bluuebunny/crossref_metadata_2025_split huggingface dataset:
Roles of Cro2and CI2binding to ORoperators in controlling lysogeny stability during prophage induction
Authors: Pang Yiyu , Lei Xue , Manuchehrfar Farid , Du Lin , Liang Jie 
Published: January 2025

AbstractThe lysogeny-lysis switch in bacteriophage lambda serves as a model for understanding cell fate decisions. The molecular network controlling this switch has been explored through extensive experimental and computational studies. Yet, the specific role of protein-DNA interactions, like the binding of CI2and Cro2proteins to operator sites, in regulating lysogeny stability during prophage induction remains less under-stood. This study employs a minimalistic model and the Accurate Chemical Master Equation (ACME) method to construct detailed probability landscapes of the network’s behavior under varying conditions, such as different dissociation and CI2degradation rates which simulate UV irradiation effects. Our findings indicate that Cro2binding at OR3 and CI2at OR1 significantly influence lysogeny stability, with the former destabilizing and the latter stabilizing it. Conversely, interactions at OR1 by Cro2and OR3 by CI show minimal impact on this stability. Through the ACME approach, we could examine the network’s global behavior under conditions unapproachable by conventional stochastic simulations. This study highlights the critical roles of specific protein-DNA interactions in maintaining lysogeny and provides insight into the broader dynamics of the lysogeny-lysis switch under various physiological stresses.
Effect of improved spatial resolution on PET SUVR estimates in the LEADS study of sporadic early-onset Alzheimer’s disease
Authors: Schonhaut Daniel R. , La Joie Renaud 
Published: January 2025

ABSTRACTBackgroundThe Longitudinal Early-onset Alzheimer’s Disease Study (LEADS) recently transitioned from processing positron emission tomography (PET) scans at 8mm to 6mm resolution in early 2024. Concurrent with this improved spatial resolution, we revised our processing methods for defining reference regions used in amyloid and tau PET analyses, with the goal to maintain alignment with MRI-based PET processing in the Alzheimer’s Disease Neuroimaging Initiative (ADNI).MethodsWe describe the following changes to the LEADS MRI-based PET processing pipeline:Transition from 8mm to 6mm PET scans.Revised method to calculate a composite reference region scaling factor for longitudinal analysis of18F-Florbetaben (FBB).Revised method to define the eroded subcortical white matter region, which is used in longitudinal analyses of both FBB and18F-Flortaucipir (FTP).Corrected method to define the inferior cerebellar gray matter reference region used in cross-sectional analysis of FTP.We evaluated these changes by comparing 8mm standardized uptake value ratios (SUVRs) processed with the original LEADS PET pipeline to 6mm SUVRs processed with the updated pipeline. This analysis was conducted in 564 FBB, 555 FTP, and 134 FDG scans acquired in LEADS participants at baseline between May 2018 and September 2023.ResultsWe found near-perfect correlations across all tracers and reference regions (R2> 0.99). However, 6mm SUVRs had greater dynamic range than 8mm SUVRs, with 8mm-to-6mm linear transformation slopes ranging from 1.08 to 1.22.ConclusionsOur findings closely parallel ADNI’s experience transitioning to higher resolution PET. Amyloid PET Centiloid conversion equations, which were originally derived using 8mm data, should be re-estimated using 6mm data to maintain optimal harmonization. LEADS data users should not mix 6mm and 8mm PET data and should instead exclusively use 6mm PET data going forward, as these measures better reflect modern scanner capabilities while maintaining compatibility with ADNI. LEADS data users who are unsure of the origin or resolution of their PET values are encouraged to contact us for advice atLEADS.PETCORE@ucsf.edu.
Toward highly accurate reference and method selection for universal cross-dataset cell type annotation
Authors: Shen Qunlun , Zhang Shuqin , Zhang Shihua 
Published: January 2025

