bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of selective digestive decontamination on the pangenome composition of ESBL-E. coli
Authors: Paganini Julian A. , Schürch A. C. , Scharringa Jelle , Bonten M. J. M. , Willems R. J. L. , Plantinga N. L. 
Published: January 2025

AbstractIn Dutch ICUs patients receive selective digestive decontamination (SDD) as a prophylactic antimicrobial treatment to prevent colonisation with potentially pathogenic microorganisms and subsequent infections, with a beneficial effect on 28-day mortality. In the R-GNOSIS ICU study, conducted outside of The Netherlands, SDD consisted of a mix of an oropharyngeal paste and a gastric suspension containing colistin, tobramycin and nystatin. These topical antimicrobial agents aim to target aerobic Gram-negative bacteria,S. aureusand yeast. SDD improves patient outcome, but its effects on the resistome and pangenome of potentially pathongenic microorganisms have not been extensively studied. In this work, we compared 129 genomes ofE. coliisolates from patients that received SDD and patients that did not receive SDD, but standard care only (baseline patients) in five ICUs located across three European countries (R-GNOSIS ICU study). We found that the overall pangenome compositions ofE. colirecovered from both patient groups were highly similar. Variations in the accessory genome were strongly associated with the phylogeny of isolates but not with the use of SDD. Similarly, the plasmidome variations were not explained by treatment, but rather by the interaction between ICU location and phylogroup. One antibiotic resistance gene, which confers resistance to tobramycin, was found to be more prevalent in SDD patients. This gene was flanked by IS26 elements and significantly co-occurred with blaCTX-M-15 in various plasmid backbones and chromosomal contexts. Notably, no mcr genes coding for colistin resistance were detected.
Occupational profile and prevalence of workplace accidents among beach workers
Authors: Cremonese Cleber , Awoniyi Adedayo Michael , dos Santos Mariela Sousa , Silva Jailma dos Santos , Nunes Thayane Silva , Dias Wiler de Paula , Rodrigues Joelma Marques , Soares Juliana Cristina dos Santos , Meyer Armando 
Published: January 2025

ABSTRACTBackgroundWorkplace accidents (WAs) are acute, often preventable events that result in injuries or functional impairments, typically arising from occupation-related activities. In 2019, an estimated 395 million workers worldwide suffered non-fatal work-related injuries, with 330,000 fatalities, the majority occurring in low- and middle-income countries (LMICs) like Brazil. The true figures may be considerably higher due to underreporting, as many informal workers lack adequate social protection and may avoid reporting accidents for fear of jeopardizing their livelihood.ObjectiveTo assess the prevalence of WAs and their association with demographic and occupational determinants among beach workers in Salvador, Bahia, Brazil, between 2023 and 2024.MethodsA cross-sectional epidemiological study was conducted with 579 urban beach workers in Salvador from November 2023 to March 2024. Following ethical approval and participants’ consent, questionnaires were administered to gather data on sociodemographic and occupational characteristics, workplace environments and processes, workplace-related injuries and illnesses, and history and characteristics of WA. WA prevalence and prevalence ratios were calculated, and associations were analyzed using a Poisson regression model with robust variance.ResultsAmong the workers, 59.4% were males, 25% were aged ≤29 years and 11.4% were ≥60 years. Black and brown individuals represented 92.9% of the population. The most performed activities were street vendors (43.6%) and waiters (25%). Informal employment was reported by 72.3% of workers, 70.2% worked ≥9 hours per day, and 88% had no occupational training. The overall WA prevalence observed was 40.3%, with workers ≤29 years old having a 2.59 times higher likelihood of experiencing WA compared to those ≥60 years old. The most common WAs were punctures (42.7%), cuts (28.4%) and burns (12.1%).ConclusionsThe high prevalence of WA among beach workers, especially those ≤29 years old, may be associated with inadequate working conditions, including long working hours and lack of occupational training. These findings highlight the need for targeted interventions to improve working conditions and reduce WA risks.
A phylogenetic method identifies candidate drivers of the evolution of the SARS-CoV-2 mutation spectrum
Authors: Corbett-Detig Russ 
Published: January 2025

