bluuebunny/crossref_metadata_2025_split huggingface dataset:
Total management of hemangiopericytoma/solitary fibrous tumor of the buttock: A case report
Authors: Hashimoto Kazuhiko , Nishimura Shunji , Ito Tomohiko , Kakinoki Ryosuke , Goto Koji 
Published: July 2024

Background:
Solitary fibrous tumors can manifest at various anatomical sites, predominantly occurring at extrapleural sites with a peak incidence between 40 and 70 years. SFT necessitates long-term follow-up owing to its tumor characteristics. However, comprehensive reports covering the period from initial diagnosis to the patient’s demise are lacking. Herein, we present a case of a malignant SFT of the buttocks that was treated at our hospital from the time of initial diagnosis to the end of life, with a literature review.

Methods:
A 54-year-old woman had a T1 low-to-isobaric and T2 isobaric-to-hyperintense mass in the psoas muscle on magnetic resonance imaging, diagnosed as an SFT. Wide excision was performed, followed by postoperative radiotherapy and chemotherapy. Multiple lung metastases were treated, while bone metastases appeared in the left femur. Multiple spinal metastases developed, causing respiratory distress due to pleural effusion. Best support care was initiated; however, a thrombus appeared in the inferior vena cava. Despite anticoagulant therapy, the patient died 11 years and 6 months after the initial surgery. Herein, marginal resection resulted in a relatively short operative time and average blood loss. The radiotherapy dose was 66 Gy; no complications occurred, and local recurrence was prevented. Tumor arthroplasty was performed to stabilize the affected limbs, and the patient required careful follow-up.

Results:
Despite the poor prognosis, the patient survived >11 years after surgery and had a favorable outcome.

Conclusion:
Long-term monitoring for potential complications remains necessary.
Mowat-Wilson syndrome: Case report
Authors: Wójcik-Niklewska Bogumiła , Filipek Erita 
Published: July 2024

Background:
Mowat-Wilson syndrome (MWS) is a rare genetic condition resulting in multiple congenital anomalies, including facial dysmorphism, structural anomalies of the internal organs, functional disorders, and, although less commonly, ocular abnormalities. To present a child with MWS and eye abnormalities.

Methods:
A 3-year-old boy was born at 37 weeks of pregnancy with dysmorphic features, neurodevelopmental disorders, genetically confirmed MWS, nystagmus, strabismus, and suspicion of congenital glaucoma. Ophthalmic examination was carried out under general anesthesia; eyeball ultrasound and electrophysiological examination (flash visual evoked potentials) were also performed.

Results:
The examinations revealed nystagmus, a normal response of pupils to light in both eyes, and normal intraocular pressure, that is, 17 and 18 mm Hg in the right and left eye, respectively. Corneal thickness was 606 µm in the right eye and 588 µm in the left eye. Gonioscopy revealed displacement of Schwalbe line anterior to the limbus of the cornea (posterior embryotoxon). Fundus examination revealed a pink optic disk with a cup-to-disc ratio of 0.5, macular pigment regrouping, and normal blood vessels. Flash visual evoked potentials: P2 latency was normal. P2 amplitude from the left hemisphere was reduced to 50%, and P2 amplitude over the right hemisphere was normal.

Conclusion:
Children with genetically determined congenital anomalies need regular ophthalmic checkups to accurately assess the eye and determine the prospects of vision function development.
A BLAST from the past: revisiting blastp’s E-value
Authors: Lu Yang Young , Noble William Stafford , Keich Uri 
Published: July 2024