AbstractCell type annotation is a critical and essential task in single-cell data analysis. Various reference-based methods have provided rapid annotation for diverse single-cell data. However, how to select the optimal references and methods is often overlooked. To this end, we present a cross-dataset cell-type annotation methodology with a universal reference data and method selection strategy (CAMUS) to achieve highly accurate and efficient annotations. We demonstrate the advantages of CAMUS by conducting comprehensive analyses on 672 pairs of cross-species scRNA-seq datasets. The annotation results with references selected by CAMUS achieved substantial accuracy gains (25.0-124.7%) across five reference-based methods. CAMUS achieved high accuracy in choosing the best reference-method pair among 3360 pairs (49.1%). Combined with reference-integrated strategies, they improved further on 3522 dataset triplets (9.3-39.3%). Moreover, CAMUS showed high accuracy in selecting the best methods on the 80 scST datasets (82.5%) and five scATAC-seq datasets (100.0%), illustrating its universal applicability. In addition, we utilized the CAMUS score with other metrics to predict the annotation accuracy, providing direct guidance on whether to accept current annotation results.
Direct binding of arsenicals to nuclear transport factors disrupts nucleocytoplasmic transport
Authors: Lorentzon Emma , Lee Jongmin , Masaryk Jakub , Keuenhof Katharina , Karlsson Nora , Galipaud Charlotte , Madsen Rebecca , Höög Johanna L. , Levin David E. , Tamás Markus J. 
Published: January 2025

ABSTRACTHuman exposure to arsenicals is associated with devastating diseases such as cancer and neurodegeneration. At the same time, arsenic-based drugs are used as therapeutic agents. The ability of arsenic to directly bind to proteins is correlated with its toxic and therapeutic effects highlighting the importance of elucidating arsenic-protein interactions. In this study, we took a proteomic approach and identified 174 proteins that bind to arsenic inSaccharomyces cerevisiae. Proteins involved in nucleocytoplasmic transport were markedly enriched among the arsenic-binding proteins, and we demonstrate that arsenic-binding to nuclear import factors results in their relocation from the nuclear envelope and subsequent aggregation in the cytosol. Similarly, nuclear pore proteins that make up the nuclear pore complex mislocalized and aggregated in arsenic-exposed cells. Consequently, arsenic was shown to inhibit nuclear protein import and export. We propose a model in which arsenic-binding to nuclear transport factors leads to their mislocalization and aggregation, which disrupts nucleocytoplasmic transport and causes arsenic sensitivity.
Behavior decoding delineates seizure microfeatures and associated sudden death risks in mice
Authors: Shen Yuyan , Thomas Jaden , Chen Xianhui , Zelidon Jaden , Hahn Abigayle , Zhang Ping , Sathyanesan Aaron , Gu Bin 
Published: January 2025

AbstractBehavior and motor manifestations are distinctive yet often overlooked features of epileptic seizures. Seizures can result in transient disruptions in motor control, often organized into specific behavioral patterns that can inform seizure types, onset zones, and outcomes. However, refined analysis of behaviors in epilepsy remains challenging in both clinical and preclinical settings. Current manual video inspection approaches are subjective, time-consuming, and often focus on gross and ambiguous descriptions of seizure behaviors, overlooking much of the intricate behavioral dynamics and action kinematics. Here, we utilized two machine learning-aided tools,DeepLabCut(DLC) andBehavior Segmentation of Open Field in DLC(B-SOiD), to decode previously underexplored behavior and action domains of epilepsy. We identified 63 interpretable behavior groups during seizures in a population of 32 genetically diverse mouse strains. Analysis of these behavior groups demonstrates significant differential behavior expression and complexity that can delineate distinct seizure states, unravel intrinsic seizure progression over time, and inform mouse strain backgrounds and genotypes. We also identified seizure behavior patterns and action/subaction kinematics that determine the risks of sudden unexpected death in epilepsy (SUDEP). These findings underscore the significant potential for translation into inpatient settings for video analysis in epilepsy monitoring units and outpatient settings via home surveillance devices and smartphones.One Sentence SummaryAI-aided behavior decoding delineates intricate seizure microfeatures in mice.
Microbiome and Genetic Predictors of Weight Loss 12 Months Post Sleeve Gastrectomy: Insights from a Pilot Retrospective Cohort Study
Authors: Pedroso Inti , Kumbhare Shreyas V. , Johnson Shaneeta , Muthukumar Karthik M. , Saravanan Santosh K. , Irudayanathan Carmel , Sharma Garima , Tabone Lawrence , Sinha Ranjan , Almonacid Daniel E. , Szoka Nova 
Published: January 2025

