bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved detection of differentially abundant proteins through FDR-control of peptide-identity-propagation
Authors: Solivais Alexander J. , Boekweg Hannah , Smith Lloyd M. , Noble William S. , Shortreed Michael R. , Payne Samuel H. , Keich Uri 
Published: November 2024

AbstractThe goal of proteomics is to identify and quantify peptides and proteins within a biological sample. Almost all algorithms for the identification of peptides in LC-MS/MS data employ two steps: peptide/spectrum matching and peptide-identity-propagation (PIP), also known as match-between-runs. PIP was originally envisioned as a backup method to overcome measurement stochasticity. However, current PIP implementations can routinely account for up to 40% of all results, with that proportion rising as high as 75% in single-cell proteomics. Unlike peptide identities derived through peptide/spectrum matches, for which error estimation has been strictly enforced for decades, peptide identities derived through PIP have not historically been subject to statistical evaluation. As an indispensable component of label free quantification, PIP needs a simple and statistically rigorous method for estimating its error rates. Although several tools claim to control the false discovery rate (FDR) of PIP, these claims cannot be validated as there is currently no accepted method to assess the accuracy of the stated FDR. We present a method for FDR control of PIP, called PIP-ECHO, and devise a rigorous protocol for evaluating FDR control of any PIP method. Using three different benchmark datasets, we evaluate PIP-ECHO alongside the PIP procedures implemented by FlashLFQ, IonQuant, and MaxQuant. These analyses show that only PIP-ECHO can accurately control the FDR of PIP at 1% across all datasets, including single cell. When analyzing spike-in datasets where different known amounts of yeast or E. coli peptides are added to a constant background of human peptides, PIP-ECHO increases both the accuracy and sensitivity of differential expression analysis, yielding 53% more differentially abundant proteins than MaxQuant and 146% more than IonQuant.
Characterization of the Subclinical Perilesional Zone in the Macula of Early-Stage ABCA4 Disease
Authors: Zee Aiden , Lee Winston , Su Pei-Yin , Zernant Jana , Tsang Stephen H. , Allikmets Rando 
Published: November 2024

AbstractPurposeTo characterize photoreceptor layer thinning in clinically unremarkable regions adjacent to the atrophic lesion in early-stage ABCA4 disease eyes.Methods27 patients with confined atrophic lesions (≤3.5mm in diameter) were included. Two pathogenic alleles were confirmed by sequencing of theABCA4locus. Multimodal imaging included color fundus photography, short wavelength-autofluorescence (SW-AF) and near infrared-autofluorescence (NIR-AF) imaging. Total receptor+ (TREC+) thickness was segmented in spectral domain-optical coherence tomography (SD-OCT) scans in patient eyes (n=27) along with age-matched healthy control eyes (n=20).Resultsµageof the study cohort was 24.1 years and 15/27 (55.6%) patients harbored genotypes consisting of the p.(Gly1961Glu) variant inABCA4. Atrophic lesions in the central macula ranged from 0.61 to 3.13 mm in diameter (µ= 1.73,σ= 0.70). Six patients had mild RPE mottling adjacent to the lesion on NIR-AF. The atrophic lesion corresponded to a disruption of photoreceptor-attributable bands on SD-OCT while all layers were visibly intact outside the lesion. TREC+ thickness in patient eyes were <0.15 mm or below 4σof normal control eyes immediately adjacent to the lesion edge and gradually normalized to within±2σat≈1.2 mm eccentricity from the fovea.ConclusionA uniform subclinical perilesional zone (SPZ) of photoreceptor thinning extends around the perimeter of early-stage atrophic lesions in ABCA4 disease. This region spatially maps to known regions of vision loss and more accurately approximates the extent of photoreceptor abnormality compared to the disease changes visible on standard fundus imaging.Translational relevanceSemi-automated segmentation of SD-OCT scans identifies a consistent subclinical biomarker relevant to early photoreceptor degeneration in ABCA4 disease.
The relationships between cochlear nerve health and AzBio sentence scores in quiet and noise in postlingually deafened adult cochlear implant users
Authors: Gao Zi , Yuan Yi , Oleson Jacob J. , Mueller Christopher R. , Bruce Ian C. , Gifford René H. , He Shuman 
Published: November 2024