AbstractThe Basic Local Alignment Search Tool, BLAST, is an indispensable tool for genomic research. BLAST established itself as the canonical tool for sequence similarity search in large part thanks to its meaningful statistical analysis. Specifically, BLAST reports the E-value of each reported alignment, which is defined as the expected number of optimal local alignments that will score at least as high as the observed alignment score, assuming that the query and the database sequences are randomly generated.Here we critically evaluate the E-values provided by the standard protein BLAST (blastp), showing that they can be at times significantly conservative while at others too liberal. We offer an alternative approach based on generating a small sample from the null distribution of random optimal alignments, and testing whether the observed alignment score is consistent with it. In contrast with blastp, our significance analysis seems valid, in the sense that it did not deliver inflated significance estimates in any of our extensive experiments. Moreover, although our method is slightly conservative, it is often significantly less so than the blastp E-value. Indeed, in cases where blastp’s analysis is valid (i.e., not too liberal), our approach seems to deliver a greater number of correct alignments. One advantage of our approach is that it works with any reasonable choice of substitution matrix and gap penalties, avoiding blastp’s limited options of matrices and penalties. In addition, we can formulate the problem using a canonical family-wise error rate control setup, thereby dispensing with E-values, which can at times be difficult to interpret.
Molecular consequences of acute versus chronic CDK12 loss in prostate carcinoma nominates distinct therapeutic strategies
Authors: Frank Sander , Persse Thomas , Coleman Ilsa , Bankhead Armand , Li Dapei , DeSarkar Navonil , Wilson Divin , Rudoy Dmytro , Vashisth Manasvita , Galipeau Patty , Yang Michael , Hanratty Brian , Dumpit Ruth , Morrissey Colm , Corey Eva , Bruce Montgomery R. , Haffner Michael C. , Pritchard Colin , Vasioukhin Valera , Ha Gavin , Nelson Peter S. 
Published: July 2024

ABSTRACTGenomic loss of the transcriptional kinaseCDK12occurs in ∼6% of metastatic castration-resistant prostate cancers (mCRPC) and correlates with poor patient outcomes. Prior studies demonstrate that acute CDK12 loss confers a homologous recombination (HR) deficiency (HRd) phenotype via premature intronic polyadenylation (IPA) of key HR pathway genes, includingATM.However, mCRPC patients have not demonstrated benefit from therapies that exploit HRd such as inhibitors of polyADP ribose polymerase (PARP). Based on this discordance, we sought to test the hypothesis that an HRd phenotype is primarily a consequence of acuteCDK12loss and the effect is greatly diminished in prostate cancers adapted toCDK12loss. Analyses of whole genome sequences (WGS) and RNA sequences (RNAseq) of human mCRPCs determined that tumors with biallelicCDK12alterations (CDK12BAL) lack genomic scar signatures indicative of HRd, despite carrying bi-allelic loss and the appearance of the hallmark tandem-duplicator phenotype (TDP). Experiments confirmed that acute CDK12 inhibition resulted in aberrant polyadenylation and downregulation of long genes (includingBRCA1andBRCA2) but such effects were modest or absent in tumors adapted to chronicCDK12BAL. One key exception wasATM, which did retain transcript shortening and reduced protein expression in the adaptedCDK12BALmodels. However,CDK12BALcells demonstrated intact HR as measured by RAD51 foci formation following irradiation.CDK12BALcells showed a vulnerability to targeting of CDK13 by sgRNA or CDK12/13 inhibitors andin vivotreatment of prostate cancer xenograft lines showed that tumors withCDK12BALresponded to the CDK12/13 inhibitor SR4835, while CDK12-intact lines did not. Collectively, these studies show that aberrant polyadenylation and long HR gene downregulation is primarily a consequence of acute CDK12 deficiency, which is largely compensated for in cells that have adapted to CDK12 loss. These results provide an explanation for why PARPi monotherapy has thus far failed to consistently benefit patients with CDK12 alterations, though alternate therapies that target CDK13 or transcription are candidates for future research and testing.
Adult caudal fin shape is imprinted in the embryonic fin fold
Authors: Surette Eric , Donahue Joan , Robinson Stephanie , McKenna Deirdre , Martinez Crisvely Soto , Fitzgerald Brendan , Karlstrom Rolf O. , Cumplido Nicolas , McMenamin Sarah K. 
Published: July 2024