AbstractBackgroundGut microbiome and genetic biomarkers are increasingly guiding obesity treatment. Bariatric surgery leads to shifts in gut microbial composition and function, while genome-wide association studies reveal genetic underpinnings of polygenic obesity, informing risk, therapeutic outcomes, and nutrigenomics-based interventions.ObjectivesThis pilot study aimed to identify gut microbiome and genetic biomarkers associated with weight loss 12 months after sleeve gastrectomy (SG).SettingSingle academic institution university clinicMethodsSixty-seven patients 12 months post-SG were enrolled: 34 had successful excess weight loss (EWL≥50%), while 33 had unsuccessful EWL (EWL<50%). Microbiome and genetic profiles were collected and analyzed using ANOVA and regression methods.ResultsThe genus Akkermansia was significantly associated with EWL (p=9.9×10^−6). Several microbial pathways, including propionate synthesis and menaquinone (vitamin K2) production, showed nominally significant (p<0.05) associations with greater weight loss. No differences emerged in the Firmicutes/Bacteroidetes ratio. Genetic analyses revealed significant correlations between EWL and polygenic scores for dietary needs and metabolic responses, including distinct vitamin D and K requirements, as well as higher LDL cholesterol levels and predisposition for major depression.ConclusionThese findings suggest that both the gut microbiome and genetics may modulate weight loss following bariatric surgery. Integrating microbiome and genetic profiling into bariatric care pathways could enhance personalized obesity treatment. While this pilot, exploratory, and proof-of-concept study has limitations, it supports prior work linking gut microbial pathways to weight loss and suggests new associations. Follow-up studies are warranted to validate these results and further inform precision obesity interventions.HighlightsAkkermansia strongly correlates with weight loss 12 months post-sleeve gastrectomy.Microbiome propionate and vitamin K2 pathways linked to higher excess weight loss.Genetic markers link vitamin needs, LDL and depression risk with lower weight loss.Microbiome and genetics integration may improve bariatric surgery outcomes.
Noncanonical EEG-BOLD coupling by default and in schizophrenia
Authors: Jacob Michael S. , Roach Brian J. , Mathalon Daniel H. , Ford Judith M. 
Published: January 2025

AbstractNeuroimaging methods rely on models of neurovascular coupling that assume hemodynamic responses evolve seconds after changes in neural activity. However, emerging evidence reveals noncanonical BOLD (blood oxygen level dependent) responses that are delayed under stress and aberrant in neuropsychiatric conditions. To investigate BOLD coupling to resting-state fluctuations in neural activity, we simultaneously recorded EEG and fMRI in people with schizophrenia and psychiatrically unaffected participants. We focus on alpha band power to examine voxelwise, time-lagged BOLD correlations. Principally, we find diversity in the temporal profile of alpha-BOLD coupling within regions of the default mode network (DMN). This includes early coupling (0-2 seconds BOLD lag) for more posterior regions, thalamus and brainstem. Anterior regions of the DMN show coupling at canonical lags (4-6 seconds), with greater lag scores associated with self-reported measures of stress and greater lag scores in participants with schizophrenia. Overall, noncanonical alpha-BOLD coupling is widespread across the DMN and other non-cortical regions, and is delayed in people with schizophrenia. These findings are consistent with a “hemo-neural” hypothesis, that blood flow and/or metabolism can regulate ongoing neural activity, and further, that the hemo-neural lag may be associated with subjective arousal or stress. Our work highlights the need for more studies of neurovascular coupling in psychiatric conditions.
Clinical and Taxonomic Characterization of a Novel Urinary Tract PathogenProvidencia lanzhouensis
Authors: Xiang Yanghui , Dong Xu , Ma Lan , Cao Dan , Li Yi , Jiang Xiuzhi , Xu Pusheng , Yuan Xin , Bi Kefan , Zhang Yiru , Han Yuxin , Zhang Ying 
Published: January 2025

