bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Risks of First Onset Primary Hypertension Diagnosis in Thermal-Injured Patients
Authors: Efejuku Tsola A. , Wolf Steven E. , Song Juquan , Golovko Georgiy , El Ayadi Amina 
Published: February 2024

INTRODUCTION
Hypertension (HTN) is a prevalent condition in the United States and leads to an increased risk of developing various comorbidities. However, the impact of new-onset hypertension following severe burns on patient outcomes is not known. We posit that hypertension onset after severe burn is associated with increased risk of developing comorbidities and mortality.

METHODS
Using the TriNetX database, burned patients diagnosed with essential hypertension after injury were compared to those who did not develop hypertension; neither had prior hypertension. Each cohort was grouped by sex, percent total body surface area (TBSA) burned, and age, then propensity-matched for sex, race, ethnicity, and lab values. Outcomes assessed were acute kidney injury (AKI), hyperglycemia, heart failure, myocardial infarction (MI), and death.

RESULTS
Those diagnosed with hypertension following severe burn were 4.9 times more likely to develop AKI, 3.6 times for hyperglycemia, 5.3 times for heart failure, 4.7 times for acute MI, and 1.5 times for mortality. Sex analysis shows that men were at greater risk for AKI (1.5 times), heart failure (1.1 times), and death (1.4 times). Women were 1.3 times more likely to develop hyperglycemia. Percent TBSA burned grouping showed increased risk for all outcomes with increasing severity. Age grouping indicated an elevated risk of developing AKI, heart failure, acute MI, and death.

CONCLUSION
New onset hypertension diagnosis in severely burned patients is associated with acute kidney injury, heart failure, acute MI, and death. Overall, males, older patients, and those with a higher % TBSA burned are at a higher risk of developing these comorbidities.
Toxin-based screening of C-terminal tags inEscherichia colireveals the exceptional potency of ssrA-like degrons
Authors: Beardslee Patrick C. , Schmitz Karl R. 
Published: February 2024

ABSTRACTAll bacteria possess ATP-dependent proteases that destroy cytosolic proteins. These enzymes help cells mitigate proteotoxic stress, adapt to changing nutrient availability, regulate virulence phenotypes, and transition to pathogenic lifestyles. Moreover, ATP-dependent proteases have emerged as promising antibacterial and antivirulence targets in a variety of pathogens. The physiological roles of these proteases are largely defined by the complement of proteins that they degrade. Substrates are typically recognized in a highly selective manner, often via short unstructured sequences termed degrons. While a few degrons have been identified and rigorously characterized, we lack a systematic understanding of how proteases select valid degrons from the vast complexity of protein sequence space. Here, we describe a novel high-throughput screening approach inEscherichia colithat couples proteolysis of a protein toxin to cell survival. We used this method to screen a combinatorial library of C-terminal pentapeptide sequences for functionality as proteolytic degrons in wild typeE. coli, and in strains lacking components of the ClpXP and ClpAP proteases. By examining the competitive enrichment of sequences over time, we found that about one percent of pentapeptide tags lead to toxin proteolysis. Interestingly, the most enriched degrons were ClpXP-dependent and highly similar to the ssrA tag, one of the most extensively characterized degrons in bacteria. Among ssrA-like sequences, we observed that specific upstream residues correlate with successful recognition. The lack of diversity among strongly enriched sequences suggests that ssrA-like tags comprise a uniquely potent class of short C-terminal degron inE. coli. Efficient proteolysis of substrates lacking such degrons likely requires adaptors or multivalent interactions. These findings broaden our understanding of the constraints that shape the bacterial proteolytic landscape. Our screening approach may be broadly applicable to probing aspects of proteolytic substrate selection in other bacterial systems.
Early body weight gain in TALLYHO/JngJ mice predicts adult diabetic phenotype, mimicking childhood obesity
Authors: Hastreiter Sieglinde , Hoffmann Sandra , Richter Kerstin , Irmler Martin , Gerlini Raffaele , Fuchs Helmut , Gailus-Durner Valérie , Körner Antje , de Angelis Martin Hrabé , Beckers Johannes 
Published: February 2024