SummaryAppendage shape is formed during development (and re-formed during regeneration) according to spatial and temporal cues that orchestrate local cellular morphogenesis. The caudal fin is the primary appendage used for propulsion in most fish species, and exhibits a range of distinct morphologies adapted for different swimming strategies, however the molecular mechanisms responsible for generating these diverse shapes remain mostly unknown. In zebrafish, caudal fins display a forked shape, with longer supportive bony rays at the periphery and shortest rays at the center. Here, we show that a premature, transient pulse ofsonic hedgehog a (shha)overexpression during late embryonic development results in excess proliferation and growth of the central rays, causing the adult caudal fin to grow into a triangular, truncate shape. Both global and regional ectopicshhaoverexpression are sufficient to alter fin shape, and forked shape may be rescued by subsequent treatment with an antagonist of the canonical Shh pathway. The induced truncate fins show a decreased fin ray number and fail to form the hypural diastema that normally separates the dorsal and ventral fin lobes. While forked fins regenerate their original forked morphology, truncate fins regenerate truncate, suggesting that positional memory of the fin rays can be permanently altered by a transient treatment during embryogenesis. Ray finned fish have evolved a wide spectrum of caudal fin morphologies, ranging from truncate to forked, and the current work offers insights into the developmental mechanisms that may underlie this shape diversity.
The asymmetric expression of HSPA2 in blastomeres governs the first embryonic cell-fate decision
Authors: Gao Jiayin , Wang Jiawei , Liu Shiyu , Song Jinzhu , Zhang Chuanxin , Liu Boyang , Wu Keliang 
Published: July 2024

AbstractThe first cell-fate decision is the process by which cells of an embryo take on distinct lineage identities for the first time, thus representing the beginning of developmental patterning. Here, we demonstrate that the molecular chaperone heat shock protein A2 (HSPA2), a member of the 70 kDa heat shock protein (HSP70) family, is asymmetrically expressed in the late 2-cell stage of mouse embryos. The knockdown ofHspa2in one of the 2-cell blastomeres prevented its progeny predominantly toward the inner cell mass (ICM) fate. In contrast, the overexpression ofHspa2in one of the two-cell blastomeres did not induce blastomeres to differentiate towards the ICM fate. Furthermore, we demonstrated that HSPA2 interacts with CARM1 and its levels correlate with ICM-associated genes and that it interacts with the CARM1. Collectively, our results identify HSPA2 as a critical early regulator of the first cell-fate decision in mammalian 2-cell embryos.
Gene Function Revealed at the Moment of Stochastic Gene Silencing
Authors: Gupta Shreyan , Cai James J. 
Published: July 2024

AbstractGene expression is a dynamic and stochastic process characterized by transcriptional bursting followed by periods of silence. Single-cell RNA sequencing (scRNA-seq) is a powerful tool to measure transcriptional bursting and silencing at the individual cell level. In this study, we introduce the single-cell Stochastic Gene Silencing (scSGS) method, which leverages the natural variability in single-cell gene expression to decipher gene function. For a target genegunder investigation, scSGS classifies cells into transcriptionally active (g+) and silenced (g-) samples. It then compares these cell samples to identify differentially expressed genes, referred to as SGS-responsive genes, which are used to infer the function of the target geneg. Analysis of real data demonstrates that scSGS can reveal regulatory relationships up- and downstream of target genes, circumventing the survivorship bias that often affects gene knockout and perturbation studies. scSGS thus offers an efficient approach for gene function prediction, with significant potential to reduce the use of genetically modified animals in gene function research.
Cross-Tissue Comparison of Epigenetic Aging Clocks in Humans
Authors: Apsley Abner T. , Ye Qiaofeng , Caspi Avshalom , Chiaro Christopher , Etzel Laura , Hastings Waylon J. , Heim Christine C. , Kozlosky John , Noll Jennie G. , Schreier Hannah M. C. , Shenk Chad E. , Sugden Karen , Shalev Idan 
Published: July 2024

