MicroRNA Expression in High-Grade B-Cell Lymphoma With 11q Aberration.

Mature aggressive B-cell lymphomas, such as Burkitt lymphoma (BL) and Diffuse large B-cell lymphoma (DLBCL), show variations in microRNA (miRNA) expression. The entity of High-grade B-cell lymphoma with 11q aberration (HGBCL-11q) shares several biological features with both BL and DLBCL but data on its miRNA expression profile are yet scarce. Hence, this study aims to analyze the potential differences in miRNA expression of HGBCL-11q compared to BL and DLBCL.

Comparative evaluation of specimen type and processing conditions for studying oyster microbiomes.

Metagenomic sequencing is increasingly being employed to understand the assemblage and dynamics of the oyster microbiome. Specimen collection and processing steps can impact the resultant microbiome composition and introduce bias. To investigate this systematically, a total of 54 farmed oysters were collected from Chesapeake Bay between May and September 2019.

Two complementing selection systems based on cca-trimming exonucleases as a tool to monitor, select and evaluate enzymatic features of tRNA nucleotidyltransferases.

tRNA nucleotidyltransferase represents a ubiquitous and essential activity that adds the indispensable CCA triplet to the 3'-end of tRNAs. To fulfill this function, the enzyme contains a set of highly conserved motifs whose coordinated interplay is crucial for the sequence-specific CCA polymerization. In the human enzyme, alterations within these regions have been shown to lead to the manifestation of disease.

Polygenic overlap with granulocyte counts identifies novel loci for clozapine metabolism and clozapine-induced agranulocytosis.

While clozapine is the most effective antipsychotic drug, its use is limited due to hematological adverse effects involving the reduction of granulocyte counts with potential life-threatening agranulocytosis. It is not yet possible to predict or prevent the risk of agranulocytosis, and the mechanisms are unknown but likely related to clozapine metabolism. Genome-wide association studies (GWASs) of clozapine metabolism and clozapine-induced agranulocytosis have identified few genetic loci.

Transient chemical-mediated epigenetic modulation confers unrestricted lineage potential on human primed pluripotent stem cells.

Human primed pluripotent stem cells are capable of generating all the embryonic lineages. However, their extraembryonic trophectoderm potentials are limited. It remains unclear how to expand their developmental potential to trophectoderm lineages.

Enhanced sampling of protein conformational changes via true reaction coordinates from energy relaxation.

The bottleneck in enhanced sampling lies in finding collective variables that effectively accelerate protein conformational changes; true reaction coordinates that accurately predict the committor are the well-recognized optimal choice. However, identifying them requires unbiased natural reactive trajectories, which, paradoxically, require effective enhanced sampling. Using the generalized work functional method, we uncover that true reaction coordinates control both conformational changes and energy relaxation, enabling us to compute them from energy relaxation simulations.

digitalMALDI: A Single-Particle-Based Mass Spectrometric Detection System for Biomolecules.

The development of a real-time system for characterizing individual biomolecule-containing aerosol particles presents a transformative opportunity to monitor respiratory conditions, including infections and lung diseases. Existing molecular assay technologies, although effective, rely on costly reagents, are relatively slow, and face challenges in multiplexing, limiting their use for real-time applications. To overcome these challenges, we developed digitalMALDI, a laser-based mass spectrometry system designed for single-particle characterization.

The relationship between the early life gastrointestinal microbiome and childhood nocturnal cough.

Background: Nocturnal cough affects approximately 1 in 3 children, can negatively impact child health, and is often attributable to asthma. The association of the gut microbiome with nocturnal cough has not been investigated.

Objective: To investigate the association between early-life gut microbiome composition and nocturnal cough overall and in the context of asthma.

Single-molecule toxicogenomics: Optical genome mapping of DNA-damage in nanochannel arrays.

Quantitative genomic mapping of DNA damage may provide insights into the underlying mechanisms of damage and repair. Sequencing based approaches are bound to the limitations of PCR amplification bias and read length which hamper both the accurate quantitation of damage events and the ability to map them to structurally complex genomic regions. Optical Genome mapping in arrays of parallel nanochannels allows physical extension and genetic profiling of millions of long genomic DNA fragments, and has matured to clinical utility for characterization of complex structural aberrations in cancer genomes.

Estimating realized relatedness in free-ranging macaques by inferring identity-by-descent segments.

Biological relatedness is a key consideration in studies of behavior, population structure, and trait evolution. Except for parent-offspring dyads, pedigrees capture relatedness imperfectly. The number and length of identical-by-descent DNA segments (IBD) yield the most precise relatedness estimates.

Gut Bacteria Encode Reductases that Biotransform Steroid Hormones.

The metabolism of steroids by the gut microbiome affects hormone homeostasis, impacting host development, mental health, and reproductive functions. In this study, we identify the Δ-3-ketosteroid 5β-reductase, 3β-hydroxysteroid dehydrogenase/Δ isomerase, and Δ-3-ketosteroid reductase enzyme families encoded by common human gut bacteria. Through phylogenetic reconstruction and mutagenesis, We show that 5β-reductase and Δ-3-ketosteroid reductase have evolved to specialize in converting diverse 3-keto steroid hormones into their 5β- and Δ-reduced derivatives.

