bluuebunny/crossref_metadata_2025 huggingface dataset:
Replicating clinical placebo effects in computational trials: Bridging the gap between in silico and clinical studies
Authors: Dominguez-Gomez Paula , Butakoff Constantine , Rast Georg , Darpo Borje , Vazquez Mariano , Aguado-Sierra Jazmin
Published: October 2024

This study replicates human cardiac safety clinical trials using computational models, which include diurnal hormonal placebo effects, aiming to create fast and efficient drug screening tools to assess QT interval prolongation preclinically. A virtual cardiac population that simulates sex-specific electrophysiological variability influenced by diurnal hormonal cycles was created to closely mirror human physiology. The goal is to assess the impact of these hormone dynamics on placebo-induced responses and evaluate the virtual population’s accuracy in reflecting clinical trial outcomes.

The study showed that the virtual population model successfully replicated about 50% of the observed QT variability seen in placebo groups. The computational framework facilitated direct comparison with human clinical trials, achieving critical concentrations, i.e., concentrations that cause a mean QTc effect of 10 ms, within a 0.6-fold range of clinical results. Additionally, the exposure-response slopes exhibited relative errors averaging 43%, which translates into mean absolute errors of 6-7 ms in comparison to clinical data. These results highlight its potential to reproduce human physiology and provide results consistent with real-world human clinical trials. Additionally, a comparison with a previously published statistical placebo model further supports this approach. By approximating the diurnal hormonal variations, as a component of the mechanistic basis of placebo, this method offers a robust decision-making tool for early-stage drug safety assessment.

Highlights

Diurnal hormonal fluctuations significantly contribute to intersubject variability observed in placebo responses.

Modeling conservative diurnal hormonal variations can reproduce approximately 50% of QT interval prolongation variability within placebo groups.

Comprehensive human clinical trials for cardiac safety drug testing, including placebo effects and placebo-corrected QT interval prolongation, can be accurately replicated through virtual human computational models showing mean absolute errors of 6-7 ms.

Graphical Abstract
Multimorbidity Patterns of Chronic Diseases Among Adults in Rural North China
Authors: Tang Shuai , Li Yanxing , Niu Meili , Qi Zijing , Hao Tianyou , Yang Hongmei , Tian Maoyi , Zhang Xinyi , Feng Xiangxian , Li Zhifang
Published: October 2024

Background

The incidence of chronic diseases is increasing, especially in rural areas, where younger patients often exhibit multimorbidity. Understanding multimorbidity in rural adults can guide the development of targeted management strategies for chronic diseases.

Methods

This cross-sectional study was conducted in rural North China using whole cluster stratified random sampling to select two counties in Shanxi Province. A total of 2,208 participants aged 30 years or older from 80 villages were enrolled, stratified by gender and age. Data collection involved questionnaires on socio-demographic characteristics, lifestyle, and disease history, along with physical measurements such as height, weight, and waist circumference.

Results

Among the 2,208 participants, 58.11% were aged 30-59 years, and 52.17% were female. The prevalence of chronic diseases was 66.53%, with a multimorbidity rate of 32.47%. The most common conditions were hypertension (43.21%), chronic digestive diseases (11.82%), and stroke (10.19%). Multimorbidity was more prevalent in those aged ≥60 years compared to the 30-59 age group (47.68% vs. 21.51%, P<0.05), with no significant gender differences. Hypertension was present in 78.52% of disease patterns, with common dyads being hypertension & stroke (7.47%), hypertension & heart disease (6.25%), and hypertension & diabetes mellitus (6.11%). In the 30-59 age group, hypertension & chronic digestive disease (3.82%) were most prevalent, while for those aged ≥60 years and males, hypertension & stroke were most common (12.65% and 9.47%, respectively). Among females, the most frequent dyad was hypertension & arthritis (8.16%).

Conclusion

Chronic diseases and multimorbidity are prevalent in rural North China, primarily driven by hypertension. Multimorbidity patterns differ by age and gender, indicating the need for targeted prevention and treatment strategies.
First trimester antidepressant use and miscarriage: a comprehensive analysis in the UK Clinical Practice Research Datalink
Authors: Martin Florence Zoe , Madley-Dowd Paul , Ahlqvist Viktor H , Sharp Gemma C , Easey Kayleigh E , Lee Brian K , Merriel Abi , Rai Dheeraj , Forbes Harriet
Published: October 2024