AbstractEpigenetic clocks are a common group of tools used to measure biological aging – the progressive deterioration of cells, tissues and organs. Epigenetic clocks have been trained almost exclusively using blood-based tissues but there is growing interest in estimating epigenetic age using less-invasive oral-based tissues (i.e., buccal or saliva) in both research and commercial settings. However, differentiated cell types across body tissues exhibit unique DNA methylation landscapes and age-related alterations to the DNA methylome. Applying epigenetic clocks derived from blood-based tissues to estimate epigenetic age of oral-based tissues may introduce biases. We tested the within-person comparability of common epigenetic clocks across five tissue types: buccal epithelial, saliva, dry blood spots, buffy coat (i.e., leukocytes), and peripheral blood mononuclear cells. We tested 284 distinct tissue samples from 83 individuals aged 9-70 years. Overall, there were significant within-person differences in epigenetic clock estimates from oral-based versus blood-based tissues, with average differences of almost 30 years observed in some age clocks. In addition, most epigenetic clock estimates of blood-based tissues exhibited low correlation with estimates from oral-based tissues despite controlling for cellular proportions and other technical factors. Our findings indicate that application of blood-derived epigenetic clocks in oral-based tissues may not yield comparable estimates of epigenetic age, highlighting the need for careful consideration of tissue type when estimating epigenetic age.
PAX proteinsin silicoprediction inLissachatina fulica
Authors: Dominova Irina N. , Golovneva Kristina , Korshunova Nadezhda , Zhukov Valery V. 
Published: July 2024

AbstractPrediction of snail PAX group proteins inLisachatina fulicawas performed. For this this purpose, homologous sequences to already known PAX proteins ofCephalopoda, GastropodaandBivalviamolluscs were predicted. The presence of certain domains (Paired box, Homeodomain and octapeptide) in the structure of the primary predicted sequences ofLisachatina fulicaproteins from the GigaDB was analyzed. Also, to confirm that the sequences found belong to the PAX family proteins, their secondary and 3D structures were predicted, and their DNA-binding capacity was compared to the control Paired box domain using molecular docking. As a result, 8 proteins ofLisachatina fulicacontaining PAX characteristic sequences were identified. Based on the results of domain structure search and phylogenetic analysis, the proteins were categorized into 5 subfamilies of PAX proteins, namely I, III, IV, β, and Pox-Neuro. The result provides a starting point for the search for the functional role of PAX proteins in theLisachatina fulica.
Epigenetics is all you need: A Transformer to decode chromatin structural compartments from the epigenome
Authors: Dodero-Rojas Esteban , Contessoto Vinícius G. , Fehlis Yao , Mayala Nicolas , Onuchic José N. 
Published: July 2024

AbstractChromatin within the nucleus adopts complex three-dimensional structures that are crucial for gene regulation and cellular function. Recent studies have revealed the presence of distinct chromatin subcompartments beyond the traditional A/B compartments (eu- and hetero-chromatin), each exhibiting unique structural and functional properties. Here, we introduce TECSAS (Transformer of Epigenetics to Chromatin Structural AnnotationS), a deep learning model based on the Transformer architecture, designed to predict chromatin subcompartment annotations directly from epigenomic data. TECSAS leverages information from histone modifications, transcription factor binding profiles, and RNA-Seq data to decode the relationship between the biochemical composition of chromatin and its 3D structural behavior. TECSAS achieves high accuracy in predicting subcompartment annotations and reveals the influence of long-range epigenomic context on chromatin organization. Furthermore, we demonstrate the model’s capability to predict the association of loci with nuclear bodies, such as the lamina, nucleoli, and speckles, providing insights into the role of these structures in shaping the 3D genome organization. This study highlights the potential of deep learning models for deciphering the complex interplay between epigenomic features and 3D genome organization, allowing us to better understand genome structure and function.
Low-dose interleukin-2 in patients with bipolar depression: a phase 2 randomised double-blind placebo-controlled trial
Authors: Leboyer Marion , Foiselle Marianne , Tchitchek Nicolas , Tamouza Ryad , Lorenzon Roberta , Richard Jean-Romain , Arrouasse Raphaele , Le Corvoisier Philippe , Le Dudal Katia , Vicaut Eric , Ellul Pierre , Rosenzwajg Michelle , Klatzmann David 
Published: July 2024

