bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pan-viral ORFs discovery using Massively Parallel Ribosome Profiling
Authors: Weingarten-Gabbay Shira , Bauer Matthew R. , Stanton Alexandra C. , Klaeger Susan , Verzani Eva K. , López Daniel , Clauser Karl R. , Carr Steven A. , Abelin Jennifer G. , Rice Charles M. , Sabeti Pardis C. 
Published: September 2023

ABSTRACTUnveiling the complete proteome of viruses is crucial to our understanding of the viral life cycle and interaction with the host. We developed Massively Parallel Ribosome Profiling (MPRP) to experimentally determine open reading frames (ORFs) in 20,170 designed oligonucleotides across 679 human-associated viral genomes. We identified 5,381 ORFs, including 4,208 non-canonical ORFs, and show successful detection of both annotated coding sequences (CDSs) and reported non-canonical ORFs. By examining immunopeptidome datasets of infected cells, we found class I human leukocyte antigen (HLA-I) peptides originating from non-canonical ORFs identified through MPRP. By inspecting ribosome occupancies on the 5’UTR and CDS regions of annotated viral genes, we identified hundreds of upstream ORFs (uORFs) that negatively regulate the synthesis of canonical viral proteins. The unprecedented source of viral ORFs across a wide range of viral families, including highly pathogenic viruses, expands the repertoire of vaccine targets and exposes new cis-regulatory sequences in viral genomes.
Increased Risk of Intracranial Hemorrhage in Older Patients Exposed to Multidrug Interactions Involving Warfarin
Authors: Ramesh Babu Prathiv Raj 
Published: September 2023

AbstractMultidrug interactions are a major cause of mortality for older patients. With an increase in “alert fatigue” for clinicians using Electronic Health Record systems (EHRs), Adverse Drug Events (ADEs) are increasing within older populations taking various drugs, because the probabilities of the adverse events associated with exposure to interacting drugs are not provided. The Observational Health Data Sciences and Informatics (OHDSI) ATLAS tool was utilized with Columbia University Irving Medical Center (CUIMC) patient data to determine whether Intracranial Hemorrhage (ICH) risk increases after being exposed to various multidrug interactions involving Warfarin in patients aged 60-90 years old one week before an ICH occurrence in patients prescribed ranges of 1-5, 6-10, and 11-15 drugs to also see the impact of polypharmacy on the prevalence of ICH amongst these patients. The prevalence of ICH in patients exposed to two and three-drug combinations involving Warfarin, Aspirin, Acetaminophen, and Amiodarone was measured. Significant increases in ICH risk and prevalence were identified in patients who had taken various combinations of these drugs with three-drug combinations involving Warfarin having a higher ICH risk than two-drug combinations involving Warfarin. Other findings also include that patients prescribed a larger number of drugs also tended to have a higher ICH risk than those prescribed a smaller number of drugs. Understanding the prevalence of such ADEs have crucial implications in the healthcare system, as the increased probabilities for certain ADEs from multidrug combinations can be applied to future EHR systems to counteract “alert fatigue” issues.
Hypothalamic representation of the imminence of predator threat detected by the vomeronasal organ in mice
Authors: Nguyen Quynh Anh Thi , Rocha Andrea , Chhor Ricky , Yamashita Yuna , Stadler Christian , Pontrello Crystal , Yang Hongdian , Haga-Yamanaka Sachiko 
Published: September 2023

