant immune checkpoint inhibitors pembrolizumab or nivolumab in melanoma patients ≥ 75 years: results of a real-world cohort including 456 patients
Gawaz A, Wolff I, Nanz L, Flatz L and Forschner A
Immune checkpoint inhibitors (ICI) applied in patients with melanoma in an adjuvant setting have proven safety and efficacy in several studies, but data on elderly patients aged 75 years or more is scarce. Aim of this study was to investigate efficacy and safety of adjuvant ICI in patients aged ≥ 75 years compared to patients < 75 years in a real-world setting.
Lesbian, gay, bisexual, and transgender clinical competence of physiotherapy students in Israel
Elboim-Gabyzon M and Klein R
Clinical competence encompasses attitudes, skills, and knowledge regarding diverse client groups. Appropriate clinical competence requires an understanding of the cultural context in which healthcare is delivered. In conservative countries such as Israel, there is a noticeable scarcity of information regarding the clinical competency of physiotherapy students (PTSs) in effectively treating lesbian, gay, bisexual and transgender (LGBT) individuals. The objective of this study was to assess the level of LGBT clinical competence among PTSs in Israel.
Single-centre real-life observational study on mortality and outcomes: decompressive craniectomy and brain death in traumatic brain injury, haemorrhage, and other cerebral diseases
Schröder I, Güresir E, Vatter H and Soehle M
Decompressive hemicraniectomy (DHC) is used after severe brain damages with elevated, refractory intracranial pressure (ICP). In a non age-restricted population, mortality rates and long-term outcomes following DHC are still unclear. This study's objectives were to examine both, as well as to identify predictors of unfavourable outcomes.
A novel approach to terminate roof-dependent atrial flutter with epicardial conduction through septopulmonary bundle
Zhou D, Zhang B, Zeng C, Yin X and Guo X
Atrial flutter, a prevalent cardiac arrhythmia, is primarily characterized by reentrant circuits in the right atrium. However, atypical forms of atrial flutter present distinct challenges in terms of diagnosis and treatment. In this study, we examine three noteworthy clinical cases of atypical atrial flutter, which offer compelling evidence indicating the implication of the lesser-known Septopulmonary Bundle (SPB). This inference is based on the identification of distinct electrocardiographic patterns observed in these patients and their favorable response to catheter ablation, which is a standard treatment for atrial flutter. Remarkably, in each case, targeted ablation at the anterior portion of the left atrial roof effectively terminated the arrhythmia, thus providing further support for the hypothesis of SPB involvement. These insightful observations shed light on the potential significance of the SPB in the etiology of atypical atrial flutter and introduce a promising therapeutic target. We anticipate that this paper will stimulate further exploration into the role of the SPB in atrial flutter and pave the way for the development of targeted ablation strategies.
UBQLN4 promotes the proliferation and invasion of non-small cell lung cancer cell by regulating PI3K/AKT pathway
He L, Chen H, Ruan B, He L, Luo M, Fu Y and Zou R
Ubiquilin-4 (UBQLN4), a member of the ubiquilin family, has received limited attention in cancer research to date. Here, we investigated for the first time the functional role and mechanism of UBQLN4 in non-small cell lung cancer (NSCLC).
Clinical outcome predictors for metastatic renal cell carcinoma: a retrospective multicenter real-life case series
Rizzo M, Pezzicoli G, Tibollo V, Premoli A and Quaglini S
Over the last decades, the therapeutic armamentarium of metastatic renal cell carcinoma (mRCC) has been revolutionized by the advent of tyrosin-kinase inhibitors (TKI), immune-checkpoint inhibitors (ICI), and immune-combinations. RCC is heterogeneous, and even the most used validated prognostic systems, fail to describe its evolution in real-life scenarios. Our aim is to identify potential easily-accessible clinical factors and design a disease course prediction system. Medical records of 453 patients with mRCC receiving sequential systemic therapy in two high-volume oncological centres were reviewed. The Kaplan-Meier method and Cox proportional hazard model were used to estimate and compare survival between groups. As first-line treatment 366 patients received TKI monotherapy and 64 patients received ICI, alone or in combination. The mean number of therapy lines was 2.5. A high Systemic Inflammation Index, a BMI under 25 Kg/m2, the presence of bone metastases before systemic therapy start, age over 65 years at the first diagnosis, non-clear-cell histology and sarcomatoid component were correlated with a worse OS. No significant OS difference was observed between patients receiving combination therapies and those receiving exclusively monotherapies in the treatment sequence. Our relapse prediction system based on pathological stage and histological grade was effective in predicting the time between nephrectomy and systemic treatment. Our multicentric retrospective analysis reveals additional potential prognostic factors for mRCC, not included in current validated prognostic systems, suggests a model for disease course prediction and describes the outcomes of the most common therapeutic strategies currently available.
