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Common obesity-related anthropometric indices and the risk of gestational diabetes mellitus in a Chinese population: a prospective cohort study
Wang H, Sui L, Xu Q, Li M, Xing Y and Li G
Anthropometric measurement provides a simple, noninvasive approach to evaluate obesity in pregnant women. We aimed to develop a predictive model utilizing anthropometric index for gestational diabetes mellitus (GDM), the most common obesity-related complications during pregnancy.
Analysis of prefrontal cerebral blood volume and flow changes in ESKD patients undergoing hemodialysis using functional near-infrared spectroscopy
Heo CM, Yi J, Park KM, Lee DA, Lee YJ, Park BS, Kim YW, Ko J, Kim H and Park S
End-stage kidney disease (ESKD) patients undergoing hemodialysis experience diverse neurological complications. This study investigated prefrontal cerebral blood volume (CBV) and cerebral blood flow (CBF) during hemodialysis using functional near-infrared spectroscopy (fNIRS) to analyze cerebral hemodynamic changes.
Rational design of glycosaminoglycan binding cyclic peptides using cPEPmatch
Santini BL, Gaardløs M, Wyrzykowski D, Rothemund S, Penk A, Zacharias M and Samsonov SA
Cyclic peptides present a robust platform for drug design, offering high specificity and stability due to their conformationally constrained structures. In this study, we introduce an updated version of the Cyclic Peptide Matching program (cPEPmatch) tailored for the identification of cyclic peptides capable of mimicking protein-glycosaminoglycan (GAG) binding sites. We focused on engineering cyclic peptides to replicate the GAG-binding affinity of antithrombin III (ATIII), a protein that plays a crucial role in modulating anticoagulation through interaction with the GAG heparin. By integrating computational and experimental methods, we successfully identified a cyclic peptide binder with promising potential for future optimization. MD simulations and MM-GBSA calculations were used to assess binding efficacy, supplemented by umbrella sampling to approximate free energy landscapes. The binding specificity was further validated through NMR and ITC experiments. Our findings demonstrate that the computationally designed cyclic peptides effectively target GAGs, suggesting their potential as novel therapeutic agents. This study advances our understanding of peptide-GAG interactions and lays the groundwork for future development of cyclic peptide-based therapeutics.
Systemic immunoinflammatory indexes in albuminuric adults are negatively associated with α-klotho: evidence from NHANES 2007-2016
Jia M, Han S and Wang Y
Systemic Immune-Inflammation Index (SII) is a novel inflammatory biomarker closely associated with the inflammatory response and chronic kidney disease. Klotho is implicated as a pathogenic factor in the progression of kidney disease, and supplementation of Klotho may delay the progression of chronic kidney disease by inhibiting the inflammatory response. Our aim is to investigate the potential relationship between SII and Klotho in adult patients in the United States and explore the differences in the populations with and without albuminuria.
Impact of low-dose ozone supplementation on motility parameters and bacterial growth in horse cryopreserved semen
Fanelli D, Moroni R, Sala G, Melanie P, Tarabella I, Telleschi N, Maltinti S, Giorgi M, Barsotti G, Passamonti F, Marmorini P, Rota A, Camillo F and Panzani D
Two studies were conducted to evaluate the use of medical ozone (O) in commercial extenders for equine semen cryopreservation. In the first study (Study 1), 0, 5, and 15 µg/mL of O were added to diluents of refrigerated or frozen semen. Samples were evaluated for sperm kinematics at different time points for the chilled samples and after a thermoresistence test for the frozen/thawed samples. In the second study (Study 2), 0, 5, and 10 µg/mL of O were added to an antibiotic-free diluent for refrigerated semen for comparison with the control group in which semen was diluted in the same diluent enriched with antibiotics. Semen sample kinematics were analyzed and an aliquot was collected after ozonification for bacteriological analyses. For Study 1 no difference was found comparing all the kinematic parameters analyzed over time, in the various treatments ( > 0.05). In Study 2 the absence of antibiotics did not affect the kinematic parameters compared to the control ( > 0.05). However when antibiotics were added, a smaller number of bacterial colony-forming units were detected compared to samples without antibiotics and without or with different O supplementations. In conclusion, O treatment at low dosages did not affect the semen kinematics, although it was ineffective in preventing bacterial overgrowth. Higher O concentrations should be evaluated to explore the possibility of reducing the use of antibiotics in equine sperm conservation.
Transient changes in mismatch negativity after two sessions of electroconvulsive therapy for atypical psychosis: A case report
Mori Y, Kanno K, Hoshino H, Takahashi Y, Suzuki Y and Miura I
Cognitive abnormalities associated with electroconvulsive therapy (ECT) are limited to the first few days after treatment. Mismatch negativity (MMN) is an event-related potential that reflects an automatic auditory change detection process under nonattention conditions and cognitive function in psychotic disorders and may be trait- or state-dependent. This study aimed to report the changes in MMN and cognitive function after two ECT treatments in a female patient who underwent maintenance ECT for atypical psychosis.
Managing rosacea using asynchronous consumer to physician teledermatology as compared to in-person visits: A retrospective study
Shah VK, Camacho RC and English JC
Interventions to optimize dispatcher-assisted CPR instructions: A scoping review
Dainty KN, Debaty G, Waddick J, Vaillancourt C, Malta Hansen C, Olasveengen T, Bray J and
To review and summarize existing literature and knowledge gaps regarding interventions that have been tested to optimize dispatcher-assisted CPR (DA-CPR) instruction protocols for out-of-hospital cardiac arrest (OHCA).
Will Precision Medicine Meet Digital Health? A Systematic Review of Pharmacogenomics Clinical Decision Support Systems Used in Clinical Practice
Farmaki A, Manolopoulos E and Natsiavas P
Digital health, an emerging scientific domain, attracts increasing attention as artificial intelligence and relevant software proliferate. Pharmacogenomics (PGx) is a core component of precision/personalized medicine driven by the overarching motto "the right drug, for the right patient, at the right dose, and the right time." PGx takes into consideration patients' genomic variations influencing drug efficacy and side effects. Despite its potentials for individually tailored therapeutics and improved clinical outcomes, adoption of PGx in clinical practice remains slow. We suggest that e-health tools such as clinical decision support systems (CDSSs) can help accelerate the PGx, precision/personalized medicine, and digital health emergence in everyday clinical practice worldwide. Herein, we present a systematic review that examines and maps the PGx-CDSSs used in clinical practice, including their salient features in both technical and clinical dimensions. Using Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines and research of the literature, 29 relevant journal articles were included in total, and 19 PGx-CDSSs were identified. In addition, we observed 10 technical components developed mostly as part of research initiatives, 7 of which could potentially facilitate future PGx-CDSSs implementation worldwide. Most of these initiatives are deployed in the United States, indicating a noticeable lack of, and the veritable need for, similar efforts globally, including Europe.
Desirable and Adverse Effects of Communicative Suicide Prevention Interventions Among Men
Wagner A and Reifegerste D
Despite men's high suicide risk, gender perspectives in suicide prevention research are scarce. The goal of this systematic review was to describe the desirable and adverse effects of distribution channels and message strategies of communicative suicide prevention interventions among men. Databases PubMed and Web of Science were searched for quantitative randomized controlled trials (RCTs) and nonrandomized studies examining the effectiveness of male-specific or general communicative interventions among men. Narrative synthesis was used to summarize findings. Fifty-five studies published in peer-reviewed articles until October 15, 2021, were included. Findings demonstrate that interpersonal, mass media, and digital media interventions impact suicide-related outcomes preventively. Mass media interventions are not suitable to impact men's emotions in a prevention-desirable way. Message strategies interactivity, emotional appeals, and clear calls to action demonstrated high effectiveness, while expert exemplars, visualizations, and personalization were rather ineffective. However, the review was not able to prove causality, could not distinguish between multichannel interventions and single-channel interventions, or between specific combinations of channels and message strategies. The systematic review provides some guidance on which channels and message strategies to apply in communicative suicide prevention for men.
Beyond the needle: a qualitative exploration of Sierra Leonean healthcare workers' post COVID-19 vaccination experiences
David I, Tefera GM and Majee W
The global health crisis precipitated by the COVID-19 pandemic underscored the necessity of swift vaccine development and distribution to curb virus transmission. However, discussions on vaccine acceptance and hesitancy have predominantly focused on pre-vaccination attitudes, often overlooking the significance of post-vaccination experiences in shaping individual and communal attitudes toward vaccines. This oversight is particularly critical among healthcare workers in low- and middle-income countries (LMICs), who play a dual role in combating the pandemic and influencing public vaccine sentiment. Using the theory of planned behavior, this study explores the post-vaccination experiences of healthcare workers in Sierra Leone and assesses how these experiences influence their attitudes toward vaccine safety, efficacy and their advocacy for vaccine uptake within their communities. Employing a qualitative design, the study interviewed 24 healthcare workers, 21 of whom were vaccinated against COVID-19. Semi-structured interviews, conducted in English or Krio, were audio recorded, transcribed verbatim and analyzed using thematic analysis to identify key themes. Three themes were identified: positive vaccination experiences exceeding initial expectations, strong belief in the vaccine's protective benefits and active roles in vaccine advocacy. Despite initial hesitations due to concerns over potential adverse effects, participants reported no significant issues post-vaccination, fostering trust in vaccine safety and effectiveness. Healthcare workers' positive post-vaccination experiences significantly bolster their vaccine advocacy, influencing their recommendations to patients, friends, families, colleagues and community members. This study highlights the importance of understanding and leveraging healthcare workers' experiences to enhance public trust and vaccine uptake, crucial for pandemic response efforts in LMICs.
Starting conversations about mental health and wellbeing in Australian culturally and linguistically diverse communities
Morse AR, Smith DG, Clifford R, Shrimpton B and Banfield M
Australia is a multicultural nation with nearly 30% of the population born overseas. Migrants' mental health can be impacted by discrimination, racism and experiences relating to asylum and immigration. These can be compounded by low help-seeking caused by stigmatized beliefs and poor mental health literacy. My Mind, My Voice (MMMV) is a co-designed program aiming to promote awareness of mental health and wellbeing for people with a culturally and linguistically diverse (CALD) background. This research project explored the perceived impacts and value of MMMV and processes leading to those impacts. A mixture of internal quantitative and qualitative evaluation surveys (n = 32) and researcher-conducted semi-structured interviews (n = 9) were conducted with CALD organization and community members who attended training workshops, presented MMMV events or attended an event. Data were analysed using a reflexive thematic analysis approach. Five themes were developed: culturally relevant and respectful, cross-cultural connections, the importance of language, increasing confidence and literacy and the potential to change attitudes. Being involved with a co-produced program that was culturally relevant and respectful was a positive experience that enhanced people's confidence and literacy. Feeling respected, valued and validated helped participants feel empowered to develop and deliver mental health and wellbeing education in their community. Open, honest conversations are an important way to break down stigma and start conversations about mental health and wellbeing in CALD communities. Evaluation outcomes demonstrate the success of MMMV's collaborative approach, which can inform the development and evaluation of CALD mental health promotion interventions.