AbstractThe molecular processes that generate new mutations evolve, but the causal mechanisms are largely unknown. In particular, the relative rates of mutation types (e.g., C>T), the mutation spectrum, sometimes vary among closely related species and populations. I present an algorithm for subdividing a phylogeny into distinct mutation spectra. By applying this approach to a SARS-CoV-2 phylogeny comprising approximately eight million genome sequences, I identify 10 shifts in the mutation spectrum. I find strong enrichment consistent with candidate causal amino-acid substitutions in the SARS-CoV-2 polymerase, and strikingly three appearances of the same homoplasious substitution are each associated with decreased C>T relative mutation rates. With rapidly growing genomic datasets, this approach and future extensions promises new insights into the mechanisms of evolution of mutational processes.
Mechanism of chaperone recruitment and retention on mitochondrial precursors
Authors: Juszkiewicz Szymon , Peak-Chew Sew-Yeu , Hegde Ramanujan S. 
Published: January 2025

AbstractNearly all mitochondrial proteins are imported into mitochondria from the cytosol. How nascent mitochondrial precursors acquire and sustain import-competence in the cytosol under normal and stress conditions is incompletely understood. Here, we show that under normal conditions, the Hsc70 and Hsp90 systems interact with and redundantly minimize precursor degradation. During acute import stress, Hsp90 buffers precursor degradation, preserving proteins in an import-competent state until stress resolution. Unexpectedly, buffering by Hsp90 relies critically on a mitochondrial targeting signal (MTS), the absence of which greatly decreases precursor-Hsp90 interaction. Site-specific photo-crosslinking and biochemical reconstitution showed how the MTS directly engages co-chaperones of Hsc70 (St13 and Stip1) and Hsp90 (p23 and Cdc37) to facilitate chaperone retention on the mature domain. Thus, the MTS has a previously unappreciated role in regulating chaperone dynamics on mitochondrial precursors to buffer their degradation and maintain import competence, functions that may facilitate restoration of mitochondrial homeostasis after acute import stress.Significance statementMitochondrial proteins encoded by the nuclear genome are synthesized in the cytosol before their subsequent import into mitochondria. The factors that recognize mitochondrial precursors in the cytosol to maintain their import-competence are incompletely defined.Using a systematic site-specific photo-crosslinking strategy, the authors find that the mitochondrial targeting signal (MTS) is directly recognized by co-chaperones of Hsc70 and Hsp90. The co-chaperones facilitate recruitment, retention, and remodeling of these general chaperones on the nascent precursor protein.Chaperone retention becomes particularly important during mitochondrial stress, when precursors must avoid degradation during a prolonged period in the cytosol.
Signal peptide-independent secretion of keratin-19 by pancreatic cancer cells
Authors: Moresco Philip , Kastan Jonathan P. , Yang Jung-in , Prabakar Rishvanth , Minicozzi Francesca , Adams Dexter W. , Cifani Paolo , Tuveson David A. , Fearon Douglas T. 
Published: January 2025

