bluuebunny/crossref_metadata_2025_split huggingface dataset:
Building protein structure-specific rotamer libraries
Authors: Grybauskas Algirdas , Gražulis Saulius 
Published: July 2023

Abstract

Motivation
Identifying the probable positions of the protein side-chains is one of the protein modelling steps that can improve the prediction of protein–ligand and protein–protein interactions. Most of the strategies predicting the side-chain conformations use predetermined dihedral angle lists, also called rotamer libraries, that are usually generated from a subset of high-quality protein structures. Although these methods are fast to apply, they tend to average out geometries instead of taking into account the surrounding atoms and molecules and ignore structures not included in the selected subset. Such simplifications can result in inaccuracies when predicting possible side-chain atom positions.

Results
We propose an approach that takes into account both of these circumstances by scanning through sterically accessible side-chain conformations and generating dihedral angle libraries specific to the target proteins. The method avoids the drawbacks of lacking conformations due to unusual or rare protein structures and successfully suggests potential rotamers with average RMSD closer to the experimentally determined side-chain atom positions than other widely used rotamer libraries.

Availability and implementation
The technique is implemented in open-source software package rotag and available at GitHub: https://www.github.com/agrybauskas/rotag, under GNU Lesser General Public License.
Neuroticism personality traits are linked to adverse cardiovascular phenotypes in the UK Biobank
Authors: Mahmood Adil , Simon Judit , Cooper Jackie , Murphy Theodore , McCracken Celeste , Quiroz Juan , Laranjo Liliana , Aung Nay , Lee Aaron Mark , Khanji Mohammed Y , Neubauer Stefan , Raisi-Estabragh Zahra , Maurovich-Horvat Pal , Petersen Steffen E 
Published: July 2023

AbstractAimsTo evaluate the relationship between neuroticism personality traits and cardiovascular magnetic resonance (CMR) measures of cardiac morphology and function, considering potential differential associations in men and women.Methods and resultsThe analysis includes 36 309 UK Biobank participants (average age = 63.9 ± 7.7 years; 47.8% men) with CMR available and neuroticism score assessed by the 12-item Eysenck Personality Questionnaire-Revised Short Form. CMR scans were performed on 1.5 Tesla scanners (MAGNETOM Aera, Siemens Healthcare, Erlangen, Germany) according to pre-defined protocols and analysed using automated pipelines. We considered measures of left ventricular (LV) and right ventricular (RV) structure and function, and indicators of arterial compliance. Multivariable linear regression was used to estimate association of neuroticism score with individual CMR metrics, with adjustment for age, sex, obesity, deprivation, smoking, diabetes, hypertension, hypercholesterolaemia, alcohol use, exercise, and education. Higher neuroticism scores were associated with smaller LV and RV end-diastolic volumes, lower LV mass, greater concentricity (higher LV mass to volume ratio), and higher native T1. Greater neuroticism was also linked to poorer LV and RV function (lower stroke volumes) and greater arterial stiffness. In sex-stratified analyses, the relationships between neuroticism and LV stroke volume, concentricity, and arterial stiffness were attenuated in women. In men, association (with exception of native T1) remained robust.ConclusionGreater tendency towards neuroticism personality traits is linked to smaller, poorer functioning ventricles with lower LV mass, higher myocardial fibrosis, and higher arterial stiffness. These relationships are independent of traditional vascular risk factors and are more robust in men than women.
Do pooled estimates from orthodontic meta-analyses change depending on the meta-analysis approach? A meta-epidemiological study
Authors: Tatas Zacharias , Koutsiouroumpa Ourania , Seehra Jadbinder , Mavridis Dimitrios , Pandis Nikolaos 
Published: July 2023

Summary

Background
In meta-analyses involving a few trials, appropriate measures should be employed to assess between-study heterogeneity. When the number of studies is less than five and heterogeneity is evident, the Hartung and Knapp (HK) correction should be used. The aim of this study was to compare the reported estimates of published orthodontic meta-analyses with the pooled effect size estimates and prediction intervals (PI) calculated using eight heterogeneity estimators and corrected using the HK correction.