AbstractAnimals have the innate ability to select optimal defensive behaviors with appropriate intensity in response to predator threats within specific contexts. Such innate behavioral decisions are thought to be computed in the medial hypothalamic nuclei, which contain neural populations that directly control defensive behavioral outputs. The vomeronasal organ (VNO) serves as a primary sensory channel for detecting predator cues by relaying signals to the medial hypothalamic nuclei, particularly the ventromedial hypothalamus (VMH), via the medial amygdala (MeA) and bed nucleus of the stria terminalis (BNST). Here, we demonstrate that cat saliva contains predator cues that signal the imminence of predator threat and modulate the intensity of freezing behavior through the VNO in mice. Cat saliva activates neurons expressing the V2R-A4 subfamily of sensory receptors, suggesting that specific receptor groups are responsible for inducing the freezing behavior. The number of VNO neurons activated in response to saliva correlates with both the freshness of saliva and the intensity of freezing behavior. In contrast, the downstream neurons in the accessory olfactory bulb (AOB) and the defensive behavioral circuit are activated to a similar extent by fresh and old saliva. Strikingly, however, the number of VMH neurons activated by fresh, but not old, saliva positively correlates with the intensity of freezing behavior. Detailed analysis of the spatial distribution of neurons responding to fresh and old saliva, as well as the overlap of those activated within the same individual mice, revealed that fresh and old saliva predominantly activate distinct neuronal populations within the VMH. Collectively, this study suggests that there is an accessory olfactory circuit in mice that is specifically tuned to time-sensitive components of cat saliva, which optimizes their defensive behavior to maximize their chance of survival according to the imminence of threat.
Gut feeling: Extent of virulence and antibiotic resistance genes inHelicobacter pyloriand campylobacteria
Authors: Rao R. Shyama Prasad , Ghate Sudeep D. , Pinto Larina , Suravajhala Prashanth , Patil Prakash , Shetty Praveenkumar , Ahsan Nagib 
Published: September 2023

AbstractBackgroundHelicobacter pylori, a member of campylobacteria, is the leading cause of chronic gastritis and gastric cancer. Virulence and antibiotic resistance ofH. pyloriare of great concern to public health. However, the relationship between virulence and antibiotic resistance genes inH. pyloriin relation to other campylobacteria remains unclear.Materials and MethodsBy using the virulence and comprehensive antibiotic resistance databases, we explored all available 354 complete genomes ofH. pyloriand compared it with 90 species of campylobacteria for virulence and antibiotic resistance genes/proteins.ResultsOn average,H. pylorihad 129 virulence genes, highest amongHelicobacter spp. and 71 antibiotic resistance genes, one of the lowest among campylobacteria. Just 2.6% of virulence genes were shared by all campylobacterial members, whereas 9.4% were unique toH. pylori.The cytotoxin-associated genes (cags) seemed to be exclusive toH. pylori. Majority of the isolates from Asia and South America werecag2-negative and many antibiotic resistance genes showed isolate-specific patterns of occurrence. Just 15 (8.8%) antibiotic resistance genes, but 103 (66%) virulence genes including 25 cags were proteomically identified inH. pylori.Arcobacterial members showed large variation in the number of antibiotic resistance genes and there was a positive relation with the genome size.ConclusionLarge repository of antibiotic resistance genes in campylobacteria and a unique set of virulence genes might have important implications in shaping the course of virulence and antibiotic resistance inH. pylori.
iMAXFRET (Information Maximized FRET) for multipoint single-molecule structural analysis
Authors: Joshi Bhagyashree S. , de Lannoy Carlos , Howarth Mark , Kim Sung Hyun , Joo Chirlmin 
Published: September 2023

AbstractUnderstanding the structure of biomolecules is vital for deciphering their characteristics and roles in biological systems. While current structural analysis techniques like nuclear magnetic resonance and X-ray crystallography excel in many aspects, they fall short in capturing comprehensive single-molecule information. To address this limitation and to better capture the heterogeneity and dynamic range of biomolecular reactions, there is a need for single-molecule structural analysis tools. To achieve this, we introduce iMAX FRET, a one-pot FRET-based single-molecule method integrated with geometrical 3D reconstruction, offering comprehensiveab initiostructural analysis. Through the stochastic exchange of fluorescent weak binders, iMAX FRET allows simultaneous assessment of multiple spatial coordinates on a biomolecule within a few minutes of time to generate distinct FRET fingerprints for 3D structural profiling. We demonstrate a mathematical approach forde novostructural prediction using iMAX data, opening avenues for native biomolecule analysis. Furthermore, this method facilitates the investigation of conformational changes in individual molecules, illuminating single-molecule structural dynamics. Our technique has the potential to emerge as a powerful approach to advance our understanding of biomolecular structures.
The expression of PKM1 and PKM2 in developing, benign, and cancerous prostatic tissues
Authors: Li Lin , Cheng Siyuan , Yeh Yunshin , Shi Yingli , Henderson Nikayla , Price David , Gu Xin , Yu Xiuping 
Published: September 2023