AbstractChildhood obesity and type 2 diabetes are two emerging health issues worldwide. To analyze their underlying causes and develop prevention strategies, mouse models are urgently needed. We present novel insights into the polygenic TALLYHO/JngJ mouse model for diabetes. By precisely analyzing our original phenotypic data, we discovered that body weight at weaning age is the main predictor of the adult phenotype in TALLYHO/JngJ mice. The higher the weaning weight of male mice, the more likely they are to develop diabetes later in life. In contrast, a low weaning weight protected against the development of the diabetic phenotype in adults. In females, we found that high weaning body weights led to a constant higher body weight throughout life. We also showed that specifically the suckling period, rather than thein uteroperiod, is crucial for the development of the metabolic phenotype in later life. We observed an earlier onset of diabetes when the mice had higher body weights at weaning, aligning with metabolic histories observed in humans. Therefore, we recommend TALLYHO/JngJ mice as a model to investigate childhood obesity and to develop prevention strategies.HighlightsThe polygenic TALLYHO/JngJ mouse model is used to investigate type 2 diabetes, but the penetrance of the phenotype is highly variable.We deeply analyzed our phenotype data and find that body weight at the age of weaning (BWW) is the main predictor for the obese and diabetic phenotype in TALLYHO/JngJ male mice later in life.We suggest that TALLYHO/JngJ male mice are an excellent and urgently needed model to study childhood obesity.Our data help the relevant scientific community to better control the penetrance of the diabetic phenotype in male TALLYHO/JngJ mice.
Average Nucleotide Identity basedStaphylococcus aureusstrain grouping allows identification of strain-specific genes in the pangenome
Authors: Raghuram Vishnu , Petit Robert A , Karol Zach , Mehta Rohan , Weissman Daniel B. , Read Timothy D. 
Published: February 2024

AbstractStaphylococcus aureuscauses both hospital and community acquired infections in humans worldwide. Due to the high incidence of infectionS. aureusis also one of the most sampled and sequenced pathogens today, providing an outstanding resource to understand variation at the bacterial subspecies level. We processed and downsampled 83,383 publicS. aureusIllumina whole genome shotgun sequences and 1,263 complete genomes to produce 7,954 representative substrains. Pairwise comparison of core gene Average Nucleotide Identity (ANI) revealed a natural boundary of 99.5% that could be used to define 145 distinct strains within the species. We found that intermediate frequency genes in the pangenome (present in 10-95% of genomes) could be divided into those closely linked to strain background (“strain-concentrated”) and those highly variable within strains (“strain-diffuse”). Non-core genes had different patterns of chromosome location; notably, strain-diffuse associated with prophages, strain-concentrated with the vSaβ genome island and rare genes (<10% frequency) concentrated near the origin of replication. Antibiotic genes were enriched in the strain-diffuse class, while virulence genes were distributed between strain-diffuse, strain-concentrated, core and rare classes. This study shows how different patterns of gene movement help create strains as distinct subspecies entities and provide insight into the diverse histories of importantS. aureusfunctions.ImportanceWe analyzed the genomic diversity ofStaphylococcus aureus, a globally prevalent bacterial species that causes serious infections in humans. Our goal was to build a genetic picture of the different strains ofS. aureusand which genes may be associated with them. We used a large public dataset (>84,000 genomes) that was re-processed and subsampled to remove redundancy. We found that individual genomes could be grouped into strains by sharing > 99.5% identical nucleotide sequence of the core part of their genome. We also showed that a portion of genes that are present in intermediate frequency in the species are strongly associated with some strains but completely absent from others, suggesting a role in strain-specificity. This work lays the foundation for understanding individual gene histories of theS. aureusspecies and also outlines strategies for processing large bacterial genomic datasets.
Cutaneous leishmaniasis in British troops following jungle training in Belize: cumulative incidence and potential risk practices
Authors: Niba Rawlings Ngwa , Bailey Mark , Craig Peter , Courtenay Orin 
Published: February 2024