Material and methods
Systematic reviews (SRs) published between 2017 and 2022 in four orthodontic journals and the Cochrane Database of Systematic Reviews with a meta-analysis of at least three studies were sourced. Study characteristics were extracted at the SR and the outcome/meta-analysis levels. All selected meta-analyses were re-analysed by fitting a random-effects model using eight different heterogeneity estimators, both with and without the HK correction. For each meta-analysis, the overall estimate, along with its standard error, the P-value, and the corresponding 95% confidence interval (CI), the between-study variance (tau2), the I2 statistic, and the PI were calculated.

Results
One-hundred-six SRs were analysed. The most prevalent type of SR was non-Cochrane (95.3%), and the most used meta-analyses synthesis model was the random effect (83.0%). The median number of primary studies was 6 (interquartile range: 5, range: 3–45). The between-study variance was reported in most of the eligible meta-analyses (91.5%), but the type of heterogeneity estimator was reported in only one of them (0.9%). In 5 of 106 meta-analyses (4.7%), the HK correction was applied to adjust the CI of the pooled estimate. The percentage of statistically significant results, which became statistically non-significant, ranged from 16.7% to 25%, depending on the heterogeneity estimator. As the number of studies in a meta-analysis increased, the difference between corrected and uncorrected CIs reduced. Based on the PIs, more than half of the meta-analyses having statistically significant results are likely to change in the future, suggesting the result of the meta-analysis is not conclusive.

Conclusions
The statistical significance of pooled estimates from meta-analyses with at least three studies is sensitive to the HK correction, the heterogeneity variance estimator, and PIs. Clinicians should be aware of the clinical implications of not appropriately assessing the effect of the small number of studies and the between-study heterogeneity when interpreting results from meta-analyses.
Considering admixture when producing draft genomes: an example in North American ratsnakes (Pantherophis alleghaniensis/Pantherophis obsoletus)
Authors: Burbrink Frank T , Harrington Sean M , Bobo Dean , Myers Edward A 
Published: July 2023

Abstract
The number of reference genomes of snakes lags behind several other vertebrate groups (e.g. birds and mammals). However, in the last two years, a concerted effort by researchers from around the world has produced new genomes of snakes representing members from several new families. Here, we present a high-quality, annotated genome of the central ratsnake (Pantherophis alleghaniensis), a member of the most diverse snake lineage, Colubroidea. Pantherophis alleghaniensis is found in the central part of the Nearctic, east of the Mississippi River. This genome was sequenced using 10X Chromium synthetic long reads and polished using Illumina short reads. The final genome assembly had an N50 of 21.82 Mb and an L50 of 22 scaffolds with a maximum scaffold length of 82.078 Mb. The genome is composed of 49.24% repeat elements dominated by long interspersed elements. We annotated this genome using transcriptome assemblies from 14 tissue types and recovered 28,368 predicted proteins. Finally, we estimated admixture proportions between two species of ratsnakes and discovered that this specimen is an admixed individual containing genomes from the western (Pantherophis obsoletus) and central ratsnakes (P. alleghaniensis). We discuss the importance of considering interspecific admixture in downstream approaches for inferring demography and phylogeny.
Whole Animal Genome Sequencing: user-friendly, rapid, containerized pipelines for processing, variant discovery, and annotation of short-read whole genome sequencing data
Authors: Cullen Jonah N , Friedenberg Steven G 
Published: July 2023

Abstract
Advancements in massively parallel short-read sequencing technologies and the associated decreasing costs have led to large and diverse variant discovery efforts across species. However, processing high-throughput short-read sequencing data can be challenging with potential pitfalls and bioinformatics bottlenecks in generating reproducible results. Although a number of pipelines exist that address these challenges, these are often geared toward human or traditional model organism species and can be difficult to configure across institutions. Whole Animal Genome Sequencing (WAGS) is an open-source set of user-friendly, containerized pipelines designed to simplify the process of identifying germline short (SNP and indel) and structural variants (SVs) geared toward the veterinary community but adaptable to any species with a suitable reference genome. We present a description of the pipelines [adapted from the best practices of the Genome Analysis Toolkit (GATK)], along with benchmarking data from both the preprocessing and joint genotyping steps, consistent with a typical user workflow.
Sex-specific estimation of cis and trans regulation of gene expression in heads and gonads of Drosophila melanogaster
Authors: Puixeu Gemma , Macon Ariana , Vicoso Beatriz 
Published: July 2023

