bluuebunny/crossref_metadata_2025_split huggingface dataset:
TFBSFootprinter: a multiomics tool for prediction of transcription factor binding sites in vertebrate species
Authors: Barker Harlan R. , Parkkila Seppo , Tolvanen Martti E.E. 
Published: January 2025

AbstractBackgroundTranscription factor (TF) proteins play a critical role in the regulation of eukaryotic gene expression via sequence-specific binding to genomic locations known as transcription factor binding sites (TFBSs). Accurate prediction of TFBSs is essential for understanding gene regulation, disease mechanisms, and drug discovery. These studies are therefore relevant not only in humans but also in model organisms and domesticated and wild animals. However, current tools for the automatic analysis of TFBSs in gene promoter regions are limited in their usability across multiple species. To our knowledge, no tools currently exist that allow for automatic analysis of TFBSs in gene promoter regions for many species.Methodology and FindingsThe TFBSFootprinter tool combines multiomic transcription-relevant data for more accurate prediction of functional TFBSs in 124 vertebrate species. In humans, this includes vertebrate sequence conservation (GERP), proximity to transcription start sites (FANTOM5), correlation of expression between target genes and TFs predicted to bind promoters (FANTOM5), overlap with ChIP-Seq TF metaclusters (GTRD), overlap with ATAC-Seq peaks (ENCODE), eQTLs (GTEx), and the observed/expected CpG ratio (Ensembl).TFBSFootprinter analyses are based on the Ensembl transcript ID for simplicity of use and require minimal setup steps. Benchmarking of the TFBSFootprinter on a manually curated and experimentally verified dataset of TFBSs produced superior results when using all multiomic data (average area under the receiver operating characteristic curve, 0.881), compared with DeepBind (0.798), FIMO (0.817) and traditional PWM (0.854). The results were further improved by selecting the best overall combination of multiomic data (0.910). Additionally, we determined combinations of multiomic data that provide the best model of binding for each TF. TFBSFootprinter is available as Conda and Python packages.
A Murine Database of Structural Variants Enables the Genetic Architecture of a Spontaneous Murine Lymphoma to be Characterized
Authors: Ren Wenlong , Fang Zhuoqing , Dolzhenko Egor , Saunders Christopher T. , Cheng Zhuanfen , Popic Victoria , Peltz Gary 
Published: January 2025

AbstractA more complete map of the pattern of genetic variation among inbred mouse strains is essential for characterizing the genetic architecture of the many available mouse genetic models of important biomedical traits. Although structural variants (SVs) are a major component of genetic variation, they have not been adequately characterized among inbred strains due to methodological limitations. To address this, we generated high-quality long-read sequencing data for 40 inbred strains; and designed a pipeline to optimally identify and validate different types of SVs. This generated a database for 40 inbred strains with 573,191SVs, which included 10,815 duplications and 2,115 inversions, that also has 70 million SNPs and 7.5 million insertions/deletions. Analysis of this SV database led to the discovery of a novel bi-genic model for susceptibility to a B cell lymphoma that spontaneously develops in SJL mice, which was initially described 55 years ago. The first genetic factor is a previously identified endogenous retrovirus encoded protein that stimulates CD4 T cells to produce the cytokines required for lymphoma growth. The second genetic factor is a newly found deletion SV, which ablates a protein whose promotes B lymphoma development in SJL mice. Characterizing the genetic architecture of SJL lymphoma susceptibility could provide new insight into the pathogenesis of a human lymphoma that has similarities with this murine lymphoma.
Absolute Quantification of Lysosomal Proteins by Multiple Reaction Monitoring Mass Spectrometry and QconCAT Protein Standards
Authors: Mosen Peter Robert , Moharana Biswajit , Fajardo-Callejon Sofía , Kaade Edgar , Rösel Norbert , Omidi Maryam , Sakson Roman , Ruppert Thomas , Pohl Sandra , Gieselmann Volkmar , Winter Dominic 
Published: January 2025