Beyond average outcomes: A latent profile analysis of diverse developmental trajectories in preterm and early term-born children from the Adolescent Brain Cognitive Development study
Menu I, Ji L, Bhatia T, Duffy M, Hendrix CL and Thomason ME
Preterm birth poses a major public health challenge, with significant and heterogeneous developmental impacts. Latent profile analysis was applied to the National Institutes of Health Toolbox performance of 1891 healthy prematurely born children from the Adolescent Brain and Cognitive Development study (970 boys, 921 girls; 10.00 ± 0.61 years; 1.3% Asian, 13.7% Black, 17.5% Hispanic, 57.0% White, 10.4% Other). Three distinct neurocognitive profiles emerged: consistently performing above the norm (19.7%), mixed scores (41.0%), and consistently performing below the norm (39.3%). These profiles were associated with lasting cognitive, neural, behavioral, and academic differences. These findings underscore the importance of recognizing diverse developmental trajectories in prematurely born children, advocating for personalized diagnosis and intervention to enhance care strategies and long-term outcomes for this heterogeneous population.
Environmental Sustainability in Oral Health Professional Education: Approaches, Challenges, and Drivers-ADEE Special-Interest Group Report
Dixon J, Field J, van Harten M, Duane B and Martin N
This paper reports on the scholarship activity of the 'Sustainability in Dentistry' Special-interest Group (SiG), which met at the Association for Dental Education in Europe (ADEE) annual conference in Liverpool on 25 August 2023. The aim of this study was to (i) identify current teaching practices and approaches to embedding Environmental Sustainability (ES) in the curriculum in ADEE attendee schools and (ii) explore existing barriers/challenges to incorporating ES in dental education and consider potential solutions.
Novel intervention based on an individualized bundle of care to decrease infection in kidney transplant recipients
de Jorge-Huerta L, Silva JT, Fernández-Ruiz M, Rodríguez-Goncer I, Pérez-Jacoiste Asín MA, Ruiz-Merlo T, Heredia-Mena C, González-Monte E, Polanco N, San Juan R, Andrés A, Aguado JM and López-Medrano F
Infection remains a relevant complication after kidney transplantation (KT). A well-established strategy in modern medicine is the application of bundles of evidence-based practice in clinical settings. The objective of this study is to explore the application of a personalized bundle of measures aimed to reduce the incidence of infection in the first 12 months after KT.
Rheumatic and Musculoskeletal Diseases and Risk of Dementia: A Nested Case-Control Study
Kiadaliri A, Dell'Isola A, Turkiewicz A and Englund M
To investigate the associations between rheumatic and musculoskeletal diseases (RMDs) and incident dementia using population register-based data.
Penalty Versus Premium: Social Disposition Differentiates Life Satisfaction Among Living-Alone Immigrant and Native-Born Older Adults-Findings From the Canadian Longitudinal Study on Aging (CLSA)
Shen J, Tong H and Fuller-Thomson E
Using data from the Canadian Longitudinal Study on Aging, in this study we provide an alternative explanation for the gap of life satisfaction between living-alone immigrants and Canadian-born older adults. Based on the Big-Five personality traits, we use the latent class analysis to generate two types of social dispositions, social independence and social dependence. With social dispositions taken into account, living alone contributes to life satisfaction in opposite ways for immigrant and Canadian-born older adults, by playing a negative role for the former group and a positive role for the latter. The trend of higher life satisfaction among the living-alone Canadian-born are mainly among the socially independent, whereas for immigrants, socially dependent older adults experience the lowest level of life satisfaction when living alone. Therefore, while socially independent Canadian-born older adults gain a "living-alone premium" in life satisfaction; their socially dependent immigrant counterparts experience a "living-alone penalty" in life satisfaction.
Exo-Glove Shell: A Hybrid Rigid-Soft Wearable Robot for Thumb Opposition with an Under-Actuated Tendon-Driven System
Kim B, Choi H, Kim K, Jeong S and Cho KJ
Usability and functionality are important when designing hand-wearable robots; however, satisfying both indicators remains a challenging issue, even though researchers have made important progress with state-of-the-art robot components. Although hand-wearable robots require sufficient actuators and sensors considering their functionality, these components complicate the robot. Further, robot compliance should be carefully considered because it affects both indicators. For example, a robot's softness makes it compact (improving usability) but also induces inaccurate force transmission (impacting functionality). To address this issue, we present in this paper a tendon-driven, hybrid, hand-wearable robot, named Exo-Glove Shell. The proposed robot assists in three primitive motions (i.e., thumb opposition motion, which is known as one of the most important hand functions, and flexion/extension of the index/middle fingers) while employing only four actuators by using an under-actuation mechanism. The Exo-Glove Shell was designed by combining a soft robotic body with rigid tendon router modules. The use of soft garments enables the robot to be fitted well to users without customization or adjustment of the mechanisms; the metal routers facilitate accurate force transmission. User tests conducted with an individual with a spinal cord injury (SCI) found that the robot could sufficiently and reliably assist in three primitive motions through its four actuators. The research also determined that the robot can assist in various postures with sufficient stability. Based on the grasp stability index proposed in this paper, user stability-when assisted by the proposed robot-was found to be 4.75 times that of an SCI person who did not use the Exo-Glove Shell.
Illness experience and (unmet) needs of women with Mayer-Rokitansky-Küster-Hauser Syndrome (MRKH): a qualitative analysis of an online forum
Di Mattei VE, Taranto P, Perego G, Caneva M, Parma M, Fontana E, Candiani M and Montali L
Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) is a congenital condition characterized by the underdevelopment or complete absence of the uterus and the upper part of the vagina. Diagnosis is commonly made during adolescence, a sensitive period for psychophysical development, following the absence of menstruation. Having MRKH syndrome can have a profound and multifaceted psychosocial impact that characterizes these women's subjective experiences, although it continues to be qualitatively understudied. This article explores the lived experience of women with MRKH spontaneously recounted on an online support forum. The aim was to gain insight into the features of the syndrome experience to understand deeply the emotional and social impact of the condition and the individual needs expressed online.
Comparison of Use Rates of Telehealth Services for Substance Use Disorder During and Following COVID-19 Safety Distancing Recommendations: Two Cross-Sectional Surveys
Pusnik A, Hartzler B, Vjorn O, Rutkowski BA, Chaple M, Becker S, Freese T, Nichols M and Molfenter T
The COVID-19 social distancing guidelines resulted in a dramatic transition to telephone and video technologies to deliver substance use disorder (SUD) treatment. Before COVID-19, the question was "Will telehealth ever take hold for SUD services?" Now that social distancing guidelines have been lifted, the question is "Will telehealth remain a commonly used care modality?"
Bethlem myopathy: A novel homozygous variant of c.385C>T (p.Arg129Cys) in the COL6A2 gene
Kachuei M, Orangi K, Mohammadi A, Mohammadi M and Mojbafan M
This case highlights the challenges in diagnosing Bethlem myopathy, the need for a high index of suspicion, and the importance of recognizing the diverse clinical presentations of this rare condition. Enhanced understanding can aid in early diagnosis and tailored management.
Exploring the interplay between Kaposi's sarcoma and SARS-CoV-2 infection: A case series and systematic review
Pietroluongo E, Luciano A, Peddio A, Buonaiuto R, Caltavituro A, Servetto A, De Angelis C, Arpino G, Palmieri G, Veneziani BM, De Placido S, Bianco R, De Placido P and Giuliano M
Kaposi's sarcoma (KS) is an angio-proliferative disease with a viral etiology and a multifactorial pathogenesis that results from immune dysfunction. In patients affected by latent viral infections such as herpesviruses, SARS-CoV-2 infection may result in lytic cycle reactivation in host cells. A robust immune system response is crucial for eliminating pathogens and resolving both latent and non-latent viral infections. We report a case series of KS characterized by tumor progression after SARS-CoV-2 infection. We performed a systematic literature review of the PubMed/MEDLINE and EMBASE databases. The keyword terms included "SARS-CoV-2," "HHV-8," "Kaposi's sarcoma," "IL-6," and "COVID-19." English language restriction was applied. Items not covered by our study were excluded. KS is a complex disease linked to an impaired immune system. Conditions that result in temporary or permanent immunodeficiency can trigger viral reactivation or exacerbate an existing disease. It is feasible that the increase in cytokine levels in COVID-19 patients, coupled with lymphocyte downregulation and treatment that induces herpesvirus lytic reactivation, may contribute to the progression of KS after SARS-CoV-2 infection. These observations suggest that patients with KS should be clinically monitored both during and after SARS-CoV-2 infection. Nevertheless, prospective data should be collected to validate this hypothesis and enhance our understanding of the mechanisms implicated in the onset or progression of KS.
Assessment of blood viral load in asymptomatic and symptomatic cases of congenital cytomegalovirus infection
Güneş Ö, Gülhan B, Üçkardeş F, Güney AY, Coşkun ZN, Özen S, Kanık-Yüksek S and Özkaya-Parlakay A
This study aimed to retrospectively evaluate the baseline and follow-up viral loads and viral clearance times in cases followed for asymptomatic and symptomatic congenital cytomegalovirus (cCMV) infection between August 2010 and August 2022. Among 93 cases, they had asymptomatic (n: 55) and symptomatic (n: 38). The median baseline blood viral load detected in the symptomatic cCMV (ScCMV) infection (13 054 IU/mL) was significantly higher than that of asymptomatic cCMV (AcCMV) infection (4636 IU/mL) (p < 0.013). There was no difference in median viral clearance times (75 and 90 days, respectively) in baseline viremic cases in the ScCMV and AcCMV infection groups. There were no differences in median baseline blood viral load (6930 IU/mL and 14 268 IU/mL, respectively) and median viral clearance times (75 and 85 days, respectively) between the 6-week and 6-month antiviral treatment group. No correlation was found between baseline blood viral load, clinical severity, and the number of systems involved. However, in initial viremic cases, the viral load threshold for a symptomatic case was 8856 IU/mL, with 85.7% sensitivity and 54.5% specificity.
Molecular evaluation of spp. Infection in the Volga-Ural Saiga antelope population of the Republic of Kazakhstan
Kidiraliyev EZ, Zhaksylykova AA, Kydyrkhanova EA, Kushaliyev KZ, Shevtsov A, Anara R, Sembaeva ZP, Arzybaev MA, Budke CM and Abdybekova AM
Saiga antelope () is a protected species in Kazakhstan. Little is known about the parasitofauna of these mammals. Therefore, the focus of this study was to evaluate the prevalence and species diversity of spp. infection in the Volga-Ural Saiga antelope population. In June 2023, 104 Saiga antelope fecal samples collected from the district of Zhanibek, located in the province of West Kazakhstan were evaluated using microscopic and molecular techniques. Based on coprovoscopy results, spp. Oocysts were present in 22 samples (21%). The four fecal samples containing the largest numbers of spp. Oocysts per 10x field were selected for further genetic analysis. DNA extraction, nested PCR amplification, and sequencing were performed on 91 clones, with 80 clones forming a distinct clade and exhibiting genetic similarity to MT801034 Ei sp. Voucher HY3. These clones possibly represent an specific to Saiga antelopes and gazelle that has previously been morphologically described as (Svanbaev, 1979), underscoring the importance of further research into parasitic infections in this protected species.