Abstract
The regulatory architecture of gene expression is known to differ substantially between sexes in Drosophila, but most studies performed so far used whole-body data and only single crosses, which may have limited their scope to detect patterns that are robust across tissues and biological replicates. Here, we use allele-specific gene expression of parental and reciprocal hybrid crosses between 6 Drosophila melanogaster inbred lines to quantify cis- and trans-regulatory variation in heads and gonads of both sexes separately across 3 replicate crosses. Our results suggest that female and male heads, as well as ovaries, have a similar regulatory architecture. On the other hand, testes display more and substantially different cis-regulatory effects, suggesting that sex differences in the regulatory architecture that have been previously observed may largely derive from testis-specific effects. We also examine the difference in cis-regulatory variation of genes across different levels of sex bias in gonads and heads. Consistent with the idea that intersex correlations constrain expression and can lead to sexual antagonism, we find more cis variation in unbiased and moderately biased genes in heads. In ovaries, reduced cis variation is observed for male-biased genes, suggesting that cis variants acting on these genes in males do not lead to changes in ovary expression. Finally, we examine the dominance patterns of gene expression and find that sex- and tissue-specific patterns of inheritance as well as trans-regulatory variation are highly variable across biological crosses, although these were performed in highly controlled experimental conditions. This highlights the importance of using various genetic backgrounds to infer generalizable patterns.
Identifying candidate de novo genes expressed in the somatic female reproductive tract of Drosophila melanogaster
Authors: Lombardo Kaelina D , Sheehy Hayley K , Cridland Julie M , Begun David J 
Published: July 2023

Abstract
Most eukaryotic genes have been vertically transmitted to the present from distant ancestors. However, variable gene number across species indicates that gene gain and loss also occurs. While new genes typically originate as products of duplications and rearrangements of preexisting genes, putative de novo genes—genes born out of ancestrally nongenic sequence—have been identified. Previous studies of de novo genes in Drosophila have provided evidence that expression in male reproductive tissues is common. However, no studies have focused on female reproductive tissues. Here we begin addressing this gap in the literature by analyzing the transcriptomes of 3 female reproductive tract organs (spermatheca, seminal receptacle, and parovaria) in 3 species—our focal species, Drosophila melanogaster—and 2 closely related species, Drosophila simulans and Drosophila yakuba, with the goal of identifying putative D. melanogaster-specific de novo genes expressed in these tissues. We discovered several candidate genes, located in sequence annotated as intergenic. Consistent with the literature, these genes tend to be short, single exon, and lowly expressed. We also find evidence that some of these genes are expressed in other D. melanogaster tissues and both sexes. The relatively small number of intergenic candidate genes discovered here is similar to that observed in the accessory gland, but substantially fewer than that observed in the testis.
Using Drosophila to identify naturally occurring genetic modifiers of amyloid beta 42- and tau-induced toxicity
Authors: Yang Ming , Zinkgraf Matthew , Fitzgerald-Cook Cecilia , Harrison Benjamin R , Putzier Alexandra , Promislow Daniel E L , Wang Adrienne M 
Published: July 2023