Objectives To investigate the risk of miscarriage associated with first trimester antidepressant use. Design Population-based cohort study. Setting UK Clinical Practice Research Datalink (CPRD) GOLD. Participants 661 825 individuals who had 1 021 384 pregnancies in CPRD GOLD between 1996 and 2018. Main outcome measures Miscarriage defined as a pregnancy loss prior to 24 weeks' gestation. Results Among the eligible pregnancies, 73 540 were prescribed antidepressants in trimester one (7.2%); 14.7% antidepressant prescribed pregnancies ended in miscarriage, as opposed to 12.4% of those not prescribed antidepressants. Antidepressant use during trimester one was associated with miscarriage in the unadjusted models (hazard ratio (HR) 1.21, 95% confidence interval (CI) 1.19 to 1.23), which attenuated following adjustment for covariates (aHR 1.04, 95% CI 1.02 to 1.06). These findings translated to an absolute risk adjusted for confounders of 13.1% (95% CI 13.0 to 13.2) in the unexposed compared to 13.6% (95% CI 13.3 to 13.8) in the first trimester antidepressant exposed. The propensity score matched model showed similar results (aHR 1.09, 95% CI 1.02 to 1.17, respectively). In those with depression or anxiety in the 12 months before pregnancy, our estimate didn't change (aHR 1.04, 95% CI 1.01 to 1.08). Conclusion First trimester antidepressant use was associated with a small yet clinically insignificant increase in risk of miscarriage, with no evidence suggesting taking antidepressants before pregnancy and into first trimester increases the risk of miscarriage. The conclusions are less clear for 'incident' antidepressant use in trimester one, however issues including gestational dating in early pregnancy and probable residual confounding prohibit us from interpreting this observation as causal.
Application of decision-analytic models to inform integrated care interventions for cardiometabolic multimorbidity: A systematic review
Authors: Wambiya Elvis O. A. , Gillespie Duncan , Akparibo Robert , Oguta James O. , Akoth Catherine , Otieno Peter , Dodd Peter J.
Published: October 2024

Introduction

Integrated care is increasingly being adopted to address the complex needs of patients with cardiometabolic multimorbidity. However, it is unclear how to cost-effectively configure health service pathways for these patients. This study aimed to review and appraise decision analytic models (DAMs) used in economic evaluations of integrated care interventions for patients with cardiometabolic multimorbidity.

Methods

We conducted a systematic search for peer-reviewed articles in eight electronic databases, published in English language until December 2023. Any study worldwide that used a decision-analytic model to conduct an economic evaluation of an integrated care model for patients with cardiometabolic multimorbidity was included. We summarised characteristics of the DAMs, integrated care models evaluated, diseases constituting multimorbidity, and critically appraised the quality of reporting of the economic evaluations using Philips (2006) checklist.

Results

Out of 16 model-based assessments of the differences between alternative integrated care pathways, most studies (n=13, 81%) were cost utility analyses, focused on care for patients with hypertension and/or diabetes concordant multimorbidity (n=11, 69%). Most studies were conducted in high-income countries (n = 11, 69%). More than half (n = 10, 63%) of the studies used simulated Markov models, while only three studies used individual sampling (microsimulation) models. Few studies were explicit about their data validation approaches against local data, quality of data incorporated in the models, and internal and external consistency.

Conclusion

Decision-analytic models investigating integrated care pathways for cardiometabolic multimorbidity should employ microsimulation to describe and incorporate repeated patient interactions with health care and multimorbidity outcomes in the economic evaluations. Consideration of uncertainty in data sources and model structure is also needed to provide robust conclusions. The study also highlighted the need for more economic evaluations using DAMs in low- and middle-income countries to evaluate integrated care models in the context of cardiometabolic multimorbidity.
Identification of novel type 1 and type 2 diabetes genes by co-localization of human islet eQTL and GWAS variants with colocRedRibbon
Authors: Piron Anthony , Szymczak Florian , Folon Lise , Crouch Daniel J. M. , Papadopoulou Theodora , Alvelos Maria Inês , Colli Maikel L. , Yi Xiaoyan , Pekalski Marcin ,   Type 2 Diabetes Global Genomics Initiative, Defrance Matthieu , Todd John A. , Eizirik Décio L. , Mercader Josep M. , Cnop Miriam
Published: October 2024

Over 1,000 distinct genetic variants have been associated with diabetes risk by genome-wide association studies (GWAS) but for most their functional impact is unknown and less than 15% of the diabetes GWAS variants have been shown in expression quantitative trait locus (eQTL) studies to alter gene expression in pancreatic islets. To fill this gap, we developed a new co-localization pipeline, called colocRedRibbon, that prefilters eQTL variants by direction of effect on gene expression, shortlists overlapping eQTL and GWAS variants and then runs the co-localization. Applying colocRedRibbon to diabetes and glycemic trait GWAS, we identified 292 co-localizing gene regions - 236 of which are new - including 24 co-localizations for type 1 diabetes and 268 for type 2 diabetes and glycemic traits. We achieved a four-fold increase in co-localizations, with the novel pipeline and updated GWAS each contributing two-fold. Among the co-localizations are a low frequency variant increasing MYO5C expression that reduces type 2 diabetes risk and a type 1 diabetes protective variant that increases FUT2 and decreases RASIP1 expression. These novel co-localizations represent a significant step forward to understand polygenic diabetes genetics and its impact on human islet gene expression.
Effect of community interventions for the prevention of suicide in adolescents and young adults: a scoping review.
Authors: Cabrera-Eraso Fernando , Torres Solano Manuela , Vasquez-Ponce Mariana , Lopez-Orozco Maria Alejandra , Tirado Carlos , Arevalo Maria Kamila , Medina Laura , Rodriguez Catalina , Rodriguez-Castellanos Valentina , Gonzalez Lina Maria
Published: October 2024