AbstractNeuroendocrine prostate cancer (NEPCa) is the most aggressive type of prostate cancer. However, energy metabolism, one of the hallmarks of cancer, in NEPCa has not been well studied. Pyruvate kinase M (PKM), which catalyzes the final step of glycolysis, has two main splicing isoforms, PKM1 and PKM2. PKM2 is known to be upregulated in various cancers, including prostate adenocarcinoma (AdPCa). In this study, we used immunohistochemistry, immunofluorescence staining, and bioinformatic analysis to examine the expression of PKM1 and PKM2 in mouse and human prostatic tissues, including developing, benign and cancerous prostate. We found that PKM2 was the predominant isoform expressed throughout prostate development and PCa progression, with slightly reduced expression in some NEPCa samples.PKM1 was mostly expressed in stromal cells but low-level PKM1 was also detected in prostate basal epithelial cells. Its expression was absent in the majority of PCa specimens but present in a subset of NEPCa. Additionally, we evaluated the mRNA levels of ten PKM isoforms that express exon 9 (PKM1-like) or exon 10 (PKM2-like). Some of these isoforms showed notable expression levels in PCa cell lines and human PCa specimens. These findings lay the groundwork for understanding PKMs’ role in PCa carcinogenesis and NEPCa progression. The distinct expression pattern of PKM isoforms in different PCa subtypes may offer insights into potential therapeutic strategies for treating PCa.
A Multimodality Video-Based AI Biomarker For Aortic Stenosis Development And Progression
Authors: Oikonomou Evangelos K. , Holste Gregory , Yuan Neal , Coppi Andreas , McNamara Robert L. , Haynes Norrisa , Vora Amit N. , Velazquez Eric J. , Li Fan , Menon Venu , Kapadia Samir R. , Gill Thomas M , Nadkarni Girish N. , Krumholz Harlan M. , Wang Zhangyang , Ouyang David , Khera Rohan 
Published: September 2023

