bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deceased Organ Donor HTLV Screening Practices Postelimination of Universal Screening in the United States
Authors: Yamauchi Junji , Raghavan Divya , Imlay Hannah , Jweehan Duha , Oygen Suayp , Marineci Silviana , Remport Adam , Hall Isaac E. , Molnar Miklos Z. 
Published: September 2024

Background.
In the United States, universal screening for human T-lymphotropic virus (HTLV) in deceased organ donors was discontinued in 2009. Since then, the transplant guideline suggests considering targeted screening. However, the outcomes of this change in HTLV screening have not been evaluated.

Methods.
Using the Organ Procurement and Transplantation Network database between 2010 and 2022, we analyzed the HTLV antibody screening frequency and seroprevalence in potential deceased organ donors and their correlations with HTLV infection risks, including race and high-risk behaviors for blood-borne pathogen infection. Although targeted screening has not been established for HTLV, we hypothesized that screening rates should correlate with the proportions of donors with infection risk if screening is targeted. We also evaluated the organ utilization of HTLV-seropositive donors.

Results.
Of 130 284 potential organ donors, 22 032 (16.9%) were tested for HTLV antibody. The proportion of donors tested for HTLV varied between Organ Procurement Organizations (median [interquartile range], 3.8% [1.0%–23.2%]; range, 0.2%–99.4%) and was not correlated to HTLV infection risks. There were 48 seropositive donors (0.22%), and at least 1 organ from 42 of these donors (87.5%) was transplanted. The number of organs recovered and transplanted per donor was significantly lower in HTLV-seropositive than in HTLV-negative donors (recovered, 2 [2–3] versus 3 [3–5], P < 0.001; transplanted, 2 [1–3] versus 3 [2–4], P < 0.001). However, HTLV-1 infection was not attributed as the cause of nonrecovery except for only 1 HTLV-seropositive donor.

Conclusions.
HTLV screening practices varied across the United States. Our findings suggest that targeted screening was not performed after the elimination of universal screening.
Accelerating Ligand Discovery for Insect Odorant Receptors
Authors: Comte Arthur , Lalis Maxence , Brajon Ludvine , Moracci Riccardo , Montagné Nicolas , Topin Jérémie , Jacquin Joly Emmanuelle , Fiorucci Sébastien 
Published: September 2024

AbstractOdorant receptors (ORs) are main actors of the insects peripheral olfactory system, making them prime targets for pest control through olfactory disruption. Traditional methods employed in the context of chemical ecology for identifying OR ligands rely on analyzing compounds present in the insect’s environment or screening molecules with structures similar to known ligands. However, these approaches can be time-consuming and constrained by the limited chemical space they explore. Recent advances in OR structural understanding, coupled with scientific breakthroughs in protein structure prediction, have facilitated the application of structure-based virtual screening (SBVS) techniques for accelerated ligand discovery. Here, we report the first successful application of SBVS to insect ORs. We developed a unique workflow that combines molecular docking predictions,in vivovalidation and behavioral assays to identify new behaviorally active volatiles for non-pheromonal receptors. This work serves as a proof of concept, laying the groundwork for future studies and highlighting the need for improved computational approaches. Finally, we propose a simple model for predicting receptor response spectra based on the hypothesis that the binding pocket properties partially encode this information, as suggested by our results onSpodoptera littoralisORs.
Thermal adaptation in worldwide collections of a major fungal pathogen
Authors: Miñana-Posada Silvia , Lorrain Cécile , McDonald Bruce A. , Feurtey Alice 
Published: September 2024

AbstractAdaptation to new climates poses a significant challenge for plant pathogens during range expansion, highlighting the importance of understanding their response to climate to accurately forecast future disease outbreaks. The wheat pathogenZymoseptoria triticiis ubiquitous across most wheat production regions distributed across diverse climate zones. We explored the genetic architecture of thermal adaptation using a global collection of 411Z. triticistrains that were phenotyped across a wide range of temperatures and then included in a genome-wide association study. Our analyses provided evidence for local thermal adaptation inZ. triticipopulations worldwide, with a significant positive correlation between bioclimatic variables and optimal growth temperatures. We also found a high variability in thermal performance amongZ. triticistrains coming from the same field populations, reflecting the high evolutionary potential of this pathogen at the field scale. We identified 69 genes putatively involved in thermal adaptation, including one high-confidence candidate potentially involved in cold adaptation. These results highlight the complex polygenic nature of thermal adaptation inZ. triticiand suggest that this pathogen is likely to adapt well when confronted with climate change.
Developmental transcriptomics inPristionchusreveals the logic of a plasticity gene regulatory network
Authors: Reich Shelley , Loschko Tobias , Jung Julie , Nestel Samantha , Sommer Ralf J. , Werner Michael S. 
Published: September 2024

