bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scoring consistency checks for the Clinician Administered PTSD Scale (CAPS-IV & CAPS-V)
Authors: Rabinowitz Jonathan , Rabinowitz Alon A. , Freedman Sara 
Published: July 2024

AbstractBackgroundThe CAPS is regarded as the “gold standard” in PTSD assessment. It is a structured interview that yields a categorical diagnosis of PTSD and also a measure of the severity of PTSD symptoms. Since a PTSD diagnosis in some settings could be connected to getting benefits, scoring inconsistencies may be more abundant with this rating scale as they not only reflect raters carelessness but intentional inaccurate reporting by the subject.ObjectiveThe objective of the current effort was to derive rating consistency flags for the CAPS-IV.MethodsWe deconstructed CAPS scoring instructions and anchors to identify potential scoring inconsistency flags. These inconsistency flags were reviewed and confirmed by expert raters. To test the ability of the flags to identify careless responses the flags were applied to Monte Carlo simulated data of 100,000 CAPS administrations.ResultsTwelve flags were derived (presented in Table 1). Two flags applied to most of the 17 symptom items (Flag 1: Frequency=0 & Intensity>0 and Flag 2: Frequency>0 & Intensity=0). The remaining 10 flags pertained to individual items. Five flags were rated as “High” flags, representing very probably or definitely incorrect rating, one as medium, reflecting probably incorrect rating. Flags were raised for 95% of the Monte Carlo simulated CAPS administrations, 78% of the administrations had 4 or more flags and 60% 5 or more.ConclusionsScoring consistency flags for the CAPS may be useful in the quest to improve reliability and validity of clinical trials. Modified flags are currently being developed to cover the CAPS-V. Further testing of flags using clinical trial data is planned to examine their potential impact on signal detection.
The Sexual Harassment of Medical Students – Victims, Experiences, Impact, and Barriers to Reporting
Authors: Menshawey Rahma , Menshawey Esraa 
Published: July 2024

AbstractBackgroundSexual harassment of medical students is a growing concern. Sexual harassment is an unethical and illegal conduct. Yet, medical students are at a unique disadvantage to be victimized to due organizational failures, fear of retaliation, and unique power dynamics. As more women, minorities, and vulnerable groups enter the medical field, the time is ripe for proactive measures to ensure their empowerment and protect in light of such heinous and harmful acts.Main body of the abstractOriginal research studies, which examined the sexual harassment of medical students were identified on the PubMed database using the key terms, “sexual harassment”, and “medical students”. A total of 36 studies were identified. The purpose of this review is to highlight the key findings in the original research literature on the sexual harassment of medical students, and to identify themes in hopes to inspire progressive solutions to embolden student safety.Short conclusionThere is a growing global body of literature that has examined the sexual harassment experiences of medical students. Themes across the studies reveal a wide array of experiences. Medical students, especially females, are faced with harassment from professors, colleagues, and patients. The impact of harassment is far reaching, and includes depression, post-traumatic stress disorder, loss of concentration and academic interests, changing specialty of interest and relocation. There is a number of barriers to reporting these events, notably including a lack of institutional response, lack of time to go forward with a complaint, fear of retaliation and career impact. Proactive measures are needed to protect the students and embolden them and provide them with safe and accessible means to reporting these events, as well as ensuring adequate responses to reports on the institutional level, and continued emotional and career support are needed.
The Open Pediatric Cancer Project
Authors: Geng Zhuangzhuang , Wafula Eric , Corbett Ryan J. , Zhang Yuanchao , Jin Run , Gaonkar Krutika S. , Shukla Sangeeta , Rathi Komal S. , Hill Dave , Lahiri Aditya , Miller Daniel P. , Sickler Alex , Keith Kelsey , Blackden Christopher , Chroni Antonia , Brown Miguel A. , Kraya Adam A. , Koschmann Carl J. , Aldape Kenneth , Huang Xiaoyan , Rood Brian R. , Mason Jennifer L. , Trooskin Gerri R. , Abdullaev Zied , Wang Pei , Zhu Yuankun , Farrow Bailey K. , Farrel Alvin , Dybas Joseph M. , Zhong Chuwei , Van Kuren Nicholas , Zhang Bo , Santi Mariarita , Phul Saksham , Chinwalla Asif T , Resnick Adam C. , Diskin Sharon J. , Tasian Sarah , Stefankiewicz Stephanie , Maris John M. , Ennis Brian M. , Lueder Matthew R. , Naqvi Ammar S. , Coleman Noel , Ma Weiping , Taylor Deanne , Rokita Jo Lynne 
Published: July 2024