Development of the 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria, Phase III-D Report: Multi Criteria Decision Analysis
Barbhaiya M, Zuily S, Amigo MC, Andrade D, Avcin T, Bertolaccini ML, Branch DW, Costedoat-Chalumeau N, Crowther M, de Jesus GR, Devreese KMJ, Frances C, Garcia D, Gómez-Puerta JA, Guillemin F, Levine SR, Levy RA, Lockshin MD, Ortel TL, Petri M, Sanna G, Sciascia S, Seshan SV, Tektonidou MG, Wahl D, Willis R, Yelnik C, Hendry A, Naden R, Costenbader K, Erkan D and
The 2023 ACR/EULAR Antiphospholipid Syndrome (APS) Classification Criteria development, aiming to identify patients with high likelihood of APS for research, employed a four-phase methodology. Phase I and II resulted in 27 proposed candidate criteria, organized into laboratory and clinical domains. Here, we summarize the last stage of Phase III efforts employing a consensus-based multi-criteria decision analysis (MCDA) to weigh candidate criteria and identify an APS classification threshold score.
PharmVar GeneFocus: CYP4F2
Zubiaur P, Rodríguez-Antona C, Boone EC, Daly AK, Tsermpini EE, Khasawneh LQ, Sangkuhl K, Duconge J, Botton MR, Savieo J, Nofziger C, Whirl-Carrillo M, Klein TE and Gaedigk A
The Pharmacogene Variation Consortium (PharmVar) serves as a global repository providing star (*) allele nomenclature for the polymorphic human CYP4F2 gene. CYP4F2 genetic variation impacts the metabolism of vitamin K, which is associated with warfarin dose requirements, and the metabolism of drugs, such as imatinib or fingolimod, and certain endogenous compounds including vitamin E and eicosanoids. This GeneFocus provides a comprehensive overview and summary of CYP4F2 genetic variation including the characterization of 14 novel star alleles, CYP4F2*4 through *17. A description of how haplotype information cataloged by PharmVar is utilized by the Pharmacogenomics Knowledgebase (PharmGKB) and the Clinical Pharmacogenetics Implementation Consortium (CPIC) is also provided.
Epidemiological characteristics and serological survey of mumps 15 years after MMR vaccine was included in the immunization program
Gong X, Fang Q, Zheng W, Lai S, Xu W and Yin Z
Mumps is a vaccine-preventable acute viral infectious disease. To understand the incidence of mumps and population immunity in Quzhou City after measles mumps rubella vaccine (MMR) was included in the immunization program, we analyzed the epidemiological characteristics of mumps cases from 2009 to 2023 and a cross-sectional serosurvey of IgG antibodies to mumps conducted in 2024. We found that 15 years after the MMR vaccine was included in the immunization program, the incidence of mumps was significantly reduced in all populations, but the incidence remained highest in vaccinated children aged 0-12 years. Vaccine escape may explain the high incidence of mumps in highly vaccinated populations. Updating vaccines or developing a new vaccine that targets multiple viral genotypes may be necessary to improve the effectiveness of the vaccine against infection and fully control infections and outbreaks. The positive rate and concentration of mumps IgG antibody were inconsistent with the incidence data. mumps IgG antibody is not an ideal substitute for immunity and cannot be used to accurately predict whether a target population is susceptible or protected. Natural infections may provide longer-lasting immunity than vaccination.
Trends in the Completeness and Validity of Sources of Death Data Against the National Death Index From 2010 to 2018
Sponholtz T, Jamal-Allial A, Vojjala SK, Papazian A, Eshete B, Paullin M, Mahmoudpour SH, Verpillat P and Beachler DC
We investigated time trends in validation performance characteristics for six sources of death data available within the Healthcare Integrated Research Database (HIRD) over 8 years.
A Dye-Sensitized Sensor for Oxygen Detection under Visible Light
Wettstein L, Specht J, Kesselring V, Sieben L, Pan Y, Käch D, Baster D, Krumeich F, El Kazzi M and Bezdek MJ
Sensors that can accurately assess oxygen (O) concentrations in real time are crucial for a wide range of applications spanning personal health monitoring, environmental protection, and industrial process development. Here a high-performance chemiresistive sensor that allows for the rapid detection of O at room temperature under visible light illumination is described. Inspired by the operating principles of dye-sensitized solar cells, the chemiresistor is based on a single-walled carbon nanotube-titania hybrid (SWCNT-TiO) bearing a molecular Re-based photosensitizer [(bpy)(CO)ReBr] (bpy = 4,4'-[P(O)(OH)]-2,2'-bipyridine). The resulting SWCNT-TiO-Re composite undergoes photoinduced charge transfer that is sensitive to ppb levels of O, thereby yielding a rapid and reversible chemiresistive response. Owing to its unique mode of operation and robust components, the sensor shows a high degree of selectivity for O over a range of interferants, humidity tolerance, and multimonth benchtop stability. The approach presented herein demonstrates the translatability of concepts in light harvesting to the development of robust, rapid, and low-power sensing technologies.
Pain Medication and Pain Intensity Following Hip Fractures-Analyses Based on the ProFem Cohort Study
Jobski K, Ritschel M, Pöggel-Krämer K, Anheier D, Haastert B, Gontscharuk V, Arend W, Baltes M, Stephan A, Meyer G, Klüppelholz B, Windolf J, Thelen S, Jaekel C, Andrich S, Icks A and Hoffmann F
Pain is a common symptom following proximal femoral fractures (PFF), however, information on its treatment in terms of agents and type of use (scheduled vs. pro re nata [PRN]) is scarce. The main objective of this study was to examine pain medication regimens according to pain intensity following PFF. Furthermore, we explored the utilization of medication plans.
The impact of telehealth cost-sharing on healthcare utilization: Evidence from high-deductible health plans
Gidwani R, Yank V, Burgette L, Kofner A, Asch SM and Wagner Z
Evaluate whether cost-sharing decreases led high-deductible health plans (HDHP) enrollees to increase their use of healthcare.
A Dynamic Prognostic Model for Identifying Vulnerable COVID-19 Patients at High Risk of Rapid Deterioration
Anand P, D'Andrea E, Feldman W, Wang SV, Liu J, Brill G, DiCesare E and Lin KJ
We aimed to validate and, if performance was unsatisfactory, update the previously published prognostic model to predict clinical deterioration in patients hospitalized for COVID-19, using data following vaccine availability.
Fabrication and biocompatibility evaluation of hydroxyapatite-polycaprolactone-gelatin composite nanofibers as a bone scaffold
Aminatun , Sujak M K A, Izak R D, Hadi S, Sari YW, Gunawarman , Cahyati N, Yusuf Y and Che Abdullah CA
One approach to addressing bone defects involves the field of bone tissue engineering, with scaffolds playing an important role. The properties of the scaffold must be similar to those of natural bone, including pore size, porosity, interconnectivity, mechanical attributes, degradation rate, non-toxicity, non-immunogenicity, and biocompatibility. The primary goals of this study are as follows: first, to evaluate hydroxyapatite (HA)/polycaprolactone (PCL)/gelatin nanofiber scaffolds based on functional groups, fibre diameter, porosity, and degradation rate; second, to investigate the interaction between HA/PCL/gelatin scaffolds and osteoblast cells (specifically, the ATCC 7F2 cell line) using assays, including cell viability and adhesion levels. The fibre samples were fabricated using an electrospinning technique with a 15 kV voltage, a spinneret-collector distance of 10 cm, and a flow rate of 0.3 mL hour. The process was applied to five different HA/PCL/gelatin concentration ratios: 50 : 40 : 10; 50 : 30 : 20; 50 : 25 : 25; 50 : 20 : 30; 50 : 35 : 15 (in %wt). Fourier Transform Infrared (FTIR) spectrum analysis and tests revealed no differences in functional groups across the five compositions. The identified functional groups include PO , OH, CO and C[double bond, length as m-dash]O stretching. Notably, an increase in PCL concentrations resulted in larger fiber diameters, ranging from 369-1403 nm with an average value of 929 ± 175 nm. The highest porosity percentage was (77.27 ± 11.57) %, and a sufficient degradation rate of up to 3.5 months facilitated the proliferation process of osteoblast cells. Tensile strength assessments revealed a significant increase in tensile strength with the addition of PCL, reaching a peak of 1.93 MPa. The MTT assay demonstrated a discernible increase in cell proliferation, as evidenced by increased cell viability percentages on days 1, 3, and 5. Concurrently, the fluorescence microscopy examination indicated an increase in cell numbers, which was especially noticeable on days 1 and 5. The SEM analysis confirmed the biocompatibility of the HA/PCL/gelatin nanofiber scaffold, as osteoblast cells attached and dispersed successfully five days after seeding. Based on these findings, the HA/PCL/gelatin nanofiber scaffold emerges as a very promising candidate for treating bone damage.
Beyond reproduction: unraveling the impact of sex hormones on cardiometabolic health
Xega V and Liu JL
This review thoroughly explores the multifaceted roles of sexual hormones, emphasizing their impact beyond reproductive functions and underscoring their significant influence on cardiometabolic regulation. It analyzes the broader physiological implications of estrogen, testosterone, and progesterone, highlighting their effects on metabolic syndrome, lipid metabolism, glucose homeostasis, and cardiovascular health. Drawing from diverse molecular, clinical, and therapeutic studies, the paper delves into the intricate interplay between these hormones and cardiometabolic processes. By presenting a comprehensive analysis that goes beyond traditional perspectives, and recognizing sexual hormones as more than reproductive agents, the review sheds light on their broader significance in health and disease management, advocating for holistic and personalized medical approaches.
Prevalence of Polypharmacy in Elderly Population Worldwide: A Systematic Review and Meta-Analysis
Wang Z, Liu T, Su Q, Luo H, Lou L, Zhao L, Kang X, Pan Y and Nie Y
Polypharmacy (PP) is common in elderly population and associated with some adverse clinical outcomes and increases healthcare burdens. We performed this systemic review and meta-analysis to estimate worldwide prevalence of PP and explore associated factors in the elderly.
Sleep, movement, and dietary behaviours: the mediating role of affect
Zhong Q and Huang J
Previous studies indicated a link between good sleep, optimal movement, and a healthy diet, but the underlying mechanisms are poorly understood. This diary study aimed to investigate the effects of sleep behaviour on movement and dietary behaviours as well as the mediating role of affect.
Post-introduction evaluation (PIE) of rotavirus vaccine in India
Kumar P, Ray A, Kumari A, Kaur A, Hora R, Singh K, Mehra R, Koshal SS, Verma S, Quadri SF and Deb Roy A
India became the first country in the WHO South-East Asia Region (SEAR) to introduce the rotavirus vaccine (RVV) in the Universal immunization programme (UIP) in 2016 with nationwide expansion by 2019. It was a landmark move to reduce the diarrheal disease burden in under-five children. To assess the implementation process of introduction of RVV, Post Introduction Evaluation (PIE) was conducted in March 2022.
