bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association Between Social Determinants of Health and Hearing Loss and Hearing Intervention in Older US Adults
Authors: Terhaar Samantha , Patel Dhruv , Fung Ethan , Mansour Febronia , Wallace Josh F. , Corsten Martin , McDonald James Ted , Johnson-Obaseki Stephanie , Quimby Alexandra E. 
Published: October 2024

Objective
Estimate the prevalence of hearing loss and hearing assistance device use among older adults in the United States, and assess for associations with select social determinants of health (SDOH).

Study Design
Cross-sectional US population-based study using National Health and Nutrition Examination Survey (NHANES) 2017–March 2020 (pre-pandemic) data.

Setting
Non-institutionalized civilian adult US population.

Methods
US adults aged ≥70 years who completed NHANES audiometry exams were included. Sample weights were applied to provide nationally representative prevalence estimates of hearing loss and hearing assistance device use. Logistic regression analyses assessed associations between SDOH and both hearing loss and hearing assistance device use.

Results
The overall prevalence of hearing loss was 73.7%. Among those with nonprofound hearing loss, the prevalence of hearing assistance device use was 31.3%. Older individuals (odds ratio [OR], 6.3 [3.668–10.694] comparing ages 80+ versus 70–74 yr) and with lower education (OR, 3.8 [1.455–9.766] comparing <ninth grade versus college graduates or above) experienced a significantly elevated prevalence of hearing loss, whereas females (OR, 0.5 [0.326–0.754] versus males) and Blacks (0.5 [0.295–0.841] versus non-Hispanic Whites) had lower prevalence. Although older individuals with hearing loss had a higher prevalence of hearing assistance device use (OR, 2.1 [1.294–3.553] comparing ages 80+ to 70–74 yr), individuals of Black and other Hispanic races had a significantly lower prevalence of hearing assistance device use than non-Hispanic Whites (OR, 0.4 [0.188–0.671]; OR 0.1 [0.012–0.459], respectively), and those with no health insurance had higher prevalence of use than those who were insured (OR, 4.8 [1.307–17.371]).

Conclusion
The prevalence of hearing loss among older adults in the United States remains roughly stable compared with previous population-based estimates, whereas the prevalence of hearing assistance device use is slightly increased. Population-level disparities exist both in the prevalence of hearing loss and hearing assistance device use across SDOH.
Analytical Validation of a Pan-Cancer NGS Assay for In-House Liquid Biopsy Testing: An International Multicenter Study
Authors: Lescuyer Gaëlle , Harlé Alexandre , Kumar Hari Shankar , Constantoulakis Pantelis , Pfarr Nicole , Heitzer Ellen , Michon Clémence , Russo Gianluca , Speel Ernst-Jan M , Piecyk Marie , Husson Marie , Christopoulou Georgia , Mayr Eva-Maria , Koppermann Mai-Lan , Passot Christophe , Graf Ricarda , Aoul Anes Hadjadj , Bourdon Violaine , Dubbink Hendrikus J , van Marion Ronald , Demers Imke , Dingemans Anne-Marie C , Troncone Giancarlo , Pepe Francesco , Muinelo-Romay Laura , Díaz-Lagares Ángel , Rodriguez-Casanova Aitor , Lago Lestón Ramón Manuel , Pathak Deepak , Shah Parth , Parillaud Romain V , Martínez de Ilarduya Oskar , Behr Jonas , Rapin Alexis , Vetterli Thomas , Boppudi Sanga Mitra , Malapelle Umberto , Payen-Gay Lea 
Published: October 2024