AbstractBackgroundIn 2019, the Open Pediatric Brain Tumor Atlas (OpenPBTA) was created as a global, collaborative open-science initiative to genomically characterize 1,074 pediatric brain tumors and 22 patient-derived cell lines. Here, we extend the OpenPBTA to create the Open Pediatric Cancer (OpenPedCan) Project, a harmonized open-source multi-omic dataset from 6,112 pediatric cancer patients with 7,096 tumor events across more than 100 histologies. Combined with RNA-Seq from the Genotype-Tissue Expression (GTEx) and The Cancer Genome Atlas (TCGA), OpenPedCan contains nearly 48,000 total biospecimens (24,002 tumor and 23,893 normal specimens).FindingsWe utilized Gabriella Miller Kids First (GMKF) workflows to harmonize WGS, WXS, RNA-seq, and Targeted Sequencing datasets to include somatic SNVs, InDels, CNVs, SVs, RNA expression, fusions, and splice variants. We integrated summarized CPTAC whole cell proteomics and phospho-proteomics data, miRNA-Seq data, and have developed a methylation array harmonization workflow to include m-values, beta-vales, and copy number calls. OpenPedCan contains reproducible, dockerized workflows in GitHub, CAVATICA, and Amazon Web Services (AWS) to deliver harmonized and processed data from over 60 scalable modules which can be leveraged both locally and on AWS. The processed data are released in a versioned manner and accessible through CAVATICA or AWS S3 download (from GitHub), and queryable through PedcBioPortal and the NCI’s pediatric Molecular Targets Platform. Notably, we have expanded PBTA molecular subtyping to include methylation information to align with the WHO 2021 Central Nervous System Tumor classifications, allowing us to create research-grade integrated diagnoses for these tumors.ConclusionsOpenPedCan data and its reproducible analysis module framework are openly available and can be utilized and/or adapted by researchers to accelerate discovery, validation, and clinical translation.
Engineering programmable CAR-T cells with tunable controls as fail-safe mechanisms during cancer immunotherapy
Authors: Dogan Mikail , Kozhaya Lina , Placek Lindsey , Karhan Ece , Yigit Mesut , Mohammed Christina , Zhao Qi , Unutmaz Derya 
Published: July 2024

AbstractChimeric antigen receptor (CAR) T-cell therapies have demonstrated remarkable efficacy in treating various cancers, but significant risks of severe adverse effects remain. In this study, we present a synthetic biology toolbox for engineering CAR-T cells with tunable and controllable features to mitigate these risks. Using this toolbox, we programmed cytotoxic CAR-T cells to be turned on and off using synthetic genes with tetracycline response elements, referred to as iOnCAR and iOffCAR. We achieved temporal regulation of CAR expression using the synthetic Notch receptor system and “AND-gate” programs, which allow for additional control using doxycycline. We also engineered cooperation among T cells through CD4 help to CD8 T cells in targeting cancer cells via synthetic Notch receptors controlled by doxycycline treatment. Additionally, we developed a T cell fratricide system by triggering a genetic “Battle Royale” mechanism that enables CAR-T cells to eliminate each other. In this system, surviving T cells become activated, proliferate, and display high cytotoxicity to target cells. In conclusion, our synthetic biology toolbox provides targeted fail-safe solutions for improving the safety and potency of CAR-T cell therapies by integrating different genetic circuits with a commonly used antibiotic.
Atomistic Prediction of Structures, Conformational Ensembles and Binding Energetics for the SARS-CoV-2 Spike JN.1, KP.2 and KP.3 Variants Using AlphaFold2 and Molecular Dynamics Simulations: Mutational Profiling and Binding Free Energy Analysis Reveal Epistatic Hotspots of the ACE2 Affinity and Immune Escape
Authors: Raisinghani Nishank , Alshahrani Mohammed , Gupta Grace , Verkhivker Gennady 
Published: July 2024