In Vitro Cytotoxic Potential and Integrated Network Pharmacology, Molecular Docking and Molecular Dynamic Approaches to Decipher the Mechanism of Gymnostachyum febrifugum Benth., in the Treatment of Breast Cancer.

Gymnostachyum febrifugum, a less-known ethnomedicinal plant from the Western Ghats of India, is used to treat various diseases and serves as an antioxidant and antibacterial herb. The present study aims to profile the cytotoxic phytochemicals in G. febrifugum roots using GC-MS/MS, in vitro confirmation of cytotoxic potential against breast cancer and an in silico study to understand the mechanism of action.

Identification of Disease-Relevant, Sex-Based Proteomic Differences in iPSC-Derived Vascular Smooth Muscle Cells.

The prevalence of cardiovascular disease varies with sex, and the impact of intrinsic sex-based differences on vasculature is not well understood. Animal models can provide important insights into some aspects of human biology; however, not all discoveries in animal systems translate well to humans. To explore the impact of chromosomal sex on proteomic phenotypes, we used iPSC-derived vascular smooth muscle cells from healthy donors of both sexes to identify sex-based proteomic differences and their possible effects on cardiovascular pathophysiology.

Single-cell and spatial transcriptomic profiling revealed niche interactions sustaining growth of endometriotic lesions.

Endometriosis is a chronic condition with limited therapeutic options. The molecular aberrations promoting ectopic attachment and interactions with the local microenvironment sustaining lesion growth have been unclear, prohibiting development of targeted therapies. Here, we performed single-cell and spatial transcriptomic profiling of ectopic lesions and eutopic endometrium in endometriosis.

Heating up three cold cases in Norway using investigative genetic genealogy.

With the advent of commercial DNA databases, investigative genetic genealogy (IGG) has emerged as a powerful forensic tool, rivalling the impact of STR analyses, introduced four decades ago. IGG has been frequently applied in the US and tested in other countries, but never in Norway. Here, we apply IGG to three cold criminal cases and successfully identify the donor of the DNA in two of these cases.

Transcription factor prediction using protein 3D secondary structures.

Motivation: Transcription factors (TFs) are DNA-binding proteins that regulate gene expression. Traditional methods predict a protein as a TF if the protein contains any DNA-binding domains (DBDs) of known TFs. However, this approach fails to identify a novel TF that does not contain any known DBDs.

Facilitators and Barriers for Physiotherapists to Engage in Goal-Setting With Patients During Their Hospital Stay-An Explanatory Sequential Mixed-Methods Study.

Background And Purpose: Goal setting is a key aspect of patient-centered physiotherapy, helping to motivate patients, align healthcare efforts, prevent oversight, and stop ineffective interventions. This study aims to identify facilitators and barriers for physiotherapists in hospitals to set and document patient treatment goals.

Methods: An explanatory sequential mixed-methods approach was used.

Inferring metabolic objectives and trade-offs in single cells during embryogenesis.

While proliferating cells optimize their metabolism to produce biomass, the metabolic objectives of cells that perform non-proliferative tasks are unclear. The opposing requirements for optimizing each objective result in a trade-off that forces single cells to prioritize their metabolic needs and optimally allocate limited resources. Here, we present single-cell optimization objective and trade-off inference (SCOOTI), which infers metabolic objectives and trade-offs in biological systems by integrating bulk and single-cell omics data, using metabolic modeling and machine learning.

High-throughput proteomics identifies inflammatory proteins associated with disease severity and genetic ancestry in patients with hidradenitis suppurativa.

Background: Hidradenitis Suppurativa (HS) is a chronic inflammatory skin condition with a greater prevalence and disease burden in patients who identify as African American and those with a family history of HS, suggesting a strong genetic component to its pathogenesis.

Objective: To evaluate the relationship between plasma inflammatory protein expression, HS disease severity, and genetic ancestry in a diverse cohort of patients with Hidradenitis Suppurativa.

Methods: We performed a case-control study of patients with HS compared to age-, sex-, and ethnicity-matched healthy controls.

Multi-dimensional analyses identify genes of high priority for pancreatic cancer research.

Pancreatic ductal adenocarcinoma (PDAC) is a drug resistant and lethal cancer. Identification of the genes that consistently show altered expression across patients' cohorts can expose effective therapeutic targets and strategies. To identify such genes, we separately analyzed five human PDAC microarray datasets.

Progression and mortality of patients with cystic fibrosis in China.

Background: Patients with cystic fibrosis (CF) are rare in China and differ significantly from the Caucasian populations in terms of clinical and genetic characteristics. However, the progression and mortality of Chinese patients with CF have not been well described.

Results: This study included all 67 patients from the Peking Union Medical College Hospital CF cohort, with a median followed up time of 5.

Integrating Interpretability in Machine Learning and Deep Neural Networks: A Novel Approach to Feature Importance and Outlier Detection in COVID-19 Symptomatology and Vaccine Efficacy.

In this study, we introduce a novel approach that integrates interpretability techniques from both traditional machine learning (ML) and deep neural networks (DNN) to quantify feature importance using global and local interpretation methods. Our method bridges the gap between interpretable ML models and powerful deep learning (DL) architectures, providing comprehensive insights into the key drivers behind model predictions, especially in detecting outliers within medical data. We applied this method to analyze COVID-19 pandemic data from 2020, yielding intriguing insights.