AbstractThe exclusion of T cells causes immune escape of pancreatic ductal adenocarcinoma (PDA). T cell exclusion is mediated by the interaction between CXCR4 on T cells and its ligand, CXCL12, which is complexed to keratin-19 (KRT19) on the surface of PDA cells. KRT19 secretion by PDA cells is essential to this process but is unusual because KRT19 lacks an endoplasmic reticulum (ER)-directing signal peptide (SP). By using biotinylation by an ER-restricted TurboID system and a split-GFP assay in PDA cells, we demonstrate that KRT19 enters the ER via its “head” domain. Additionally, KRT19 is shown to interact with the signal recognition particle and its secretion is sensitive to canonical protein secretion inhibitors. In vivo, mouse tumors formed with ER-TurboID-expressing PDA cells contain biotinylated KRT19. In contrast, keratin-8 (KRT8), which colocalizes with KRT19 on the surface of PDA cells, does not enter the ER. Rather, KRT8 is externalized via secretory autophagy possibly in a complex with KRT19. Thus, despite lacking a classical SP, PDA cells secrete KRT19 to capture CXCL12 and protect against immune attack.Significance StatementPancreatic ductal adenocarcinoma (PDA) is resistant to immunotherapy because T cells are excluded from cancer cell nests. Cancer cells capture cancer associated fibroblast sourced CXCL12, which ligates T cell CXCR4, to exclude T cells from cancer cell nests. CXCL12 is captured by cancer cells via the externalization of the normally intracellular intermediate filament keratin-19 (KRT19). We studied the unconventional secretion of KRT19 and found it is secreted by signal peptide independent entry into the endoplasmic reticulum, as well as via secretory autophagy. Thus, PDA externalized immunosuppressive KRT19 through two unconventional means.
Few-Shot Learning for Prostate Cancer Detection on MRI: Comparative Analysis with Radiologists’ Performance
Authors: Yamagishi Yosuke , Baba Yasutaka , Suzuki Jun , Okada Yoshitaka , Kanao Kent , Oyama Masafumi 
Published: January 2025

AbstractBackgroundDeep-learning models for prostate cancer detection often require large datasets, which can be challenging to obtain and may lead to domain shift issues in various clinical settings.PurposeThis study aimed to develop a deep-learning model for prostate cancer detection on magnetic resonance images using few-shot learning and compare its performance with radiologists.Materials and MethodsThis retrospective study used 99 cases (80 positive, 19 negative) of confirmed prostate cancer, diagnosed through needle biopsy from 2017 to 2022, with 20 cases for training, 5 for validation, and 74 for testing. The 2D transformer model was trained on T2-weighted, diffusion-weighted, and apparent diffusion coefficient map images. Model predictions were compared between the two radiologists using the Matthews correlation coefficient (MCC) and F1 score, and the bootstrap method was used to calculate 95% confidence intervals (CIs).ResultsSeventy-four patients (mean age, 71 years ± 8; 60 men) were included in the test set. The model achieved an MCC of 0.297 (95% CI: 0.095–0.474) and F1 score of 0.707 (95% CI: 0.598–0.847). Radiologist 1 had an MCC of 0.276 (95% CI: 0.054–0.484) and an F1 score of 0.741 (95% CI: 0.632–0.832), while Radiologist 2 had an MCC of 0.504 (95% CI: 0.289–0.703) and an F1 score of 0.871 (95% CI: 0.800–0.931). The performance of the model was not significantly different from that of Radiologist 1 (MCC difference: 0.021, 95% CI: −0.270–0.306; F1 score difference: −0.034, 95% CI: −0.153–0.078), but was lower than that of Radiologist 2 (F1 difference: −0.16, 95% CI: −0.287– - 0.061).ConclusionA deep-learning model trained on only 20 cases achieved a performance comparable to one radiologist in detecting prostate cancer on magnetic resonance images, demonstrating the potential of few-shot learning in addressing domain shift challenges.Key ResultsA deep learning model for prostate cancer detection on MRI was developed using only 20 training cases.The model achieved performance comparable to one radiologist (MCC: 0.297 vs 0.276) but lower than another (F1: 0.707 vs 0.871).Few-shot learning demonstrated potential for addressing domain shift challenges in medical imaging AI.Summary StatementFew-shot learning enables development of prostate cancer detection models on MRI with performance comparable to radiologists, using minimal training data.
BREATH-PATH – Protocol for lung cancer management in surgical patients through analysis of breath profiles
Authors: Barata Rita , Carvalheiro Catarina , Raimundo Bernardo S. , Pantarotto Marcos , Vaz Pedro D. 
Published: January 2025