Introduction: Suicide is a significant public health issue, especially in middle- and low-income countries, with higher rates among young people. Suicidal behavior includes suicide, suicidal ideation, attempts, and gestures, each with distinct definitions. Community-based interventions are crucial for suicide prevention, but there is limited research on their effectiveness, especially in low-resource settings. This review aims to assess and categorize such interventions for adolescents and young adults globally. Objective: To assess the effect of community interventions for the prevention of suicide in adolescents and young adults. Methods: A scoping review was conducted following the methodological framework of the Joanna Briggs Institute and the PRISMA-ScR extension. The goal was to examine the effectiveness of community-based interventions for suicide prevention among adolescents and young adults (15-30 years). After searching various databases, articles were independently reviewed, and selected studies were analyzed in collaborative meetings to reach conclusions regarding the validity and outcomes of the interventions. Results: 2162 references were found, but only 12 studies met the eligibility criteria for the analysis phase. The studies explored various community-based suicide prevention interventions, including educational programs for parents, dialectical behavioral therapy, and culturally adapted initiatives for Indigenous populations. Key findings demonstrated reductions in suicidal thoughts and behaviors, though challenges such as small sample sizes, cultural nuances, and long-term effectiveness were noted.
Machine learning analysis of the UNOS database fails to predict lung transplant outcomes
Authors: Luo Lucy , Możejko Marcin , Markov Nikolay S. , Peltekian Alec , Moshin Suror , Carns Mary , Cooper Phillip , Lysne Jeffrey , Joudi Anthony , Betensley Alan , Bemiss Bradford C. , Myers Catherine , Bharat Ankit , Tomic Rade , Arunachalam Ambalavanan , Szczurek Ewa , Budinger GR Scott , Misharin Alexander V. , Subramani Mrinalini Venkata
Published: October 2024

Background

Lung transplantation is the only life-saving therapy for end-stage lung disease. However, lung transplantation has the worst survival among all solid organ transplants.1We applied machine learning to a large standardized electronic health record (EHR) dataset from the United Network for Organ Sharing (UNOS) to test whether pre- transplant and peri-transplant donor and recipient features can predict one-, three- and five-year survival, or favorable long-term outcomes in lung transplant.

Methods

We used data from 43,869 first time lung transplant recipients >18 years old from 1987 to November 2022 for whom one-, three-, and five-year survival outcomes were available. We applied XGBoost or a tabular BERT model called EHRFormer to the UNOS EHR dataset.

Results

Using pre-transplant features XGBoost predicted one year mortality with a test AUC = 0.6 [0.57, 0.64] 95% CI. Addition of peri-transplant features only modestly improved AUC for one-year mortality prediction (test AUC = 0.63 [0.60, 0.67] 95% CI and 0.64 [0.63, 0.66] 95% CI for XGBoost and EHRFormer, respectively). Top predictive features of one year mortality using peri-transplant features from each model were length of index stay, transplant type, recipient age, ventilation status during the index stay, and creatinine at the time of transplant. Both XGBoost and EHRFormer performed better when predicting lung function at one-year post-transplant (XGBoost test AUC = 0.74; EHRFormer test AUC = 0.76). Both models identified and used features previously associated with transplant outcomes to inform predictions.

Conclusions

Despite machine learning approaches identifying known risk factors for transplant outcomes, EHR data collected by UNOS poorly predict one-, three-, and five-year mortality outcomes of lung transplantation. These results suggest caution when using pre-transplant EHR features to predict lung transplant outcomes.
Hybrid incompatibility emerges at the one-cell stage in interspeciesCaenorhabditisembryos
Authors: Bloom Jessica , Green Rebecca , Desai Arshad , Oegema Karen , Rifkin Scott A.
Published: October 2024

Intrinsic reproductive isolation occurs when genetic differences between populations disrupt the development of hybrid organisms, preventing gene flow and enforcing speciation.1–4While prior studies have examined the genetic origins of hybrid incompatibility,5–18the effects of incompatible factors on development remain poorly understood. Here, we investigate the mechanistic basis of hybrid incompatibility inCaenorhabditisnematodes by capitalizing on the ability ofC. brennerifemales to produce embryos after mating with males from several other species. Contrary to expectations, hybrid incompatibility was evident immediately after fertilization, suggesting that post-fertilization barriers to hybridization originate from physical incompatibility between sperm and oocyte-derived factors rather than from zygotic transcription, which starts after the 4-cell stage.19–22Sperm deliver chromatin, which expands to form a pronucleus, and a pair of centrioles, which form centrosomes that attach to the sperm-derived pronucleus and signal to establish the embryo’s anterior-posterior axis.23,24InC. brennerioocytes fertilized withC. eleganssperm, sperm pronuclear expansion was compromised, frequent centrosome detachment was observed, and cortical polarity was disrupted. Live imaging revealed that defective polar body extrusion contributes to defects in mitotic spindle morphology.C. brennerioocytes fertilized withC. remaneiorC. sp. 48sperm showed similar defects, and their severity and frequency increased with phylogenetic distance. Defective expansion of the sperm-derived pronucleus and unreliable polar body extrusion immediately after fertilization generally underlie the inviability of hybrid embryos in this clade. These results indicate that physical mismatches between sperm and oocyte-derived structures may be a primary mechanism of hybrid incompatibility.
From Exercise to Strain: Rapid and Accurate Prediction of Femoral Neck Loading
Authors: Altai Zainab , Phillips Andrew T.M. , Moran Jason , Zhai Xiaojun , Mei Qichang , Liew Bernard X.W.
Published: October 2024