AI models predicting breast cancer distant metastasis using LightGBM with clinical blood markers and ultrasound maximum diameter
Tan Y, Zhang WH, Huang Z, Tan QX, Zhang YM, Wei CY and Feng ZB
Breast cancer metastasis significantly impacts women's health globally. This study aimed to construct predictive models using clinical blood markers and ultrasound data to predict distant metastasis in breast cancer patients, ensuring clinical applicability, cost-effectiveness, relative non-invasiveness, and accessibility of these models. Analysis was conducted on data from 416 patients across two centers, focusing on clinical blood markers (tumor markers, liver and kidney function indicators, blood lipid markers, cardiovascular biomarkers) and maximum lesion diameter from ultrasound. Feature reduction was performed using Spearman correlation and LASSO regression. Two models were built using LightGBM: a clinical model (using clinical blood markers) and a combined model (incorporating clinical blood markers and ultrasound features), validated in training, internal test, and external validation (test1) cohorts. Feature importance analysis was conducted for both models, followed by univariate and multivariate regression analyses of these features. The AUC values of the clinical model in the training, internal test, and external validation (test1) cohorts were 0.950, 0.795, and 0.883, respectively. The combined model showed AUC values of 0.955, 0.835, and 0.918 in the training, internal test, and external validation (test1) cohorts, respectively. Clinical utility curve analysis indicated the combined model's superior net benefit in identifying breast cancer with distant metastasis across all cohorts. This suggests the combined model's superior discriminatory ability and strong generalization performance. Creatine kinase isoenzyme (CK-MB), CEA, CA153, albumin, creatine kinase, and maximum lesion diameter from ultrasound played significant roles in model prediction. CA153, CK-MB, lipoprotein (a), and maximum lesion diameter from ultrasound positively correlated with breast cancer distant metastasis, while indirect bilirubin and magnesium ions showed negative correlations. This study successfully utilized clinical blood markers and ultrasound data to develop AI models for predicting distant metastasis in breast cancer. The combined model, incorporating clinical blood markers and ultrasound features, exhibited higher accuracy, suggesting its potential clinical utility in predicting and identifying breast cancer distant metastasis. These findings highlight the potential prospects of developing cost-effective and accessible predictive tools in clinical oncology.
Association between atherogenic index of plasma and gestational diabetes mellitus: a prospective cohort study based on the Korean population
Zhang J, Suo Y, Wang L, Liu D, Jia Y, Fu Y, Fan W and Jiang Y
Atherogenic index of plasma (AIP) is a non-traditional lipid parameter that can reflect the burden of atherosclerosis. A lipid profile resembling atherosclerosis emerged during pregnancy. Although lipid metabolism is pivotal in diabetes pathogenesis, there is no evidence linking AIP to gestational diabetes mellitus (GDM). Therefore, our objective was to explore the relationship between AIP and GDM and assess AIP's predictive capability for GDM.
