bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Tophus Impact Questionnaire (TIQ-20): responsiveness to change during urate-lowering therapy
Authors: Cao Cindy , Gamble Greg , Horne Anne , Aati Opetaia , Doyle Anthony , Drake Jill , Stamp Lisa K , Dalbeth Nicola 
Published: September 2023

Abstract

Objectives
In 2015, the 20-item Tophus Impact Questionnaire (TIQ-20) was developed as a tophus-specific patient-reported outcome measure. The aim of this study was to determine whether TIQ-20 scores change during urate-lowering therapy.

Methods
We analysed data from a 2-year clinical trial of allopurinol dose escalation using a treat-to-target serum urate approach. For participants with tophaceous gout, the longest diameter of up to three index tophi was measured, using Vernier calipers, and the TIQ-20 was recorded at study visits. Participants at the one site were invited to participate in a dual-energy CT (DECT) substudy. Participants were included in this analysis if they had tophaceous gout and TIQ-20 scores available at baseline, Year 1 and Year 2 (n = 58, 39 with DECT data). Data were analysed using a mixed-model approach to repeated measures.

Results
Improvements were observed in all tophus measures over the 2-year period. The mean (s.d.) TIQ-20 scores reduced over 2 years from 3.59 (1.77) to 2.46 (1.73), P &lt; 0.0001, and the mean (95% CI) TIQ-20 change over the 2 years was –1.13 (–1.54, –0.71). The effect size (Cohen’s d) for the change in the sum of the index tophi diameter over 2 years was 0.68, for the DECT urate volume was 0.50, and for the TIQ-20 was 0.71.

Conclusion
For people with tophaceous gout treated with allopurinol using a treat-to-target serum urate approach, improvements in TIQ-20 occurred, as did improvements in physical and imaging tophus measures. These findings demonstrate that the TIQ-20 is a responsive patient-reported instrument of tophus impact.
Fitness effects of mutations to SARS-CoV-2 proteins
Authors: Bloom Jesse D , Neher Richard A 
Published: September 2023

Abstract
Knowledge of the fitness effects of mutations to SARS-CoV-2 can inform assessment of new variants, design of therapeutics resistant to escape, and understanding of the functions of viral proteins. However, experimentally measuring effects of mutations is challenging: we lack tractable lab assays for many SARS-CoV-2 proteins, and comprehensive deep mutational scanning has been applied to only two SARS-CoV-2 proteins. Here, we develop an approach that leverages millions of publicly available SARS-CoV-2 sequences to estimate effects of mutations. We first calculate how many independent occurrences of each mutation are expected to be observed along the SARS-CoV-2 phylogeny in the absence of selection. We then compare these expected observations to the actual observations to estimate the effect of each mutation. These estimates correlate well with deep mutational scanning measurements. For most genes, synonymous mutations are nearly neutral, stop-codon mutations are deleterious, and amino acid mutations have a range of effects. However, some viral accessory proteins are under little to no selection. We provide interactive visualizations of effects of mutations to all SARS-CoV-2 proteins (https://jbloomlab.github.io/SARS2-mut-fitness/). The framework we describe is applicable to any virus for which the number of available sequences is sufficiently large that many independent occurrences of each neutral mutation are observed.
Evolution of transient RNA structure–RNA polymerase interactions in respiratory RNA virus genomes
Authors: Rigby Charlotte V , Sabsay Kimberly R , Bisht Karishma , Eggink Dirk , Jalal Hamid , te Velthuis Aartjan J W 
Published: September 2023