AbstractThe most recent wave of SARS-CoV-2 Omicron variants descending from BA.2 and BA.2.86 exhibited improved viral growth and fitness due to convergent evolution of functional hotspots. These hotspots operate in tandem to optimize both receptor binding for effective infection and immune evasion efficiency, thereby maintaining overall viral fitness. The lack of molecular details on structure, dynamics and binding energetics of the latest FLiRT and FLuQE variants with the ACE2 receptor and antibodies provides a considerable challenge that is explored in this study. We combined AlphaFold2-based atomistic predictions of structures and conformational ensembles of the SARS-CoV-2 Spike complexes with the host receptor ACE2 for the most dominant Omicron variants JN.1, KP.1, KP.2 and KP.3 to examine the mechanisms underlying the role of convergent evolution hotspots in balancing ACE2 binding and antibody evasion. Using the ensemble-based mutational scanning of the spike protein residues and computations of binding affinities, we identified binding energy hotspots and characterized molecular basis underlying epistatic couplings between convergent mutational hotspots. The results suggested that the existence of epistatic interactions between convergent mutational sites at L455, F456, Q493 positions that enable to protect and restore ACE2 binding affinity while conferring beneficial immune escape. To examine immune escape mechanisms, we performed structure-based mutational profiling of the spike protein binding with several classes of antibodies that displayed impaired neutralization against BA.2.86, JN.1, KP.2 and KP.3. The results confirmed the experimental data that JN.1, KP.2 and KP.3 harboring the L455S and F456L mutations can significantly impair the neutralizing activity of class-1 monoclonal antibodies, while the epistatic effects mediated by F456L can facilitate the subsequent convergence of Q493E changes to rescue ACE2 binding. Structural and energetic analysis provided a rationale to the experimental results showing that BD55-5840 and BD55-5514 antibodies that bind to different binding epitopes can retain neutralizing efficacy against all examined variants BA.2.86, JN.1, KP.2 and KP.3. The results support the notion that evolution of Omicron variants may favor emergence of lineages with beneficial combinations of mutations involving mediators of epistatic couplings that control balance of high ACE2 affinity and immune evasion.
Association of Alzheimer’s disease polygenic risk score with concussion severity and recovery metrics
Authors: Dybing Kaitlyn M. , McAllister Thomas W. , Wu Yu-Chien , McDonald Brenna C. , Broglio Steven P. , Mihalik Jason P. , Guskiewicz Kevin M. , Goldman Joshua T. , Jackson Jonathan C. , Risacher Shannon L. , Saykin Andrew J. , Nudelman Kelly N. H. 
Published: July 2024

AbstractIdentification of genetic alleles associated with both Alzheimer’s disease (AD) and concussion severity/recovery could help explain the association between concussion and elevated dementia risk. However, there has been little investigation into whether AD risk genes associate with concussion severity/recovery, and the limited findings are mixed. We used AD polygenic risk scores (PRS) andAPOEgenotypes to investigate any such associations in the NCAA-DoD Grand Alliance CARE Consortium (CARE) dataset. We assessed six outcomes in 931 total participants. The outcomes were two concussion recovery measures (number of days to asymptomatic status, number of days to return to play (RTP)) and four concussion severity measures (scores on SAC and BESS, SCAT symptom severity, and total number of symptoms). We calculated PRS using a published score [1] and performed multiple linear regression (MLR) to assess the relationship of PRS with the outcomes. We also used t-tests and chi-square tests to examine outcomes byAPOEgenotype, and MLR to analyze outcomes in European and African genetic ancestry subgroups. Higher PRS was associated with longer injury to RTP in the normal RTP (<24 days) subgroup (p= 0.024), and one standard deviation increase in PRS resulted in a 9.89 hour increase to the RTP interval. There were no other consistently significant effects, suggesting that high AD genetic risk is not strongly associated with more severe concussions or poor recovery in young adults. Future studies should attempt to replicate these findings in larger samples with longer follow-up using PRS calculated from diverse populations.
Perceptions of Water Security and Climate Change in Lima, Peru: Qualitative Study of Mothers and Healthcare Providers
Authors: Morales Danna Obregon , Ramos Karen , Jauregui Elena , Dueñas Milagros , Rumaldo Nancy , Gogia Shruti , Lecca Leonid , Shin Sonya S. 
Published: July 2024