AbstractBackgroundLiquid biopsy (LBx) assays are transforming precision oncology by the screening of genomic alterations in cfDNA. These assays provide a less invasive alternative to tissue biopsies, which are not always feasible. Molecular pathology laboratories require LBx assays that detect variants at low allele frequencies using standardized methods.MethodsThis study evaluated the Hedera Profiling 2 ctDNA test panel (HP2) (Hedera Dx, Epalinges, Switzerland), a hybrid capture-based NGS assay for the detection of somatic alterations from cfDNA. Covering 32 genes, HP2 enables the detection of SNVs, Indels, Fusions, CNVs, and MSI status from a single DNA-only workflow. The analytical performance was assessed using reference standards and a diverse cohort of 137 clinical samples pre-characterized by orthogonal methods.ResultsIn reference standards at 0.5% VAF, detection sensitivity and specificity for SNVs/Indels were 96.92% and 99.67%, respectively, and 100% each for Fusions. For MSI with VAFs of ≥1% and CNVs with VAFs of ≥ 2% both achieved 100% sensitivity.ConclusionThis international, multicenter analytical performance evaluation study across a large number of hospital laboratories demonstrated high concordance of HP2 assay with orthogonal methods, confirming its significant potential as a highly sensitive, and efficient Pan-Cancer test for future decentralized LBx testing.
Are we in a Big Data era for multiple sclerosis? Lessons from integrating clinical trials and observational studies data into the PRIMUS precision medicine platform
Authors: Demuth Stanislas , Faddeenkov Igor , Paris Julien , Rousseau Olivia , Baciotti Béatrice , Payet Marianne , Casey Romain , Vukusic Sandra , Doyle Senan , Jarre Guillaume , Vince Nicolas , Limou Sophie , Sèze Jérôme De , Kerbrat Anne , Laplaud David , Edan Gilles , Gourraud Pierre-Antoine ,   the PRIMUS Consortium
Published: October 2024

ABSTRACTObjectiveThe “Projections In Multiple Sclerosis” (PRIMUS) project aims to develop a precision medicine platform enabling neurologists to support therapeutic decisions in multiple sclerosis by visualizing similar patient data among a reference database. We present a data integration method to combine randomized clinical trials (RCTs) and observational studies data and optimize their informativeness.MethodsWe developed an extract-transform-load data integration pipeline to combine 13 source databases with 31,786 patients: the “mother” and “high-definition” cohorts from the French MS registry and eleven industrial RCTs. We aimed to inform each treatment class initiation with at least 500 patients with 2-year clinical and MRI follow-up. Our data integration strategy used every patient visit as a potential baseline time point to inform a specific neurologist’ query to the platform, thus tailoring the actual analysis cohort to each patient.ResultsThe resulting PRIMUS database had 12,953 patients with at least one informative visit. It could inform 7/8 common treatment initiation scenarios with at least 500 patients (range: 485 for glatiramer acetate; 1,754 for natalizumab). The per-visit integration identified 696 more patients in the high-definition cohort than the classical epidemiological per-patient integration (+114 %). Although the mother cohort’s longitudinal data were deemed to be sparse, we identified 6,128 informative patients (yield: 27.8%; mean: 2.2 visits per patient).InterpretationA data integration pipeline and per-visit integration enabled us to build a highly informative reference database to be queried by neurologists through a web application to support discussions with their patients and the selection of disease-modifying treatments.
ENACT: End-to-End Analysis of Visium High Definition (HD) Data
Authors: Kamel Mena , Song Yiwen , Solbas Ana , Villordo Sergio , Sarangi Amrut , Senin Pavel , Mathew Sunaal , Ayestas Luis Cano , Wang Seqian , Classe Marion , Bar-Joseph Ziv , Planas Albert Pla 
Published: October 2024

MotivationSpatial transcriptomics (ST) enables the study of gene expression within its spatial context in histopathology samples. To date, a limiting factor has been the resolution of sequencing based ST products. The introduction of the Visium High Definition (HD) technology opens the door to cell resolution ST studies. However, challenges remain in the ability to accurately map transcripts to cells and in assigning cell types based on the transcript data.ResultsWe developed ENACT, the first tissue-agnostic pipeline that integrates advanced cell segmentation with Visium HD transcriptomics data to infer cell types across whole tissue sections. Our pipeline incorporates novel bin-to-cell assignment methods, enhancing the accuracy of single-cell transcript estimates. Validated on diverse synthetic and real datasets, our approach is both scalable and effective offering a robust solution for spatially resolved transcriptomics analysis.Availability and implementationENACT source code is available athttps://github.com/Sanofi-Public/enact-pipeline. Experimental data is available athttps://zenodo.org/records/13887921. Supplementary information: Supplementary data are available at BiorXiv online.
An envelope stress response governs long-chain fatty acid metabolism via a small RNA to maintain redox homeostasis inEscherichia coli
Authors: Shrivastava Megha , Kaur Manmehar , Luke Liz Maria , Kakkar Richa Ashok , Roy Deeptodeep , Singla Shivam , Sharma Vanshika , Sharma Gaurav , Chaba Rachna 
Published: October 2024