ABSTRACTLysosomes are membrane-enclosed organelles that play a crucial role in the degradation of intra- and extracellular substrates and the regulation of metabolic signaling. These functions are carried out by a variety of proteins, of which > 150 are currently known to be located in the lysosomal lumen or to be embedded in its membrane. These proteins are typically low abundant, necessitating organelle enrichment experiments to enable their investigation by unbiased mass spectrometry-based proteomics analyses. Enrichment strategies have been applied in a plethora of studies to gain a deeper understanding of lysosomal composition and relative changes of lysosomal proteome abundance in a variety of pathological conditions. Such experiments are restricted, however, to selected cell lines and tissues and do not allow a direct analysis of the lysosomal proteome from whole cell or tissue lysates. Furthermore, they do not provide absolute quantities. We developed a multiple reaction monitoring mass spectrometry-based assay for the highly sensitive and reproducible absolute quantification of 143 mouse lysosomal proteins from any type of sample following the QconCAT strategy. We applied our approach to the investigation of mouse embryonic fibroblast whole cell lysates and lysosome-enriched fractions, providing absolute copy numbers per cell/lysosome for lysosomal hydrolases and membrane proteins. These data reveal a dynamic range of more than three orders of magnitude in protein expression and strong differences in the subcellular distribution of individual lysosomal proteins. Furthermore, we applied our strategy to the investigation of four primary cell types (macrophages, lung fibroblasts, osteoblasts, and osteoclasts), demonstrating pathway-specific heterogeneity of individual lysosomal protein classes and indicating protein-specific post-transcriptional regulation of expression levels.
The carrying capacity of a fragmented landscape depends on the home-range size of a species
Authors: Pereira Henrique M. , Daily Gretchen C. 
Published: January 2025

ABSTRACTPopulation models have not considered the problem of home-range settlement when the grain of the landscape is smaller than the home-range size. We present an individual-based model addressing this problem that combines age-structured population dynamics, optimal foraging and habitat selection. During home-range settlement each juvenile tries to maximize her fitness, which depends on the proportion of high-quality habitat in her home range. We assume that home ranges do not overlap, which can happen because the home range is defended as a territory or because individuals avoid areas used by conspecifics. We show that the population supported by the landscape at equilibrium, the carrying capacity of the landscape, decreases with the amount of low-quality habitat cover. However, this decrease is non-linear, the carrying capacity starts to decline only below a critical habitat threshold. Furthermore, when the home-range size is larger than the grain of the landscape, the carrying capacity declines faster when the habitat is fragmented. Therefore species with small home-ranges persist in instances where species with large home-ranges go deterministically extinct. Species with large population growth rates have low critical habitat sizes, and are more resilient to habitat conversion.
Long-term multichannel recordings inDrosophilaflies reveal distinct responses to deviant visual stimuli during sleep compared to wake
Authors: Van De Poll Matthew N. , van Swinderen Bruno 
Published: January 2025

ABSTRACTDuring sleep, behavioral responsiveness to external stimuli is decreased. This classical definition of sleep has been applied effectively across the animal kingdom to identify this common behavioral state in a growing list of creatures, from mammals to invertebrates. Yet it remains unclear whether decreased behavioral responsiveness during sleep is necessarily associated with decreased responsiveness in brain activity, especially in relative latecomers to the sleep field, such as insects. Here, we perform long-term multichannel electrophysiology in tetheredDrosophila melanogasterflies exposed continuously to flashing visual stimuli. Flies were still able to sleep under these visual stimulation conditions, as determined by traditional immobility duration criteria for the field. Interestingly, local field potentials (LFPs) recorded in a transect through the fly brain failed to show any difference in amplitude during sleep compared to wake when the visual stimuli were invariant. In contrast, LFP responses were lower when visual stimuli were variable and of lower probability, especially in the central brain. Central brain responses to ‘deviant’ stimuli were lowest during the deepest stage of sleep, characterized by more regular proboscis extensions. This shows that the sleeping fly brain processes low-probability visual stimuli in a different way than more repeated stimuli and presentsDrosophilaas a model system for studying the potential role of sleep in regulating predictive processing.SUMMARY STATEMENTThe sleeping fly brain still responds to visual stimuli. However, response amplitudes depend on stimulus history and probability, as well as recording location.
Neural decoding of competitive decision-making in Rock-Paper-Scissors using EEG hyperscanning
Authors: Moerel Denise , Grootwagers Tijl , Chin Jessica L. L. , Ciardo Francesca , Nijhuis Patti , Quek Genevieve L. , Smit Sophie , Varlet Manuel 
Published: January 2025