AbstractDevelopmental plasticity enables the production of alternative phenotypes in response to different environmental conditions. While significant advances in understanding the ecological and evolutionary implications of plasticity have been made, understanding its genetic basis has lagged. However, a decade of genetic screens in the model nematodePristionchus pacificushas culminated in 30 genes which affect mouth-form plasticity. We also recently reported the critical window of environmental sensitivity, and therefore have clear expectations for when differential gene expression should matter. Here, we collated previous data into a gene-regulatory network (GRN), and performed developmental transcriptomics across different environmental conditions, genetic backgrounds, and mouth-form mutants to assess the regulatory logic of plasticity. We found that only two genes in the GRN (eud-1andseud-1/sult-1) are sensitive to the environment during the critical window. Interestingly, the time points of their sensitivity differ, suggesting that they act as sequential checkpoints. We also observed temporal constraint upon the transcriptional effects of mutating the GRN and revealed unexpected feedback between mouth-form genes. Surprisingly, expression ofseud-1/sult-1, but noteud-1, correlated with mouth form biases across different strains and species. Finally, a comprehensive analysis of all samples identified metabolism as a shared pathway for regulating mouth-form plasticity. These data are presented in a Shiny app to facilitate gene-expression comparisons across development in up to 14 different conditions. Collectively, our results suggest that mouth-form plasticity evolved a constrained, two-tiered logic to integrate environmental information leading up to the final developmental decision.
Inhibition of glutaminase elicits senolysis in therapy-induced senescent melanoma cells
Authors: Kim Justin , Brunetti Bryce , Kumar Ayanesh , Mangla Ankit , Honda Kord , Yoshida Akihiro 
Published: September 2024

AbstractThe cyclin D1-Cyclin-Dependent Kinases 4 and 6 (CDK4/6) complex is crucial for the development of melanoma. We previously demonstrated that targeting CDK4/6 using small molecule inhibitors (CDK4/6i) suppresses BrafV600Emelanoma growthin vitroandin vivothrough induction of cellular senescence. Clinical trials investigating CDK4/6i in melanoma have not yielded successful outcomes, underscoring the necessity to enhance the therapeutic efficacy of CDK4/6i. Accumulated research has shown that while senescence initially suppresses cell proliferation, a prolonged state of senescence eventually leads to tumor relapse by altering the tumor microenvironment, suggesting that removal of those senescent cells (in a process referred to as senolysis) is of clinical necessity to facilitate clinical response. We demonstrate that glutaminase 1 (GLS1) expression is specifically upregulated in CDK4/6i-induced senescent BrafV600Emelanoma cells. Upregulated GLS1 expression renders BrafV600Emelanoma senescent cells vulnerable to GLS1 inhibitor (GLS1i). Furthermore, we demonstrate that this senolytic approach targeting upregulated GLS1 expression is applicable even though those cells developed resistance to the BrafV600Einhibitor vemurafenib, a frequently encountered substantial clinical challenge to treating patients. Thus, this novel senolytic approach may revolutionize current CDK4/6i mediated melanoma treatment if melanoma cells undergo senescence prior to developing resistance to CDK4/6i. Given that we demonstrate that a low dose of vemurafenib induced senescence, which renders BrafV600Emelanoma cells susceptible to GLS1i and recent accumulated research shows many cancer cells undergo senescence in response to chemotherapy, radiation, and immunotherapy, this senolytic therapy approach may prove applicable to a wide range of cancer types once senescence and GLS1 expression are induced.Key pointsUpregulated GLS1 expression renders senescent BrafV600Emelanoma cells induced by CDK4/6 inhibitor (CDK4/6i) or vemurafenib susceptible to GLS1 inhibitor (GLS1i) even with BrafV600Einhibitor resistance. This senolytic therapy combining CDK4/6i and GLS1i provides insights into potential novel therapeutic strategies for metastatic melanoma and may be applicable to various types of cancers providing alternative therapy options.
PSMA+ Extracellular Vesicles are a Biomarker for SABR in Oligorecurrent Prostate Cancer Analysis from the STOMP-like and ORIOLE trial cohorts
Authors: Andrews Jack , Kim Yohan , Horjeti Edlira , Arafa Ali , Gunn Heather , De Bruycker Aurélie , Phillips Ryan , Song Daniel , Childs Daniel S. , Sartor Oliver A. , Orme Jacob J. , Chaudhuri Aadel A. , Tran Phuoc , Kiess Ana , Sutera Philip , Mercier Carole , Ost Piet , Park Sean S. , Lucien Fabrice 
Published: September 2024