AbstractBackgroundThe genusProvidenciaincludes species of ecological and clinical significance, with some acting as opportunistic pathogens in hospital-acquired infections such as urinary tract infection (UTI). However, overlapping phenotypic traits and genetic similarities pose challenges for accurate species characterization. This study exemplifies this challenge by identifying a novelProvidenciaisolate through genomic analysis.ResultsIn this study, strain PAZ2 was isolated from the urine sample of a hospitalized patient in Lanzhou, Gansu Province, China. Initial mass spectrometry analysis identified the strain asProvidencia alcalifaciens. It exhibits a resistance profile against antibiotics including ampicillin, tetracycline, tigecycline, polymyxin B, colistin, trimethoprim-sulfamethoxazole, and ciprofloxacin. However, whole-genome sequence analysis indicated that this strain is a novel species with an average nucleotide identity (ANI) values ranging from 79.92% to 94.73% and digital DNA-DNA hybridization (dDDH) values between 21.2% and 57.6% when compared with all knownProvidenciaspecies. Furthermore, strain PAZ2 exhibited unique biochemical properties that differentiated it from all previously described species within the genus.ConclusionsGenomic and biochemical evidence supports PAZ2 as a novelProvidenciaspecies, which we namedProvidencia lanzhouensissp. nov. This finding enhances the taxonomy ofProvidenciaand underscores its clinical relevance, notably in UTIs and other nosocomial infections. Accurate identification is crucial for guiding effective treatment and preventing misdiagnosis. Further studies should investigate its pathogenicity, antimicrobial resistance, and epidemiology to inform infection control measures.
N-acetylcysteine to reduce kidney and liver injury associated with drug-resistant tuberculosis treatment
Authors: Meadows Idu , Mvungi Happiness , Salim Kassim , Kaswaga Oscar , Mbelele Peter , Liyoyo Alphonce , Semvua Hadija , Ngoma Athumani , Heysell Scott , Mpagama Stellah 
Published: January 2025

AbstractBackgroundNew drug classes and regimens have shortened the treatment duration for drug-resistant tuberculosis, but adverse events (AEs) and organ toxicity remain unacceptably common. N-acetylcysteine (NAC) has demonstrated potential in reducing kidney and liver toxicity in other clinical settings, but efficacy in drug-resistant tuberculosis treatment has not been rigorously evaluated.MethodA randomized controlled trial (PACTR202007736854169) was conducted at Kibong’oto Infectious Disease Hospital in Tanzania to assess the efficacy of NAC in reducing AEs in patients undergoing rifampin-resistant pulmonary tuberculosis treatment. Participants received an all-oral standardized rifampin-resistant regimen alone, with NAC 900 mg daily, or NAC 900 mg twice daily for 6 months. AEs, severe AEs, and renal and liver toxicity were monitored monthly and classified according to the Risk, Injury, Failure, Loss, and End-stage kidney disease criteria and National Cancer Institute Common Terminology Criteria for Adverse Events. Incident ratios and Kaplan-Meier curves were employed to compare group event occurrences.Results66 patients (mean age 47±12 years; 80% male) were randomized into three groups of 22. One hundred and fifty-eight AEs were recorded: 52 (33%) in the standard treatment group, 55 (35%) in the NAC 900 mg daily group, and 51 (32%) in the NAC 900 mg twice daily group (p>0.99). Severe AEs were observed in 4 patients in the standard group, 2 in the NAC 900 mg daily group, and 3 in the NAC 900 mg twice daily group. Renal toxicity was more prevalent in the standard treatment group (45% vs. 23%; p=0.058), with a shorter onset of time to toxicity (χ2 = 3.199; p=0.074). Liver injury events were rare across all groups.ConclusionAmong Tanzanian adults receiving rifampin-resistant tuberculosis treatment, NAC did not significantly reduce overall AEs but demonstrated important trends in reducing renal toxicity.
Epidemiology of vascular access for outpatient hemodialysis procedures and renal transplantation in Brazil between 2008 and 2022: A cross-sectional nationwide analysis
Authors: Jeronimo Ponte Bruno , Sorbello Carolina Carvalho Jansen , Redivo Basani Lucas , Fiorelli Alexandrino da Silva Marcelo , Teivelis Marcelo Passos , Kuzniec Sergio , Wolosker Nelson 
Published: January 2025