Effects of MIND diet and propolis supplementation on metabolic syndrome indices and cognitive function among patients with metabolic syndrome in Isfahan, Iran, 2024. A rationale and study protocol for randomized controlled trial
Gholami Z, Maracy MR and Paknahad Z
Metabolic syndrome (MetS) is the main general and clinical health challenge worldwide. Based on the National Cholesterol Education Program, if the person has three or more indices containing: elevated fasting blood sugar, high levels of triglycerides, hypertension, low levels of high-density lipoprotein cholesterol, and central obesity, he suffers MetS. The Mediterranean-Dietary Approaches to Stop Hypertension (DASH) Intervention for Neurodegenerative Delay diet is a novel diet that with the specific aim of safeguarding cognitive function. Propolis is a resinous substance produced by bees from the combination of buds and secretions of plants with saliva and bee enzymes. After propolis supplementation, a significant reduction in fasting plasma glucose levels and lipid profiles has been observed. Considering the importance of chronic diseases like MetS on health, the role of the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet and propolis supplement that will improve blood sugar, blood lipid, anthropometric indicators, blood pressure, and cognitive function, and limited contradictory studies, we decided to conduct this study. This study, which is a randomized controlled clinical trial study, will be conducted on adults with MetS who will visit Hazrat Ali Health Center in Isfahan. Participants must provide informed consent before engaging in the study. Demographic data such as age, gender, and medical history will be recorded. Then, anthropometric indices, MetS indices, and cognitive function will be measured in all subjects. The study participants will be divided into three groups and will be controlled for 12 weeks. We will have a MIND diet + placebo group, a MIND diet + propolis supplement group, and a control group that will receive a microcrystalline cellulose placebo and usual dietary advice. At the end of the intervention, all indices will be assessed again. The data obtained in the study will be analyzed at descriptive and analytical levels by the statistical software SPSS. The present study's protocol was approved by the Iranian Registry of Clinical Trials (www.irct.ir) on 3/28/2023 and a registration reference is IRCT20230105057054N1.
Novel mutation patterns in children with steroid-resistant nephrotic syndrome
Prasad N, Meyyappan J, Dhanorkar M, Kushwaha R, Mandal K, Veeranki V, Behera M, Patel M, Yadav B, Bhadauria D, Kaul A, Yaccha M, Bhatt M, Agarwal V and Jain M
Idiopathic nephrotic syndrome (NS) in children poses treatment challenges, with a subset developing steroid-resistant nephrotic syndrome (SRNS). Genetic factors play a role, yet data on paediatric SRNS genetics in India are scarce. We conducted a prospective study using whole-exome sequencing to explore genetic variants and their clinical correlations.
Ubiquitin-specific protease 22 controls melanoma metastasis and vulnerability to ferroptosis through targeting SIRT1/PTEN/PI3K signaling
Sun H, Meng Y, Yao L, Du S, Li Y, Zhou Q, Liu Y, Dian Y, Sun Y, Wang X, Liang XW, Deng G, Chen X and Zeng F
Metastasis is a major contributing factor that affects the prognosis of melanoma patients. Nevertheless, the underlying molecular mechanisms involved in melanoma metastasis are not yet entirely understood. Here, we identified ubiquitin-specific protease 22 (USP22) as a pro-oncogenic protein in melanoma through screening the survival profiles of 52 ubiquitin-specific proteases (USPs). USP22 demonstrates a strong association with poor clinical outcomes and is significantly overexpressed in melanoma. Ablation of USP22 expression remarkably attenuates melanoma migration, invasion, and epithelial-mesenchymal transition in vitro and suppresses melanoma metastasis in vivo. Mechanistically, USP22 controls melanoma metastasis through the SIRT1/PTEN/PI3K pathway. In addition, we conducted an United States Food and Drug Administration-approved drug library screening and identified topotecan as a clinically applicable USP22-targeting molecule by promoting proteasomal degradation of USP22. Finally, we found that both pharmacological and genetic silence of USP22 sensitize RSL3-induced ferroptosis through suppressing the PI3K/Akt/mTOR pathway and its downstream SCD, and ferroptosis inhibitor could partly rescued the decreased lung metastasis by topotecan in vivo. Overall, our findings reveal a prometastatic role of USP22 and identify topotecan as a potent USP22-targeting drug to limit melanoma metastasis.
Anaemia and quality of life in chronic kidney disease: a consensus document from the European Anaemia of CKD Alliance
Dasgupta I, Bagnis CI, Floris M, Furuland H, Zurro DG, Gesualdo L, Heirman N, Minutolo R, Pani A, Portolés J, Rosenberger C, Alvarez JES, Torres PU, Vanholder RC, Wanner C and
Anaemia is common in chronic kidney disease (CKD) and has a significant impact on quality of life (QoL), work productivity and outcomes. Current management includes oral or intravenous iron and erythropoiesis-stimulating agents (ESAs), to which hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) have been recently added, increasing the available therapeutic options. In randomised controlled trials, only intravenous iron improved cardiovascular outcome, while some ESAs were associated with increased adverse cardiovascular events. Despite therapeutic advances, several challenges and unmet needs remain in the current management of anaemia of CKD. In particular, clinical practice does not include an assessment of QoL, which prompted a group of European nephrologists and representatives of patient advocacy groups to revisit the current approach. In this consensus document, the authors propose a move towards a more holistic, personalised and long-term approach, based on existing evidence. The focus of treatment should be on improving QoL without increasing the risk of adverse cardiovascular events, and tailoring management strategies to the needs of the individual. In addition, the authors discuss the suitability of a currently available anaemia of CKD-specific health-related QoL measure for inclusion in the routine clinical management of anaemia of CKD. The authors also outline the logistics and challenges of incorporating such a measure into electronic health records and how it may be used to improve QoL for people with anaemia of CKD.
Expanding Hepatitis C Virus Treatment in the New Mexico State Prison System: Using the ECHO Model for Provider and Prison Peer Education
Thornton KA, Deming PD, Archer GRD, Ceniceros JA, Tomedi LE, Selvage D, Jablonski D, Rowan DH, Paul D, Asonganyi W and Arora S
It is critical to address hepatitis C virus (HCV) in carceral settings to achieve worldwide elimination of the virus. We describe New Mexico's (NM) experience expanding HCV treatment in state prisons, supplemented with Project ECHO (ECHO; virtual mentorship through guided practice) and the NM Peer Education Program (NMPEP). We describe how using these programs may be a model for expanding treatment in prisons globally. ECHO, NM Corrections Department (NMCD) and Wexford Health Services (WHS) collaborate to treat HCV in state prisons and increase HCV knowledge among incarcerated persons using NMPEP. Each person arriving in prison is tested for HCV and those with active infection receive baseline labs, which are reviewed. Patients not meeting criteria for simplified treatment are presented to ECHO for expert guidance. Otherwise, patients are treated by WHS without consultation. NMPEP provides patient-to-patient education in prisons, addressing HCV myths and exploring treatment refusals. From December 2020 to June 2023, 3603 people had HCV viremia. In this study, 1685 people started treatment: 1280 were treated using the simplified algorithm and 405 were presented to ECHO. Of the 988 people who completed treatment and had sustained virologic response (SVR) labs drawn, 89.2% achieved SVR (i.e., cure). Most of the 107 people who did not achieve SVR had presumed reinfection. NMPEP trained 148 peer educators who educated 3832 peers about HCV prevention and treatment. HCV treatment in prisons can be expanded by implementing simplified treatment algorithms, use of the ECHO model for patients with advanced disease and peer education.
Epidemiology of patients with severe asthma in Japan: a nationwide descriptive study
Kimura Y, Suzukawa M, Jo T, Hashimoto Y, Kumazawa R, Ishimaru M, Matsui H, Yokoyama A, Tanaka G and Yasunaga H
The 2014 European Respiratory Society/American Thoracic Society guidelines defined severe asthma based on treatment intensity and estimated the proportion of severe asthma among all asthma cases to be 5-10%. However, data supporting the estimate and comprehensive and sequential data on asthma cases are scarce. We aimed to estimate the national prevalence and proportion of severe asthma during the last decade.
DECODING STROKE DISPARITIES: ZIP CODES, COLOR CODES, AND EPIGENETIC CODES
Ovbiagele B
Despite decreases in overall stroke incidence and mortality in the United States, racial and ethnic disparities continue unabated. Of note, the long-standing disproportionate burden of stroke on African Americans compared to other racial and ethnic groups persists, and national projections indicate this toll will likely worsen over the next decade. Why have we not been able to bend the stroke disparities curve for African Americans? Well, this is mainly because traditional stroke risk factors, such as hypertension, diabetes, etc., account for just half of the Black vs. non-Hispanic White stroke disparity. As such, there is increasing interest in evaluating understudied factors like upstream social determinants of health, including geography, psychosocial stress, and environmental pollution; identifying potential mediators; and testing multilevel interventions to address them. This paper highlights emerging avenues that may help decode the excess stroke risk in African Americans, focusing on zip codes, color codes, and epigenetic codes.
That was just your life: rethinking dementia for advance directives
Vulliermet F and Kenis D
Over the past decades, literature in dementia ethics has extensively looked at moral questions revolving around the care of older people living with dementia. Particularly prevalent are autonomy-related concerns regarding topics such as advance directives. In this paper, we argue that these discussions are crucially premised on how dementia is understood and represented. Despite the multiplicity of dementia presentations in people, the dominant discourse predominantly frames dementia as 'monstrous,' an 'enemy,' a destructive experience in need of eradication. We contend that such a monolithic approach, from a moral standpoint, is problematic in several respects. Indeed, framing heavily influences the way dementia is understood and experienced, leading to stigmatization, bias, and distress. Not only does it influence decisions and discussions on advance directives, but we argue that this flawed understanding of dementia is rooted in and contributes to epistemic harm. In the first section, we introduce the ethics of advance directives. More specifically, we introduce the view developed by Dworkin who has largely influenced the debate by making the case for advance directives by grounding them in the principles of autonomy and beneficence. In the second section, we show how dementia is still mostly framed monolithically as a 'destructive experience.' We then show that this framing is problematic because it oversteps the different pathologies dementia implies, which leads to an inaccurate representation of the condition. In the third section, we present possible alternative framings: dementia as normal aging, a person-centered care framework, and an embodied view. In the fourth section, drawing on recent developments in the epistemic injustice literature, we explore how maintaining and utilizing flawed understandings of dementia may lead to distinct moral-epistemic harms for those living with dementia and inform ongoing discussions on advance directives. Finally, in the concluding section, we return to the case of advance directives and what the implications of rethinking dementia are.
Implementing a scoping review to explore sport officials' mental health
Carter TB, Gorczynski P, Coady CJ, Cunningham IJ, Mascarenhas DRD, Grant M, Sullivan P, Webb T, Livingston LA and Hancock DJ
Sport officials are tasked with applying rules, maintaining fairness, and ensuring athlete safety. However, sport officials experience anxiety, burnout, and non-accidental violence, with the incidence of these events increasing worldwide. This has led to rising attrition rates among sport officials, with many sport organizations concerned for their operational capacity. The effects of anxiety, burnout, and non-accidental violence might contribute to or be indicative of sport officials' negative mental health outcomes. To develop a clear understanding of how sport officials' mental health is affected by their occupation, it is necessary to identify the mental health outcomes and predictors they experience, and to what extent. The purpose of this scoping review was to identify and examine the empirical research and policy documents surrounding sport officials' mental health.