Quantifying impairment and disease severity using AI models trained on healthy subjects
Yu B, Kaku A, Liu K, Parnandi A, Fokas E, Venkatesan A, Pandit N, Ranganath R, Schambra H and Fernandez-Granda C
Automatic assessment of impairment and disease severity is a key challenge in data-driven medicine. We propose a framework to address this challenge, which leverages AI models trained exclusively on healthy individuals. The COnfidence-Based chaRacterization of Anomalies (COBRA) score exploits the decrease in confidence of these models when presented with impaired or diseased patients to quantify their deviation from the healthy population. We applied the COBRA score to address a key limitation of current clinical evaluation of upper-body impairment in stroke patients. The gold-standard Fugl-Meyer Assessment (FMA) requires in-person administration by a trained assessor for 30-45 minutes, which restricts monitoring frequency and precludes physicians from adapting rehabilitation protocols to the progress of each patient. The COBRA score, computed automatically in under one minute, is shown to be strongly correlated with the FMA on an independent test cohort for two different data modalities: wearable sensors (ρ = 0.814, 95% CI [0.700,0.888]) and video (ρ = 0.736, 95% C.I [0.584, 0.838]). To demonstrate the generalizability of the approach to other conditions, the COBRA score was also applied to quantify severity of knee osteoarthritis from magnetic-resonance imaging scans, again achieving significant correlation with an independent clinical assessment (ρ = 0.644, 95% C.I [0.585,0.696]).
A meta-analysis of randomized controlled trials evaluating the effectiveness of fecal microbiota transplantation for patients with irritable bowel syndrome
Wang Y, Hu Y and Shi P
Multiple randomized controlled trials (RCTs) have investigated the efficacy of fecal microbiota transplantation (FMT) for irritable bowel syndrome (IBS), but have yielded inconsistent results. We updated the short-term and long-term efficacy of FMT in treating IBS, and performed a first-of-its-kind exploration of the relationship between gut microbiota and emotions.
Imagined speech event detection from electrocorticography and its transfer between speech modes and subjects
de Borman A, Wittevrongel B, Dauwe I, Carrette E, Meurs A, Van Roost D, Boon P and Van Hulle MM
Speech brain-computer interfaces aim to support communication-impaired patients by translating neural signals into speech. While impressive progress was achieved in decoding performed, perceived and attempted speech, imagined speech remains elusive, mainly due to the absence of behavioral output. Nevertheless, imagined speech is advantageous since it does not depend on any articulator movements that might become impaired or even lost throughout the stages of a neurodegenerative disease. In this study, we analyzed electrocortigraphy data recorded from 16 participants in response to 3 speech modes: performed, perceived (listening), and imagined speech. We used a linear model to detect speech events and examined the contributions of each frequency band, from delta to high gamma, given the speech mode and electrode location. For imagined speech detection, we observed a strong contribution of gamma bands in the motor cortex, whereas lower frequencies were more prominent in the temporal lobe, in particular of the left hemisphere. Based on the similarities in frequency patterns, we were able to transfer models between speech modes and participants with similar electrode locations.
Change in suicidal ideation, depression, and anxiety following collaborative care in the community
Khazanov GK, Wolk CB, Lorenc E, Candon M, Pieri MF, Oslin DW, Press MJ, Anderson E, Famiglio E and Jager-Hyman S
The Collaborative Care Model (CoCM) increases access to mental health treatment and improves outcomes among patients with mild to moderate psychopathology; however, it is unclear how effective CoCM is for patients with elevated suicide risk.
Superiority of the triglyceride glucose index over the homeostasis model in predicting metabolic syndrome based on NHANES data analysis
Wan H, Cao H and Ning P
The triglyceride-glucose (TyG) index is a simple and inexpensive new marker of insulin resistance that is being increasingly used for the clinical prediction of metabolic syndrome (MetS). Nevertheless, there are only a few comparative studies on its predictive capacity for MetS versus those using the traditional homeostasis model assessment (HOMA). We conducted a cross-sectional study using a database from the National Health and Nutrition Examination Survey (1999 March to 2020 pre-pandemic period). Using statistical methods, we compared the predictive abilities of the TyG index and HOMA (including HOMA of insulin resistance [HOMA-IR] and HOMA of beta-cell function [HOMA-β]) for MetS. A total of 34,195 participants were enrolled and divided into the MetS group (23.1%) or no MetS group (76.9%) according to the International Diabetes Federation (IDF) diagnostic criteria. After applying weighted data, the baseline characteristics of the population were described. Following the exclusion of medication influences, the final count was 31,304 participants. Receiver operating characteristic curve analysis revealed that while distinguishing between MetS and no MetS, the TyG index had an area under the curve (AUC) of 0.827 (sensitivity = 71.9%, specificity = 80.5%), and the cutoff was 8.75, slightly outperforming HOMA-IR (AUC = 0.784) and HOMA-β (AUC = 0.614) with a significance of P < 0.01. The prevalence of MetS in the total population calculated using the TyG index cutoff value was 30.9%, which was higher than that reported in the IDF diagnostic criteria. Weighted data analysis using univariate and multivariate logistic regression displayed an independent association between elevated TyG and HOMA-IR with the risk of MetS. Subgroup analysis further revealed differences in the predictive ability of the TyG index among adult populations across various genders and ethnicities, whereas such differences were not observed for children and adolescents. The TyG index is slightly better than HOMA in predicting MetS and may identify more patients with MetS; thus, its applications in a clinical setting can be appropriately increased.