3.ABSTRACTBACKGROUND AND HYPOTHESISChronic kidney disease (CKD) represents a significant global public health challenge, affecting up to 13.4% of the population and ranking as the third fastest-growing cause of mortality. Progression of CKD to end stage kidney disease (ESKD) is the initial milestone for renal replacement therapy, which includes hemodialysis and renal transplantation, the latter marking the final therapy for ESKD patients. Arteriovenous fistulas (AVFs) are preferred for hemodialysis due to lower infection risks and superior patency compared to long-staying tunneled catheters (LSTC). Despite the importance of vascular access and transplantation, nationwide data correlating their utilization over time remains scarce. This study aimed to analyze outpatient hemodialysis vascular access procedures in Brazilian public health system from 2008 to 2022, comparing the temporal trends with renal transplantation.METHODSThis study employed a cross-sectional, population-based analysis of publicly available data pertaining outpatient vascular access procedures for hemodialysis and renal transplantation in the brazilian public health system between 2008 and 2022. Linear regression and correlation between both were then carried out.RESULTSBetween 2008 and 2022, 937,739 procedures were realized, including vascular access confection, ending procedures and renal transplants. Arteriovenous fistulas accounted for the majority of procedures (55%), followed by LSTC (34%), renal transplants in cadaveric donors (5.6%), catheter removals (2.2%), renal transplants with living donors (1.6%) and fistula ligation (1.4%). The increase in AVF creation was not proportional to the growth of the hemodialysis population(p<0.001), in contrast to catheter implants, which increased substantially over the study period (p<0.001). Vascular access-ending procedures demonstrated a significant correlation with renal transplants(p<0.001).CONCLUSIONIn Brazil, the number of LSTC for hemodialysis has increased over the years, while the number of AVFs significantly decreased. Additionally access-ending procedures, such as fistula ligation and catheter removals, have risen annually since 2010 and demonstrated a correlation with renal transplantation.Key Points:
Keratin intermediate filaments mechanically position melanin pigments for genome photoprotection
Authors: Benito-Martínez Silvia , Salavessa Laura , Macé Anne-Sophie , Lardier Nathan , Fraisier Vincent , Sirés-Campos Julia , Jani Riddhi Atul , Romao Maryse , Gayrard Charlène , Plessis Marion , Hurbain Ilse , Nait-Meddour Cécile , Morel Etienne , Boniotto Michele , Manneville Jean-Baptiste , Bernerd Françoise , Duval Christine , Raposo Graça , Delevoye Cédric 
Published: January 2025

ABSTRACTMelanin pigments block genotoxic agents by positioning on the sun-exposed side of human skin keratinocytes’ nucleus. How this position is regulated and its role in genome photoprotection remains unknown. By developing a model of human keratinocytes internalizing extracellular melanin into pigment organelles, we show that keratin 5/14 intermediate filaments mechanically control the 3D perinuclear position of pigments, shielding DNA from photodamage. Imaging and microrheology in human disease-related model identify structural keratin cages surrounding pigment organelles to stiffen their microenvironment and maintain their 3D position. Optimum pigment spatialization is required for DNA photoprotection and rely on the interplay between intermediate filaments and microtubules bridged by plectin cytolinkers. Thus, the mechanically-driven proximity of pigment organelles to the nucleus is a key photoprotective parameter. Uncovering how human skin counteracts solar radiation by positioning the melanin microparasol next to the genome anticipates that dynamic spatialization of organelles is a physiological UV stress response.Short summaryMelanin pigments shield DNA from photodamage by positioning atop nuclei in skin keratinocytes. We show keratin 5/14 intermediate filaments control this 3D spatialization, forming protective cages around pigments. This positioning, together with microtubule function, optimizes genome protection, revealing cytoskeletons and organelle dynamics as a UV stress response.
Quantitative analysis of the frequency of chromosome loss following DSB induction
Authors: Matsuno Seiya , Ishida Ryo , Kawasumi Ryotaro , Hirota Kouji , Abe Takuya 
Published: January 2025

AbstractNumerical abnormalities in chromosomal states, referred to as aneuploidy, is commonly observed in many cancer cells. Although numerous internal and external factors induce aneuploidy, the primary cause of aneuploidy in humans remains unclear. DNA damage is identified as a potential cause of aneuploidy by inducing chromosome segregation errors. However, a direct relationship between DNA damage and aneuploidy remains poorly understood. A major reason for this is the extremely low frequency of aneuploidy in cultured cells, making quantitative analyses challenging. In this study, we investigated the relationship between DNA damage and aneuploidy in cell lines containing minichromosomes. These chromosomes are more prone to loss than normal chromosomes, with the rate of loss substantially increased following exposure to various DNA-damaging agents. To determine whether damaged chromosomes were subjected to direct loss or whether chromosome loss occurred as an indirect consequence of a prolonged G2 phase or other factors, we used the CRISPR-Cas9 system to introduce a single DNA double-strand break (DSB) on a minichromosome. The rate of minichromosome loss increased by approximately seven-fold compared with that of the control. Furthermore, the loss rate was significantly elevated in the absence of KU70, a key factor in non-homologous end joining, and upon inhibition of ataxia telangiectasia mutated (ATM), a DNA damage checkpoint protein. Finally, two closely spaced nicks, believed to generate a 5’-overhang, were also shown to induce minichromosome loss. These findings indicated that a single DSB or two closely spaced nicks can cause aneuploidy if improperly repaired in vertebrates.