ABSTRACTObjectivesThis study investigated the relationships between the cochlear nerve (CN) health and sentence-level speech perception outcomes measured in quiet and noise in postlingually deafened adult cochlear implant (CI) users.DesignStudy participants included 24 postlingually deafened adult CI users with a Cochlear® Nucleus™ device. For each participant, only one ear was tested. Neural health of the CN was assessed at three or four electrode locations across the electrode array using two parameters derived from results of the electrically evoked compound action potential (eCAP). One parameter was the phase locking value (PLV) which estimated neural synchrony in the CN. The other parameter was the sensitivity of the eCAP amplitude growth function (AGF) slope to changes in the interphase gap (IPG) of biphasic electrical pulses (i.e., the IPGEslope). Speech perception was tested using AzBio sentences in both quiet and a ten-talker babble background noise with +5 dB and +10 dB signal-to-noise ratios (SNR). IPGEslopeand PLV values were averaged across electrodes for each subject, both with and without weighting by the frequency importance function (FIF) of the AzBio sentences. Pearson and Spearman correlations were used to assess the pairwise relationships between the IPGEslope, the PLV, and age. Multiple linear regression models with AzBio score as the outcome and the PLV and the IPGEslopeas predictors were used to evaluate the associations between the three variables while controlling for age.ResultsThe correlation between the IPGEslopeand the PLV was negligible and not statistically significant. The PLV, but not the IPGEslope, differed significantly across electrodes, where the apical electrodes had larger PLVs (better neural synchrony) than the basal electrodes. The IPGEslope, but not the PLV, was significantly correlated with participant’s age, where smaller IPGEslopevalues (poorer CN health) were associated with more advanced age. The PLV, but not the IPGEslope, was significantly associated with AzBio scores in noise, where larger PLVs predicted better speech perception in noise. Neither the PLV nor the IPGEslopewas significantly associated with AzBio score in quiet. The result patterns remained the same regardless of whether the mean values of the IPGEslopeand the PLV were weighted by the AzBio FIF.ConclusionsThe IPGEslopeand the PLV quantify different aspects of CN health. The positive association between the PLV and AzBio scores suggests that neural synchrony is important for speech perception in noise in adult CI users. The lack of association between age and the PLV indicates that reduced neural synchrony in the CN is unlikely the primary factor accounting for the greater deficits in understanding speech in noise observed in elderly, as compared to younger, CI users.
PDE5 inhibition and Alzheimer’s disease risk: a mendelian randomisation study
Authors: Alcalde-Herraiz Marta , Woolf Benjamin , Xie Junqing , Anderson Emma , Gill Dipender , Tzoulaki Ioanna , Winchester Laura M , Yarmolinsky James , Prieto-Alhambra Daniel , Newby Danielle 
Published: November 2024

AbstractINTRODUCTIONWhile preclinical studies suggest that Phosphodiesterase 5 (PDE5) inhibition may reduce cognitive impairment, findings from observational studies on whether PDE5 inhibitors reduce Alzheimer’s disease (AD) risk have been inconsistent.METHODSA two-samplecis-Mendelian Randomisation (MR) analysis was conducted to estimate the causal effect of PDE5 inhibition on AD risk. The analysis was performed across four different genome-wide association studies (GWAS) of AD to enhance evidence reliability through triangulation. Additionally, a sex-stratified MR analysis using data from UK Biobank was performed to assess potential sex-specific effects.RESULTSNo evidence of a causal association between PDE5 inhibition and AD risk was found in the main analyses or sex-stratified analysis.DISCUSSIONMR findings suggest that PDE5 inhibitors are unlikely to decrease the risk of AD. Further research is needed to thoroughly understand the impact of PDE5 inhibitors on the risk of Alzheimer’s disease.
Optimising the mirror illusion during mirror therapy: evidence from unimpaired individuals
Authors: Kim J.M. , Challis F.O. , Koo C.Y. , Leung C.L. , Lo L.H. , Yeo S.H. , Punt T.D. 
Published: November 2024