Abstract
RNA viruses are important human pathogens that cause seasonal epidemics and occasional pandemics. Examples are influenza A viruses (IAV) and coronaviruses (CoV). When emerging IAV and CoV spill over to humans, they adapt to evade immune responses and optimize their replication and spread in human cells. In IAV, adaptation occurs in all viral proteins, including the viral ribonucleoprotein (RNP) complex. RNPs consist of a copy of the viral RNA polymerase, a double-helical coil of nucleoprotein, and one of the eight segments of the IAV RNA genome. The RNA segments and their transcripts are partially structured to coordinate the packaging of the viral genome and modulate viral mRNA translation. In addition, RNA structures can affect the efficiency of viral RNA synthesis and the activation of host innate immune response. Here, we investigated if RNA structures that modulate IAV replication processivity, so-called template loops (t-loops), vary during the adaptation of pandemic and emerging IAV to humans. Using cell culture-based replication assays and in silico sequence analyses, we find that the sensitivity of the IAV H3N2 RNA polymerase to t-loops increased between isolates from 1968 and 2017, whereas the total free energy of t-loops in the IAV H3N2 genome was reduced. This reduction is particularly prominent in the PB1 gene. In H1N1 IAV, we find two separate reductions in t-loop free energy, one following the 1918 pandemic and one following the 2009 pandemic. No destabilization of t-loops is observed in the influenza B virus genome, whereas analysis of SARS-CoV-2 isolates reveals destabilization of viral RNA structures. Overall, we propose that a loss of free energy in the RNA genome of emerging respiratory RNA viruses may contribute to the adaption of these viruses to the human population.
Viral community composition of hypersaline lakes
Authors: Le Lay Callum , Hamm Joshua N , Williams Timothy J , Shi Mang , Cavicchioli Ricardo , Holmes Edward C 
Published: September 2023

AbstractDespite their widespread distribution and remarkable antiquity no RNA viruses definitively associated with the domain Archaea have been identified. In contrast, 17 families of DNA viruses are known to infect archaea. In an attempt to uncover more of the elusive archaeal virosphere, we investigated the metatranscriptomes of hypersaline lakes that are a rich source of archaea. We sequenced RNA extracted from water filter samples of Lake Tyrrell (Victoria, Australia) and cultures seeded from four lakes in Antarctica. To identify highly divergent viruses in these data, we employed a variety of search tools, including Hidden Markov models (HMMs) and position-specific scoring matrices (PSSMs). From this, we identified 12 highly divergent, RNA virus-like candidate sequences from the virus phyla Artverviricota, Duplornaviricota, Kitrinoviricota, Negarnaviricota, and Pisuviricota, including those with similarity to the RNA-dependent RNA polymerase (RdRp). An additional analysis with an artificial intelligence (AI)-based approach that utilises both sequence and structural information identified seven putative and highly divergent RdRp sequences of uncertain phylogenetic position. A sequence matching the Pisuviricota from Deep Lake in Antarctica had the strongest RNA virus signal. Analyses of the dinucleotide representation of the virus-like candidates in comparison to that of potential host species were in some cases compatible with an association to archaeal or bacterial hosts. Notably, however, the use of archaeal CRISPR spacers as a BLAST database failed to detect any RNA viruses. We also described DNA viruses from the families Pleolipoviridae, Sphaerolipoviridae, Halspiviridae, and the class Caudoviricetes. Although we were unable to provide definitive evidence the existence of an RNA virus of archaea in these hypersaline lakes, this study lays the foundations for further investigations of highly divergent RNA viruses in natural environments.
Sigma factors of RNA polymerase in the pathogenic spirochaete Leptospira interrogans, the causative agent of leptospirosis
Authors: Kędzierska‐Mieszkowska Sabina 
Published: September 2023

AbstractThe aim of this review is to summarize the current knowledge on the role of σ factors in a highly invasive spirochaete Leptospira interrogans responsible for leptospirosis that affects many mammals, including humans. This disease has a significant impact on public health and the economy worldwide. In bacteria, σ factors are the key regulators of gene expression at the transcriptional level and therefore play an important role in bacterial adaptative response to different environmental stimuli. These factors form a holoenzyme with the RNA polymerase core enzyme and then direct it to specific promoters, which results in turning on selected genes. Most bacteria possess several different σ factors that enable them to maintain basal gene expression, as well as to regulate gene expression in response to specific environmental signals. Recent comparative genomics and in silico genome‐wide analyses have revealed that the L. interrogans genome, consisting of two circular chromosomes, encodes a total of 14 σ factors. Among them, there is one putative housekeeping σ70‐like factor, and three types of alternative σ factors, i.e., one σ54, one σ28 and 11 putative ECF (extracytoplasmic function) σE‐type factors. Here, characteristics of these putative σ factors and their possible role in the L. interrogans gene regulation (especially in this pathogen's adaptive response to various environmental conditions, an important determinant of leptospiral virulence), are presented.
Chewing Gum Cannot Reduce Postoperative Abdominal Pain and Nausea After Posterior Spinal Fusions in Patients With Adolescent Idiopathic Scoliosis
Authors: Tong Bingdu , Chen Zefu , Li Gaoyang , Zhang Li , Chen Yaping 
Published: September 2023

Study Design:
A systematic review and meta-analysis of randomized controlled trials.