Femoral neck fractures pose significant morbidity and mortality risks, particularly among osteoporotic patients. This study aims to identify effective exercises for enhancing bone health and develop a neural network model to predict femoral neck strains during exercise using inertial measurement unit (IMU) data. We employed musculoskeletal modeling (MSK) and finite element (FE) analysis to assess femoral neck strains during various ballistic exercises—walking, running, countermovement jumps, squat jumps, unilateral hopping, and bilateral hopping—across three intensity levels: high, moderate, and low. Results showed that running at all intensities produced significantly higher strains compared to walking (1985 ± 802 µε tensile, 5053 ± 181 µε compressive, p < 0.001), with peak tensile strains reaching 3731 µε and compressive strains up to 9541 µε. Low-intensity unilateral hopping also yielded significantly higher strains (3003 µε, p < 0.001) than walking, suggesting its osteogenic potential. In contrast, squat jumps, countermovement jumps, and bilateral hopping generated lower peak strains. The neural network model demonstrated high prediction accuracy, achieving correlations up to 0.97 and root mean square errors as low as 145.20 µε. These findings support the use of neural networks and IMU sensors for practical, cost-effective interventions to improve bone health and reduce fracture risk.
Polygenic scores for obstructive sleep apnea based on BMI-adjusted and -unadjusted genetic associations reveal pathways contributing to cardiovascular disease
Authors: Kurniansyah Nuzulul , Strausz Satu J , Chittoor Geetha , Gupta Shreyash , Justice Anne E , Hrytsenko Yana , Keenan Brendan T , Cade Brian E , Spitzer Brian W , Wang Heming , Huffman Jennifer , Moll Matthew R , Haring Bernhard , Jung Su Yon , Raffield Laura M , Kaplan Robert , Rotter Jerome I , Rich Stephen S , Gharib Sina A , Bartz Traci M , Liu Peter Y , Chen Han , Fornage Myriam , Hou Lifang , Levy Daniel , Morrison Alanna , Ochs-Balcom Heather M , Psaty Bruce , Wilson Peter WF , Cho Kelly , Pack Allan I , Ollila Hanna M , Redline Susan , Gottlieb Daniel J , Sofer Tamar ,   FinnGen,   Trans-Omics in Precision Medicine Consortium,   VA Million Veteran Program
Published: October 2024

Background

Obstructive sleep apnea (OSA) is a heterogeneous disease, with obesity a significant risk factor via increased airway collapsibility, reduced lung volumes, and possibly body fat distribution.

Methods

Using race/ethnic diverse samples from the Million Veteran Program, FinnGen, TOPMed, All of Us (AoU), Geisinger’s MyCode, MGB Biobank, and the Human Phenotype Project (HPP), we developed, selected, and assessed polygenic scores (PGSs) for OSA, relying on genome-wide association studies both adjusted and unadjusted for BMI: BMIadjOSA- and BMIunadjOSA-PGS. We tested their associations with CVD in AoU.

Results

Adjusted odds ratios (ORs) for OSA per 1 standard deviation of the PGSs ranged from 1.38 to 2.75. The associations of BMIadjOSA- and BMIunadjOSA-PGSs with CVD outcomes in AoU shared both common and distinct patterns. For example, BMIunadjOSA-PGS was associated with type 2 diabetes, heart failure, and coronary artery disease, but the associations of BMIadjOSA-PGS with these outcomes were statistically insignificant with estimated OR close to 1. In contrast, both BMIadjOSA- and BMIunadjOSA-PGSs were associated with hypertension and stroke. Sex stratified analyses revealed that BMIadjOSA-PGS association with hypertension was driven by data from OR=1.1, p-value=0.002, OR=1.01 p-value=0.2 in males). OSA PGSs were also associated with dual-energy X-ray absorptiometry (DXA) body fat measures with some sex-specific associations.

Conclusions

Distinct components of OSA genetic risk are related to obesity and body fat distribution, and may influence clinical outcomes. These may explain differing OSA risks and associations with cardiometabolic morbidities between sex groups.
Local activity alterations in autism spectrum disorder correlate with neurotransmitter properties and ketamine induced brain changes
Authors: Grumbach Pascal , Kasper Jan , Hipp Joerg F. , Forsyth Anna , Valk Sofie L. , Muthukumaraswamy Suresh , Eickhoff Simon B. , Schilbach Leonhard , Dukart Juergen
Published: October 2024