AbstractIntroductionBritish soldiers undergoing jungle training (JT) in Belize typically experience a relatively low risk of developing cutaneous leishmaniasis (CL). However, an uncharacteristically large outbreak of CL occurred in 2022. This study aimed to determine the cumulative incidence (CUMI) of the disease and highlight potential shortcomings in personal protective measures (PPMs) to mitigate exposure to sand fly vector bites.MethodsA retrospective analysis was conducted on medical records of CL cases between 2005 and 2022, as well as on questionnaire responses regarding PPMs administered to CL cases in 2022. Data were sourced from Defence Public Health Unit, Military Environmental Health Department and British Army Training Support Unit Belize.ResultsEighty-one confirmed clinical CL cases were recorded between 2005 and 2022, with a substantial peak (38 cases) in 2022. Most cases occurred during the wet season. Pre-2022, the median CUMI per 8-week deployment was 0.90% (Q1–Q3: 0.34%–1.34%), with an annual variation of 0.2% to 2.0%. In 2022, the CUMI spiked to 4.22%, associated with a risk ratio of 5.3 (95% C.I.s: 3.41, 8.16), and rising to a CUMI of 7.3% in a single unit of 450 men (33 CL cases) in late 2022. These values are significantly higher than the median CUMI of all previous years, and to published reports for other CL-endemic regions. Troop responses identified limitations in the supply of optimal equipment, and in sand fly bite and leishmaniasis risk avoidance information provided by the pre-deployment health education (PDHE) programme. Compliance with PDHE advise was also suboptimal, with irregular use of insect repellents, protective clothing / head netting, and insecticide-treated hammocks.ConclusionsThe reasons behind the unusually high numbers of CL cases and CUMI in 2022 remain unclear, emphasising the need to improve PPM provision and implement a comprehensive PDHE programme for troops undergoing JT in Belize.
The collective application of shorebird tracking data to conservation
Authors: Harrison Autumn-Lynn , Stenzel Candace , Anderson Alexandra , Howell Jessica , Lanctot Richard B. , Aikens Marley , Aldabe Joaquín , Berigan Liam A. , Bêty Joël , Blomberg Erik , Bosi de Almeida Juliana , Boyce Andy J. , Bradley David W. , Brown Stephen , Carlisle Jay , Cheskey Edward , Christie Katherine , Christin Sylvain , Clay Rob , Dayer Ashley , Deppe Jill L. , English Willow , Flemming Scott A. , Gilg Olivier , Gilroy Christine , Heath Susan , Hill Jason M. , Hipfner J. Mark , Johnson James A. , Johnson Luanne , Kempenaers Bart , Knaga Paul , Kwon Eunbi , Lagassé Benjamin J. , Lamarre Jean-François , Latty Christopher , Léandri-Breton Don-Jean , Lecomte Nicolas , Loring Pam , McGuire Rebecca , Moorhead Scott , Navedo Juan G. , Newstead David , Nol Erica , Olalla-Kerstupp Alina , Olson Bridget , Olson Elizabeth , Paquet Julie , Pierce Allison K. , Rausch Jennie , Regan Kevin , Reiter Matt , Roth Amber M. , Russell Mike , Saalfeld Sarah T. , Scarpignato Amy L. , Schulte Shiloh , Senner Nathan R. , Smith Joseph A. M. , Smith Paul A. , Spector Zach , Srigley Werner Kelly , Stantial Michelle L. , Taylor Audrey R. , Valcu Mihai , Wehtje Walter , Winn Brad , Wunder Michael B. 
Published: February 2024

AbstractAddressing urgent conservation issues, like the drastic declines of North American migratory birds, requires creative, evidence-based, efficient, and collaborative approaches. Over 50% of monitored North American shorebird populations have lost over 50% of their abundance since 1980. To address these declines, we developed a partnership of scientists and practitioners called the Shorebird Science and Conservation Collective (hereinafter “the Collective”). Here, we present this successful case study as an example for others engaged in translational science. The Collective acts as an intermediary whereby dedicated staff collate and analyze data contributions from scientists to support knowledge requests from conservation practitioners. Data contributions from 74 organizations include over 6.7 million shorebird locations forming movement paths of 3,345 individuals representing 36 species tracked across the Americas. We describe the founding and structure of the Collective and conservation activities we supported in our first two years. As the volume of scientific data on animal movements continues to grow, groups like the Collective can be vital liaisons to rapidly integrate and interpret research to support conservation action.
Parsnp 2.0: Scalable Core-Genome Alignment for Massive Microbial Datasets
Authors: Kille Bryce , Nute Michael G. , Huang Victor , Kim Eddie , Phillippy Adam M. , Treangen Todd J. 
Published: February 2024