AbstractLong-chain fatty acids (LCFAs) are a tremendous source of energy for several bacteria but are complex to use because they induce redox stress. We previously showed that LCFA degradation impedes oxidative protein folding in theEscherichia colienvelope, an issue that arises due to the insufficiency of ubiquinone, a lipid-soluble electron carrier in the electron transport chain (ETC). To maintain redox homeostasis,E. coliactivates the CpxAR two-component system; however, the nature of feedback imparted by this envelope stress response (ESR) remained unknown. Here, we show that contrary to the well-recognized remedial mode of Cpx restoring envelope integrity by upregulating protein quality control factors, in LCFA-grown cells, it uses a preventive measure to maintain homeostasis. Cpx increases ubiquinone availability for oxidative protein folding by suppressing LCFA metabolism and directly increasing ubiquinone levels. Further, rather than using its conventional mode of imparting regulation via CpxR working as a transcriptional regulator, during LCFA metabolism, Cpx mainly uses its non-coding arm to counteract envelope redox stress. The Cpx-regulated small RNA CpxQ repressesfadgenes involved in LCFA transport and β-oxidation, downregulates components of glyoxylate shunt, gluconeogenesis, and ETC, and increases ubiquinone content. Corroborating with its role in repressing LCFA metabolism and maintaining redox homeostasis, CpxQ overexpression impairs growth ofE. coliin LCFAs and CpxQ deletion renders LCFA-grownE. colihypersensitive to a thiol agent. Our foremost work studying the interconnection between LCFA metabolism, redox stress, and ESR inE. coliprovides a rationale for investigating similar networks in other LCFA-utilizing bacteria.Significance StatementLong-chain fatty acids (LCFAs) are energy-rich nutrients forEscherichia coli; however, their utilization hampers disulfide bond (DSB) formation in secreted proteins, an essential process that occurs in the envelope compartment. Here, we show that an envelope stress response manipulates LCFA metabolism inE. coliand uses a small RNA (sRNA) to restore homeostasis. Several bacteria with a huge impact on human health use host-derived LCFAs during infection. Because many virulence factors require DSB formation, the present study offers a basis to examine whether sRNAs play a role in governing envelope redox balance during LCFA metabolism in pathogens. The sRNA-mediated control is likely an ideal strategy both for rapid response to and quick recovery from LCFA-induced stress.
YebC2 resolves ribosome stalling at polyprolines independent of EF-P and the ABCF ATPase YfmR
Authors: Hong Hye-Rim , Prince Cassidy R. , Wu Letian , Lin Isabella N. , Feaga Heather A. 
Published: October 2024

AbstractPolyproline motifs are essential structural features of many proteins, and recent evidence suggests that EF-P is one of several factors that facilitate their translation. For example, YfmR was recently identified as a protein that prevents ribosome stalling at proline-containing sequences in the absence of EF-P. Here, we show that the YebC-family protein YebC2 (formerly YeeI) functions as a translation factor inB. subtilisthat resolves ribosome stalling at polyprolines. We demonstrate that YebC2, EF-P and YfmR act independently to support cellular fitness. Moreover, we show that YebC2 interacts directly with the 70S ribosome, supporting a direct role for YebC2 in translation. Finally, we assess the evolutionary relationship between YebC2 and other characterized YebC family proteins, and present evidence that transcription and translation factors within the YebC family have evolved separately. Altogether our work identifies YebC2 as a translation factor that resolves ribosome stalling and provides crucial insight into the relationship between YebC2, EF-P, and YfmR, three factors that prevent ribosome stalling at prolines.
Discovery of broad-spectrum bacterial polyamine detoxification inhibitors as potential antivirulence agents and antibiotic adjuvants
Authors: Moulding Peri B. , Flannagan Ronald S. , Wong Jonas , Soliman Ahmed M. , Elhenawy Wael , Heinrichs David E. , El-Halfawy Omar M. 
Published: October 2024