Autism spectrum disorder (ASD) is a neurodevelopmental condition associated with altered resting-state brain function. An increased excitation-inhibition (E/I) ratio is discussed as a potential pathomechanism but in-vivo evidence of disturbed neurotransmission underlying these functional alterations remains scarce. We compared rs-fMRI local activity (LCOR) between ASD (N=405, N=395) and neurotypical controls (N=473, N=474) in two independent cohorts (ABIDE1 and ABIDE2). We then tested how these LCOR alterations co-localize with specific neurotransmitter systems derived from nuclear imaging and compared them with E/I changes induced by GABAergic (midazolam) and glutamatergic medication (ketamine). Across both cohorts, ASD subjects consistently exhibited reduced LCOR, particularly in higher-order default mode network nodes, alongside increases in bilateral temporal regions, the cerebellum, and brainstem. These LCOR alterations negatively co-localized with dopaminergic (D1, D2, DAT), glutamatergic (NMDA, mGluR5), GABAergic (GABAa) and cholinergic neurotransmission (VAChT). The NMDA-antagonist ketamine, but not GABAa-potentiator midazolam, induced LCOR changes which co-localize with D1, NMDA and GABAa receptors, thereby resembling alterations observed in ASD. We find consistent local activity alterations in ASD to be spatially associated with several major neurotransmitter systems. NMDA-antagonist ketamine induced neurochemical changes similar to ASD-related alterations, supporting the notion that pharmacological modulation of the E/I balance in healthy individuals can induce ASD-like functional brain changes. These findings provide novel insights into neurophysiological mechanisms underlying ASD.

One Sentence Summary:

Local activity alterations in ASD co-localize with glutamatergic and GABAergic neurotransmission and were similar to ketamine-induced brain changes.
Shared Genetic Architecture Between Eating Disorders, Mental Health Conditions, and Cardiometabolic Diseases: A Comprehensive Population-Wide Study Across Two Countries
Authors: Meijsen Joeri , Hu Kejia , Wei Dang , Aicoboaie Stefana , Davies Helena L , Zhang Ruyue , Lundberg Mischa , Zetterberg Richard , Pasman Joëlle , Ye Weimin , Werge Thomas , Bulik Cynthia M. , Fang Fang , Buil Alfonso , Micali Nadia
Published: October 2024

Eating disorders arise from a complex interaction of genetic and environmental influences. Here we provide comprehensive population-level estimates of the heritability of eating disorders and their genetic relationships with various mental health and cardiometabolic disorders (CMDs), expanding beyond genome-wide association studies. We examined the heritability of three eating disorders—anorexia nervosa (AN), bulimia nervosa (BN), and other eating disorders (OED)—and investigated shared familial and genetic risk factors with mental health disorders and CMDs. Using national-register data from Denmark and Sweden (1972-2016), we analyzed clinical diagnoses for over 67,000 individuals with eating disorders, their first-degree relatives, and matched controls from populations totaling 17 million. Heritability estimates were moderate,and genetic correlations revealed substantial overlap between AN and obsessive-compulsive disorder (rg= 0.65) and moderate correlations with other mental health disorders such as autism (rg= 0.36). Significant genetic associations were also identified between eating disorders and CMDs, showing strong replication across both countries. These findings emphasize the genetic foundations of eating disorders and their shared genetic architecture with mental health and CMDs. This research enhances our understanding of comorbidity patterns and has important implications for developing integrated treatment approaches.
Precise amplification-free detection of highly structured RNA with an enhanced SCas12a assay
Authors: Zhang Junqi , Jiang Qingyuan , Deng Wenwen , Jin Shuqi , Wang Xinping , He Ruyi , Yin Wenhao , Qiao Jie , Liu Yi
Published: October 2024

The CRISPR/Cas12a system has revolutionized molecular diagnostics; however, its application in directly detecting complex structured RNA remains challenging. Recently, we have developed a RNA detection method called SCas12a, which exhibits high sensitivity and efficiency in detecting RNA molecules devoid of intricate secondary structures. Here, we present an enhanced SCas12a assay (SCas12aV2) that facilitates precise amplification-free detection of highly structured RNA molecules. Our approach reengineers the split Cas12a system by optimizing the scaffold RNA length and targeting asymmetric RNA structures, thereby minimizing steric hindrance. We observe that utilization of a dsDNA-ssDNA hybrid DNA activator significantly enhances both the sensitivity and kinetics compared to those achieved using traditional ssDNA or dsDNA activators. The SCas12aV2 assay demonstrates exceptional sensitivity, with a limit of detection reaching 246 aM for pooled activators and 10 pM for single-site targeting. It also exhibits high specificity for single nucleotide polymorphisms (SNPs) and successfully identifies viable bacterial populations and SARS-CoV-2 infections from clinical samples. The assay’s versatility is further highlighted by its applicability to various Cas12a orthologs, including the thermostable CtCas12a. This work offers a significant advance in molecular diagnostics, enhancing the potential for accurate and efficient RNA detection.
Direct-acting antivirals for chronic hepatitis C infection: a protocol for a systematic review of observational studies
Authors: Kumburegama Buddheera W.M.B. , Kristensen Andreas T. , Bjelakovic Goran , Nikolova Dimitrinka , Asante Mark A. , Bjelakovic Milica , Koretz Ronald L. , Balakumar Mithuna M. , Michelsen Martin E. , Klingenberg Sarah L. , Gluud Christian
Published: October 2024

Background

Chronic hepatitis C virus infection presents a substantial global health burden, frequently resulting in severe liver conditions. Hepatitis C virus (HCV) therapy requires complex decision-making. Direct-acting antivirals (DAAs) offer a potential solution by targeting viral proteins to inhibit replication. Understanding DAAs real-world effectiveness and how they impact long-term outcomes beyond clinical trials is essential. We aim to comprehensively evaluate the benefits and harms of DAAs in individuals with chronic HCV infection, reported in observational studies.