AbstractBackgroundAnatomical surgical resection is the treatment of choice for early-stage non–small cell lung cancer (NSCLC) and is a part of the multimodality treatment for resectable, locally advanced NSCLC. Local, regional and distant recurrence is the most common cause of treatment failure after resection. Multiple studies have recommended chest computed tomography (CT) for lung cancer (LC) patient’s follow-up. Even though adopting this strategy, the recurrence will only be detected months after the onset of the disease once imaging changes will only occur with a high tumor burden.MethodsBreath analysis is a promising technology and useful addition to the currently available modalities to achieve lung cancer diagnosis and management. The volatile organic compounds (VOCs) produced as end-products of metabolism by the LC cells (and present on the exhaled breath of the patients) seem to have a unique pattern that can be used as a tool to detect lung cancer (VOC profile).DiscussionThe BREATH-PATH study aims to establish a VOC profile for all LC patients at diagnosis and understand its variations with the different implemented treatments in order to find response patterns. By understanding these patterns and identifying their deviations thereof with disease relapse supported by imaging methods we will be able to validate the breath analysis as a useful tool for LC recurrence detection.This study intents not only to reiterate the methods’ efficacy but also to understand how high its sensitivity is in detecting a tumor recurrence, allowing breath analysis to be integrated into clinical decision algorithms.
Vestibulo-Ocular Reflex Function in Individuals with Car Sickness: A Cross-Sectional Study
Authors: Ambode Oluwaseun I. , Johnson Eric G. , Mleziva Pablo , San Lucas Summer , Daher Noha S. 
Published: January 2025

AbstractObjectiveTo determine whether Vestibulo-ocular reflex (VOR) integrity is different between young adults with and without car sickness, To assess the effect of gender on VOR integrity in young adults with and without car sickness and To compare postural stability across different levels of physical activity in young adults with and without car sickness.DesignCross-sectional studySettingGeneral communityParticipantsForty-six healthy young adult men and women (ages 20-40 years) with and without car sicknessMain Outcome measuresBertec Vision Advantage (BVA) was used to assess VOR integrity, computerized dynamic posturography with immersion virtual reality(CDP-IVR) was used to assess postural stability and the International Physical Activity Questionnaire (IPAQ-SF) was used to assess physical activity.ResultsAmong females, there was no significant difference in BVA outcomes between the car sickness and no car sickness groups (p>0.05, Table 2), In males, there was no significant difference in median (Inter quartile range (IQR) outcomes by study group except for DVA lines lost. Male participants in the car sickness group had more lines lost compared to males in the no car sickness group.ConclusionOur findings showed that male participants with car sickness appeared to have a weaker VOR compared to females. Also, we found no significant interaction between physical activity and postural stability in young adults with and without car sickness. Future studies should consider assessing postural stability in the sitting position to better replicate the functional position of driving.
Systematic druggable genome-wide Mendelian randomization identifies therapeutic target genes for chronic periodontitis
Authors: Cheng Zhongwei , Wang Fang , Ran Meimei , Liang Shenhu , Song Qinggao 
Published: January 2025

AbstractCurrently,the treatment of chronic periodontitis (CP) still has challenges. This study aimed to identify novel drug targets for the treatment of chronic periodontitis in the druggable genome using the Mendelian randomization (MR) method.In this study,based on the list of 4479 drug gene targets,overlapping genes were selected in blood expression Quantitative Trait Loci(eQTL), which were then subjected to Two-Sample MR(TSMR) and validated Fusion Transcriptome-Wide Association Study(TWAS) with data from the Genome-Wide Association Study(GWAS) of CP to confirm drug genes genetically associated with CP and tested for multiplicity of effects using Summary-data-based Mendelian randomization(SMR) analysis and colocalisation. Finally, Phenome-Wide association study(PheWAS) was executed on the identified drug targets.We applied SMR,TSMR,Fusion TWAS,and a series of manners of co-localisation to assess the genetic association between drugable targets and CP. In conclusion,Metalloproteinase 25(MMP25)was considered the most promising drug target,in addition to which we maintained some confidence in TNFRSF18,CDC25B,STK10 and ACVR2B.Finally,the PheWAS-MR results showed that the possible side effects of applying MMP25 inhibitors were Otitis externa as well as some metabolic disorders,among others.In summary,we identified five potential CP drug targets using TSMR,Fusion TWAS,SMR,and co-localisation a series of methods,of which MMP25 passed all the tests.Such discovery offered an academic basis for future CP drug development and reduce drug development time and economic costs to some extent.
Pregnancy-related risk and birth setting trends: Insights from Indonesian Demographic Health Survey data
Authors: Hodgkin Kai , Joshy Grace , Lokuge Kamalini 
Published: January 2025