AbstractPatients recovering from hemiparetic stroke have been shown to benefit from mirror therapy in terms of improving their motor function. The clinical improvement in motor function may differ depending on the mirror therapy protocol used. Previous studies have shown that four parameters are influential: the size of the mirror (large and small), manipulation of objects (with or without), the complexity of action (simple and complex), and movement execution (unilateral and bilateral). We examined the impact of these parameters on the subjective quality (believability) of the mirror illusion in unimpaired participants. Forty healthy participants completed 16 different combinations of the four parameters during mirror visual feedback. Participants rated each trial for its level ofbelievabilityon a 10-point Likert scale. A repeated measures ANOVA was used to examine the data. The large mirror consistently elicited higher ratings than the small mirror. And while bimanual movements generally elicited higher ratings than unimanual movements, ratings for bimanual movements were significantly reduced when participants made complex movements with objects. We attributed these results to the congruency of multisensory information. Conditions that elicit congruency between illusory information and other sensory inputs appear to maximise believability over the illusory hand. The findings of this study reveal the parameters maximising illusion believability in unimpaired participants and have implications for optimal mirror therapy conditions in patients’ groups.
Multiscale networks in Alzheimer’s disease identify brain hypometabolism as central across biological scales
Authors: Lara-Simon Elena , Gispert Juan Domingo , Garcia-Ojalvo Jordi , Villoslada Pablo ,   Alzheimer’s Disease Neuroimaging Initiative
Published: November 2024

AbstractAlzheimer’s disease encompasses multiple biological scales, spanning molecular factors, cells, tissues, and behavioral manifestations. The interplay among these scales in shaping the clinical phenotype is not yet fully comprehended. In particular, there is great interest in understanding the heterogeneity of the clinical aspects of AD in order to improve treatment and prevention, by targeting those aspects most susceptible to the disease. Here we employed a systems biology approach to address this issue, utilizing multilayer network analysis and deep phenotyping. This integrative analysis incorporated genomics, cerebrospinal fluid biomarkers, tau and amyloid beta (Aβ) PET imaging, brain MRI data, risk factors, and clinical information (cognitive tests scores, Clinical Dementia Rating and clinical diagnosis) obtained through the ADNI collaboration. Multilayer networks were built based on mutual information between the elements of each layer and between layers. Boolean simulations allowed us to identify paths that transmit dynamic information across layers. The most prominent path that significantly predicted the average cognitive phenotype included the PET radiotracer fluorodeoxyglucose (FDG) in the posterior cingulate. Combinations of different symptomatic variables, mainly related to mental health (depression, mood swings, drowsiness) and vascular features (hypertension, cardiovascular history), were also part of the paths explaining the average phenotype. Our results show that integrating the flow of information across biological scales reveals relevant paths for AD, which can be subsequently explored as potential biomarkers or therapeutic targets.Author summaryComplex diseases such as Alzheimer’s Disease (AD) involve a diverse array of biological processes. In our investigation, we undertook a systems biology approach to AD using network analysis and deep phenotyping within a prospective cohort of patients, incorporating clinical, imaging, genetics, and omics assessments. The gene, molecular and imaging paths explained variation in central nervous system damage, and in metrics of disease severity. The elucidation of multilayer paths in this context provides insights into the diverse phenotypes of the disease and holds the potential to improve understanding of its pathogenesis.
The Relationship of Antepartum Fetal Heart Rate Patterns to Adverse Pregnancy Outcomes
Authors: Cooke William , Albert Beth , Vatish Manu , Davis Jones Gabriel 
Published: November 2024