Correlation between gross motor coordination and basic coordination capacities in normal-weight and overweight/obese children aged 9-10 years
Sui Y, Cui L, Jia B, Ding X, He M, Da Y, Shi Y, Li F and Li P
Gross motor coordination (GMC) plays a crucial factor in children's motor development and daily activities. It encompasses various sub-capacities, such as spatial orientation, rhythm, and motor reaction, collectively referred to as basic coordination capacities (BCC). However, children who are overweight and obese (OW/OB) often display poorer GMC. This study aims to examine the impact of gender and weight status (BMI categories) on children's GMC and BCC. It also seeks to investigate the impact of BCC and BMI on GMC.
Toripalimab plus chemotherapy in the treatment of metastatic triple-negative breast cancer: a cost-effectiveness analysis
Cai H, Huang L and Zheng Z
This study focuses on assessing the cost-effectiveness of incorporating toripalimab alongside chemotherapy for the treatment of patients diagnosed with metastatic triple-negative breast cancer from the perspective of the Chinese healthcare system.
Factors Influencing the Use and Demand of New Coronavirus Therapy Drugs Among the Adults During COVID-19 in China
Chen C, Zhang H, Feng X and Wang H
This alteration in the policy of COVID-19 resulted in widespread infections throughout China. Most people only need some antiviral drugs such as lopinavir/ritonavir or Chinese herbal preparations for treatment. In this context, the lack of drug knowledge and inadequate drug availability are evident. This study aims to explore the factors influencing drug use and demand during the COVID-19 epidemic.
A Comprehensive Evaluation of 16 Old and New Intraocular Lens Power Calculation Formulas in Pediatric Eyes
Achiron A, Yahalomi T, Biran A, Levinger E, Cohen E, Elbaz U, Ali A, Mireskandari K, Tuuminen R and Voytsekhivskyy OV
To compare the accuracy of 16 intraocular lens (IOL) power calculation formulas in pediatric cataract eyes.
Factor H-related protein 1 in systemic lupus erythematosus
Kleer JS, Klehr J, Dubler D, Infanti L, Chizzolini C, Huynh-Do U, Ribi C and Trendelenburg M
Factor H (FH) is a major soluble inhibitor of the complement system and part of a family comprising five related proteins (FHRs 1-5). Deficiency of FHR1 was described to be linked to an elevated risk of systemic lupus erythematosus (SLE). As FHR1 can partially antagonize the functionality of FH, an altered FHR1/FH ratio could not only enhance SLE vulnerability but also affect the disease expression. This study focuses on the analysis of FH and FHR1 at a protein level, and the occurrence of anti-FH autoantibodies (anti-FH) in a large cohort of SLE patients to explore their association with disease activity and/or expression.
Exploring Associations Between Device-Based Occupational Sedentary Behavior and Need for Recovery in White Collar Workers: A Compositional Data-Analysis
Smit DJM, Burgers LJGC, van Oostrom SH, Vähä-Ypyä H, Husu P, Verswijveren SJJM and Proper KI
White collar workers spend an increasing amount of time in occupational sedentary behavior (OSB) and are thereby at risk for adverse health outcomes. Nevertheless, the association between OSB and the need for recovery (NFR), an important indicator of wellbeing, is unknown and therefore examined.
Pictures versus words: can we use a pictorial scale to measure child health-related quality of life?
Tang TCW, Wong M, Li JB and Chan DKC
Measuring health-related quality of life (HRQoL) is important because it can serve as an indicator or a predictor of subsequent mortality or morbidity. HRQoL has been shown to be directly related to child growth and development and indirectly related to the healthcare costs of young children. Existing measures of HRQoL in children have heavily relied on traditional questionnaires that use age-suited versions or parent proxy questionnaires. However, both of these methods may present with different types of biases and may misrepresent underlying HRQoL. The current mini reivew will first illustrate these methodological limitations and highlight the potential use of pictorial scales in addition to discussing their suitability for specifically measuring HRQoL as an alternative. We will also synthesize existing recommendations on the development of pictorial scales to provide a protocol as a recommendation to researchers who are aiming to develop an overall HRQoL pictorial scale that is suited for children.
Effectiveness of engaging religious leaders in maternal health education for improving maternal health service utilization in Ethiopia: cluster randomized controlled trial
Sadore AA, Kebede Y and Birhanu Z
High mortality rates for pregnant women and their new-borns are one of Africa's most intractable public health issues today, and Ethiopia is one of the countries most afflicted. Behavioral interventions are needed to increase maternal health service utilizations to improve outcomes. Hence, this trial aimed to evaluate effectiveness of trained religious leaders' engagement in maternal health education on maternal health service utilization.
Association between relative grip strength and depression among U.S. middle-aged and older adults: results from the NHANES database
Sun A and Liu Z
Mental health issues among middle-aged and older adults are gaining increasing attention. Recent studies have shown that relative grip strength is associated with cardiovascular diseases and various cancers, but its relationship with depression remains unclear.
Associations between PM, ambient heat exposure and congenital hydronephrosis in southeastern China
Huang Z, Zhong X, Shen T, Gu S, Chen M, Xu W, Chen R, Wu J and Yang X
This research aims to analyze how exposure to fine particulate matter (PM5) and ambient heat during pregnancy increases the risk of congenital hydronephrosis (CH) in newborns.
Tumor-informed ctDNA assessment as a valuable prognostic and predictive biomarker in diffuse large B-cell lymphoma
Narkhede M, Tomassetti S, Iqbal M, Tin A, Rivero-Hinojosa S, George GV, Widden H, Benrud R, Malhotra M, Rodriguez A and Liu MC
A novel approach for molecular residual disease (MRD) detection and treatment monitoring is needed in diffuse large B-cell lymphoma (DLBCL) to identify patients with a poor prognosis. We performed a retrospective evaluation of commercial ctDNA testing in patients with stage I-IV DLBCL to evaluate the prognostic and predictive role of tumor-informed ctDNA assessment.
Exploring gut microbiota and metabolite alterations in patients with thyroid-associated ophthalmopathy using high-throughput sequencing and untargeted metabolomics
Zhang X, Dong K, Zhang X, Kang Z and Sun B
Thyroid-associated ophthalmopathy (TAO) is an autoimmune-driven orbital inflammatory disease. Despite research efforts, its exact pathogenesis remains unclear. This study aimed to characterize the intestinal flora and metabolic changes in patients with TAO to identify the flora and metabolites associated with disease development.
Single-cell RNA sequencing reveals that MYBL2 in malignant epithelial cells is involved in the development and progression of ovarian cancer
Shao W, Lin Z, Xiahou Z, Zhao F, Xu J, Liu X and Cai P
Ovarian carcinoma (OC) is a prevalent gynecological malignancy associated with high recurrence rates and mortality, often diagnosed at advanced stages. Despite advances in immunotherapy, immune exhaustion remains a significant challenge in achieving optimal tumor control. However, the exploration of intratumoral heterogeneity of malignant epithelial cells and the ovarian cancer tumor microenvironment is still limited, hindering our comprehensive understanding of the disease.
Waist circumference glucose, a novel and effective predictor of type 2 diabetes: a prospective cohort study
Zhao X, Song B, Yao T, Fan H, Liu T, Gao G, Wang K, Lu W and Liu C
Waist circumference (WC) and fasting plasma glucose (FPG) have been demonstrated as risk factors for type 2 diabetes mellitus (T2DM). Evidence is limited regarding the association of the combination of WC and FPG (WyG) with the risk of T2DM. The primary aim of the study was to investigate the relationship between WyG and T2DM.
Drug repurposing in Rett and Rett-like syndromes: a promising yet underrated opportunity?
Fuchs C, 't Hoen PAC, Müller AR, Ehrhart F and Van Karnebeek CDM
Rett syndrome (RTT) and Rett-like syndromes [i.e., CDKL5 deficiency disorder (CDD) and FOXG1-syndrome] represent rare yet profoundly impactful neurodevelopmental disorders (NDDs). The severity and complexity of symptoms associated with these disorders, including cognitive impairment, motor dysfunction, seizures and other neurological features significantly affect the quality of life of patients and families. Despite ongoing research efforts to identify potential therapeutic targets and develop novel treatments, current therapeutic options remain limited. Here the potential of drug repurposing (DR) as a promising avenue for addressing the unmet medical needs of individuals with RTT and related disorders is explored. Leveraging existing drugs for new therapeutic purposes, DR presents an attractive strategy, particularly suited for neurological disorders given the complexities of the central nervous system (CNS) and the challenges in blood-brain barrier penetration. The current landscape of DR efforts in these syndromes is thoroughly examined, with partiuclar focus on shared molecular pathways and potential common drug targets across these conditions.
Humanitarian health education and training state-of-the-art: a scoping review
Bahattab A, Trentin M, Hubloue I, Della Corte F and Ragazzoni L
In the past decade, humanitarian emergencies have been increasing, leading to an higher demand for humanitarian health professionalization. Education and training are critical for preparing these workers to provide effective care during crises. Understanding the current state-of-the-art in humanitarian health education is essential to inform research and development of future educational programs. This review surveys the peer-reviewed literature to provide insights into the current thinking in the field.
The value of metagenomic next-generation sequencing with different nucleic acid extracting methods of cell-free DNA or whole-cell DNA in the diagnosis of non-neutropenic pulmonary aspergillosis
Cai X, Sun C, Zhong H, Cai Y, Cao M, Wang L, Sun W, Tao Y, Ma G, Huang B, Yan S, Zhong J, Wang J, Lu Y, Guan Y, Song M, Wang Y, Li Y and Su X
Metagenomic next-generation sequencing(mNGS) is a novel molecular diagnostic technique. For nucleic acid extraction methods, both whole-cell DNA (wcDNA) and cell-free DNA (cfDNA) are widely applied with the sample of bronchoalveolar lavage fluid (BALF). We aim to evaluate the clinical value of mNGS with cfDNA and mNGS with wcDNA for the detection of BALF pathogens in non-neutropenic pulmonary aspergillosis.
Artificial intelligence assisted preoperative planning and 3D-printing guiding frame for percutaneous screw reconstruction in periacetabular metastatic cancer patients
Wang J, Zhao Z, Liang H, Zhang R, Liu X, Zhang J, Singh S, Guo W, Yan T, Hoang BH, Geller DS, Tang X and Yang R
The percutaneous screw reconstruction technique, known as the "Tripod Technique," has demonstrated favorable clinical outcomes in the management of metastatic periacetabular lesions, as evidenced by our prior investigations and corroborated by independent studies. Nevertheless, there is a steep learning curve in handling this technique, with possible complications such as intraarticular screw placement.
mucinous phenotypes and operon mutant characteristics obtained from inpatients with bronchiectasis and their correlation with acute aggravation
Tan Y and Dai Z
Although the mechanism is unclear, (PA) infection directly affects the frequency of acute exacerbations in patients with bronchiectasis. The aims of this article are to analyze the genetic mutation characteristics of the operon in PA, isolated from hospitalized patients with bronchiectasis, and to explore independent risk factors for frequent acute exacerbations of bronchiectasis.