Objective:
The aim of this study was to determine the effect of chewing gum on postoperative abdominal pain, nausea, and hospital stays after posterior spinal fusions (PSFs) in patients with adolescent idiopathic scoliosis (AIS).

Summary of Background Data:
Chewing gum had been extensively reported to improve bowel motility and is recommended to hasten bowel recovery following gastrointestinal surgery. However, there is no conclusive evidence regarding the effect of chewing gum on postoperative abdominal pain, nausea, and hospital stays after PSFs in AIS patients.

Methods:
A comprehensive literature search was performed for relevant randomized controlled trials using PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and Embase. Studies were selected to compare the use of chewing gum versus standard care in the management of postoperative abdominal pain and nausea in AIS patients undergoing PSFs. Hospital stays were also investigated. The study was conducted using the checklist for PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses).

Results:
Three randomized controlled trials were included in the systematic review and the meta-analysis. No significant effect of chewing gum was highlighted concerning the postoperative abdominal pain scores at 24 and 48 hours [24 h: mean difference (MD)=0.45, 95% CI=−0.97 to 0.07, P=0.09; 48 h: MD=−0.24, 95% CI=−0.79 to 0.32, P=0.41]. No significant difference regarding the postoperative nausea scores was found at 24 and 48 hours (24 h: MD=0.26, 95% CI=−0.27 to 0.79, P=0.34; 48 h: MD=0.06, 95% CI=−0.36 to 0.48, P=0.77). No significant difference regarding hospital stays was found (MD=0.13, 95% CI=−0.02 to 0.28, P=0.09).

Conclusions:
Based on the current studies, chewing gum does not have a significant effect on postoperative abdominal pain, nausea, or hospital stays after PSFs in AIS patients. As the effect of chewing gum in reducing postoperative abdominal pain exhibits a tendency towards statistical significance (P=0.09), the effect of chewing gum in spinal surgery merits further studies with larger sample size.
A single-cell transcriptome analysis and prognostic model construction of stromal cells for renal cell carcinoma
Authors: Liao Kuo , Wang Yifan , Liu Shuangxin , Li Quhuan 
Published: September 2023

AbstractRenal cell carcinoma (RCC) is among the top three cancers of the urinary system and its incidence keeps increasing worldwide in recent decades. However, methods for accurate prognosis evaluation and effective treatment are still lacking nowadays. Here, to explore the molecular expression features of RCC and establish a new RCC clinical prognosis evaluation model, a cell landscape of 187,263 renal cells obtained from eight patients with RCC was analyzed in this study. And by extracting and focusing on the main stromal cells from RCC tissues, innovative molecular characteristics and pathways of tumors were identified, like the well-known hypoxia pathway. By analyzing cell-cell communication, fibroblasts were found to promote tumor development by repressing natural killer cells. Based on Cox and least absolute shrinkage and selection operator regression analysis, four risk factors were screened and used to construct a reliable RCC clinical risk estimation model. In conclusion, our work provides new insights into the tumor microenvironment of RCC, as well as potential therapeutic targets and a clinical risk model for RCC invasiveness. Hopefully, these findings will be useful for cancer research and clinical treatment in future.
Critical Behavioral Traits Foster Peer Engagement in Online Mental Health Communities
Authors: Srivastava Aseem , Gupta Tanya , Cerezo Alison , (Grin) Lord Sarah Peregrine , Akhtar Md Shad , Chakraborty Tanmoy 
Published: September 2023

ABSTRACTOnline Mental Health Communities (OMHCs), such as Reddit, have witnessed a surge in popularity as go-to platforms for seeking information and support in managing mental health needs. Platforms like Reddit offer immediate interactions with peers, granting users a vital space for seeking mental health assistance. However, the largely unregulated nature of these platforms introduces intricate challenges for both users and society at large. This study explores the factors that drive peer engagement within counseling threads, aiming to enhance our understanding of this critical phenomenon. We introduce BeCOPE, a novel behavior encoded Peer counseling dataset comprising over 10,118 posts and 58,279 comments sourced from 21 mental health-specific subreddits. The dataset is annotated using three major fine-grained behavior labels: (a) intent, (b) criticism, and (c) readability, along with the emotion labels. Our analysis indicates the prominence of “self-criticism” as the most prevalent form of criticism expressed by help-seekers, accounting for a significant 43% of interactions. Intriguingly, we observe that individuals who explicitly express their need for help are 18.01% more likely to receive assistance compared to those who present “surveys” or engage in “rants.” Furthermore, we highlight the pivotal role of well-articulated problem descriptions, showing that superior readability effectively doubles the likelihood of receiving the sought-after support. Our study emphasizes the essential role of OMHCs in offering personalized guidance and unveils behavior-driven engagement patterns.
Hemoglobin specific volume width might promote the prevalence and poor long-term prognosis of American cardiovascular disease adult patients: the NHANES 1999-2020
Authors: Zhang Lin , Chang Jun , Wang Kaiyue , Zhou Ying , Wang Liming , Zhang Lele , Zhang Xuemei , Fu Zhifei , Han Lifeng , Gao Xiumei 
Published: September 2023