AbstractBackgroundWater insecurity, a global public health crisis, will be intensified by climate change. In coastal Peru, little is known about the health effects of water insecurity from a community perspective. Understanding first-hand experiences and perceptions of mothers and healthcare providers can inform strategies to mitigate the effects of water insecurity and climate change on health outcomes and health disparities.MethodsThis qualitative study took place in 2023 in Carabayllo, the Northernmost region of Lima, Peru comprised of urban and rural communities. We conducted six focus groups with 10 pregnant women and 23 mothers of children ages 0 to 10, as well as individual interviews with 22 healthcare providers. Data were analyzed through rapid qualitative analysis combining deductive and inductive methods.Principal findingsWater insecurity was common among community members and was normalized as part of daily life. Access to water varied based on socioeconomic status and geography. Perceived health impacts were primarily related to hygiene and sanitation (e.g. diarrheal disease), water storage (dengue), and longer-term effects such as nutrition and child development. Respondents agreed that climate change would exacerbate water insecurity and endorsed strategies to take action.Conclusions and significanceThe lived experiences of water insecurity and its health impacts in Lima, Peru highlight the importance of mobilizing community stakeholders, health systems and local government to increase water security and support healthcare facilities and communities on water conservation and climate preparedness efforts.
Cervical mucosal inflammation expands functional polymorphonuclear myeloid-derived suppressor cells
Authors: Pieren Daan K.J. , Benítez-Martínez Aleix , Descalzo Vicente , Arando Maider , Álvarez-López Patricia , Garcia-Perez Jorge N. , Massana Núria , Castellón Júlia , Hoyos-Mallecot Yannick , Alvárez-Sierra Daniel , Ramírez-Serra Clara , Rodriguez Nuria Laia , Mañalich-Barrachina Laura , Centeno-Mediavilla Cristina , Castellví Josep , Falcó Vicenç , Buzón María J. , Genescà Meritxell 
Published: July 2024

AbstractThe mucosal immune system plays a fundamental role in maintaining microbial balance. Microbial imbalance in the female genital tract increases the risk for adverse health outcomes in women and may increase susceptibility to genital tract infections. Among different relevant immune subsets, myeloid-derived suppressor cells (MDSCs) remain understudied in the context of female genital tract conditions. Here we show that frequency of polymorphonuclear (PMN-) MDSCs increased in the cervical mucosa of women withChlamydia trachomatis, bacterial vaginosis, or with a coinfection, but not in women with human papillomavirus. Mucosal PMN-MDSC frequencies correlated with mucosal IL-1β inC. trachomatispatients and ex vivoexposure of cervical tissue toC. trachomatiselevated both PMN-MDSC frequencies and IL-1β secretion. Likewise, exposure of cervical tissue to cervicovaginal lavage fluid fromC. trachomatisand bacterial vaginosis patients also enhanced PMN-MDSC frequencies. Lastly, cervical MDSCs expressed suppressive mediators and functionally suppressed cytotoxic T-cell responses. Our study identifies IL-1β-stimulated PMN-MDSCs as an immune suppressive mediator in female genital tract infections, potentially contributing to susceptibility to acquiring secondary infections at this site.
Medical Findings in Infants Prenatally Identified with Sex Chromosome Trisomy in Year One of Life
Authors: Tartaglia Nicole , Davis Shanlee , Howell Susan , Bothwell Samantha , Nocon Kayla , Kowal Karen , Ikomi Chijioke , Keene Andrew , Reynolds Victoria , Berglund Agnethe , Ross Judith 
Published: July 2024

ABSTRACTBACKGROUND AND OBJECTIVESex chromosome trisomies (SCT), including XXY, XYY, and XXX syndromes, have been historically underdiagnosed. Noninvasive prenatal cell-free DNA screening has significantly increased identification of these conditions, leading to a need for pediatric care for a growing population of newborns with SCT. Our goal was to analyze and compare perinatal features, medical diagnoses, and physical features in infants with prenatal identification of SCT conditions through the first year of life.METHODSThe eXtraordinarY Babies Study is an ongoing, prospective natural history study of prenatally identified children with SCT conducted by interdisciplinary teams in Colorado and Delaware. Participants were enrolled prior to 12 months of age and had pregnancy, birth, medical histories, and physical exams completed by board-certified pediatricians at 2, 6, and/or 12-month visits. Descriptive statistics were followed by comparisons between SCT groups using t-tests or ANOVA, Fisher exact, and correlations between medical features with alpha of 0.05. Relative risks were calculated compared to general population rates.RESULTS327 infants were included in the analysis (XXY=195, XXX=79, XYY=53). Major congenital anomalies were rare (1.7%). Relative risk compared to general population was elevated for breastfeeding difficulties (51.7%;RR 2.7), positional torticollis (28.2%;RR 7.2), eczema (48.0%;RR 3.5), food allergies (19.3%;RR 2.4), constipation requiring intervention (33.9%;RR 7.6), small cardiac septal defects (7.7%;RR 17.2), and structural renal abnormalities (4.4%;RR 9.7). Inpatient hospitalization was required for 12.4%, with 59.5% of hospitalizations attributable to respiratory infections.DISCUSSIONThese findings of medical conditions with a higher prevalence can inform anticipatory guidance and medical management for pediatricians caring for infants with SCT.Article SummaryMedical findings in largest cohort of prenatally identified infants with XXY, Trisomy X, and XYY from birth to 12 months and implications for pediatric care.What’s Known on This SubjectOne in ∼500 individuals have an extra X or Y chromosome, or sex chromosome trisomy (SCT). Prenatal screening is now routinely identifying SCT, however there are few studies to guide perinatal and infant care for these individuals.What This Study AddsThis prospective observational study presents medical features for 327 infants with prenatally identified SCT from birth through the first year of life. Results identify where proactive screenings and/or interventions may be warranted for infants with SCT.
Application of REDECA Framework to Improve Safety and Health of Agricultural Tractor Drivers
Authors: Ashrafi Negin , Alaei Kamiar , Placencia Greg , Pishgar Maryam 
Published: July 2024