Methods

We will consider for inclusion prospective and retrospective observational studies with quasirandomised, cohort, case-control, controlled before-and-after, and cross-sectional designs. Our experimental interventions will be any class of DAAs available on the market or in development. DAAs could have been administered alone, in combination, or with other medical co-interventions. Our control interventions will be untreated chronic HCV conditions, with or without placebo.

Participants will be adults, regardless of demographics, treatment history, or healthcare setting. Our primary outcomes will be participants experiencing hepatitis C-related morbidity or all-cause mortality, serious adverse events, and health-related quality of life. Secondary outcomes will include all-cause mortality, cirrhosis, variceal bleeding, hepato-renal syndrome, hepatocellular carcinoma, hepatic encephalopathy, non-serious adverse events, liver transplantation, lack of sustained virological response, histological improvement, and decreases in alanine aminotransferase and aspartate aminotransferase levels.

We will apply search strategies to search MEDLINE, Embase, Web of Science, grey literature, and trial registers. We will use Covidence®to screen the result, including citations. Individual double-data extraction will include study details and outcomes, with independent review authors resolving discrepancies. We will assess bias using the ROBINS-I tool. Meta-analyses will employ random-effects models for both dichotomous and continuous outcomes, assessing heterogeneity. Subgroup and sensitivity analyses will explore effect modifications and address missing data. Trial Sequential Analysis will control type I and type II errors. We will evaluate publication bias using funnel plots and Egger’s regression test and assess certainty of evidence using GRADE.

Discussion

The findings will inform clinical decisions and benefit those affected by HCV, healthcare professionals, and policymakers.

Systematic review registration

PROSPERO: CRD42023494844
Ultrasensitive allele inference from immune repertoire sequencing data with MiXCR
Authors: Mikelov Artem , Nefediev George , Tashkeev Alexander , Rodriguez Oscar L. , Aguilar Ortmans Diego , Skatova Valeriia , Izraelson Mark , Davydov Alexey N. , Poslavsky Stanislav , Rahmouni Souad , Watson Corey T. , Chudakov Dmitriy , Boyd Scott D. , Bolotin Dmitry
Published: October 2024

Allelic variability in the adaptive immune receptor loci, which harbor the gene segments that encode B cell and T cell receptors (BCR/TCR), is of critical importance for immune responses to pathogens and vaccines. Adaptive immune receptor repertoire sequencing (AIRR-seq) has become widespread in immunology research making it the most readily available source of information about allelic diversity in immunoglobulin (IG) and T cell receptor (TR) loci. Here, we present a novel algorithm for extrasensitive and specific variable (V) and joining (J) gene allele inference, allowing the reconstruction of individual high-quality gene segment libraries. The approach can be applied for inferring allelic variants from peripheral blood lymphocyte BCR and TCR repertoire sequencing data, including hypermutated isotype-switched BCR sequences, thus allowing high-throughput novel allele discovery from a wide variety of existing data sets. The developed algorithm is a part of the MiXCR software. We demonstrate the accuracy of this approach using AIRR-seq paired with long-read genomic sequencing data, comparing it to a widely used algorithm, TIgGER. We applied the algorithm to a large set of IG heavy chain (IGH) AIRR-seq data from 450 donors of ancestrally diverse population groups, and to the largest reported full-length TCR alpha and beta chain (TRAandTRB) AIRR-seq data set, representing 134 individuals. This allowed us to assess the genetic diversity within theIGH,TRA, andTRBloci in different populations and to establish a database of alleles of V and J genes inferred from AIRR-seq data and their population frequencies with free public access through VDJ.online database.
Comment on “Recovering noise-free quantum observables”
Authors: Etxezarreta Martinez Josu , Sanz Larrarte Olatz , Oliva del Moral Javier , Dastbasteh Reza , Otxoa Ruben M.
Published: October 2024

Zero-noise extrapolation (ZNE) stands as the most widespread quantum error mitigation technique used in the recovery of noise-free expectation values of observables of interest by means of noisy intermediate-scale quantum (NISQ) machines. Recently, Otten and Gray proposed a multidimensional generalization of polynomial ZNE for systems where there is no tunable global noise source [M. Otten , ]. Specifically, the authors refer to multiqubit systems where each of the qubits experiences several noise processes with different rates, i.e., a nonidentically distributed noise model. The authors proposed a hypersurface method for mitigating such noise, which is technically correct in the sense that if the required samples are obtained, the observable can be mitigated. However, the proposed method presents an excessive experiment repetition overhead, making it impractical, at least from the perspective of quantum computing. Specifically, we discuss that in order to perform a simple mitigation task to multinomial order 3 considering 100 qubits, there, 2.5 years or over a million quantum processors running in parallel would be required. In this Comment, we show that the traditional extrapolation techniques can be applied for such a nonidentically distributed noise setting consisting of many different noise sources, implying that the measurement overhead is practical. In fact, we discuss that the previous mitigation task can be resolved in the order of minutes using a single quantum processor by means of standard ZNE. To do so, we clarify what it is meant by a tunable global noise source in the context of ZNE, a concept that we consider important to be clarified for a correct understanding of how and why these methods work.