AbstractPurposeTwo randomized clinical trials (STOMP and ORIOLE) demonstrated that stereotactic ablative radiotherapy (SABR) can prolong ADT-free survival or progression-free survival (PFS) in patients with metachronous oligometastatic prostate cancer (omCSPC) patients. While most omCSPC patients have a more modest delay in progression, a small subset achieves a durable response following SABR. We investigated the prognostic and predictive value of circulating PSMA-positive extracellular vesicles (PSMA+EV) and prostate specific antigen (PSA) in a biomarker correlative study using blood samples from three independent patient cohorts.MethodsPlasma samples from 46 patients on the ORIOLE trial and 127 patietns on the STOMP trial protocol with omCSPC patients treated with SABR. Pre-SABR PSMA+EV levels (EVs/ml) were measured by nanoscale flow cytometry. Kaplan-Meier curves and logistic regression models were used to determine the association of PSMA+EV and PSA levels with clinical outcomes.ResultsIn the pooled cohorts, median bPFS were 26.1 and 15.0 months (p=0.005) and median rPFS were 36.0 and 25.0 months (p=0.003) for PSMA+EV low and high groups, respectively. The combination of pre-SABR low levels of both PSMA+EV and PSA was associated with lower risk of radiographic progression (HR=0.34, 95% CI: 0.18-0.58, p=0.0002). In the ORIOLE cohort, which included both a SABR arm and an observation arm, low PSMA+EV was predictive of benefit from SABR (p=0.012).ConclusionsPSMA+EV is a novel prognostic and predictive biomarker of radiographically occult tumor burden in omCSPC. PSMA+EV may inform clinical decisions regarding which patients achieve a durable benefit from consolidative SABR alone.
Leveraging an Online Dashboard to Inform on Infectious Disease Surveillance: A case Study of COVID-19 in Kenya
Authors: Mwanga Mike J. , Guzman-Rincon Laura M. , Kingwara Leonard , Odhiambo Don B. , Gathuri Henry , Lambisia Arnold , Mwita John Morobe , Moraa Edidah , Kutima Bernadette , Gitonga John , Mugo Daisy , Agoti Charles N. , Nyagwange James , Warimwe George , Oyier Isabella , Nokes D. James , Agweyu Ambrose , Kagucia E Wangeci , Etyang Anthony , Kiiru John , Githinji George 
Published: September 2024

AbstractA multi-pronged approach to combating the COVID-19 pandemic in Kenya resulted in the formation of multidisciplinary research initiatives including genomic sequencing, syndromic surveillance, sero-surveillance, vaccination, and mathematical modelling. These initiatives generated an overwhelming amount of data that posed a challenge to researchers and public health officials, to effectively manage, analyse and promptly interpret for immediate pandemic response. As a result, there was demand for a platform to collate and integrate these datasets with interpretable findings to aid in pandemic management. In response, we developed a web-based dashboard, and integrated multidisciplinary datasets collected by the Ministry of Health-Kenya (MoH-K) and other research organizations, to support surveillance and monitoring of COVID-19 in Kenya. The developed dashboard combines genomics, epidemiological, seroprevalence, modelling, vaccination, syndromic and phylogenetic data and provides real-time updates to the public and health sector experts. The dashboard provides temporal trends of reported COVID-19 cases, fatalities, variants, and vaccination, in addition to summary reports from multiple cross-sectional seroprevalence studies and ongoing facility-based inpatient syndromic surveillance from 15 health facilities across Kenya. This is the first detailed interactive dashboard in Kenya that combines multiple datasets from a disease outbreak to provide valuable insights to researchers, health policy makers, the media and public not only during pandemic but also during routine surveillance. This resource is a model for digital platform for infectious disease surveillance and for informing public health planning and intervention.Dashboard Linkhttps://kcd.kemri-wellcome.org/
INCIDENCE OF BENIGN PROSTATIC HYPERPLASIA IN TESTICULAR CANCER SURVIVORS IN THE VETERANS AFFAIRS HEALTH SYSTEM
Authors: Pandit Kshitij , Morgan Kylie , Riviere Paul , Cortez-Ryes Josue , Meagher Margaret , Nelson Tyler , Puri Dhruv , Yodkhunnatham Nuphat , Millard Frederick , Mckay Rana R. , Rose Brent , Bagrodia Aditya 
Published: September 2024