AbstractIntroduction:Despite tremendous efforts, including research, teaching, and extension, toward improving the safety of agricultural tractor drivers, the number of incidents related to agricultural tractor drivers has not declined. This evidence points out an urgent need to explore artificial intelligence (AI) solutions to improve the safety of tractor drivers.Methods:This paper uses 171 Fatality Assessment and Control Evaluation (FACE) reports related to tractor drivers and a new framework called Risk Evolution, Detection, Evaluation, and Control of Accidents (REDECA) to identify existing AI solutions and specific areas where AI solutions are missed and can be developed to reduce incidents and recovery time. Fatality reports of tractor drivers were categorized into six main categories, including run over, pinned by, fall, others (fire and crashes), roll over, and overturn. Each category was then subcategorized based on similarities of incident causes in the reports.Results:The application of the REDECA framework revealed potential AI solutions that could improve the safety of tractor drivers. In all categories, the REDECA framework lacks AI solutions for three elements, including the probability of reducing recovery time in R3, detecting changes between R2 and R3, and intervention to send workers to R2. Except for the run over category, all other categories were missing AI solutions for interventions to prevent entry to the R3 element of the REDECA. In addition, the fall, roll over, and overturn categories lacked AI intervention that minimized damage and recovery in R3.Conclusions:The outcome of this study shows an urgent need to develop AI solutions to improve tractor driver safety.
The Effect of Medical Therapy on Reducing the Risk of Pacing Induced Cardiomyopathy
Authors: Agha Mahdi S , Schaich Christopher L , Rikhi Rishi , Hari Krupal , Bodziock George , Bhave Prashant 
Published: July 2024

AbstractBackgroundHigh right ventricular (RV) pacing burden can result in pacing-induced cardiomyopathy (PICM).ObjectivesTo investigate whether ACE inhibitors (ACEI), angiotensin receptor blockers (ARB), and beta blockers (BB) reduce the risk of PICM in patients with high RV pacing burden.MethodsThis was a single center, retrospective study which included patients with normal ejection fraction (EF) and complete heart block who underwent pacemaker implantation between 1992 and 2013. The medical therapy group included patients who received ACEI/ARB, BB, or combination of these classes. The control group received neither ACEI/ARB nor BB. The primary endpoint was PICM, defined as upgrade to a biventricular device or reduction in EF to ≤40% without another etiology identified. Fine-Gray subdistribution hazard models accounting for death as a competing risk were used to determine the relationship between medical therapy (ACEI/ARB, BB, or combination) and cumulative incidence of PICM.ResultsThe study included 642 patients (mean [SD] age 71 [14] years; 51% women). Over 10 years of follow-up, 76 (11.8%) patients received ACEI/ARB therapy only; 49 (7.6%) received BB therapy only; and 86 (13.4%) were exposed to both. PICM occurred in 10 of 211 patients in the medical therapy group (4.7%) and in 30 of 431 in the control group (7.0%). In adjusted analyses weighted for group-switching, the risk of PICM was significantly lower in the medical therapy group compared to the control group (HR 0.59, 95% CI 0.45 – 0.77). Patients exposed to combination therapy had the lowest risk (HR 0.46, 95% CI 0.31 – 0.69).ConclusionIn patients with high RV pacing burden, BB therapy alone or in combination with ACEI/ARBs appears to reduce the risk of PICM within 10 years of pacemaker implantation.