ABSTRACTImportanceAortic stenosis (AS) is a major public health challenge with a growing therapeutic landscape, but current biomarkers do not inform personalized screening and follow-up.ObjectiveA video-based artificial intelligence (AI) biomarker (Digital AS Severity index [DASSi]) can detect severe AS using single-view long-axis echocardiography without Doppler. Here, we deploy DASSi to patients with no or mild/moderate AS at baseline to identify AS development and progression.Design, Setting, and ParticipantsWe defined two cohorts of patients without severe AS undergoing echocardiography in the Yale-New Haven Health System (YNHHS) (2015-2021, 4.1[IQR:2.4-5.4] follow-up years) and Cedars-Sinai Medical Center (CSMC) (2018-2019, 3.4[IQR:2.8-3.9] follow-up years). We further developed a novel computational pipeline for the cross-modality translation of DASSi into cardiac magnetic resonance (CMR) imaging in the UK Biobank (2.5[IQR:1.6-3.9] follow-up years). Analyses were performed between August 2023-February 2024.ExposureDASSi (range: 0-1) derived from AI applied to echocardiography and CMR videos.Main Outcomes and MeasuresAnnualized change in peak aortic valve velocity (AV-Vmax) and late (>6 months) aortic valve replacement (AVR).ResultsA total of 12,599 participants were included in the echocardiographic study (YNHHS:n=8,798, median age of 71 [IQR (interquartile range):60-80] years, 4250 [48.3%] women, and CSMC:n=3,801, 67 [IQR:54-78] years, 1685 [44.3%] women). Higher baseline DASSi was associated with faster progression in AV-Vmax(per 0.1 DASSi increments: YNHHS: +0.033 m/s/year [95%CI:0.028-0.038], n=5,483, and CSMC: +0.082 m/s/year [0.053-0.111], n=1,292), with levels ≥ vs <0.2 linked to a 4-to-5-fold higher AVR risk (715 events in YNHHS; adj.HR 4.97 [95%CI: 2.71-5.82], 56 events in CSMC: 4.04 [0.92-17.7]), independent of age, sex, ethnicity/race, ejection fraction and AV-Vmax. This was reproduced across 45,474 participants (median age 65 [IQR:59-71] years, 23,559 [51.8%] women) undergoing CMR in the UK Biobank (adj.HR 11.4 [95%CI:2.56-50.60] for DASSi ≥vs<0.2). Saliency maps and phenome-wide association studies supported links with traditional cardiovascular risk factors and diastolic dysfunction.Conclusions and RelevanceIn this cohort study of patients without severe AS undergoing echocardiography or CMR imaging, a new AI-based video biomarker is independently associated with AS development and progression, enabling opportunistic risk stratification across cardiovascular imaging modalities as well as potential application on handheld devices.
Impact of Fludrocortisone on the Outcomes of Subarachnoid Hemorrhage Patients: A Retrospective Analysis
Authors: Mistry Akshitkumar M. , Naidugari Janki , Feldman Michael J. , Magarik Jordan A. , Ding Dale , Abecassis Isaac J. , Semler Matthew W. , Rice Todd W. 
Published: September 2023

ABSTRACTBackgroundWhether the use of fludrocortisone affects outcomes of patients with aneurysmal subarachnoid hemorrhage (aSAH) and its usage rate in the United States remain unknown.MethodsWe conducted a retrospective analysis of 78 consecutive patients with a ruptured aSAH at a single academic center in the United States. The primary outcome was the score on the modified Rankin scale (mRS, range, 0 [no symptoms] to 6 [death]) at 90 days. We adjusted the primary outcome for age, hypertension, aSAH grade, and time from aSAH onset to aneurysm treatment. Secondary outcomes were brain and cardiopulmonary dysfunction events.ResultsAmong 78 patients at a single center, the median age was 58 years [IQR, 49 to 64.5]; 64% were female, and 41 (53%) received fludrocortisone. The adjusted common odds ratio, aOR, of a proportional odds regression model of fludrocortisone use with mRS was 0.33 (95% CI, 0.14-0.80; P=0.02), with values <1.0 favoring fludrocortisone. Organ-specific dysfunction events were not statistically different: delayed cerebral ischemia (22% vs. 39%, P=0.16); cardiac dysfunction (0% vs. 11%; P=0.10); and pulmonary edema (15% vs. 8%; P=0.59).ConclusionsThe risk of disability or death at 90 days was lower with the use of fludrocortisone in aSAH patients.
Video feedback for young babies and maternal perinatal mental illness: Adaptation, feasibility and qualitative interviews
Authors: Barnicot Kirsten , Stevens Eloise , Robinson Fiona , Labovitch Sarah , Ballman Rajinder , Miele Maddalena , Lawn Tara , Sundaresh Sushma , Iles Jane 
Published: September 2023