Transcriptomics-based characterization of the immuno-stromal microenvironment in pediatric low-grade glioma
Körner M, Spohn M, Schüller U and Bockmayr M
Immunologic treatment options are uncommon in low-grade gliomas, although such therapies might be beneficial for inoperable and aggressive cases. Knowledge of the immune and stromal cells in low-grade gliomas is highly relevant for such approaches but still needs to be improved. Published gene-expression data from 400 low-grade gliomas and 193 high-grade gliomas were gathered to quantify 10 microenvironment cell populations with a deconvolution method designed explicitly for brain tumors. First, we investigated general differences in the microenvironment of low- and high-grade gliomas. Lower-grade and high-grade tumors cluster together, respectively, and show a general similarity within and distinct differences between these groups, the main difference being a higher infiltration of fibroblasts and T cells in high-grade gliomas. Among the analyzed entities, gangliogliomas and pleomorphic xanthoastrocytomas presented the highest overall immune cell infiltration. Further analyses of the low-grade gliomas presented three distinct microenvironmental signatures of immune cell infiltration, which can be divided into T-cell/dendritic/natural killer cell-, neutrophilic/B lineage/natural killer cell-, and monocytic/vascular/stromal-cell-dominated immune clusters. These clusters correlated with tumor location, age, and histological diagnosis but not with sex or progression-free survival. A survival analysis showed that the prognosis can be predicted from gene expression, clinical data, and a combination of both with a support vector machine and revealed the negative prognostic relevance of vascular markers. Overall, our work shows that low- and high-grade gliomas can be characterized and differentiated by their immune cell infiltration. Low-grade gliomas cluster into three distinct immunologic tumor microenvironments, which may be of further interest for upcoming immunotherapeutic research.
Differences in checkpoint-inhibitor-induced hypophysitis: mono- versus combination therapy induced hypophysitis
van der Leij S, Suijkerbuijk KPM, van den Broek MFM, Valk GD, Dankbaar JW and van Santen HM
Immune checkpoint inhibitors (ICIs) are revolutionary in oncology but may cause immune-related (IR) side effects, such as hypophysitis. Treatment with anti-PD-(L)1, anti-CTLA-4 or anti-CLTA-4/PD-1 may induce hypophysitis, but little is known about the differences in clinical presentation or need for different treatment. We analyzed the differences of anti-PD-(L)1, anti-CTLA-4 and anti-CTLA-4/PD-1 induced hypophysitis.
Multiplex spatial analysis reveals increased CD137 expression and m-MDSC neighboring tumor cells in refractory classical Hodgkin Lymphoma
Solórzano JL, Menéndez V, Parra E, Solis L, Salazar R, García-Cosío M, Climent F, Fernández S, Díaz E, Francisco-Cruz A, Khoury J, Jiang M, Tamegnon A, Montalbán C, Melero I, Wistuba I, De Andrea C and F García J
The Hodgkin and Reed - Sternberg (HRS) cells in classical Hodgkin Lymphoma (cHL) actively modify the immune tumor microenvironment (TME) attracting immunosuppressive cells and expressing inhibitory molecules. A high frequency of myeloid cells in the TME is correlated with an unfavorable prognosis, but more specific and rare cell populations lack precise markers. Myeloid-derived suppressor cells (MDSCs) have been identified in the peripheral blood of cHL patients, where they appear to be correlated with disease aggressiveness. TNFRSF9 (CD137) is a T cell co-stimulator expressed by monocytic and dendritic cells. Its expression has also been described in HRS cells, where it is thought to play a role in reducing antitumor responses. Here, we perform qualitative and quantitative analyses of lymphocytic and MDSC subtypes and determine the CD137 cell distribution in cHL primary tumors using multiplex immunofluorescence and automated multispectral imaging. The results were correlated with patients' clinical features. Cells were stained with specific panels of immune checkpoint markers (PD-1, PD-L1, CD137), tumor-infiltrating T lymphocytes (CD3, PD-1), and monocytic cells/MDSCs (CD68, CD14, CD33, Arg-1, CD11b). This approach allowed us to identify distinct phenotypes and to analyze spatial interactions between immune subpopulations and tumor cells. The results confirm CD137 expression by T, monocytic and HRS cells. In addition, the expression of CD137, T exhausted cells, and monocytic MDSCs (m-MDSCs) in the vicinity of malignant HRS cells were associated with a worse prognosis. Our findings reveal new elements of the TME that mediate immune escape, and confirm CD137 as a candidate target for immunotherapy in cHL.
The effect of hyperuricemia and its interaction with hypertension towards chronic kidney disease in patients with type 2 diabetes: evidence from a cross- sectional study in Eastern China
Chen XY, Lu F, Zhang J, Xu CX, Du XF, Liang MB, Chen LJ and Zhong JM
This study aimed to explore the synergistic interaction effect between hyperuricemia and hypertension towards chronic kidney disease in patients with type 2 diabetes.
Current status and future directions of nanovaccine for cancer: a bibliometric analysis during 2004-2023
Hou Y, Li Y, Zhang Y, Zhang J and Wu D
Nanovaccine treatment is an exciting area of research in immunology and personalized medicine, holding great promise for enhancing immune responses and targeting specific diseases. Their small size allows efficient uptake by immune cells, leading to robust immune activation. They can incorporate immune-stimulating molecules to boost vaccine efficacy. Therefore, nanovaccine can be personalized to target tumor-specific antigens, activating the immune system against cancer cells. Currently, there have been ample evidence showing the effectiveness and potential of nanovaccine as a treatment for cancer. However, there was rare bibliometric analysis of nanovaccine for cancer. Here we performed a bibliometric and visual analysis of published studies related to nanovaccine treatment for cancer, providing the trend of future development of nanovaccine.
Immunotherapy revolutionizing brain metastatic cancer treatment: personalized strategies for transformative outcomes
Li T, Sun S, Li Y, Zhang Y and Wei L
Brain metastatic cancer poses a significant clinical challenge, with limited treatment options and poor prognosis for patients. In recent years, immunotherapy has emerged as a promising strategy for addressing brain metastases, offering distinct advantages over conventional treatments. This review explores the evolving landscape of tumor immunotherapy in the context of brain metastatic cancer, focusing on the intricate interplay between the tumor microenvironment (TME) and immunotherapeutic approaches. By elucidating the complex interactions within the TME, including the role of immune cells, cytokines, and extracellular matrix components, this review highlights the potential of immunotherapy to reshape the treatment paradigm for brain metastases. Leveraging immune checkpoint inhibitors, cellular immunotherapies, and personalized treatment strategies, immunotherapy holds promise in overcoming the challenges posed by the blood-brain barrier and immunosuppressive microenvironment of brain metastases. Through a comprehensive analysis of current research findings and future directions, this review underscores the transformative impact of immunotherapy on the management of brain metastatic cancer, offering new insights and opportunities for personalized and precise therapeutic interventions.
PRELIMINARY IMPACT OF SUPPORTIVE HOUSING ON HOSPITAL UTILIZATION FOR INDIVIDUALS EXPERIENCING HOMELESSNESS
Miller RG, Wright RS, Hatton CR, Lepley D and Lindamood K
Housing instability has been shown to negatively impact physical and mental health, with a corresponding increase in health care utilization. In 2019, through a Maryland Medicaid 1115 Health Choice Waiver, 10 Baltimore city hospitals joined with the city of Baltimore and the local nonprofit Health Care for the Homeless to support an innovative program that provides permanent housing and wraparound services to individuals at risk of homelessness. Here, we describe the inception of the program and its subsequent expansion with the investment of the city hospitals. Participants in the program experienced a 48% reduction in all hospital visits and a 51% reduction in emergency department visits in the 12 months following their receipt of housing compared to the 12 months before enrollment. These data suggest the potential health benefits of housing and supportive services as an intervention.
Lower incidence of grade II-IV acute Graft-versus-Host-Disease in pediatric patients recovering with high Vδ2+ T cells after allogeneic stem cell transplantation with unmanipulated bone marrow grafts: a prospective single-center cohort study
Müller T, Alasfar L, Preuß F, Zimmermann L, Streitz M, Hundsdörfer P, Eggert A, Schulte J, von Stackelberg A and Oevermann L
Gamma delta (γδ) T cells represent a minor fraction of human T cell repertoire but play an important role in mediating anti-infectious and anti-tumorous effects in the context of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We performed a prospective study to analyze the effect of different transplant modalities on immune reconstitution of γδ T cells and subsets. CD3, CD4 and CD8 T cells were analyzed in parallel. Secondly, we examined the impact of γδ T cell reconstitution on clinical outcomes including acute Graft-versus-Host-Disease (aGvHD) and viral infections. Our cohort includes 49 pediatric patients who received unmanipulated bone marrow grafts from matched unrelated (MUD) or matched related (MRD) donors. The cohort includes patients with malignant as well as non-malignant diseases. Cell counts were measured using flow cytometry at 15, 30, 60, 100, 180 and 240 days after transplantation. Cells were stained for CD3, CD4, CD8, CD45, TCR, TCRγδ, TCRVδ1, TCRVδ2, HLA-DR and combinations. Patients with a MRD showed significantly higher Vδ2+ T cells than those with MUD at timepoints +30, +60, +100 (p<0.001, respectively) and +180 (p<0.01) in univariate analysis. These results remained significant in multivariate analysis. Patients recovering with a high relative abundance of total γδ T cells and Vδ2+ T cells had a significantly lower cumulative incidence of grade II-IV aGvHD after transplantation (p=0.03 and p=0.04, respectively). A high relative abundance of Vδ2+ T cells was also associated with a lower incidence of EBV infection (p=0.02). Patients with EBV infection on the other hand showed higher absolute Vδ1+ T cell counts at days +100 and +180 after transplantation (p=0.046 and 0.038, respectively) than those without EBV infection. This result remained significant in a multivariate time-averaged analysis (q<0.1). Our results suggest a protective role of γδ T cells and especially Vδ2+ T cell subset against the development of aGvHD and EBV infection after pediatric HSCT. Vδ1+ T cells might be involved in the immune response after EBV infection. Our results encourage further research on γδ T cells as prognostic markers after HSCT and as possible targets of adoptive T cell transfer strategies.
WALKING BACKWARDS: REFLECTING ON THE VALUE OF MENTORS
Burks W
The author, Dr. A. Wesley Burks, reflects on his life's work to improve the lives of his patients.
Searching for the perfect goalkeeping personality. Myth or reality?
Spielmann J, Otte F, Schumacher T, Mayer J and Klatt S
Psychological factors such as personality characteristics are influential factors of the goalkeeping performance in football (soccer). Not only for individualized treatment in practice, also from a scientific point of view, profiling goalkeepers is a relevant part of understanding athletes. The aim of this study was to investigate personality traits of goalkeepers of different expertise, age, and sex.
Prognostic role of chemokine-related genes in acute myeloid leukemia
Hou Y, Chen Y, Zhang Y, Li M and Chen J
Chemotactic cytokines play a crucial role in the development of acute myeloid leukemia (AML). Thus, investigating the mechanisms of chemotactic cytokine-related genes (CCRGs) in AML is of paramount importance.