Published by the American Physical Society
2024
Fully strange tetraquark resonant states as the cousins of
X(6900)
Authors: Ma Yao , Wu Wei-Lin , Meng Lu , Chen Yan-Ke , Zhu Shi-Lin
Published: October 2024

We conduct systematic calculations of the S-wave fully strange systems with “normal” (JPC=0++,1+−,2++) and “exotic” (JPC=0+−,1++,2+−) C-parities, which are the strange analog of the fully charmed tetraquark state X(6900). Within a constituent quark potential model, we employ the Gaussian expansion method to solve the four-body Schrödinger equation and the complex scaling method to identify resonant states. We obtain a series of resonant states and zero-width states in the mass range of 2.7 to 3.3 GeV, with their widths ranging from less than 1 to about 50 MeV. Their rms radii strongly indicate that they are compact tetraquark states. Among these states, the T4s,2++(2714) may be the most likely one to be observed experimentally. We urge the experimental exploration of the 2++  sss¯s¯ state around 2.7 GeV in the ϕϕ channel. Since the lowest S-wave sss¯s¯ state is around 2.7 GeV, the compact wave sss¯s¯ states are expected to be heavier. Hence, ϕ(2170) and X(2370) are unlikely to be compact tetraquark states.

Published by the American Physical Society
2024
Boltzmann sampling with quantum annealers via fast Stein correction
Authors: Shibukawa Ryosuke , Tamura Ryo , Tsuda Koji
Published: October 2024

Despite the attempts to apply a quantum annealer to Boltzmann sampling, it is still impossible to perform accurate sampling at arbitrary temperatures. Conventional distribution correction methods such as importance sampling and resampling cannot be applied, because the analytical expression of sampling distribution is unknown for a quantum annealer. Stein correction [Q. Liu and J. Lee, in , Proceedings of Machine Learning Research (PMLR, 2017), Vol. 54, pp. 952–961] can correct the samples by weighting without the knowledge of the sampling distribution, but the naive implementation requires the solution of a large-scale quadratic program, hampering usage in practical problems. In this article, a fast and approximate method based on a random feature map and exponentiated gradient updates is developed to compute the sample weights and is used to correct the samples generated by D-Wave quantum annealers. In benchmarking problems, it is observed that the residual error of thermal average calculations is reduced significantly. If combined with our method, quantum annealers may emerge as a viable alternative to long-established Markov chain Monte Carlo methods.

Published by the American Physical Society
2024
Exploring the potential of resonance islands and bent crystals for a slow extraction from circular hadron accelerators
Authors: Veres D. E. , Giovannozzi M. , Franchetti G.
Published: October 2024

New developments in accelerator physics have broadened the set of available techniques for manipulating charged-particle beams. Adiabatic trapping and transport of a beam in resonance islands has been studied and successfully implemented at the CERN Proton Synchrotron to perform multiturn extraction. Bent crystals have been successfully installed in the CERN Large Hadron Collider, improving the cleaning performance of the collimation system, and at the CERN Super Proton Synchrotron for reducing losses at the extraction septum in the case of slow extraction. In this Letter, we discuss the potential of the combined use of resonance islands and bent crystals to devise a technique to perform slow extraction in circular hadron accelerators. The proposed approach is promising, particularly for applications with high-intensity beams, as it could dramatically reduce the losses on the extraction devices.

Published by the American Physical Society
2024
Digital Quantum Simulation of a (1+1)D SU(2) Lattice Gauge Theory with Ion Qudits
Authors: Calajó Giuseppe , Magnifico Giuseppe , Edmunds Claire , Ringbauer Martin , Montangero Simone , Silvi Pietro
Published: October 2024

We present a quantum simulation strategy for a (1+1)-dimensional SU(2) non-Abelian lattice gauge theory with dynamical matter, a hardcore-gluon Hamiltonian Yang-Mills, tailored to a six-level trapped-ion-qudit quantum processor, as recently experimentally realized [Nat. Phys. 18, 1053 (2022)]. We employ a qudit encoding fulfilling gauge invariance, an SU(2) Gauss’s law. We discuss the experimental feasibility of generalized Mølmer-Sørensen gates used to efficiently simulate the dynamics. We illustrate how a shallow circuit with these resources is sufficient to implement scalable digital quantum simulation of the model. We also numerically show that this model, albeit simple, can dynamically manifest physically relevant properties specific to non-Abelian field theories, such as baryon excitations.

Published by the American Physical Society
2024
Exploring the job (dis)satisfaction indicators of online food delivery employees: insights from employees' online reviews
Authors: Saydam Mehmet Bahri , Altun Ozlem , Karatepe Tuna , Olorunsola Victor , Naderiadib Alpler Nazanin
Published: October 2024

Purpose

The present study sought to determine the main themes employees discussed in online reviews associated with satisfaction (pros) and dissatisfaction (cons).

Design/methodology/approach

This study used qualitative content analysis to examine employee reviews working in India's largest food delivery company.