Evaluation of the accuracy of conventional and digital implant impression techniques in bilateral distal extension cases: a randomized clinical trial
Elashry WY, Elsheikh MM and Elsheikh AM
This clinical study aims to evaluate the accuracy of the conventional implant impression techniques compared to the digital impression ones in bilateral distal extension cases.
Scene semantics affects allocentric spatial coding for action in naturalistic (virtual) environments
Baltaretu BR, Schuetz I, Võ ML and Fiehler K
Interacting with objects in our environment requires determining their locations, often with respect to surrounding objects (i.e., allocentrically). According to the scene grammar framework, these usually small, local objects are movable within a scene and represent the lowest level of a scene's hierarchy. How do higher hierarchical levels of scene grammar influence allocentric coding for memory-guided actions? Here, we focused on the effect of large, immovable objects (anchors) on the encoding of local object positions. In a virtual reality study, participants (n = 30) viewed one of four possible scenes (two kitchens or two bathrooms), with two anchors connected by a shelf, onto which were presented three local objects (congruent with one anchor) (Encoding). The scene was re-presented (Test) with 1) local objects missing and 2) one of the anchors shifted (Shift) or not (No shift). Participants, then, saw a floating local object (target), which they grabbed and placed back on the shelf in its remembered position (Response). Eye-tracking data revealed that both local objects and anchors were fixated, with preference for local objects. Additionally, anchors guided allocentric coding of local objects, despite being task-irrelevant. Overall, anchors implicitly influence spatial coding of local object locations for memory-guided actions within naturalistic (virtual) environments.
Analysis of anatomic location of burns inpatients in China from 2009 to 2018
Yang J, Liu J, Ma K, Bai H, Ran M, Tian G, Yang S and Fu X
Burns cause serious physical and psychological harm to patients, placing a heavy burden on the global healthcare system. Our previous study detailed the epidemiological characteristics of burn injuries in Chinese inpatients from 2009 to 2018. Interestingly, the anatomic locations of burn injuries vary by gender, age, provinces, and outcomes among different causes. Therefore, this current study aims to analyze the characteristics of burn injuries in inpatients with various burn sites by collecting data in China from 2009 to 2018. This analysis will inform future healthcare system decisions and provide effective strategies.
Control over self and others' face: exploitation and exploration
Wen W, Mei J, Aktas H, Chang AY, Suzuishi Y and Kasahara S
The face serves as a crucial cue for self-identification, while the sense of agency plays a significant role in determining our influence through actions in the environment. The current study investigates how self-identification through facial recognition may influence the perception of control via motion. We propose that self-identification might engender a belief in having control over one's own face, leading to a more acute detection and greater emphasis on discrepancies between their actions and the sensory feedback in control judgments. We refer to the condition governed by the belief in having control as the exploitation mode. Conversely, when manipulating another individual's face, the belief in personal control is absent. In such cases, individuals are likely to rely on the regularity between actions and sensory input for control judgments, exhibiting behaviors that are exploratory in nature to glean such information. This condition is termed the explorative mode. The study utilized a face-motion mixing paradigm, employing a deep generative model to enable participants to interact with either their own or another person's face through facial and head movements. During the experiment, participants observed either their own face or someone else's face (self-face vs. other-face) on the screen. The motion of the face was driven either purely by their own facial and head motion or by an average of the participant's and the experimenter's motion (full control vs. partial control). The results showed that participants reported a higher sense of agency over the other-face than the self-face, while their self-identification rating was significantly higher for the self-face. More importantly, controlling someone else's face resulted in more movement diversity than controlling one's own face. These findings support our exploration-exploitation theory: When participants had a strong belief in control triggered by the self-face, they became highly sensitive to any sensorimotor prediction errors, leading to a lower sense of agency. In contrast, when the belief of control was absent, the exploration mode triggered more explorative behaviors, allowing participants to efficiently gather information to establish a sense of agency.