THE JEREMIAH METZGER LECTURE: ENVIRONMENTAL INFLUENCES ON COLORECTAL CANCER
Carethers JM
Gene-environmental interactions create risk profiles for sporadic cancer development in patients with colorectal cancer (CRC). For instance, a person's socioeconomic status over their lifetime can affect their level of physical activity and type of diet, and their exposure to tobacco and alcohol may affect their gut microbiome and ultimate risk for developing CRC. Metabolic disease can independently or further change the gut microbiome and alter the typical timing of CRC development, such as is observed and linked with early-onset disease. Patients with microsatellite unstable tumors where DNA mismatch repair is defective have altered immune environments as a result of tumor hypermutability and neoantigen generation, allowing for immune checkpoint inhibitor susceptibility; in such cases, the genetics of the tumor changed the environment. The environment can also change the genetics, where interleukin-6-generated inflammation can inactivate MSH3 protein function that is associated with CRCs which are more metastatic, and patients show poor outcomes. Some specific aspects of the local microbial environment that may be influenced by diet and metabolism are associated with CRC risk, such as infection, and may affect the initiation, perpetuation, and spread of CRC. Overall, both the macro- and microenvironments associated with a person play a major role in CRC formation, progression, and metastases.
Servant leadership and employee voice behavior: the role of employee work reflection and employee proactive personality
Xu Z, Gu Y, Wang H and Liu L
Despite the recent proliferation of scholarly investigations on servant leadership, clarity remains elusive regarding the specific mechanisms and conditions underpinning employee cognitive processes and their responses to servant leadership. Drawing upon social cognitive theory, proposes a moderated mediation model tested through a time-lagged field data from 489 employees in Study 1 and an experimental data in Study 2. We found that servant leadership indirectly enhances employee voice behavior through increased employee work reflection. Additionally, we considered employee proactive personality as a boundary condition for the positive effect of servant leadership. Our results show that servant leadership prompts employee work reflection only when the level of employee proactive personality is high, which in turn increases employee voice behavior. This study presents significant theoretical and practical implications through the integration of social cognitive theory with servant leadership research.
ALTERATIONS IN HISTIDINE METABOLISM IS A FEATURE OF EARLY AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE (ADPKD)
Chapman A and Chen P
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by epithelial proliferation and progressive cyst enlargement. Using a non-targeted high-resolution metabolomics approach, we analyzed biofluids from 36 ADPKD and 18 healthy controls with estimated glomerular filtration rate (eGFR) > 60 ml/min to identify features specific to ADPKD or that associate with disease severity [eGFR or height-corrected total kidney volume (htTKV)]. Multiple pathways differed between ADPKD subjects and controls, with the histidine pathway being the most highly represented. Plasma histidine, urinary N-methylhistamine, methylimidazole-acetaldehyde, and imidazole-acetaldehyde, as well as 3-methylhistidine and anserine were increased, while plasma N-acetylhistamine and urinary imidazole-acetic acid were decreased in ADPKD compared to controls. In ADPKD, urinary histidine and a histidine derivative, urocanate (a precursor of glutamate), were significantly associated. HtTKV and eGFR were inversely associated with urinary glutamine and plasma 4-imidazolone-5-propionic acid, respectively. Supernatant from cultured human ADPKD renal cystic epithelia demonstrated increased aspartate and glutamate levels at 8 and 24 hours compared to primary tubular epithelia (p < 0.001). Following exposure over 48 hours to α-fluromethylhistidine, an inhibitor of histamine production, primary human cyst epithelia proliferation increased significantly from baseline (p < 0.01) and greater than non-cystic epithelia (p < 0.05). The histidine ammonia lyase inhibitor nitromethane reversed α-fluromethylhistidine-induced cyst epithelia proliferation indicating a role for glutamate in cyst growth. In conclusion, histidine metabolism is altered preferentially leading to glutamate production and epithelial proliferation in ADPKD and associates with disease severity.
Case report: Effective treatment of rituximab-resistant minimal change disease with obinutuzumab in an adult
Wang Q, Lin L, Zhen J, Jiang B and Liu G
Minimal change disease (MCD) is a common cause of adult nephrotic syndrome. Most adults with MCD achieve complete remission (CR) after initial steroid therapy. However, approximately 30% of adults who respond to steroids experience frequent relapses, becoming steroid-dependent and potentially developing refractory MCD. Treating refractory MCD in adults poses a significant challenge.
Genetic variability in the glucocorticoid pathway and treatment outcomes in hospitalized patients with COVID-19: a pilot study
Štampar P, Blagus T, Goričar K, Bogovič P, Turel G, Strle F and Dolžan V
Corticosteroids are widely used for the treatment of coronavirus disease (COVID)-19. Genetic polymorphisms of the glucocorticoid receptor, metabolizing enzymes, or transporters may affect treatment response to dexamethasone. This study aimed to evaluate the association of the glucocorticoid pathway polymorphisms with the treatment response and short-term outcomes in patients with severe COVID-19. Our pilot study included 107 hospitalized patients with COVID-19 treated with dexamethasone and/or methylprednisolone, genotyped for 14 polymorphisms in the glucocorticoid pathway. In total, 83% of patients had severe disease, 15.1% had critical disease and only 1.9% had moderate disease. rs35599367 was the major genetic determinant of COVID-19 severity as carriers of this polymorphism had higher risk of critical disease (OR = 6.538; 95% confidence interval = 1.19-35.914: = 0.031) and needed intensive care unit treatment more frequently (OR = 10; 95% CI = 1.754-57.021: = 0.01). This polymorphism was also associated with worse disease outcomes, as those patients had to switch from dexamethasone to methylprednisolone more often (OR = 6.609; 95% CI = 1.137-38.424: = 0.036), had longer hospitalization ( = 0.022) and needed longer oxygen supplementation ( = 0.040). Carriers of rs6198 polymorphic allele required shorter dexamethasone treatment ( = 0.043), but had higher odds for switching therapy with methylprednisolone (OR = 2.711; 95% CI = 1.018-7.22: = 0.046). Furthermore, rs6198 was also associated with longer duration of hospitalization ( = 0.001) and longer oxygen supplementation ( = 0.001). rs33388 polymorphic allele was associated with shorter hospitalization ( = 0.025) and lower odds for ICU treatment (OR = 0.144; 95% CI = 0.027-0.769: = 0.023). rs1695 was associated with duration of hospitalization ( = 0.015), oxygen supplementation and ( = 0.047) dexamethasone treatment ( = 0.022). Our pathway-based approach enabled us to identify novel candidate polymorphisms that can be used as predictive biomarkers associated with response to glucocorticoid treatment in COVID-19. This could contribute to the patient's stratification and personalized treatment approach.
Novel insights and therapeutic approaches in secondary AML
Marconi G, Rondoni M, Zannetti BA, Zacheo I, Nappi D, Mattei A, Rocchi S and Lanza F
Secondary acute myeloid leukemia (sAML) presents as a complex and multifaceted ensemble of disorders, positioning itself as both a challenge and an intriguing frontier within hematologic oncology. Its origins are diverse, stemming from antecedent hematologic conditions, germline predisposing mutations, or the sequelae of cytotoxic therapies, and its development is driven by intricate genetic and epigenetic modifications. This complexity necessitates a diverse array of therapeutic strategies, each meticulously tailored to address the distinctive challenges sAML introduces. Such strategies require a personalized approach, considering the variegated clinical backgrounds of patients and the inherent intricacies of the disease. Allogeneic stem cell transplantation stands as a cornerstone, offering the potential for curative outcomes. This is complemented by the emergence of innovative treatments such as CPX-351, venetoclax, and glasdegib, which have demonstrated promising results in enhancing prognosis. The evolving landscape of sAML treatment underscores the importance of continued research and innovation in the field, aiming not only to improve patient outcomes but also to deepen our understanding of the disease's biological underpinnings, thereby illuminating pathways toward more effective and individualized therapies.
The distribution and maturation of tertiary lymphoid structures can predict clinical outcomes of patients with gastric adenocarcinoma
Sun H, Liu Y, Cheng W, Xiong R, Gu W, Zhang X, Wang X, Wang X, Tan C, Weng W, Zhang M, Ni S, Huang D, Xu M, Sheng W and Wang L
Tertiary lymphoid structures (TLSs) are analogues of secondary lymphoid organs that contain various immune cells. The spatial distribution, maturation and composition of TLSs have differential effects on prognosis, and the roles of TLSs in gastric adenocarcinoma (GA) have not been revealed.
Spinal Gout: An Unusual Cause of Low Back Pain
Shu S and Garrison GM
Low back pain is the most common musculoskeletal complaint accounting for over 30 million visits to primary care physicians annually. Serious pathology is found in less than 1% of these visits. Therefore it is often a challenge to distinguish worrisome findings requiring further workup and treatment from common complaints of pain. Gout is an inflammatory arthritis that most commonly affects the appendicular skeleton. It is characterized by the saturation of uric acid and deposition of monosodium urate crystals in joints and tissues. Spinal involvement is rare and is not typically considered on the differential diagnosis for a patient presenting with acute low back pain. We present such a case of a 35-year-old male who presented with intractable back pain, highlighting the need to recognize signs and symptoms that raise suspicion for spinal gout.
Multi-omics analysis of overexpressed tumor-associated proteins: gene expression, immunopeptide presentation, and antibody response in oropharyngeal squamous cell carcinoma, with a focus on cancer-testis antigens
Abou Kors T, Meier M, Mühlenbruch L, Betzler AC, Oliveri F, Bens M, Thomas J, Kraus JM, Doescher J, von Witzleben A, Hofmann L, Ezic J, Huber D, Benckendorff J, Barth TFE, Greve J, Schuler PJ, Brunner C, Blackburn JM, Hoffmann TK, Ottensmeier C, Kestler HA, Rammensee HG, Walz JS and Laban S
The human leukocyte antigen complex (HLA) is essential for inducing specific immune responses to cancer by presenting tumor-associated peptides (TAP) to T cells. Overexpressed tumor associated antigens, mainly cancer-testis antigens (CTA), are outlined as essential targets for immunotherapy in oropharyngeal squamous cell carcinoma (OPSCC). This study assessed the degree to which presentation, gene expression, and antibody response (AR) of TAP, mainly CTA, are correlated in OPSCC patients to evaluate their potential as immunotherapy targets.
Exploring how the design and provision of digital self-management technology can improve the uptake by older adults with chronic kidney disease, diabetes and dementia: A modified e-Delphi study
Moody L, Wood E, Needham A, Booth A and Tindale W
As development and introduction of digital self-management technologies continues to increase, the gap between those who can benefit, and those who cannot correspondingly widens. This research aimed to explore the use of digital self-management technology by older adults with three highly-prevalent long-term conditions (chronic kidney disease, diabetes and dementia), and build expert consensus across the conditions on changes needed to improve effective usage. This qualitative research involved a modified e-Delphi Study. The Delphi panel was comprised of experts with personal, academic or clinical expertise related to one of the long-term conditions and/or the development and use of digital self-management technology. The e-Delphi involved a round of online semi-structured interviews followed by two rounds of a structured online survey. Fourteen experts participated in the study, with eleven of the fourteen completing all three rounds. Analysis of the interviews (round 1 of the Delphi) led to 7 main themes and 29 sub-themes. These were translated into 26 statements that formed the basis of the online survey questions. In the first administration of the survey (round 2) 19 statements reached consensus. After the second administration a further 6 statements reach consensus. The findings reflect expert consensus on barriers to the use of digital self-management by older adults with 3 different, but inter-related conditions, and identify ways in which the design and provision of such technologies could be improved to facilitate more effective use. It is concluded that both the design and the provision of technologies should consider a combination of individual, condition-specific and age-related requirements. By building a consensus on issues and potential strategies common across the three conditions, we aim to inform future research and practice and facilitate effective self-management by older adults.