AbstractIntroductionAntepartum fetal heart rate (FHR) patterns are routinely assessed to evaluate fetal wellbeing. Despite their clinical use, the relationship between specific FHR patterns and adverse pregnancy outcomes (APOs) remains unclear. This study aims to investigate the association between antepartum FHR patterns and APOs to improve fetal risk assessment.MethodsIn this retrospective case–control study, we extracted raw antepartum FHR traces from singleton pregnancies between 27+0and 41+6weeks’ gestation recorded at Oxford University Hospitals from January 1991 to February 2024. Adverse outcomes included acidaemia, stillbirth, asphyxia, extended neonatal care unit (NCU) admission, hypoxic–ischaemic encephalopathy (HIE), low Apgar scores and neonatal resuscitation at delivery. After applying inclusion and exclusion criteria, 938 FHR traces with APOs were matched using propensity score matching with 938 traces from normal pregnancy outcomes (NPOs), controlling for gestational age, fetal sex, maternal BMI, maternal age, parity, and trace duration. FHR patterns were extracted using a validated automated algorithm and analysed statistically.ResultsThe APO cohort showed significantly higher basal heart rates (BHR), fewer accelerations, more decelerations, lower short-term variability (STV), and spent a greater proportion of the trace in periods of low variation compared to the NPO cohort (p<0.001). Logistic regression identified prolonged periods of low variation (odds ratio [OR] = 1.92, 95% CI 1.60–2.30,p<0.001), increased decelerations (OR = 1.40, 95% CI 1.22–1.60,p<0.001), reduced accelerations (OR = 0.66, 95% CI 0.55–0.78,p<0.001), elevated BHR (OR = 0.70, 95% CI 0.61–0.80,p<0.001), and decreased STV (OR = 0.72, 95% CI 0.57–0.91,p= 0.006) as significant predictors of APOs.ConclusionsSpecific antepartum FHR patterns are significantly associated with adverse pregnancy outcomes. Detailed analysis of these patterns can enhance fetal risk assessment and inform clinical decision-making. Adoption of standardised interpretation criteria for antepartum FHR monitoring may improve perinatal outcomes.
Clinical Features of Long COVID Patients Coinfected withMycoplasma pneumoniae
Authors: Zhu Xiaodan , Li Yanhua , Wang Jinghua , Gao Weifei 
Published: November 2024

AbstractBackgroundSince the SARS-CoV-2 pandemic, many patients have suffered prolonged complications, called “long COVID”.Mycoplasma pneumoniaeis a common respiratory pathogen, Reports of simultaneous long COVID andM. pneumoniaeinfections are rare in the literature.MethodsWe analyzed the clinical data of patients with long COVID-19 who visited the Respiratory Clinic of The Affiliated Hospital of Hangzhou Normal University between January 1 and January 31, 2023, together with their laboratory and radiographic findings, with Pearson’s χ2test.ResultsFifty-two patients diagnosed with both long COVID andM. pneumoniaeinfection and 77 with long COVID only were compared. The ages, clinical symptoms, and comorbidities of the two groups did not differ significantly (P > 0.05). However, sex and imaging findings differed between the groups.ConclusionsOur study showed that long COVID–M. pneumoniaecoinfection was more commonly seen in females and patients with typical chest computed tomography images.
Mapping rare protein-coding variants on multi-organ imaging traits
Authors: Fan Yijun , Chen Jie , Fan Zirui , Chirinos Julio , Stein Jason L. , Sullivan Patrick F. , Wang Rujin , Nadig Ajay , Zhang David Y. , Huang Shuai , Jiang Zhiwen , Guan Peter Yi , Qian Xinjie , Li Ting , Li Haoyue , Sun Zehui , Ritchie Marylyn D. , O’Brien Joan , Witschey Walter , Rader Daniel J. , Li Tengfei , Zhu Hongtu , Zhao Bingxin 
Published: November 2024

AbstractHuman organ structure and function are important endophenotypes for clinical outcomes. Genome-wide association studies (GWAS) have identified numerous common variants associated with phenotypes derived from magnetic resonance imaging (MRI) of the brain and body. However, the role of rare protein-coding variations affecting organ size and function is largely unknown. Here we present an exome-wide association study that evaluates 596 multi-organ MRI traits across over 50,000 individuals from the UK Biobank. We identified 107 variant-level associations and 224 gene-based burden associations (67 unique gene-trait pairs) across all MRI modalities, includingPTENwith total brain volume,TTNwith regional peak circumferential strain in the heart left ventricle, andTNFRSF13Bwith spleen volume. The singleton burden model and AlphaMissense annotations contributed 8 unique gene-trait pairs including the association between an approved drug target gene ofKCNA5and brain functional activity. The identified rare coding signals elucidate some shared genetic regulation across organs, prioritize previously identified GWAS loci, and are enriched for drug targets. Overall, we demonstrate how rare variants enhance our understanding of genetic effects on human organ morphology and function and their connections to complex diseases.
Microbiome Dynamics in Tank- and Pond-Reared GIFT Tilapia
Authors: Delamare-Deboutteville Jérôme , Mahmuddin Mahirah , Gan Han Ming , Rodde Charles , Khor Laura , Verner-Jeffreys David , Chadag Vishnumurthy Mohan , Benzie John A.H. 
Published: November 2024