Intrauterine fetal death due to rupture of umbilical vessels: a rare case of furcate cord insertion
Xu H, Lu JP and Xu QL
Furcate cord insertion refers to the separation of umbilical vessels before reaching the placenta, where the branching vessels normally attach at the edge of the placental parenchyma or near the placental membranes. This is an extremely rare abnormal umbilical cord insertion. This paper reported a case of a furcate cord insertion, where the rupture of exposed umbilical vessels led to intrauterine fetal death at full term. Through literature review, we analyzed the prenatal ultrasound characteristics and pregnancy outcomes of furcate cord insertions, with the aim to improve detection rates and reduce the risk of adverse pregnancy outcomes.
The way we look at an image or a webpage can reveal personality traits
Le Bras T, Allibe B and Doré-Mazars K
Personality is a central concept and a cross-domain explanatory factor in psychology to characterize and differentiate individuals. Surprisingly, among the many studies on oculomotor behavior, only a few have investigated how personality influences the exploration of a visual stimulus. Due to the limited number of existing studies, it is still uncertain if markers of personality in eye movements are always observable in eye movements across various exploration contexts. Here, introducing a novel concept of gaze-based signatures of personality, we used visual exploration metrics to detect personality signatures across various exploration contexts (visual search and free-viewing on images and webpages) in 91 participants. Personality data were collected as in the reference paper that validated the French version of the Big Five Inventory. Linear regression analyses demonstrated that while Extraversion and Openness to Experience did not correlate with any particular exploration metric, the other three traits-Conscientiousness, Agreeableness, and Neuroticism-correlated robustly with all exploration metrics in different visual exploration contexts. Our study provides evidence for the capture of the gaze-based signature of personality from very brief eye movement recordings.
The impact of hospital saturation on non-COVID-19 hospital mortality during the pandemic in France: a national population-based cohort study
Boyer L, Pauly V, Brousse Y, Orleans V, Tran B, Yon DK, Auquier P, Fond G and Duclos A
A previous study reported significant excess mortality among non-COVID-19 patients due to disrupted surgical care caused by resource prioritization for COVID-19 cases in France. The primary objective was to investigate if a similar impact occurred for medical conditions and determine the effect of hospital saturation on non-COVID-19 hospital mortality during the first year of the pandemic in France.
Evidence of membranolytic targeting and intracellular citrullination in neutrophils isolated from patients with rheumatoid arthritis
Moadab F, Wang X, Le E, Gazitt T, Najjar R, Nelson JL, Joshua V, Malmström V, Elkon K, Grönwall C and Mustelin T
Anti-citrullinated protein autoantibodies (ACPA) are diagnostic for rheumatoid arthritis (RA). The antigens recognized by these autoantibodies are produced by protein arginine deiminases (PADs), particularly PAD4. However, it remains unknown why and how PAD4 causes this aberrant citrullination in RA. Here, we report that poly-perforin pores are present on freshly isolated neutrophils from RA patients, but not on healthy donor neutrophils. Neutrophils with perforin pores also contained intracellular citrullinated proteins in the region adjacent to the pores. This response was replicated in vitro by treating neutrophils with purified perforin, which generated intense dots of anti-perforin immunofluorescence, calcium influx, and intracellular citrullination. Extensive neutrophil killing in Felty's syndrome, an aggressive form of RA, correlated with particularly high ACPA, and PAD4 autoantibodies. In contrast, other forms of death, including NETosis, apoptosis, and pyroptosis, produced minimal citrullination. We conclude that neutrophil targeting by perforin leading to intracellular citrullination takes place in patients with RA.