BackgroundCardiovascular disease (CVD) patients are always accompanied by erythrocyte dysfunction. However, current erythrocyte-related indicators can’t explain the prevalence and long-term prognosis of CVD. Therefore, hemoglobin specific volume width (HSW) was first created to explain this phenomenon.MethodsHSW’s quartiles were determined with Q1 [1.88,3.64] cL/g, Q2 (3.64,3.85] cL/g, Q3 (3.85,4.11] cL/g, and Q4 (4.11,11.74] cL/g. Among the 57,894 participants derived from National Health and Nutrition Examination Survey (NMAHES), 5,623 CVD patients had a whole following time (median 79 months). Logistic regression, Cox regression, Kaplan–Meier curves, and restricted cubic spline were utilized for analysis.ResultsAmong the non-CVD (n=51,243) and CVD (n=6,651) individuals, the percentages of CVD in quartiles of HSW (Q1, Q2, Q3, and Q4) were 4.95%, 7.11%, 10.51%, and 16.14% (P< 0.0001). Adjusted odds ratio (OR) was still significant, 1.46 (95% CI 1.33, 1.60). Processing Q1 as reference, the adjusted ORs for Q3 and Q4 were 1.19(95% CI 1.05,1.35) and 1.54 (95% CI 1.36,1.73). Females had a higher risk (OR 1.49, 95% CI 1.32, 1.68) of CVD than males with increasing HSW. Diabetes mellitus (DM) patients had the highest risk of CVD (OR 1.54, 95% CI 1.30,1.84) than preDM or healthy individuals. Among dead (n=2,517) and alive CVD (n=3,106) patients, the adjusted HSW hazard ratio (HR) was 1.70 (95% CI 1.48,1.95). An inverse L-curve with an inflexion point of 3.96 was observed between HR and CVD. CVD patients with HSW > 3.96 had a poor prognosis than HSW <= 3.96.ConclusionsHSW is a novel risk for CVD prevalence and long-term prognosis. Females and DM patients have a higher risk of CVD when HSW increases.
Core gene set of the speciesSaccharomyces cerevisiae
Authors: Dietrich Fred S. , Magwene Paul , McCusker John 
Published: September 2023

AbstractExamination of the genome sequence ofSaccharomyces cerevisiaestrain S288c and 93 additional diverse strains allows identification of the 5873 genes that make up the core set of genes in this species and gives a better sense of the organization and plasticity of this genome.S. cerevisiaestrains each contain dozens to hundreds of strain specific genes. In addition to a variable content of retrotransposons, some strains contain a novel transposable element, Ty7. Examination further shows that some annotated putative protein coding genes are likely artifacts. We propose altering approximately 5% of the current annotations in the widely used reference strain S288c. Potential null alleles are common and found in all 94 strains examined, with these potential null alleles typically containing a single stop codon or frameshift. There are also gene remnants, pseudogenes, and variable arrays of genes. Among the core genes there are now only 373 protein coding genes of unknown function, classified as uncharacterized in the Saccharomyces Genome Database. This work suggests that there is a role for carefully edited and annotated genome sequences in understanding the genome organization and content of a species. We propose that gene remnants be added to the repertoire of features found in theS. cerevisiaegenome, and likely other fungal species.
MacaqueNet: big-team research into the biological drivers of social relationships
Authors: De Moor Delphine ,   MacaqueNet, Skelton Macaela , Schülke Oliver , Ostner Julia , Neumann Christof , Duboscq Julie , Brent Lauren J. N. 
Published: September 2023