AbstractThe alarming rise in antimicrobial resistance reinforces an urgent need for new antimicrobial strategies. Chemicals at infection sites, such as polyamines, often influence microbial virulence and antibiotic response. Polyamines are cationic small molecules overproduced by the host during infection, modulating immune responses—the ability of several pathogens to detoxify polyamines correlated with hypervirulence. We sought to uncover inhibitors of polyamine detoxification through a high-throughput whole-cell screen against the community-acquired methicillin-resistantStaphylococcus aureusUSA300, identifying the polyamine analog OES2-0017. This inhibitor synergized with polyamines at the low micromolar range, inhibiting a polyamine detoxification spermine/spermidine acetyltransferase SSAT (SpeG) and another previously uncharacterizedS. aureusSSAT (denoted PaiASaherein). OES2-0017 showed growth-inhibitory effects at higher concentrations, perturbing the bacterial membrane with no detectable effects against eukaryotic membranes at the same concentration range. OES2-0017 showed similar broad-spectrum activities against various Gram-positive and Gram-negative pathogens. OES2-0017 abolished the polyamine-mediated resistance to antibiotics, including vancomycin, in MRSA USA300, phenocopying the ΔspeGmutant and suggesting its potential utility as an antibiotic adjuvant. OES2-0017 eradicated SpeG-expressingSalmonellaTyphimurium inside murine macrophages, suggesting its potential as an antivirulence agent. Small-scale structure-activity relationship, eukaryotic toxicity, and enzymatic inhibition against the human SSAT (SAT1) assays identified analogs with higher bacterial enzyme specificity and no toxicity at the antimicrobial range. Our screen also uncovered additional inhibitors, including the catechol derivative isoproterenol (OES1-1087), showing a similar mode of action and activity as OES2-0017 but with lower potency. This study provides novel antimicrobial compounds with broad-spectrum activity and a novel mode of action for multidrug-resistant priority pathogens.
Semi-automated monitoring of longitudinal microbial metabolic dynamics: A study case for lignin degradation
Authors: Guimarães Ferreira João Vítor , Arini Gabriel Santos , da Rosa-Garzon Nathalia Gonsales , Casanova Turatti Izabel Cristina , Borelli Tiago Cabral , Tsuji Henrique Marcel Yudi de Oliveira , Cabral Hamilton , da Silva Ricardo Roberto 
Published: October 2024

ABSTRACTThis study introduces a low-cost, open-source, semi-automated bioreactor system, developed using Arduino and Raspberry Pi, for longitudinal microbial culture studies. The system protocol includes detailed instructions for custom-designed components, specifications for easily purchasable parts, and open-source code for a web-based control interface. It was validated for sterility and tested in a case study involving the cultivation ofPhanerochaete chrysosporiumandTrichoderma reeseito assess their metabolic dynamics, both in isolation and co-culture, for lignin degradation. Using mass spectrometry coupled with gas chromatography, several lignin degradation intermediates were annotated, including 4-hydroxybenzoic acid, vanillic acid, and ferulic acid, along with their temporal variation profiles over 25 days. The results highlighted potential synergy between the two fungal species in lignin breakdown, while also demonstrating the bioreactor’s flexibility and suitability for diverse biotechnological applications, particularly in the field of bio-degradation and waste valorization.
Morph-specific selection pressures drive phenotypic divergence in a color polymorphic bird
Authors: Passarotto Arianna , Lürig Moritz D. , Aaltonen Esa , Karell Patrik 
Published: October 2024

AbstractThere is a long tradition of using heritable color polymorphisms in natural populations to study selection, gene flow, and other evolutionary processes. However, we still have only limited knowledge on how continuous color variation within genetically discrete morphs affects selective dynamics, which narrows our understanding of how color polymorphisms persist. Our comprehensive analysis of 43 years of plumage color scores from a bi-morphic Finnish population of tawny owls (Strix aluco) reveals that intra-morph variation is substantial, but also unexpectedly dynamic. We show that both morphs recently diverged in their plumage coloration: while the brown morph is on a steady trajectory toward more intense plumage pigmentation, the gray morph has recently shifted toward lighter plumage, following a series of extreme winters. Evidence suggests that this divergence is driven by the brown morph’s higher reproductive success and greater plasticity in response to seasonality, while the gray morph, with its more genetically determined plumage color and limited standing variation, has a reduced capacity to respond to selection and track new phenotypic optima. Our study confirms the presence of substantial and dynamic phenotypic variation within genetically discrete color morphs, and demonstrates its relevance for the evolutionary potential of populations to respond to environmental change.
Packaged delivery of CRISPR-Cas9 ribonucleoproteins accelerates genome editing
Authors: Karp Hannah , Zoltek Madeline , Wasko Kevin , Vazquez Angel Luis , Brim Jinna , Ngo Wayne , Schepartz Alanna , Doudna Jennifer 
Published: October 2024