Psychometric properties of the arabic version of PHEEM applied on a sample of medical residents in Syria
Alfakhry G, Kodmani R and Almasri IA
The clinical learning environment (CLE) plays a crucial role in shaping the learning experiences and professional development of medical professionals. Understanding and optimising this environment is essential for improving doctors' knowledge acquisition, clinical skills, and overall well-being. The development of the Postgraduate Hospital Educational Environment Measure (PHEEM) and its translation to numerous languages has been a milestone in clinical education. Even though PHEEM was recently translated into Arabic, its psychometric properties in this form remain unevaluated. Therefore, this study aims to conduct a comprehensive psychometric analysis of the Arabic version of the PHEEM questionnaire.
Development and validation of risk prediction model for post-donation renal function in living kidney donors
Lim SJ, Kwon J, Ko Y, Kwon HE, Lee JJ, Kim JM, Jung JH, Kwon H, Kim YH, Park JB, Lee KW and Shin S
This study aimed to create and validate a predictive model for renal function following live kidney donation, using pre-donation factors. Accurately predicting remaining renal function post live kidney donation is currently insufficient, necessitating an effective assessment tool. A multicenter retrospective study of 2318 live kidney donors from two independent centers (May 2007-December 2019) was conducted. The primary endpoint was the reduction in eGFR to below 60 mL/min/m 6 months post-donation. The primary endpoint was achieved in 14.4% of the training cohort and 25.8% of the validation cohort. Sex, age, BMI, hypertension, preoperative eGFR, and remnant kidney proportion (RKP) measured by computerized tomography (CT) volumetry were found significant in the univariable analysis. These variables informed a scoring system based on multivariable analysis: sex (male: 1, female: 0), age at operation (< 30: 0, 30-39: 1, 40-59: 2, ≥ 60: 3), preoperative eGFR (≥ 100: 0, 90-99: 2, 80-89: 4, < 80: 5), and RKP (≥ 52%: 0, < 52%: 1). The total score ranged from 0 to 10. The model showed good discrimination for the primary endpoint in both cohorts. The prediction model provides a useful tool for estimating post-donation renal dysfunction risk, factoring in the side of the donated kidney. It offers potential enhancement to pre-donation evaluations.
Analytical and clinical performance evaluation of a new NT-proBNP assay
Feng P, Qin J, Chai Z, Zhang Y, Zhao M, Liu L, Zhang L, Chen Y and Xiong Y
The study evaluated the performance of the Mindray N-terminal pro-B-type natriuretic peptide (NT-proBNP) in a healthy population in China, focusing on creating a reference range for future clinical applications adjusted according to different demographics.
Oral antidiabetic therapy versus early insulinization on glycemic control in newly diagnosed type 2 diabetes patients: a retrospective matched cohort study
Lee YM, Lin PR and Sia HK
Our study aims to compare the efficacy of oral antidiabetic therapy to early insulinization on glycemic control among newly diagnosed type 2 diabetes patients in real-world clinical practice. A retrospective cohort study conducted at a medical center in Taiwan analyzed 1256 eligible patients from January 2007 to December 2017. Propensity score matching resulted in well-balanced groups of 94 patients each in the oral antidiabetic drug (OAD) and early insulinization cohorts. Glycemic outcomes were assessed in both groups. Patients exclusively using OAD showed consistently lower glycated hemoglobin (HbA1c) levels at 3, 12, 24, and 36 months compared to insulin users. At later periods, 77.7% of OAD users achieved glycemic control versus 64.9% of insulin users, with a marginally significant difference. Subgroup analyses suggested a trend favoring well-controlled diabetes in the OAD group, though not statistically significant. Our study finds oral antidiabetic therapy is not inferior to early insulinization for glycemic control in newly diagnosed type 2 diabetes patients, irrespective of initial HbA1c levels. This supports oral therapy as a rational treatment option, even in cases with elevated HbA1c at diagnosis.