AbstractAims/ BackgroundWe aimed to adapt, test and explore experiences of the video feedback intervention for positive parenting (VIPP) for 2 to 6 month old babies and for mothers experiencing moderate to severe perinatal mental health difficulties.Design/ MethodsThe VIPP intervention was adapted to include developmentally appropriate activities and developmental psychoeducation for 2 to 6 month olds, alongside psychoeducation on emotion regulation. Subsequently, the adapted intervention was trialled in 14 mothers experiencing moderate to severe perinatal mental health difficulties (registrationISRCTN64237883). Observational and self-reported pre-post outcome data was collected, and post-intervention qualitative interviews were conducted with participating mothers and clinicians.ResultsConsent (67%), intervention completion (79%) and follow-up rates (93%) were high. Effect sizes on pre-post outcome measures indicated large improvements in parenting confidence and perceptions of the parent-infant relationship, and a medium-size improvement in maternal sensitivity. Qualitative interviews suggested that clinicians and mothers were able to use the video feedback to identify young babies’ subtle behavioural cues and moments of mother-infant connection, enhancing maternal sensitivity. Mothers’ initial anxieties about being filmed were overcome by the experience of receiving positive and strengths-focussed feedback, boosting their confidence in themselves as parents. The interviews also generated recommendations for minor modifications to optimise intervention feasibility and acceptability, such as streamlining the information provided on maternal emotion regulation, and allowing increased use of clinical judgement to tailor intervention delivery.ConclusionVIPP can potentially be beneficial for enhancing maternal sensitivity with very young babies in mothers experiencing perinatal mental health difficulties.
Non-invasive vagus nerve stimulation conditions increased invigoration and wanting in depression
Authors: Ferstl Magdalena , Kühnel Anne , Klaus Johannes , Lin Wy Ming , Kroemer Nils B. 
Published: September 2023

AbstractBackgroundMajor depressive disorder (MDD) is often marked by impaired motivation and reward processing, known as anhedonia. Many patients do not respond to first-line treatments, and improvements in motivation can be slow, creating an urgent need for rapid interventions. Recently, we demonstrated that transcutaneous auricular vagus nerve stimulation (taVNS) acutely boosts effort invigoration in healthy participants, but its effects on depression remain unclear.ObjectiveTo assess the impact of taVNS on effort invigoration and maintenance in a sample that includes patients with MDD, evaluating the generalizability of our findings.MethodsWe used a single-blind, randomized crossover design in 30 patients with MDD and 29 matched (age, sex, and BMI) healthy control participants (HCP).ResultsConsistent with prior findings, taVNS increased effort invigoration for rewards in both groups during Session 1 (p=.040), particularly for less wanted rewards in HCP (pboot<.001). However, invigoration remained elevated in all participants, and no acute changes were observed in Session 2 (Δinvigoration=3.52,p=.093). Crucially, throughout Session 1, we found taVNS-induced increases in effort invigoration (pboot=.008) and wanting (pboot=.010) in patients with MDD, with gains in wanting maintained across sessions (Δwanting=0.06,p=.97).ConclusionsOur study replicates the invigorating effects of taVNS in Session 1 and reveals its generalizability to depression. Furthermore, we expand upon previous research by showing taVNS-induced conditioning effects on invigoration and wanting within Session 1 in patients that were largely sustained. While enduring motivational improvements present challenges for crossover designs, they are highly desirable in interventions and warrant further follow-up research.Graphical abstract
COVID-related Excess Missed HIV Diagnoses in the United States in 2021: Follow-up to 2020
Authors: Viguerie Alex , Song Ruiguang , Johnson Anna Satcher , Lyles Cynthia M. , Hernandez Angela , Farnham Paul G. 
Published: September 2023