ABSTRACTSocial interactions are fundamental to daily life, yet social neuroscience research has often studied individuals’ brains in isolation. Hyperscanning, the simultaneous recording of neural data from multiple participants, enables real-time investigation of social processes by examining multiple brains while they interact. Previous hyperscanning research has mostly focused on cooperative tasks and remains limited in competitive contexts. Here, we obtained electroencephalography (EEG) hyperscanning data for 62 participants (31 pairs) who played a computerised version of the Rock-Paper-Scissors game, a classic paradigm for studying competitive decision-making. Although the optimal strategy is to be unpredictable and thus act randomly, participants exhibited behavioural biases, deviating from this ideal. Using multivariate decoding methods, we found that neural signals contained information about decisions made by participants during gameplay, revealing certain strategies. Notably, losers showed unique reliance on prior trials, suggesting memory-based strategies that may impair optimal performance. These results reveal how competitive decision-making is shaped by cognitive biases and memory of previous outcomes, highlighting the difficulty of achieving randomness in strategic contexts. This work advances our understanding of decision-making and cognitive dynamics in competitive interactions.
Stable isotope labeling kinetics of neurofilament lightin vitroandin vivo
Authors: Leckey Claire A. , Giovannucci Tatiana A. , Coulton John B. , He Yingxin , Sato Chihiro , Ghoshal Nupur , Vignarajah Tharini , Jaunmuktane Zane , Barthélemy Nicolas R. , Zetterberg Henrik , Elbert Donald L. , Mills Kevin , Wray Selina , Bateman Randall J. , Paterson Ross W. 
Published: January 2025

AbstractImportanceNeurofilament light (NfL) is elevated in CSF and blood across a range of traumatic, inflammatory and neurodegenerative diseases of the central nervous system, and has been increasingly included in clinical trials as an outcome measure of target engagement. Interpreting trajectories of NfL post-treatment has been challenging, prompting a greater need and focus on understanding its pathophysiology.ObjectiveWe measured NfL kinetics in the human central nervous system using stable isotope labeling kinetics (SILK).DesignObservational study. Participants underwent SILK protocol. Infusion of 16 hours with 4mg/kg/h and follow-up lumbar punctures scheduled at 7, 14, 60 and 120 days post-labeling.SettingReferral center – specialist neurology clinic.ParticipantsParticipants with diagnosed primary tauopathies (n=10) were recruited to the Human CNS Tau Kinetics in Tauopathies (TANGLES) study. A control case was examinedpost-mortemto assess the technical background of the SILK method.ExposureIntravenous infusion of13C6-leucine, with rates of label incorporation representative of fractional synthesis and fractional clearance ratesin vivoandin vitro.Main outcome and MeasureLevel of incorporation of13C6-leucine tracer into newly-translated NfL divided by the pool of NfL with previously incorporated12C6-leucine, expressed as a percentage tracer-to-tracee (TTR) ratio.ResultsNfL is rapidly translated in human brain within hours but takes 53 – 162 days to appear in cerebrospinal fluid (CSF). Labeled NfL remains detectable inpost-mortembrain tissue 1.5 years post-labeling, indicating an extremely slow turnover in the human CNS. Together, these data suggest the greatest contribution of CSF NfL in neurodegeneration is from slow release of a large pool of previously translated NfL. However, release of newly translated NfL makes a significant contribution.Conclusion and relevanceRapid increases in CSF NfL seen within weeks of disease processes or interventions are likely to reflect release of pre-existing NfL from damaged neurons, but later increases in NfL (>3 months) may also reflect new NfL translation and release. Clinical trials using NfL as an outcome measure to track neurodegeneration would particularly benefit from substantially longer follow-up periods due to the slow turnover of the protein in the central nervous system.
A Method for Sensitivity Analysis of Automatic Contouring Algorithms Across Different MRI Contrast Weightings Using SyntheticMR
Authors: McCullum Lucas , Belal Zayne , Floyd Warren , Ali Alaa Mohamed Shawky , West Natalie , Mulder Samuel , Ding Yao , Xu Jiaofeng , Thill Dan , O’Connell Nicolette , Stancanello Joseph , Wahid Kareem A. , Fuentes David T. , Hwang Ken-Pin , Fuller Clifton D. 
Published: January 2025