AbstractTilapia (Oreochromisspp.) are among the most widely cultivated freshwater finfish species worldwide. The industry increasingly relies on tilapia strains selected for improved growth and other traits, particularly the Genetically Improved Farmed Tilapia (GIFT) strain. Despite the industry’s reliance on tilapia, knowledge of microbiome dynamics in reared tilapia remains limited. Understanding normal successional patterns in the microbiome of farmed tilapia is essential to identify characteristics of what constitutes a healthy microbial community. In this study, we assessed the microbiomes of tank and pond-reared GIFT tilapia by analyzing 568 samples, including water, gut, skin, and gill microbiomes of tilapia, from tank systems housing the source GIFT populations in Malaysia, and compared them to those reared in earthen ponds on another farm in Malaysia. A total of 2,307 amplicon sequence variants (ASVs) were identified, encompassing a broad taxonomic diversity of 39 phyla, 86 classes, 180 orders, 299 families, 501 genera, and 399 species.Our findings elucidated distinct microbial community structures between rearing environments and across fish tissues, shedding light on intricate host-microbe interactions shaped by environmental conditions and management practices. The gut microbiome of tank-reared tilapia was dominated by Fusobacteriota (71.14%), in contrast to pond-reared fish (22%), while other taxa, such as Bacteroidota, Firmicutes_A, and Cyanobacteria, also varied markedly between environments and sampling periods. Skin and gill samples showed notable variability in the relative abundances of Fusobacteriota and Deinococcota between the two rearing sites. Principal Coordinates Analysis (PCoA) highlighted the distinct clustering of samples by rearing environment, particularly within gut microbiomes. Biomarkers such as Cyanobiaceae (pond water) and Sphingomonadaceae (tank water) underscored the impact of rearing conditions on microbial composition.These results establish valuable baseline information on the types of bacteria associated with healthy, genetically defined (GIFT) tilapia strains. This foundational information will help identify specific microbial taxa associated with beneficial or detrimental effects on tilapia health and productivity across varying rearing conditions. Such insights can guide the development of targeted microbiome management strategies to enhance tilapia health and optimize performance.
Identification of a Neuroimmune Circuit that Regulates Allergic Inflammation in the Esophagus
Authors: Kellerman Kendall , Natale Mia , Gerstner Eddie , Rochman Yrina , Rochman Mark , Jankowski Michael P. , Rothenberg Marc E. 
Published: November 2024

AbstractEosinophilic esophagitis is a chronic food antigen-driven allergic inflammatory disease associated with symptoms involving the nervous system such as refractory pain. Yet, the role of the nervous system in disease pathogenesis has not received much attention. Herein, we demonstrate that allergen exposure evokes pain-like behavior in association with increased nociceptor signaling and transcriptional responses in dorsal root ganglia. NaV1.8+ sensory nerves were found traveling along the length of the esophagus, organized in distinct bundles adjacent to the basal epithelium, with beta III-tubulin+ sensory nerves distributed more distal to the lumen. Targeted deletion ofIl4rain NaV1.8+ neurons impeded allergen-induced increases in nerve innervation density. Furthermore,Il4ra-/-NaV1.8micehad diminished allergen-induced allergic inflammation in the esophagus including eosinophilia and transcription of pro-inflammatory genes. Translational studies revealed extensive myelinated nerve innervation in the human esophagus, which was increased in patients with eosinophilic esophagitis. Taken together, these data indicate that allergic inflammation is associated with an increase in non-evoked pain, esophageal nerve density, altered sensitivity of sensory neurons, and transcriptional changes in dorsal root ganglia. These finding identify a type 2 neuroimmune circuit that involves the interplay of allergen-induced IL-4 receptor-dependent DRG responses that modify esophageal end-organ inflammatory responses.