AbstractEffective genome editing requires a sufficient dose of CRISPR-Cas9 ribonucleoproteins (RNPs) to enter the target cell while minimizing immune responses, off-target editing and cytotoxicity. Clinical use of Cas9 RNPs currently entails electroporation into cellsex vivo, but no systematic comparison of this method to packaged RNP delivery has been made. Here we compared two delivery strategies, electroporation and enveloped delivery vehicles (EDVs), to investigate the Cas9 dosage requirements for genome editing. Using fluorescence correlation spectroscopy (FCS), we determined that >1300 Cas9 RNPs per nucleus are typically required for productive genome editing. EDV-mediated editing was >30-fold more efficient than electroporation, and editing occurs at least two-fold faster for EDV delivery at comparable total Cas9 RNP doses. We hypothesize that differences in efficacy between these methods result in part from the increased duration of RNP nuclear residence resulting from EDV delivery. Our results directly compare RNP delivery strategies, showing that packaged delivery could dramatically reduce the amount of CRISPR-Cas9 RNPs required for experimental or clinical genome editing.Graphical Abstract
Characterization of Newly Discovered Polyester Polyurethane-degradingMethylobacterium AquaticumStrain A1
Authors: Lee SeongHyeon , Jeong Haemin , Jung Injun , Choi Myounghyun , Kim Ah-Ram 
Published: October 2024

ABSTRACTIn this study, we presentMethylobacterium aquaticumA1, a novel strain capable of degrading polyester polyurethane (PE-PUR). The attachment ofM. aquaticumA1 to PE-PUR and its degradation capabilities were verified using Scanning Electron Microscopy (SEM) and Fourier-Transform Infrared Spectroscopy (FT-IR). Analysis of the reference genome ofM. aquaticumrevealed genes encoding enzymes with potential PE-PUR degrading activity, including esterases, lipase, proteases and amidase such astesA,pgpB,aes,aprE,lon,degQ,andgatA. An esterase activity assay usingp-nitrophenyl acetate (p-NPA) showed increased ester bond-cleaving activity whenM. aquaticumA1 was exposed to polyurethane diol (PU-diol), suggesting inducible enzymatic activity involved in PE-PUR degradation. These findings highlight the potential ofM. aquaticumA1 as a promising biocatalyst for PE-PUR degradation.IMPORTANCEMicrobial biodegradation is increasingly recognized as a sustainable approach to addressing microplastic pollution. This study introducesM. aquaticumA1, a newly isolated strain capable of adhering to and degrading polyester polyurethane (PE-PUR), one of the most widely utilized plastics. To our knowledge, this is the first report of PE-PUR degradation by a member of theMethylobacteriumgenus. This paper provides a detailed characterization ofM. aquaticumA1 and identifies several enzyme candidates—tesA,pgpB,aes,aprE,lon,degQ,andgatA—as potentially involved in the degradation process. Given thatMethylobacteriumspecies are known to be ecologically beneficial and inhabit diverse environments, the capacity ofM. aquaticumA1 to degrade PE-PUR presents a promising strategy for mitigating microplastic pollution across a range of ecosystems.
Revealing the range of maximum likelihood estimates in the admixture model
Authors: Heinzel Carola Sophia , Baumdicker Franz , Pfaffelhuber Peter 
Published: October 2024

AbstractMany ancestry inference tools, including STRUCTURE and ADMIXTURE, rely on the admixture model to infer both, allele frequenciespand individual admixture proportionsqfor a collection of individuals relative to a set of hypothetical ancestral populations. We show that under realistic conditions the likelihood in the admixture model is typically flat in some direction around a maximum likelihood estimate (MLE). In particular, the maximum likelihood estimator is non-unique and there is a complete spectrum of possible estimates. Common inference tools typically identify only a few points within this spectrum.We provide an algorithm which computes the set of equally likely, when starting from. It is analytic forK= 2 ancestral populations and numeric forK> 2. We apply our algorithm to data from the 1000 genomes project, and show that inter-European estimators ofqcan come with a large set of equally likely possibilities. In general, markers with large allele frequency differences between populations in combination with individuals with concentrated admixture proportions lead to small areas with a flat likelihood.Our findings imply that care must be taken when interpreting results from STRUCTURE and ADMIXTURE if populations are not separated well enough.