Abstract
Alzheimer's disease is characterized by 2 pathological proteins, amyloid beta 42 and tau. The majority of Alzheimer's disease cases in the population are sporadic and late-onset Alzheimer's disease, which exhibits high levels of heritability. While several genetic risk factors for late-onset Alzheimer's disease have been identified and replicated in independent studies, including the ApoE ε4 allele, the great majority of the heritability of late-onset Alzheimer's disease remains unexplained, likely due to the aggregate effects of a very large number of genes with small effect size, as well as to biases in sample collection and statistical approaches. Here, we present an unbiased forward genetic screen in Drosophila looking for naturally occurring modifiers of amyloid beta 42- and tau-induced ommatidial degeneration. Our results identify 14 significant SNPs, which map to 12 potential genes in 8 unique genomic regions. Our hits that are significant after genome-wide correction identify genes involved in neuronal development, signal transduction, and organismal development. Looking more broadly at suggestive hits (P &lt; 10−5), we see significant enrichment in genes associated with neurogenesis, development, and growth as well as significant enrichment in genes whose orthologs have been identified as significantly or suggestively associated with Alzheimer's disease in human GWAS studies. These latter genes include ones whose orthologs are in close proximity to regions in the human genome that are associated with Alzheimer's disease, but where a causal gene has not been identified. Together, our results illustrate the potential for complementary and convergent evidence provided through multitrait GWAS in Drosophila to supplement and inform human studies, helping to identify the remaining heritability and novel modifiers of complex diseases.
Oral Omilancor Treatment Ameliorates Clostridioides difficile Infection During IBD Through Novel Immunoregulatory Mechanisms Mediated by LANCL2 Activation
Authors: Tubau-Juni Nuria , Bassaganya-Riera Josep , Leber Andrew J , Alva Sameeksha S , Hontecillas Raquel 
Published: July 2023

Abstract

Background
Clostridioides difficile infection (CDI) is an opportunistic infection of the gastrointestinal tract, commonly associated with antibiotic administration, that afflicts almost 500 000 people yearly only in the United States. CDI incidence and recurrence is increased in inflammatory bowel disease (IBD) patients. Omilancor is an oral, once daily, first-in-class, gut-restricted, immunoregulatory therapeutic in clinical development for the treatment of IBD.

Methods
Acute and recurrent murine models of CDI and the dextran sulfate sodium–induced concomitant model of IBD and CDI were utilized to determine the therapeutic efficacy of oral omilancor. To evaluate the protective effects against C. difficile toxins, in vitro studies with T84 cells were also conducted. 16S sequencing was employed to characterize microbiome composition.

Results
Activation of the LANCL2 pathway by oral omilancor and its downstream host immunoregulatory changes decreased disease severity and inflammation in the acute and recurrence models of CDI and the concomitant model of IBD/CDI. Immunologically, omilancor treatment increased mucosal regulatory T cell and decreased pathogenic T helper 17 cell responses. These immunological changes resulted in increased abundance and diversity of tolerogenic gut commensal bacterial strains in omilancor-treated mice. Oral omilancor also resulted in accelerated C. difficile clearance in an antimicrobial-free manner. Furthermore, omilancor provided protection from toxin damage, while preventing the metabolic burst observed in intoxicated epithelial cells.

Conclusions
These data support the development of omilancor as a novel host-targeted, antimicrobial-free immunoregulatory therapeutic for the treatment of IBD patients with C. difficile–associated disease and pathology with the potential to address the unmet clinical needs of ulcerative colitis and Crohn’s disease patients with concomitant CDI.
Bird scaring lines reduce seabird mortality in mid-water and bottom trawlers in Argentina
Authors: Tamini L L , Dellacasa R F , Chavez L N , Marinao C J , Góngora M E , Crawford R , Frere E 
Published: July 2023