AbstractFor many animals, social relationships are a key determinant of fitness. However, major gaps remain in our understanding of the adaptive function, ontogeny, evolution, and mechanistic underpinnings of social relationships. There is a vast and ever-accumulating amount of social behavioural data on individually recognised animals, an incredible resource to shed light onto the biological basis of social relationships. Yet, the full potential of such data lies in comparative research across taxa with distinct life histories and ecologies. Substantial challenges impede systematic comparisons, one of which is the lack of persistent, accessible, and standardised databases.Here, we advocate for the creation of big-team collaborations and comparative databases to unlock the wealth of behavioural data for research on social relationships by introducing MacaqueNet (https://macaquenet.github.io/).As a global collaboration of over 100 researchers, the MacaqueNet database encompasses data from 1981 to the present on 14 species and is the first publicly searchable and standardised database on affiliative and agonistic animal social networks. With substantial inter-specific variation in ecology and social structure and the first published record on macaque behaviour dating back to 1956, macaque research has already contributed to answering fundamental questions on the biological bases and evolution of social relationships. Building on these strong foundations, we believe that MacaqueNet can further promote collaborative and comparative research on social behaviour.We believe that big-team approaches to building standardised databases, bringing together data contributors and researchers, will aid much-needed large-scale comparative research in behavioural ecology and beyond. We describe the establishment of MacaqueNet, from starting a large-scale collective to the creation of a cross-species collaborative database and the implementation of data entry and retrieval protocols. As such, we hope to provide a functional example for future endeavours of large-scale collaborative research into the biology of social behaviour.
Tissue-resident uterine regulatory T cells support fetal growth
Authors: Florez Laura Maria , Fourcade Gwladys , Darrassse-Jèze Guillaume , Barennes Pierre , Gan-Fernandez Karina , Régnier Paul , Nehar-Belaid Djamel , Courau Tristan , Ruocco Maria Grazia , Zacchigna Serena , Giacca Mauro , Lion Julien , Mooney Nuala , Tchitchek Nicolas , Mariotti-Ferrandiz Encarnita , Klatzmann David 
Published: September 2023

SUMMARYRegulatory T cells (Tregs) are known to contribute to successful allogeneic pregnancy by promoting maternal-fetal tolerance. Here, phenotypic studies and parabionts identified a population of uterine tissue-resident Tregs (uTregs) with trophic functions in the non-pregnant mouse endometrium. Phenotypically, uTregs are CD25-/loand they present characteristic phenotypic attributes of tissue-resident memory T cells with effector functions. Transcriptionally, uTregs are distinguishable from other peripheral or tissue-resident Tregs by their expression of genes related to extracellular matrix remodeling and vasculogenesis, and they express a polyclonal T cell receptor (TCR) repertoire. Pregnancy triggers the expansion of uTregs, which remain CD25-/lo, retain their polyclonal TCR repertoire, and increase the expression of genes involved in regulation of hypoxia and vasculogenesis. Functionally, we show that uTregs support the proliferation of primary uterine microvascular endothelial cellsin vitroand that a specific depletion of uTregs in pregnant mice leads to fetal intra-uterine growth retardation (IUGR). Thus, a previously unidentified population of CD25-/louTregs promotes uterine tissue remodeling before and during pregnancy, and contributes to fetal growth.
Development of a cellular reporter assay to measure activity of MutSβ, a therapeutic target for Huntington’s disease
Authors: An Jian , Towle Theresa , Aksit Melis Atalar , Mohiuddin Mohiuddin , Castaneda Samantha , Nakashima Reiko , Moccia Rob , Bulawa Christine , Fleming James 
Published: September 2023

AbstractGenetic modifiers of age of onset in Huntington’s disease (HD) provide compelling evidence that somatic expansion of the CAG repeats is a critical driver of pathogenesis and demonstrate that repeat instability is modulated by DNA mismatch repair (MMR). A component of this pathway, MutSβ, a heterodimer comprised of MSH2 and MSH3, has emerged as a potential target for small-molecule therapeutic intervention. However, a robust cellular assay to interrogate genetic and pharmacological modifiers of MutSβ has not been reported. We have repurposed and optimized a tetranucleotide reporter assay to measure MutSβ activity in MMR-competent cells. We show that repeat instability is modulated by MSH3 protein levels and by its ATPase activity. In addition, we show that an inhibitor of HDAC3 modulates repeat instability, demonstrating the utility of the assay for pharmacological studies.