AbstractTestosterone and prostatic inflammation have been postulated to influence the development of benign prostatic hyperplasia (BPH). Our study aims to evaluate the incidence of BPH in Testicular Cancer (TCa) survivors, focusing on the impact of chemotherapy and post TCa diagnosed hypogonadism. We conducted a retrospective cohort analysis of US veterans diagnosed with TCa between 1990 to 2021, using the Veterans affairs database. BPH was defined using International Classification of Diseases (ICD) codes, Current Procedural Terminology (CPT) codes, or a 6-month prescription of medications. Associations with BPH were analysed, stratifying the cohort by receipt of chemotherapy and presence of hypogonadism. Multivariable cox regression models were used to determine statistical significance (p-value <0.05). Our cohort included 2038 TCa survivors with a median age at diagnosis of 41 years. On multivariable cox regression analysis, receipt of chemotherapy wasn’t significantly associated with incidence of BPH (p-value= 0.13). When stratified by diagnosis of hypogonadism prior to BPH, no significant associations were found on univariable (p=0.81) as well as multivariable (p=0.65) analyses. In the multivariable model, age at diagnosis was significantly associated with an increased incidence of BPH (Hazard ratio: 1.06, p<0.001). Our findings demonstrate that age is a significant factor associated with development of BPH in this population, while suggesting that chemotherapy for TCa and hypogonadism might not substantially alter the development of BPH.Patient summaryIn this study, we looked at whether testicular cancer survivors are more likely to develop an enlarged prostate (Benign Prostatic Hyperplasia), especially if they received chemotherapy or had low testosterone afterward. We found that age, rather than cancer treatment or testosterone levels, was the main factor linked to developing an enlarged prostate.
In computer explore The neutralization mechanism of Amubarvimab and Romlusevimab against SARS-COV-2 mutants
Authors: Huan Xinkang , Gao Hongwei 
Published: September 2024

ABSTRACTSince the end of 2019, The coronavirus disease 2019 (COVID-19) has been endemic worldwide for three years, causing more than 6.95 million deaths and having a massive impact on the global political economy. With time, the Severe acute respiratory syndrome coronavirus 2(SARS-COV-2) is also constantly mutating. Mutations lead to stronger infectivity or virulence of the virus, and some monoclonal antibodies against wild-type SARS-COV-2 are also challenging to play a role. Amubarvimab and Romlusevimab were originally developed against wild-type SARS-COV-2; however, these monoclonal antibodies’ neutralizing efficacy and mechanism against these mutants are unknown. In this study, the binding ability of Amubarvimab and Romlusevimab to 7 mutant strains were tested by computer method and the interaction mechanism was explored. Our experimental data show that Amubarvimab can effectively bind most mutations and maintain the stability of the complexes mainly through hydrogen bond interaction; However, the binding efficiency of Romlusevimab was lower than that of Amubarvimab, and the stability of the complexes was maintained mainly through electrostatic interaction. Both Amubarvimab and Romlusevimab show low binding potency against E406W and Q498Y mutations, so there is a certain probability of immune escape in the face of variants carrying E406W and Q498Y mutations when Amubarvimab and Romlusevimab are used in combination.
Whole-exome sequencing study of opioid dependence offers novel insights into the contributions of exome variants
Authors: Wang Lu , Nuñez Yaira Z. , Kranzler Henry R. , Zhou Hang , Gelernter Joel 
Published: September 2024