AbstractImmune abnormalities including an insufficiency of regulatory T cells (Treg) and increased blood-based inflammatory markers have been observed in bipolar disorders (BD), particularly during depression. As Tregs are pivotal to control inflammation, Treg stimulation by low-dose IL-2 (IL-2LD) could have a therapeutic impact on bipolar depression. We performed a randomized, double-blind, placebo-controlled (2 active: 1 placebo) proof-of-concept trial of add-on IL-2LDin patients with bipolar depression. Patients received a placebo or IL-2LD(1MIU) once a day for 5 days, and then once a week for 4 weeks starting on week 2. The primary objective was to demonstrate a biological Treg response to IL-2LDassessed by fold increase in Treg percentage of CD4+ cells from baseline to day 5. Secondary objectives included safety assessment and mood improvement throughout the study period. This trial is registered with ClinicalTrials.gov, numberNCT04133233. Fourteen patients with bipolar depression were included, with 4 receiving placebo and 10 IL-2LD. Baseline clinical and biological characteristics were balanced between groups. The primary evaluation criterion was met, with IL-2LDexpanding 1.17 [95% CI 1.01-1.34] vs 1.01 [95% CI 0.90 - 1.12] (p=0.0421) and activating Tregs. Secondary evaluation criteria were also met with significant improvements of depressive symptoms and global functioning from day-15 onwards in the IL-2LDtreated patients. The treatment was well-tolerated, with no serious adverse events related to treatment. This proof-of-concept trial shows that stimulating Tregs in patients with bipolar depression is safe and associated with clinical improvements. This supports a pathophysiological role of inflammation in BD and warrants pursuing the evaluation of IL-2LDas an adjunct treatment of major mood disorders.
Exposomics and Cardiovascular Diseases: A Scoping Review of Machine Learning Approaches
Authors: Argyri Katerina D. , Gallos Ioannis K. , Amditis Angelos , Dionysiou Dimitra D. 
Published: July 2024

ABSTRACTCardiovascular disease has been established as the world’s number one killer, causing over 20 million deaths per year. This fact, along with the growing awareness of the impact of exposomic risk factors on cardiovascular diseases, has led the scientific community to leverage machine learning strategies as a complementary approach to traditional statistical epidemiological studies that are challenged by the highly heterogeneous and dynamic nature of exposomics data. The principal objective served by this work is to identify key pertinent literature and provide an overview of the breadth of research in the field of machine learning applications on exposomics data with a focus on cardiovascular diseases. Secondarily, we aimed at identifying common limitations and meaningful directives to be addressed in the future. Overall, this work shows that, despite the fact that machine learning on exposomics data is under-researched compared to its application on other members of the -omics family, it is increasingly adopted to investigate different aspects of cardiovascular diseases.
An Application of Nowcasting Methods: Cases of Norovirus during the Winter 2023/2024 in England
Authors: Mellor Jonathon , Tang Maria L , Finch Emilie , Christie Rachel , Polhill Oliver , Overton Christopher E , Hoban Ann , Douglas Amy , Deeny Sarah R , Ward Thomas 
Published: July 2024

AbstractBackgroundNorovirus is a leading cause of acute gastroenteritis, adding to strain on healthcare systems. Diagnostic test reporting of norovirus is often delayed, resulting in incomplete data for real-time surveillance.MethodsTo nowcast the real-time case burden of norovirus a generalised additive model, semi-mechanistic Bayesian joint process and delay model, and Bayesian structural time series model including syndromic surveillance data were developed. These models were evaluated over weekly nowcasts using a probabilistic scoring framework.ResultsModelling current cases clearly outperforms a simple heuristic approach. Models that harnessed a time delay correction had higher skill, overall, relative to forecasting techniques. However, forecasting approaches were found to be more reliable in the event of temporally changeable reporting patterns. The incorporation of norovirus syndromic surveillance data was not shown to improve model skill in this nowcasting task, which may be indicative poor correlation between the indicator and norovirus incidence.InterpretationAnalysis of surveillance data enhanced by nowcasting reporting delays improves understanding over simple model assumptions, which is important for real-time decision making. The structure of the modelling approach needs to be informed by the patterns of the reporting delay and can have large impacts on operational performance and insights produced.