AbstractMotivationSince 2016, the number of microbial species with available reference genomes in NCBI has more than tripled. Multiple genome alignment, the process of identifying nucleotides across multiple genomes which share a common ancestor, is used as the input to numerous downstream comparative analysis methods. Parsnp is one of the few multiple genome alignment methods able to scale to the current era of genomic data; however, there has been no major release since its initial release in 2014.ResultsTo address this gap, we developed Parsnp v2, which significantly improves on its original release. Parsnp v2 provides users with more control over executions of the program, allowing Parsnp to be better tailored for different use-cases. We introduce a partitioning option to Parsnp, which allows the input to be broken up into multiple parallel alignment processes which are then combined into a final alignment. The partitioning option can reduce memory usage by over 4x and reduce runtime by over 2x, all while maintaining a precise core-genome alignment. The partitioning workflow is also less susceptible to complications caused by assembly artifacts and minor variation, as alignment anchors only need to be conserved within their partition and not across the entire input set. We highlight the performance on datasets involving thousands of bacterial and viral genomes.AvailabilityParsnp is available athttps://github.com/marbl/parsnp
Temporal variability in host availability alters the outcome of competition between two parasitoid species
Authors: Wang Hua , Liu Tiantian , Sun Shucun , Lewis Owen T. , Xi Xinqiang 
Published: February 2024

AbstractVariability in the availability of resources through time is a common attribute in trophic interactions, but its effects on the fitness of different consumer species and on interspecific competition between them are not clearly understood.To investigate this, we allowed two parasitoid species,Trichopria drosophilaeandPachycrepoideus vindemiae, to exploitDrosophilahost pupae under three temporal variability treatments, either on their own or simultaneously.When tested individually (in the absence of interspecific competition), both parasitoid species had lower fitness when hosts were exposed for a short duration at high density than when exposed for a long duration at low density. When both parasitoid species exploited hosts simultaneously, interspecific competition significantly decreased the number of offspring for both parasitoid species. The outcome of this interspecific competition depended on host temporal variability, withT. drosophilaeorP. vindemiaedominating in short and long host exposure treatments, respectively.These results can be explained by the combination of host availability and egg load of female adult parasitoids. When abundant hosts are provided for a short period, the ample mature eggs of the proovigenicT. drosophilaeenable them to exploit hosts more efficiently thanP. vindemiae, which is synovigenic. However,P. vindemiaeis an intrinsically superior competitor and dominates when multiparasitism occurs. Multiparasitism is more frequent when hosts are at low levels relative to the egg load of the parasitoids.Our results clearly demonstrate that resource temporal availability can alter the outcome of competition between consumers with different reproductive traits.
RNF43 is a gatekeeper for colitis-associated cancer
Authors: Dietl Alisa , Ralser Anna , Taxauer Karin , Dregelies Theresa , Sterlacci William , Stadler Mara , Olayo-Alarcon Roberto , Margaryan Shushan , Skerhut Martin , Groll Tanja , Steiger Katja , Singh Dharmesh , Li Xue , Oellinger Rupert , Rad Roland , Janssen Klaus Peter , Mueller Christian L. , Vieth Michael , Gerhard Markus , Mejías-Luque Raquel 
Published: February 2024

SUMMARYSomatic mutations in the tumor suppressor Ring finger protein 43 (RNF43) were frequently found in colitis-associated cancer (CAC) and related to the duration of chronic inflammation, but their significance in inflammation and inflammation-associated carcinogenesis remained elusive.We assessed the onset ofRNF43mutations at different stages of human CAC development by exome sequencing, and comprehensively characterizedRNF43loss-of-function-driven malignant transformation in mice by RNA sequencing, flow cytometry, immunohistochemistry, computational transcriptome-microbiome associations, and determined the underlying mechanisms by performing functional stem-cell derived organoid studies and fecal microbiota transfers.Mutations inRNF43were frequent (12.9 %) in precancerous lesions of ulcerative colitis (UC) patients and eventually detectable in 24.4 % of CAC patients. In a bacterial-induced colitis mouse model,Rnf43mutations caused invasive colorectal carcinomas by aggravating and perpetuating inflammation due to impaired epithelial barrier integrity and pathogen control. We could demonstrate thatRnf43loss-of-function-mutations were even sufficient to cause spontaneous intestinal inflammation, resulting in UC-typical pathological features and subsequent invasive carcinoma development. In detail, mutantRnf43impaired intestinal epithelial and particularly goblet cell homeostasis in a cell-intrinsic manner, and caused dysbiosis. The altered microbiota composition induced epithelial DNA damage and spontaneous mucosal inflammation characterized by TGF-ß-activating dendritic cells and pro-inflammatory (IL-17+, IL-22+, TNFα+) T cells. Over time, the continuous epithelial and goblet cell dysfunction, combined with pro-tumorigenic and pro-inflammatory microbiota, resulted in accumulated epithelial damage with transformation into inflammation-associated cancer in the presence of constitutive WNT signaling activation.We identified mutantRNF43as susceptibility gene for UC and bona fide driver of CAC.
Pyruvate metabolism dictates fibroblast sensitivity to GLS1 inhibition during fibrogenesis
Authors: Contento Greg , Wilson Jo-Anne A , Selvarajah Brintha , Platé Manuela , Guillotin Delphine , Morales Valle , Trevisani Marcello , Pitozzi Vanessa , Bianchi Katiuscia , Chambers Rachel C 
Published: February 2024