Clinical efficacy and safety of transvaginal natural orifice transluminal endoscopic surgery for benign adnexal disease: a prospective trial
Yan J, Zhou D, Zhang S, Zhang B, Tuo X, Meng Q and Lv Q
There is a scarcity of prospective clinical research evidence regarding the utilization of transvaginal natural orifice translumenal endoscopic surgery (vNOTES) as a treatment option for ovarian cysts. The objective of this study was to assess the feasibility and safety of employing vNOTES for the management of ovarian cysts.
A retrospective study on the impact of radiotherapy on the survival outcomes of small cell lung cancer patients based on the SEER database
Chen Y, Yao L, Chen Q, Hu Y, Zhu X, Dai R, Chen X, Zeng Y, Zhu Y, Song D and Zhang Y
Small cell lung cancer (SCLC) patients exhibit significant heterogeneity in tumor burden, physical condition, and responses to initial treatment. This diversity in treatment responses can result in varying treatment outcomes. The primary objective of this study was to explore the patient demographics associated with improved survival outcomes through radiotherapy. Based on the SEER database, we identified 42,824 SCLC patients enrolled between 2004 and 2015. These patients were stratified into radiotherapy (n = 20,360) and non-radiotherapy groups (n = 22,464). We controlled for confounding factors using propensity score matching (PSM) analysis. Subsequently, Kaplan-Meier (KM) analysis was employed to evaluate the impact of radiotherapy on patients' overall survival (OS) and cancer-specific survival (CSS). Cancer-specific mortality was further analyzed using competitive risk models. Cox analysis was also conducted to examine additional variables potentially affecting the survival of SCLC patients. We identified a total of 42,824 eligible patients, and following PSM, 13,329 patients were successfully matched in both the radiotherapy and non-radiotherapy groups. The KM analysis showed that the median OS was 9 months in the radiotherapy group and 6 months in the non-radiotherapy group. The median CSS was 10 months in the radiotherapy group and 7 months in the non-radiotherapy group. The 5-year OS and 10-year OS rates were 6.2% versus 1.6% in the radiotherapy group and 2.6% versus 0.8% in the non-radiotherapy group (P < 0.001). Competitive risk analysis showed that cancer-specific mortality was significantly higher in the non-radiotherapy group than in the radiotherapy group (P < 0.001). Multivariate Cox analysis showed that the radiotherapy group (relative non-radiotherapy group) showed a significant positive effect on survival outcomes (OS: HR 0.658 95% CI [0.642, 0.675] P < 0.001; CSS: HR 0.662 95% CI [0.645, 0.679], P < 0.001). In addition, age, gender, race, primary tumor site, T stage, N stage, M stage, chemotherapy, and surgery were also considered as important predictors of SCLC outcome. The results of the subgroup analysis showed that the radiotherapy group showed a significant survival advantage regardless of age, sex, race, primary tumor site, M stage, chemotherapy, and surgery (P < 0.001). Radiotherapy may improve both OS and CSS in SCLC patients. Patients with SCLC may benefit from radiotherapy regardless of age, sex, race, primary tumor site, M stage, chemotherapy, and surgery.
Macro and micro structural preservation of grey matter integrity after 24 weeks of rTMS in Alzheimer's disease patients: a pilot study
Mencarelli L, Torso M, Borghi I, Assogna M, Pezzopane V, Bonnì S, Di Lorenzo F, Santarnecchi E, Giove F, Martorana A, Bozzali M, Ridgway GR, Chance SA and Koch G
Alzheimer's Disease (AD) is characterized by structural and functional dysfunction involving the Default Mode Network (DMN), for which the Precuneus (PC) is a key node. We proposed a randomized double-blind pilot study to determine neurobiological changes after 24 weeks of PC-rTMS in patients with mild-to-moderate AD. Sixteen patients were randomly assigned to SHAM or PC-rTMS, and received an intensive 2-weeks course with daily rTMS sessions, followed by a maintenance phase in which rTMS has been applied once a week. Before and after the treatment structural and functional MRIs were collected. Our results showed macro- and micro-structural preservation in PC-rTMS compared to SHAM-rTMS group after 24 weeks of treatment, correlated to an increase of functional connectivity (FC) within the PC in the PC-rTMS group. Even if preliminary, these results trigger the possibility of using PC-rTMS to arrest atrophy progression by manipulating distributed network connectivity patterns.
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