Abstract
Seabird bycatch in fisheries, and the development of effective mitigation to minimize this, have been subject to increasing research attention over the past three to four decades. Trawl fisheries represent a particular challenge, as bird mortalities (especially highly threatened albatrosses and large petrels, Procellariforms) occur primarily through difficult-to-detect collisions with warp and net monitoring cables. Effectiveness of bird-scaring lines (BSLs) as a mitigation measure can be fleet-specific, and studies relating specifically to reducing collisions with the net monitoring cable are rare. To support improved assessment and mitigation of seabird bycatch in trawl fisheries, we studied the mortality associated with mid-water and bottom factory trawl vessels along the southern tip of the Argentine Patagonian shelf, across 2144 trawls from 2012 to 2019, with three specific objectives: (i) inform improved bycatch management in this (and other) trawl fisheries by analysing differences in seabird collision rates and outcomes between net monitoring and warp cables, as well as the effect of mitigation measures in reducing collisions; (ii) explore the effects of key fishing operation variables on seabird impact outcomes; and (iii) estimate the annual seabird mortality in the study fleet. We tested the efficacy of BSLs as a mitigation measure to reduce seabird mortality, on warps and net monitoring cables. Our results show that seabird mortality increases in the presence of a net monitoring cable. Our estimation of fishery-wide mortality without the use of BSLs includes 108 [31–186] Southern royal albatross (Diomedea epomophora) and 279 [108–465] Black-browed albatross (Thalassarche melanophris) killed annually by the collisions with the net monitoring cable. We demonstrate the efficacy of BSLs in reducing the number of collisions and in combination with no discarding of fishes, seabird interactions fell to c. zero. Our study builds the case for better bycatch data collection in trawl fisheries, the strong influence of discarding, and the feasibility of simple mitigation measures to reduce seabird bycatch, including on the net monitoring cable.
Location of Small Points on an Elliptic Curve by an Equidistribution Argument
Authors: Plessis Arnaud 
Published: July 2023

Abstract
Let $E$ be an elliptic curve defined over a number field $K$ without complex multiplication. If $\Gamma \subset E(\overline{K})$ is a subgroup of finite rank, a very special case of a conjecture of Rémond predicts that points of small height in $E(K(\Gamma ))$ lie in the division group of $\Gamma $. Using an equidistribution argument, we will show that this conjecture is true for groups of rank arbitrarily large.
From Knowledge to Wisdom: Uncertainty and Ontological (In)Security in Iran’s Foreign Policy
Authors: Shadunts Alen 
Published: July 2023

AbstractIt has become the convention to associate the exposure of foundational indeterminacies in a state’s identity with change. Many of the ontological security and poststructuralist works in international relations argue that revealing such uncertainties is a threat to the status quo—maintaining the existing narratives and practices used for constituting subjectivity. The article claims that such a revelation does not necessarily lead to a rupture; moreover, it can be used to keep the status quo. It investigates the case of the Islamic Republic of Iran to show how a polity can try to conceal uncertainties related to self-identification and simultaneously embrace them. In the case of the former, Iran pursues certainty in regard to its self through a process of othering: Its identity is constituted in opposition to certain antagonistic others. In the case of the latter, the Iranian subjectivity is articulated in a non-Western context, where the modern gaze of knowledge-seeking and categorizations is rejected. Instead, an “authentic” mode of wisdom is introduced that makes it possible to incorporate indeterminacies and incompatibilities in self-identification. As a result, both concealing and embracing identity-related uncertainties serve the reproduction of the status quo.
Reducing Central Line-Associated Bloodstream Infections in a Burn Intensive Care Unit: Using a Business Framework for Quality Improvement
Authors: Effendi Maleeh , Roberto Amy , Dale Slater Elizabeth 
Published: July 2023

Abstract
Central line-associated bloodstream infections (CLABSIs) pose a unique risk in burn patients, with rates of infection 2–3 times that of other Intensive Care Unit (ICU) populations. Here we present a detailed account of our experience in reducing CLABSI rates utilizing a business framework called the Four Disciplines of Execution (4DX). The Burn ICU CLABSI rate had risen to the 90th percentile nationally when compared to other burn units on the National Healthcare Safety Network. We applied the 4DX framework. This is a four-step method which includes creating a Wildly Important Goal, establishing measurable and accomplishable process measures, creating a scoreboard, and using a weekly meeting to provide accountability. Process changes included both physician and nursing practices. The physicians changed the criteria for when to order blood cultures, as well as requiring attending approval for cultures. The nurses engaged in a peer-observation practice improvement for “scrub the hub” and line dressing conditions and improved their own expertise for peripheral IV placement. The multidisciplinary team initiated a daily review of line indications to ensure removal as soon as possible. Overall, the CLABSI rate decreased from 7.39 infections per 1000 line days to 2.29 infections per 1000 line days over 1 year. We subsequently achieved over 635 days without a CLABSI. In conclusion, the 4DX was a successful quality improvement technique in our healthcare context. Because of the simplicity of implementation, we think it is broadly applicable in the healthcare setting.