ObjectiveCOVID-19 and related disruptions led to a significant drop in HIV diagnoses in the US in 2020. Recent analyses found 18% fewer diagnoses than expected among persons with HIV (PWH) acquiring infection in 2019 or earlier, suggesting that the drop in diagnoses cannot be attributed solely to decreased transmission. This analysis evaluates the progress made towards closing the 2020 diagnosis deficit in 2021.MethodsWe apply modified versions of previously developed methods analyzing 2021 diagnosis data from the National HIV Surveillance System to determine whether the 2021 diagnosis levels of PWH infected pre-2020 are above or below the projected pre-COVID trends. We apply these analyses on stratifications based on assigned sex at birth, transmission group, geographic region, and race/ethnicity.ResultsIn 2021, HIV diagnoses returned to pre-COVID levels among all PWH acquiring infection 2011-19. Among Hispanic/Latino PWH and males, diagnoses returned to pre-COVID levels. White PWH, men who have sex with men, and PWH living in the south and northeast showed higher-than-expected levels of diagnosis in 2021. For the remaining populations, there were fewer HIV diagnoses in 2021 than expected.ConclusionsWhile overall diagnoses returned to pre-COVID levels, the large diagnosis gap observed in 2020 remained unclosed at the end of 2021. Lower than expected diagnosis levels among certain populations indicates that COVID-19 related disruptions to HIV diagnosis trends were present in 2021. Although some groups showed higher-than-projected levels of diagnoses, such increases were smaller than the corresponding 2020 decreases. Expanded testing programs designed to close these gaps are essential.
Effectiveness of the adjuvanted Sanofi/GSK (VidPrevtyn Beta) and Pfizer-BioNTech (Comirnaty Original/Omicron BA.4-5) bivalent vaccines against hospitalisation amongst adults aged 75 years and older in England, estimated using a test-negative case control study design
Authors: Kirsebom Freja Cordelia Møller , Andrews Nick , Stowe Julia , Dabrera Gavin , Ramsay Mary , Bernal Jamie Lopez 
Published: September 2023

AbstractBackgroundIn England, the Joint Committee for Vaccination and Immunisation recommended a spring 2023 booster programme for all adults aged 75 years and older and the immunosuppressed. The vaccines advised were the Sanofi/GSK AS03-adjuvanted monovalent beta variant (VidPrevtyn Beta) booster vaccine and the Pfizer-BioNTech mRNA (Comirnaty Original/Omicron BA.4-5) bivalent vaccine. This is the first time an adjuvanted COVID-19 vaccine has been administered as part of a UK COVID-19 vaccination programme. In clinical trials, the antibody levels generated by the Sanofi/GSK vaccine were comparable to levels generated by COVID-19 mRNA vaccines but to date there are no real-world data on the effectiveness or duration of protection of this vaccine.MethodsWe used a test-negative case-control study design to estimate the incremental vaccine effectiveness of the Sanofi/GSK and Pfizer bivalent BA.4-5 boosters against hospitalisation amongst those aged 75 years and older in England. The study period for tests contributing to all analyses was from 3rd April 2022 to 27th August 2023. Vaccine effectiveness was estimated relative to those who had received at least two doses prior to their spring booster, with their last dose being an autumn 2022 booster given at least 3 months prior.FindingsOverall, there were 14,174 eligible tests from hospitalised individuals aged 75 years and older, with 3,005 being cases and 11,169 being controls. Effectiveness against hospitalisation was highest in the period 9 to 13 days post vaccination for both manufacturers at about 50%; 43.6% (95% C.I.; 20.1 to 60.2%) and 56.4% (95% C.I; 25.8 to 74.4%) for Sanofi/GSK and Pfizer BA.4-5, respectively. There was some evidence of waning with a reduction to about 30% for both manufacturers 5-9 weeks post vaccination.InterpretationTogether, these results provide reassuring evidence that both the adjuvanted Sanofi/GSK and Pfizer BA.4-5 booster vaccines provided a good boost to protection against hospitalisation amongst adults aged 75 years and older. The finding that the adjuvanted vaccine targeting the now distant Beta strain had similar effectiveness to the mRNA vaccine targeting more closely matched Omicron sub-lineages BA.4-5 during a period of Omicron circulation may reflect improved protection due to the adjuvant in the Sanofi/GSK product.FundingNo external funding.