AbstractBackgroundCurrently, a majority of institution-specific automatic MRI-based contouring algorithms are trained, tested, and validated on one contrast weighting (i.e., T2-weighted), however their actual performance within this contrast weighting (i.e., across different repetition times, TR, and echo times, TE) is under-investigated and poorly understood. As a result, external institutions with different scan protocols for the same contrast weighting may experience sub-optimal performance.PurposeThe purpose of this study was to develop a method to evaluate the robustness of automatic contouring algorithms to varying MRI contrast weightings.MethodsOne healthy volunteer and one patient was scanned using SyntheticMR on the MR-Simulation device. The parotid and submandibular glands in these subjects were contoured using an automatic contouring algorithm trained on T2-weighted MRIs. For ground truth manual contours, two radiation oncology residents and one pre-resident physician were recruited and their STAPLE consensus was determined. A total of 216 different MRI TR and TE combinations were simulated across T1-, T2-, and PD-weighted contrast ranges using SyntheticMR’s post-processing software, SyMRI. Comparisons between automatic contouring algorithm contours and the ground truth were determined using the Dice similarity coefficient (DSC) and 95thpercentile Hausdorff distance (HD95).ResultsNotable differences in the automatic contouring model’s performance were seen across the contrast-weighted range, even within the T2-weighted range. Further, some models even performed as well or better across subsets of the T1-weighted range. The PD-weighted range saw the worst performance. The range of discrepancy in DSC and HD95 exceeded 0.2 and 3.66 mm, respectively, in some structures. In the T2-weighted contrast region where the model was trained, 100%, 40%, 24%, and 57% for the DSC in the left parotid, right parotid, left submandibular, and right submandibular gland, respectively, exceeded interobserver variability.ConclusionsThis study demonstrates the variable performance of MRI-based automatic contouring algorithms across varying TR and TE combinations. This methodology could be applied in future studies as a method for evaluating model sensitivity, out of distribution detection ability, and performance drift.
Distinct temporal stages of infant brain processing associate with early versus later autism diagnosis
Authors: Bazelmans T. , Charman T. , Johnson M. H. , Jones E.J.H. ,   BASIS Team
Published: January 2025

AbstractBackgroundThe expression of autism traits sufficient to meet criteria for a diagnosis can occur early (by 3 years) or later (from mid-childhood onwards). It remains unknown whether variation in age of onset is due to clinical recognition or whether it reflects distinct biological pathways. One way of addressing this question is by investigating biological differences very early in development associated with age of onset. We use a prospective design to look at event related potentials to faces, one of the most robust biomarkers in autism.MethodsA sample of 102 infants (aged 6-10 months, 54% female) with an older autistic sibling had EEG recorded whilst viewing faces (faces versus noise; gaze towards versus away). Autism diagnostic assessments were conducted at three years and again in mid-childhood (aged 6-12 years), resulting in early diagnosed (at age 3; N=22), later diagnosed (at mid-childhood; N=21) and no autism (N=59) groups.ResultsWhile a short latency response (P1) does not associate with autism outcome, a mid-latency component (N290) associates with early onset autism only, and a later latency component (P400) associates with both early and later onset autism.ConclusionTemporal stages of face processing in infancy differentially associate with age of autism onset such that an earlier age of diagnosis is associated with earlier stage deviation within the event-related waveform. Early and later onset autism may represent different biological subtypes, with different early brain development, challenging the view of one etiological pathway and that variation in diagnostic age is solely due to clinical ascertainment.
The Role of Fermented Pickles in Shaping Gut Microbiota and Immune Response in Women: A Community-Based Trial in Pakistan
Authors: Hafeez Sumbal , Khalid Aqsa , Ahmed Sheraz , Umrani Fayaz , Qureshi Abdul Khaliq , Ahmed Kumail , Shaheen Fariha , Hotwani Aneeta , Kabir Furqan , Moore Sean R. , Ali Syed Asad , Iqbal Junaid , Iqbal Najeeha Talat 
Published: January 2025