AbstractBackgroundMost maternal and neonatal deaths occur in low- and middle-income countries and are largely preventable with quality care. In Indonesia, 98% of pregnant people receive antenatal care and birth commonly occurs in community settings or hospitals. Outside of high-income countries, few studies identify where women with pregnancy-related risk factors give birth. Accurate identification of pregnancy risk factors and referral to an appropriate birth setting is considered an essential element of quality antenatal care, though its efficacy in Indonesia is unknown.MethodsThis study aimed to identify suitable indicators of pregnancy risk factors for Indonesia and examine population-level patterns in pregnancy-related risk, care and appropriateness of birth setting. Risk factors in pregnancy based on internationally relevant referral guidelines were identified from literature search and mapped to available indicators. Using self-reported data from three waves of the Indonesian Demographic Health Survey (2007, 2012, 2017), a representative survey of women aged 15-49 years, we examined receipt of maternity care, prevalence of pregnancy risk factors and time trends in birth setting, overall and by presence of risk factors.ResultsIn the weighted sample (n=43,846), one quarter of women reported pregnancy risk factors. From 2002-2017, numbers of births in hospitals have doubled and births at home have halved. However, the proportions of women with pregnancy risk in each setting remains largely unchanged.DiscussionThese findings identify opportunities for shifting care in Indonesia to ensure women are receiving the appropriate level of care at birth.
Genetic markers of enhanced functional antibody responses to COVID-19 vaccination
Authors: Purcell Ruth A , Aurelia L Carissa , Allen Lilith F , Bond Katherine A , Williamson Deborah A , Trevillyan Janine M , Trubiano Jason A , Wines Bruce D , Hogarth P Mark , Juno Jennifer A , Wheatley Adam K , Nguyen Thi HO , Subbarao Kanta , Kedzierska Katherine , Kent Stephen J , Mahanty Siddhartha , John Selva Kevin , Chung Amy W 
Published: January 2025

AbstractIntroductionSubstantial population-level variation in vaccine-specific antibody responses has been observed following global coronavirus disease 2019 (COVID-19) vaccination efforts. Beyond the influence of clinical and demographic features, immunogenetic variation is suggested to underlie divergent serological responses following COVID-19 vaccination of distinct populations.MethodsImmunoglobulin G1 (IgG1) allotypic markers (G1m) for 121 COVID-19 vaccinated healthy adults were genotyped via Sanger sequencing. Vaccine-specific IgG and Fc gamma receptor (FcγR) engagement were characterised via bead-based multiplex array.ResultsFollowing two COVID-19 vaccine doses, G1m1,17+/+compared to G1m-1,3+/+vaccinees had increased IgG and FcγR engagement specific for the antigenically conserved SARS-CoV-2 Spike 2 (S2) domain. IgG targeting antigenically novel SARS-CoV-2 receptor binding domain (RBD) trended higher in G1m1,17+/+vaccinees, facilitating increased RBD-specific FcγR2a-R131 and FcγR2b binding.ConclusionPrimary COVID-19 vaccination induced increased S2-specific IgG in G1m1,17+/+vaccinees, potentially facilitating enhanced anti-viral FcγR activation. Validation in larger cohorts may inform optimisation of next-generation vaccination strategies.