Consistent condom use among Botswana's female population and associated factors
Mlandu C, Machisa M and Christofides N
Botswana is one of the countries severely impacted by the HIV/AIDS pandemic. Despite an extensive HIV prevention campaign, the incidence of HIV, particularly among women, remains high. Condoms play a significant role in preventing new HIV infections, although men and women do not consistently use them.
Efficacy and safety of a proposed omalizumab biosimilar compared to the reference product in the management of uncontrolled moderate-to-severe allergic asthma: a multicenter, phase III, randomized, double-blind, equivalency clinical trial
Ghanei M, Ghalebaghi B, Sami R, Torabizadeh M, Mirsadraee M, Amra B, Tavakol M, Raji H, Fallahpour M, Kiani A, Abedini A, Jabbari Azad F, Mahdaviani SA, Attaran D, Samet M, Tavana S, Haddadzadeh Shoushtari M, Nazari J, AghaeiMeybodi F, Fazlollahi MR, Ghasemi R, Sabzvari A, Kafi H and Idani E
Allergic asthma has a considerable burden on the quality of life. A significant portion of moderate-to-severe allergic asthma patients need omalizumab, an anti-immunoglobulin-E monoclonal antibody, as an add-on therapy. In this phase III clinical trial P043 (Zerafil, CinnaGen, Iran) efficacy, safety, and immunogenicity were compared with Xolair (the originator omalizumab). The primary outcome was the rate of protocol-defined asthma exacerbations.
Ceramide metabolism alterations contribute to Tumor Necrosis Factor-induced melanoma dedifferentiation and predict resistance to immune checkpoint inhibitors in advanced melanoma patients
Dufau C, Genais M, Mucher E, Jung B, Garcia V, Montfort A, Tosolini M, Clarke CJ, Medin JA, Levade T, Delord JP, Meyer N, Pancaldi V, Andrieu-Abadie N and Ségui B
Advanced cutaneous melanoma is a skin cancer characterized by a poor prognosis and high metastatic potential. During metastatic spread, melanoma cells often undergo dedifferentiation toward an invasive phenotype, resulting in reduced expression of microphthalmia-associated transcription factor (MITF)-dependent melanoma antigens and facilitating immune escape. Tumor Necrosis Factor (TNF) is known to be a key factor in melanoma dedifferentiation. Interestingly, accumulating evidence suggests that TNF may play a role in melanoma progression and resistance to immunotherapies. Additionally, TNF has been identified as a potent regulator of sphingolipid metabolism, which could contribute to melanoma aggressiveness and the process of melanoma dedifferentiation.
The longitudinal characterization of immune responses in COVID-19 patients reveals novel prognostic signatures for disease severity, patients' survival and long COVID
Noviello M, De Lorenzo R, Chimienti R, Maugeri N, De Lalla C, Siracusano G, Lorè NI, Rancoita PMV, Cugnata F, Tassi E, Dispinseri S, Abbati D, Beretta V, Ruggiero E, Manfredi F, Merolla A, Cantarelli E, Tresoldi C, Pastori C, Caccia R, Sironi F, Marzinotto I, Saliu F, Ghezzi S, Lampasona V, Vicenzi E, Cinque P, Manfredi AA, Scarlatti G, Dellabona P, Lopalco L, Di Serio C, Malnati M, Ciceri F, Rovere-Querini P and Bonini C
SARS-CoV-2 pandemic still poses a significant burden on global health and economy, especially for symptoms persisting beyond the acute disease. COVID-19 manifests with various degrees of severity and the identification of early biomarkers capable of stratifying patient based on risk of progression could allow tailored treatments.
Development and validation of a predictive model assessing the risk of sarcopenia in rheumatoid arthritis patients
Qu Y, Zhang L, Liu Y, Fu Y, Wang M, Liu C, Wang X, Wan Y, Xu B, Zhang Q, Li Y and Jiang P
Sarcopenia is linked to an unfavorable prognosis in individuals with rheumatoid arthritis (RA). Early identification and treatment of sarcopenia are clinically significant. This study aimed to create and validate a nomogram for predicting sarcopenia risk in RA patients, providing clinicians with a reliable tool for the early identification of high-risk patients.
Efgartigimod as a promising add-on therapy for myasthenic crisis: a prospective case series
Song J, Wang H, Huan X, Jiang Q, Wu Z, Yan C, Xi J, Zhao C, Feng H and Luo S
Efgartigimod is effective and well-tolerated in patients with anti-acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (MG). However, the therapeutic potential and the safety profile of efgartigimod in myasthenic crisis (MC) remained largely unknown.
Identifying risk and prognostic factors for synchronous liver metastasis in small bowel adenocarcinoma: a predictive analysis using the SEER database
Xu D, He Y, Liao C and Tan J
Small bowel adenocarcinoma (SBA) is a rare gastrointestinal malignancy with an increasing incidence and a high propensity for liver metastasis (LM). This study aimed to investigate the risk factors for synchronous LM and prognostic factors in patients with LM.
Association between endometriosis and arthritis: results from NHANES 1999-2006, genetic correlation analysis, and Mendelian randomization study
Xu H, Zou H, Wen Q, Xing X, Xu N and Wu S
Previous studies reported that endometriosis may have a higher risk of arthritis. However, it remains unclear whether the association between endometriosis and arthritis has genetic correlations, or the relationship is causal. Linkage Disequilibrium Score (LDSC) and Mendelian Randomization (MR) analyses use genetic variation as a natural experiment to explore genetic correlations and causal inferences from observational data, reducing unmeasured confounding factors.
Detection of autoantibodies to heat shock protein 70 in the saliva and urine of normal individuals
Sitko K, Mantej J, Bednarek M and Tukaj S
Cells exposed to stressors of various origin activate protective mechanisms that include the expression of heat shock proteins (Hsps)/molecular chaperones belonging to several families. Well-characterized inducible Hsp70 is present in all human cell-types and biological fluids, including blood, urine, and saliva. The presence of anti-Hsp70 autoantibodies in the serum of healthy individuals has already been confirmed, and their elevated titers positively correlated with the severity of several pathological conditions, including coeliac disease and dermatitis herpetiformis - a cutaneous manifestation of coeliac disease. Here, using an indirect enzyme-linked immunosorbent assay, we demonstrate, for the first time, that anti-Hsp70 autoantibodies are present in the saliva and urine of healthy individuals. Although the occurrence of anti-Hsp70 autoantibodies in the biological fluids of healthy individuals is intriguing, their physiological role is currently unknown. It is believed that antibodies reacting with self-molecules present in the serum of healthy individuals are part of natural autoantibody pool with multiple regulatory functions. On the other hand, some autoantibodies (e.g., typical of autoimmune bullous skin diseases or systemic lupus erythematosus) may be present before the onset of the disease and serve as specific predictive biomarkers. Therefore, we would like to initiate a discussion or future research direction on the use of anti-Hsp70 autoantibodies as a potential "biomarker" in the diagnosis or prediction of autoimmune diseases. Our findings can be considered in biomedical research to develop noninvasive, inexpensive and easy-to-use tests. Nevertheless, large-scale comparative studies should be initiated, involving the collection and analysis of biological samples such as saliva or urine from patients suffering from autoimmune diseases or other inflammatory or neoplastic diseases, to determine whether the levels of anti-Hsp70 autoantibodies are indeed elevated and whether they correlate with the clinical picture of any disease or established biomarkers.
Clinical, genomic and immune microenvironmental determinants of nivolumab response in head and neck squamous cell carcinoma
Tsujikawa T, Ohno K, Morita KI, Saburi S, Mitsuda J, Yoshimura K, Kimura A, Morimoto H, Ogi H, Shibata S, Akashi T, Kurata M, Imoto I, Shimizu Y, Kano S, Watanabe A, Yamazaki T, Asada Y, Hayashi R, Saito Y, Ozawa H, Tsukahara K, Oridate N, Sano D, Horii A, Ueki Y, Maruo T, Mukoyama N, Hanai N, Fukusumi T, Iwai H, Fujisawa T, Fujii T, Nibu KI, Iwae S, Ueda T, Chikuie N, Yasumatsu R, Matsuo M, Umeno H, Ono T, Masuda M, Toh S, Itoh K, Hirano S and Asakage T
In view of improving biomarkers predicting the efficacy of immunotherapy for head and neck squamous cell carcinoma (R/M HNSCC), this multicenter retrospective study aimed to identify clinical, tumor microenvironmental, and genomic factors that are related to therapeutic response to the anti- Programmed cell death protein 1 (PD-1) antibody, nivolumab, in patients with R/M HNSCC.
Editorial: Liquid biopsy in oncology: opportunity and challenges
Kumar A, Singh R, Arya N, Lueong S and Jain A
Association between inflammatory bowel disease and osteoporosis in European and East Asian populations: exploring causality, mediation by nutritional status, and shared genetic architecture
Kang J, Wu X, Li Y, Zhao S, Wang S and Yu D
While previous research has established an association between inflammatory bowel disease (IBD) and osteoporosis (OP), the nature of this association in different populations remains unclear.
Analysis of Risk Factors for Postoperative Deep Vein Thrombosis in Traumatic Spinal Fracture Complicated with Spinal Cord Injury
Yang D, Chen S, Zhuo C and Chen H
The purpose of this study is to investigate the risk factors for postoperative deep vein thrombosis (DVT) in patients with traumatic spinal fractures complicated with Spinal Cord Injury(SCI). We conducted a retrospective analysis of 110 patients with traumatic spinal fractures and SCI admitted to our hospital from March 2021 to April 2024. DVT was diagnosed using ultrasound. Patient history, general data, surgical data, laboratory tests, and thromboelastogram (TEG) results were collected. The patients were divided into a DVT group and a non-DVT group according to the results of ultrasound one week after surgery. The risk factors and diagnostic value were analyzed using binary logistic regression and receiver operating characteristic (ROC) curves in both univariate and multivariate analyses. Multivariate and ROC analysis results showed that D-dimer, lower extremity, duration of bedrest, and MA values of TEG were independent risk factors for DVT in SCI, with D-dimer having the highest diagnostic value (AUC = 0.883). The AUC values for lower extremity, duration of bedrest, and MA were 0.731, 0.750, and 0.625. In conclusion, Postoperative D-dimer > 5.065 mg/l, lower extremity < 3, duration of bedrest, and MA value of TEG are independent risk factors for postoperative DVT in SCI patients, D-dimer having the highest diagnostic value. When the above risk factors occur, clinicians need to be vigilant and take appropriate prevention and treatment measures.
Rural-Urban mild cognitive impairment comparison in West Michigan through EHR
Zhang X, Witteveen-Lane M, Skovira C, Dave AA, Jones JS, McNeely ER, Lawrence MR, Morgan DG, Chesla D and Chen B
Mild cognitive impairment (MCI) is a significant public health concern and a potential precursor to Alzheimer's disease (AD). This study leverages electronic health record (EHR) data to explore rural-urban differences in MCI incidence, risk factors, and healthcare navigation in West Michigan.
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