AbstractA gut microbiome-targeted diet can potentially mitigate chronic diseases like malnutrition. In a prospective 12-week intervention trial, we evaluated the effects of six different plant-based fermented pickles (∼50g/day) on clinical, inflammatory, and gut-microbiome parameters in women (n=230) in a rural setting with a high prevalence of undernutrition. Blood was collected at two, whereas stool was collected at three timepoints. Among fecal biomarkers, myeloperoxidase (MPO), Lipocalin-2 (LCN2), and 16S rRNA sequencing were measured at baseline, 8th,and 12thweeks. Overall compliance rate was >70%. WBC and neutrophils significantly decreased among radish (p=0.002, p=0.01) and carrot (p=0.005, p=0.006) groups compared to controls. In lemon-chili groups, platelets significantly decreased (p<0.001) while MCV increased (p=0.02). In onion and lemon-chili groups, the alpha (р=0.001 and p=0.0005, respectively) and beta diversities (p=9e-04 and p=0.0223, respectively) were significantly increased. Post-intervention linear discriminant analysis (LDA) identified 25 bacterial taxa markers at 8thand 12thweek, that includedEggerthellaceaeandOscillospiraceae, ErysipelatoclostridiaceaeandSubdoligranumlum,predominantly in lemon-chili group. Correlation analysis revealed six taxa negatively associated with inflammatory markers such as CRP, LCN2, and platelets. Our study provides preliminary information about consumption of culturally acceptable fermented pickles exerting beneficial changes in hematological and gut microbiome profiles of women, post-intervention.
Effect of Oxygen Saturation Targets on Neurologic Outcomes after Cardiac Arrest: A Secondary Analysis of the PILOT Trial
Authors: DeMasi Stephanie C. , Clark Alexander T. , Muhs Amelia L. , Han Jin H. , Shipley Kipp , McKinney Jared J. , Wang Li , Rice Todd W. , Moskowitz Ari , Prekker Matthew E. , Johnson Nicholas J , Self Wesley H. , Casey Jonathan D. , Semler Matthew W. , Seitz Kevin P. ,   Pragmatic Critical Care Research Group
Published: January 2025

ABSTRACTBackgroundMore than 600,000 adults in the United States experience a cardiac arrest each year. After resuscitation from cardiac arrest, most patients receive mechanical ventilation. The oxygenation target that optimizes neurologic outcomes after cardiac arrest is uncertain.Research QuestionAfter cardiac arrest, does a lower oxygen saturation (SpO2) target improve neurologic outcomes compared to a higher SpO2target?Study Design and MethodsWe conducted a secondary analysis of patients who experienced a cardiac arrest before enrollment in the Pragmatic Investigation of optimal Oxygen Targets (PILOT) trial. The PILOT trial assigned critically ill adults receiving mechanical ventilation to a lower (88-92%), intermediate, (92-96%), or higher (96-100%) SpO2target. This subgroup analysis compared patients randomized to a lower-or-intermediate SpO2target (88-96%) versus a higher SpO2target (96-100%) with regard to the primary outcome of survival with a favorable neurologic outcome at hospital discharge (Cerebral Performance Category 1 or 2). The secondary outcome was in-hospital death.ResultsOf 2,987 patients in the PILOT trial, 339 (11.3%) experienced a cardiac arrest before enrollment: 221 were assigned to a lower-or-intermediate SpO2target, and 118 were assigned to a higher SpO2target. Overall, the median age was 60 years, 43.5% were female, 58.7% experienced an in-hospital cardiac arrest, and 10.2% had an initial shockable rhythm. Survival with a favorable neurologic outcome occurred in 50 patients (22.6%) assigned to a lower-or-intermediate SpO2target and 15 (12.7%) patients assigned to a higher SpO2target (P=0.03). In-hospital death occurred in 146 patients (66.1%) assigned to a lower-or-intermediate SpO2target and 89 (75.4%) assigned to a higher target (P=0.08).InterpretationAmong patients receiving mechanical ventilation after a cardiac arrest, use of a lower-or-intermediate SpO2target was associated with a higher incidence of a favorable neurologic outcome compared with a higher target. A randomized trial comparing these targets in the cardiac arrest population is needed to confirm these findings.