Aggregator

Current anomaly detection methods excel with benchmark industrial data but struggle with natural images and medical data due to varying definitions of 'normal' and 'abnormal.' This makes accurate identification of deviations in these fields particularly challenging. Especially for 3D brain MRI data, all the state-of-the-art models are reconstruction-based with 3D convolutional neural networks which are memory-intensive, time-consuming and producing noisy outputs that require further...

A critical assessment of computational hit-finding experiments (CACHE) challenge was conducted to predict ligands for the SARS-CoV-2 Nsp13 helicase RNA binding site, a highly conserved COVID-19 target. Twenty-three participating teams comprised of computational chemists and data scientists used protein structure and data from fragment-screening paired with advanced computational and machine learning methods to each predict up to 100 inhibitory ligands. Across all teams, 1957 compounds were...

Gene regulatory changes acting cis and trans to a gene can be inferred with allele-specific expression (ASE) transcriptomes from interspecies and inter-population hybrids and their parents. Problems of mapping bias and excessive information loss, however, can arise unintentionally from cumbersome analysis pipelines. We introduce CompMap, a self-contained method in Python that generates allele-specific expression counts from genotype-specific alignments. CompMap sorts and counts reads, not just...

Axial optical tweezers provide a natural geometry for performing biomechanical assays such as rupture force measurements of protein binding. Axial traps, however, are typically weaker than their lateral counterparts requiring high laser power to maintain a well calibrated, linear restoring force. Here we show how to extend the spatial range over which well calibrated forces can be applied by considering aberration effects and extend the range of applied forces by accounting for the nonlinear...

CONCLUSIONS: We demonstrate that movement disorders in adults with 22q11.2DS exhibit greater clinical complexity than previously reported, which could reflect innate vulnerability and pathologic mechanisms beyond medication side effects. In those with a confirmed 22q11.2 microdeletion, periodic neurologic evaluations, supported by electrophysiologic investigations, enable accurate diagnosis and implementation of personalized management strategies.

CONCLUSION AND RELEVANCE: In this study, the identification of symptom groups of mental illness robustly defined by precisely characterized brain mechanisms enabled the characterization of dimensions of psychopathology based on quantifiable neurobiological measures.

Phenotypic screens of living organisms often require real-time, high spatial resolution imaging. We report here on the design and application of a line-scan imaging platform that enables bright-field imaging of live nematodes using a 96-well plate configuration. The system optics are such that each individual well is projected across the full field of view of a 4 K line scanning camera. To minimize motional artifacts, the camera system is translated, while the sample is kept stationary. We...

CONCLUSIONS: This is the first published clinical trial of a novel unidirectional brachytherapy device. CivaSheet proved to be a feasible technique to deliver intraoperative radiation to patients with high-risk pelvic malignancies after surgical resection, and warrants further study and clinical consideration, particularly in settings where other IORT options are not available.

Proteogenomics is limited by the challenge of modeling the complexities of gene expression. We create moPepGen, a graph-based algorithm that comprehensively generates non-canonical peptides in linear time. moPepGen works with multiple technologies, in multiple species and on all types of genetic and transcriptomic data. In human cancer proteomes, it enumerates previously unobservable noncanonical peptides arising from germline and somatic genomic variants, noncoding open reading frames, RNA...

Myelin ensheathment is essential for rapid axonal conduction, metabolic support and neuronal plasticity. In Alzheimer's disease (AD), disruptions in myelin and axonal structures occur, although the underlying mechanisms remain unclear. We implemented proximity labeling subcellular proteomics of the myelin-axon interface in postmortem human brains from AD donors and 15-month-old male and female 5XFAD mice. We uncovered multiple dysregulated signaling pathways and ligand-receptor interactions,...

Background: Beach volleyball (BVb) is a highly demanding Olympic sport characterized by intense physical activity and unique environmental challenges, including varying weather conditions and sandy, unstable court surfaces. Despite its popularity, there is a notable lack of scientific research addressing the metabolic and immune responses of elite female athletes in this sport. This study aims to address this gap by investigating two world-class Olympic medalists, female BVb players, who...

CONCLUSIONS: Findings indicate that dual inflammation exacerbates the acute phase clinical outcome of COVID-SZs. Suggesting a combined anti-inflammatory drug or the use of potentially anti-inflammatory antipsychotics in the acute phase of treatment to mitigate central nervous system damage. Regular monitoring of inflammatory marker levels can help reduce the risk of fluctuating psychiatric symptoms in patients with schizophrenia caused by inflammatory storms.

RUVBL1 and RUVBL2 proteins assemble into a heterohexameric ring and are essential for DNA repair in prokaryotes and chromatin homeostasis in eukaryotes. These proteins function as potential chaperones and ATPases. While most studies on eukaryotic RUVBL1/2 proteins have focused on human and yeast orthologs, they have revealed notable differences in conformational dynamics, protein interactions, and ATPase activity between these species. By investigating orthologs in other eukaryotic organisms,...

CONCLUSION: Ethiopian nurse-physician mentorship pairs supporting mentee hospitals in standardizing assessments of respiratory distress and optimizing the use of CPAP increased the number of preterm infants treated with CPAP. Significant reduction in preterm mortality postintervention is encouraging as CPAP use continues to scale up globally.

Prostate cancer cell lines are particularly clinically homogenous, mostly representing metastatic states rather than localized disease. While there has been significant work in the development of additional models, few have been created without oncogenic transformation. We derived a primary prostate cancer cell line from a patient with localized Gleason 7 prostate cancer-designated CaB34-which spontaneously immortalized. We leveraged CaB34 to generate a paired radioresistant subline, CaB34-CF,...

Diverse small RNA pathways, composed of Argonaute effector proteins and their bound small RNA molecules, define critical systems for regulating gene expression in all domains of life. Some small RNA pathways have experienced significant evolutionary change across metazoans, including gains of novel Argonaute genes and losses of entire pathways. Differences in Argonaute functional complement among species therefore profoundly influence the available repertoire of mechanisms for gene regulation....

Cardiac fibrosis during Duchenne muscular dystrophy (DMD) arises from cellular damage and inflammation and is associated with metabolic dysfunction. The extent to which these relationships develop across all 4 cardiac chambers, particularly during early-stage disease, remains unknown. We discovered that very young D2.mdx mice exhibit fibrosis exclusively in the right ventricle (RV) and left atrium. Concurrent myocardial disorganization in the RV was related to a highly specific inflammatory...

CONCLUSIONS: The workshop provided a unique opportunity for early-career researchers to expand their network, and for all participants to discuss new or improved approaches to advance the field, including international consortia and data sharing. The highlights and outcomes from this OA epigenetics workshop are described in this report.

Transposable elements (TEs) provide a source of transcription factor (TF) binding sites that can rewire gene regulatory networks. NF-kB is an evolutionarily conserved TF complex primarily involved in innate immunity and inflammation. The extent to which TEs have contributed to NF-kB responses during mammalian evolution is not well established. Here, we performed a multi-species analysis of TEs bound by the NF-kB subunit RELA in response to the proinflammatory cytokine TNF. By comparing RELA...

CONCLUSIONS: These data yield insights into the role of PTCHD1 in neurodevelopment and neurotransmission and suggest a neuropathological mechanism for missense variants. These findings provide a platform for diagnostic assay and VUS interpretation, allowing for clinical reclassification of these variants.