Findings

The analyses revealed the existence of seven themes: company environment, employees, salary, work–life balance, company culture and values, flexibility and favoritism. Negative themes were associated with the “work-life balance” and “favoritism” themes. The results provided valuable insights into online food delivery platform employees' overall experiences based on social media information and aided in identifying key themes associated with various satisfaction levels.

Originality/value

This study contributes to the literature by uniquely utilizing user-generated content from an employment search engine as a novel data source to investigate the factors influencing satisfaction and dissatisfaction among online food delivery employees. This approach represents a significant departure from traditional survey-based methods, filling a gap in the literature by offering insights directly from employees' unfiltered perspectives. By leveraging this innovative methodology, our research provides a fresh and nuanced understanding of the experiences and concerns of online food delivery workers, thereby adding substantial value to the fields of organizational behavior and human resource management.
Leader controlling behaviors and proactive behavior among police officers: perceived powerlessness mechanism
Authors: Abdillah Muhammad Rasyid , Lambiombir Josina , Anita Rizqa , Rahmat Adi
Published: October 2024

Purpose

This study explores how controlling leadership behaviors, such as authoritarian leadership and abusive supervision, affect police officers’ proactive behavior. Specifically, it examines how perceived powerlessness mediates the relationship between these leadership styles and officers’ proactive behavior.

Design/methodology/approach

We employed structural equation modeling with partial least squares analysis to test our hypotheses, utilizing a sample of police officers employed within a regional police institution in Indonesia.

Findings

The findings of this study indicate that both authoritarian leadership and abusive supervision have the potential to diminish or impede the proactive behavior of police officers by shaping their perception of powerlessness.

Originality/value

This study contributes to the broader understanding of how leader-controlling behaviors, such as authoritarian leadership and abusive supervision, impact the proactive behavior of police officers within the specific context of Indonesia.
A qualitative study revisiting the theoretical lens of brand image and developing the consumer brand image schema
Authors: Pich Christopher , Armannsdottir Guja
Published: October 2024

Purpose

Brand image remains a “nebulous” construct with very few frameworks dedicated to understanding the process of uncovering brand image. This is supported by explicit calls for greater clarity on how to examine brand image, particularly in different settings. Political branding is one setting that has received some attention, however, research has focused on “party” political brands and neglected “non-party” brands (independent candidates). Therefore, this study aims to examine how young citizens interpret independent non-party brands through the theoretical lens of brand image in the context of Guernsey and develop a systematic brand image framework that provides greater clarity to this topic area.

Design/methodology/approach

A qualitative interpretivist approach using focus group discussions was adopted to investigate the phenomenon from the perspective of young voters 18–24 years of age. Focus group discussions ceased upon reaching theoretical saturation and a six-staged thematic analytical strategy was adopted to analyse the findings.

Findings

This study revealed deep insight into the political brand image of non-party brands from the perspective of young voters in an under-explored context. More specifically, this study uncovered that Guernsey’s political brands were seen as “accessible”; however, there was little differentiation, identification and connection between young voters and politicians. Further, this study uncovered a series of opportunities for strategists such as the desire for a younger generational view and younger representation in the Guernsey Parliament and greater clarity, distinction and authenticity related to political brand image.

Originality/value

This study addresses explicit calls for further research on brand image with a distinct focus on non-party political brands. Further, this study concludes by presenting the “consumer brand image schema”; a systematic framework which can be used to uncover brand image within and beyond the setting of politics. Further, the framework operationalises the complex concept of brand image and provides a three-stage process to examine and develop brand image. This will enable strategists to develop targeted strategies and adopt appropriate tactics to manage brand image to ensure brands are differentiated and interpreted as authentic, relatable, engaging, accessible and identifiable.
A higher tissue fraction of parenchyma in secondary xylem supports growth recovery of angiosperm trees after drought
Authors: Zhang Xijin , Li Qingyao , Yang Yongchuan , Fukuda Kenji , Morris Hugh , Jansen Steven , Da Liangjun , Song Kun
Published: October 2024

Resilience to drought represents an important focus for trees during climate change, with the aim of predicting the resistance and recovery of species worldwide. Previous studies mainly linked tree growth resilience to plant functional traits that are related to resource acquisition and investment. Here, we investigate a potential link between resilience and the amount of parenchyma tissue in wood, a multifunctional tissue that may provide various physiological benefits to drought‐related mechanisms.

We compiled a global tree‐ring data set to evaluate the relationship between growth resistance, resilience or recovery from drought and xylem parenchyma tissue fractions of 50 angiosperms, which was complemented with a local study of nine species from Mt. Tiantong in China. We also assessed the influence of climate and phylogeny on these relationships.

We found that growth recovery after drought was positively related to the fractions of total parenchyma locally and globally. This association remained statistically significant when accounting for the effects of climate and phylogeny. No other associations between parenchyma fractions and growth resilience metrics were statistically significant.

Our results suggest that drought recovery of angiosperm trees is affected by the amount of parenchyma. Incorporating xylem parenchyma fraction with other traits, such as hydraulic traits, could therefore enhance our comprehension of how various angiosperm tree species will respond to future droughts. Further studies should focus on unravelling the physiological roles of xylem parenchyma fraction.

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