AbstractFibrosis is a chronic disease characterized by excessive extracellular matrix (ECM) production which leads to destruction of normal tissue architecture and disruption of organ function. Fibroblasts are key effector cells of this process and respond to a host of pro-fibrotic stimuli, including notably the pleiotropic cytokine, TGF-β1, which promotes fibroblast to myofibroblast differentiation. This is accompanied by the simultaneous rewiring of metabolic networks to meet the biosynthetic and bioenergetic needs of contractile and ECM-synthesizing cells, but the exact mechanisms involved remain poorly understood. In this study, we report that extracellular nutrient availability profoundly influences the TGF-β1transcriptome of primary human lung fibroblasts (pHLFs) and the “biosynthesis of amino acids” emerges as a top enriched transcriptional module influenced by TGF-β1. We subsequently uncover a key role for pyruvate in influencing the pharmacological impact of glutaminase (GLS1) inhibition during TGF-β1-induced fibrogenesis. In pyruvate replete conditions which mimic the physiological concentration of pyruvate in human blood, GLS1 inhibition is ineffective in blocking TGF-β1-induced fibrogenesis, as pyruvate is able to be used as the substrate for glutamate and alanine production via glutamate dehydrogenase (GDH) and glutamic-pyruvic transaminase 2 (GPT2), respectively. We further show that dual targeting of either GPT2 or GDH in combination with GLS1-inhibition is required to fully block TGF-β1-induced collagen synthesis. These findings embolden a therapeutic strategy aimed at additional targeting of mitochondrial pyruvate metabolism in the presence of a glutaminolysis inhibitor in order to interfere with the pathological deposition of collagen in the setting of pulmonary fibrosis and potentially other fibrotic conditions.
Protein language models learn evolutionary statistics of interacting sequence motifs
Authors: Zhang Zhidian , Wayment-Steele Hannah K. , Brixi Garyk , Wang Haobo , Dal Peraro Matteo , Kern Dorothee , Ovchinnikov Sergey 
Published: February 2024

Protein language models (pLMs) have emerged as potent tools for predicting and designing protein structure and function, and the degree to which these models fundamentally understand the inherent biophysics of protein structure stands as an open question. Motivated by a discovery that pLM-based structure predictors erroneously predict nonphysical structures for protein isoforms, we investigated the nature of sequence context needed for contact predictions in the pLM ESM-2. We demonstrate by use of a “categorical Jacobian” calculation that ESM-2 stores statistics of coevolving residues, analogously to simpler modelling approaches like Markov Random Fields and Multivariate Gaussian models. We further investigated how ESM-2 “stores” information needed to predict contacts by comparing sequence masking strategies, and found that providing local windows of sequence information allowed ESM-2 to best recover predicted contacts. This suggests that pLMs predict contacts by storing motifs of pairwise contacts. Our investigation highlights the limitations of current pLMs and underscores the importance of understanding the underlying mechanisms of these models.Significance StatementProtein language models (pLMs) have exhibited remarkable capabilities in protein structure prediction and design. However, the extent to which they comprehend the intrinsic biophysics of protein structures remains uncertain. We present a suite of analyses that dissect how the flagship pLM ESM-2 predicts structure. Motivated by a consistent error of protein isoforms predicted as structured fragments, we developed a completely unsupervised method to uniformly evaluate any protein language model that allows for us to compare coevolutionary statistics to older linear models. We further identified t hat E SM-2 a ppears to have a precise context size that is needed to predict inter-residue contacts. Our study highlights the current limitations of pLMs and contributes to a deeper understanding of their underlying mechanisms, paving the way for more reliable protein structure predictions.