AbstractOpioid dependence (OD) is epidemic in the United States and it is associated with a variety of adverse health effects. Its estimated heritability is ∼50%, and recent genome-wide association studies have identified more than a dozen common risk variants. However, there are no published studies of rare OD risk variants. In this study, we analyzed whole-exome sequencing data from the Yale-Penn cohort, comprising 2,100 participants of European ancestry (EUR; 1,321 OD cases) and 1,790 of African ancestry (AFR; 864 cases). A novel low-frequency variant (rs746301110) in theRUVBL2gene was identified in EUR (p=6.59×10-10). Suggestive associations (p<1×10-5) were observed inTMCO3in EUR, inNEIL2andCFAP44in AFR, and inFAM210Bin the cross-ancestry meta-analysis. Gene-based collapsing tests identifiedSLC22A10,TMCO3,FAM90A1,DHX58,CHRND,GLDN,PLAT,H1-4,COL3A1,GPHB5andQPCTLas top genes (p<1×10-4) with most associations attributable to rare variants and driven by the burden of predicted loss-of-function and missense variants. This study begins to fill the gap in our understanding of the genetic architecture of OD, providing insights into the contribution of rare coding variants and potential targets for future functional studies and drug development.
Hospital-onset bacteraemia and fungaemia as a novel automated surveillance indicator: results from four European university hospitals
Authors: Aghdassi Seven J.S. , van der Werff Suzanne D. , Catho Gaud , Brekelmans Manon , Peña Diaz Luis A. , Buetti Niccolò , Rüther Ferenc D. , Teixeira Daniel Dinis , Sjöholm Daniel , Nauclér Pontus , Behnke Michael , van Mourik Maaike S.M. 
Published: September 2024

AbstractBackgroundConventional manual surveillance of healthcare-associated infections is labour-intensive and therefore often restricted to areas with high-risk patients. Fully automated surveillance of hospital-onset bacteraemia and fungaemia (HOB) may facilitate hospital-wide surveillance.AimTo develop an algorithm and minimal dataset (MDS) required for automated surveillance of HOB and apply it to real-life routine data in four European hospitals.MethodsThrough consensus discussion a HOB definition with MDS suitable for automated surveillance was developed and applied in a retrospective multicentre observational study including all admitted adult patients (2018-2022). HOB was defined as a positive blood culture with a recognised pathogen two or more days after hospital admission. For common commensals, two blood cultures with the same commensal within two days were required. Annual HOB rates were calculated per 1,000 patient days for the hospital and for intensive care units (ICU) and non-ICU.ResultsHOB rates were comparable between the four hospitals (1.0 to 2.2 per 1,000 patient days). HOB rates were substantially higher in ICU than non-ICU across the four hospitals, and HOB with common commensals accounted for 14.8-28.2% of all HOB. HOB rates per 1,000 patient days were rather consistent over time, but were higher in 2020 and 2021. HOB caused by Staphylococcus aureus accounted for 8.4-16.0% of all HOB.ConclusionAutomated HOB surveillance using a common definition was feasible and reproducible across four European hospitals. Future studies should investigate clinical relevance and preventability of HOB, and focus on strategies to make the automated HOB metric an actionable infection control tool.
Electroencephalographic (EEG) Changes Accompanying Normal Breathing of Concentrated Oxygen (Hyperoxic Ventilation) by Healthy Adults: A Systematic Review
Authors: Barnes Lachlan D. , Hallum Luke E. , Vrijdag Xavier C.E. 
Published: September 2024

AbstractIntroductionDivers often increase their fraction of inspired oxygen (FiO2) to decrease their risk of decompression sickness. However, breathing concentrated oxygen can cause hyperoxia, and central nervous system oxygen toxicity (CNS-OT). This study aims to review the literature describing hyperoxic ventilation’s effect on the electroencephalogram (EEG), thus exploring the potential for real-time detection of impending CNS-OT seizure.MethodsWe searched Medline, Embase, Scopus, and Web of Science for articles that reported EEG measures accompanying hyperoxic ventilation (FiO2= 1.0) in healthy participants. We included peer-reviewed journal articles, books, and government reports with no language or date restrictions. Randomised controlled trials and cross-over studies were included; case reports were excluded. We used the Newcastle-Ottawa scale to evaluate evidence quality.ResultsOur search strategy returned 1025 unique abstracts; we analysed the full text of 40 articles; 22 articles (16 studies) were included for review. Study cohorts were typically small, and comprised of male non-divers. We discovered a variety of EEG analysis methods: studies performed spectral analysis (n= 12), the analysis of sensory-evoked potentials (n= 4), connectivity/complexity analysis (n= 3), source localization (n= 1), and expert qualitative analyses (n= 4). Studies of severe exposures (long duration at hyperbaric pressure) typically reported qualitative measures, and studies of mild exposures typically reported quantitative measures.ConclusionsThere is a need for a large randomised controlled trial (RCT) reporting quantitative measures to better understand hyperoxic ventilation’s effect on EEG, thus enabling the development of real-time monitoring of CNS-OT risk.