Solu: a cloud platform for real-time genomic pathogen surveillance.

Background: Genomic surveillance is extensively used for tracking public health outbreaks and healthcare-associated pathogens. Despite advancements in bioinformatics pipelines, there are still significant challenges in terms of infrastructure, expertise, and security when it comes to continuous surveillance. The existing pipelines often require the user to set up and manage their own infrastructure and are not designed for continuous surveillance that demands integration of new and regularly generated sequencing data with previous analyses.

Predictive equation derived from 6,497 doubly labelled water measurements enables the detection of erroneous self-reported energy intake.

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years.

Rice transcription factor bHLH25 confers resistance to multiple diseases by sensing HO.

Hydrogen peroxide (HO) is a ubiquitous signal regulating many biological processes, including innate immunity, in all eukaryotes. However, it remains largely unknown that how transcription factors directly sense HO in eukaryotes. Here, we report that rice basic/helix-loop-helix transcription factor bHLH25 directly senses HO to confer resistance to multiple diseases caused by fungi or bacteria.

ESKAPE pathogens rapidly develop resistance against antibiotics in development in vitro.

Despite ongoing antibiotic development, evolution of resistance may render candidate antibiotics ineffective. Here we studied in vitro emergence of resistance to 13 antibiotics introduced after 2017 or currently in development, compared with in-use antibiotics. Laboratory evolution showed that clinically relevant resistance arises within 60 days of antibiotic exposure in Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii and Pseudomonas aeruginosa, priority Gram-negative ESKAPE pathogens.

Tissue fibrosis in cardiorenal syndrome: crosstalk between heart and kidneys.

Cardiorenal syndrome (CRS) is represented as an intricate dysfunctional interplay between the heart and kidneys, marked by cardiorenal inflammation and fibrosis. Unlike other organs, the repair process in cardiorenal injury involves a regenerative phase characterized by proliferation and polyploidization, followed by a subsequent pathogenic phase of fibrosis. In CRS, acute or chronic cardiorenal injury leads to hyperactive inflammation and fibrotic remodeling, associated with injury-mediated immune cell (Macrophages, Monocytes, and T-cells) infiltration and myofibroblast activation.

Neurons as Immunomodulators: From Rapid Neural Activity to Prolonged Regulation of Cytokines and Microglia.

Regulation of the brain's neuroimmune system is central to development, normal function, and disease. Neuronal communication to microglia, the primary immune cells of the brain, is well known to involve purinergic signaling mediated via ATP secretion and the cytokine fractalkine. Recent evidence shows that neurons release multiple cytokines beyond fractalkine, yet these are less studied and poorly understood.

QTL-Based Evidence of Population Genetic Divergence in Male Territorial Aggressiveness of the Japanese Freshwater Threespine Stickleback.

Territorial aggression is widespread across the animal kingdom and is expressed in diverse ecological and social contexts. In addition, there are marked variations in the degree of male reproductive territoriality within and between species. These differences are often attributed to genetic components.

A human skin-on-a-chip platform for microneedling-driven skin cancer treatment.

Skin-on-a-chip models provide physiologically relevant platforms for studying diseases and drug evaluation, replicating the native skin structures and functions more accurately than traditional 2D or simple 3D cultures. However, challenges remain in creating models suitable for microneedling applications and monitoring, as well as developing skin cancer models for analysis and targeted therapy. Here, we developed a human skin/skin cancer-on-a-chip platform within a microfluidic device using bioprinting/bioengineering techniques.

Developing a Research Center for Artificial Intelligence in Medicine.

Artificial intelligence (AI) and machine learning (ML) are driving innovation in biosciences and are already affecting key elements of medical scholarship and clinical care. Many schools of medicine are capitalizing on the promise of these new technologies by establishing academic units to catalyze and grow research and innovation in AI/ML. At Stanford University, we have developed a successful model for an AI/ML research center with support from academic leaders, clinical departments, extramural grants, and industry partners.

Dual-Cys bacteriophytochromes: intermediates in cyanobacterial phytochrome evolution?

Previous studies have identified three families of knotted phytochrome photoreceptors in cyanobacteria. We describe a fourth type: 'hybrid' phytochromes with putative bilin-binding cysteine residues in both their N-terminal 'knot' extensions and cGMP-phosphodiesterase/adenylate cyclase/FhlA (GAF) domains, which we designate as dual-cysteine bacteriophytochromes (DCBs). Recombinant expression of DCBs in Escherichia coli yields photoactive phycocyanobilin (PCB) adducts with red/far-red photocycles similar to those of the GAF-Cys-containing cyanobacterial phytochromes (Cph1s).

Visualizing Cancer Heterogeneity at the Molecular and Cellular Levels: Lessons from Rosetta.

Understanding tumor heterogeneity is a major challenge that was recognized as one of the first Cancer Grand Challenges, with a call to provide solutions to visualize tumor heterogeneity. The Rosetta team took on this challenge, exploiting advances in spatial-omics approaches centered around mass spectrometry imaging to map tumor heterogeneity at the cellular and molecular scales with different levels of resolution. See related article by Bressan et al.

Conserved ancillary residues situated proximally to the VIM-2 active-site affect its metallo β-lactamase activity.

Verona-integron-metallo-β-lactamase (VIM-2) is one of the most widespread class B β-lactamase responsible for β-lactam resistance. Although active-site residues help in metal binding, the residues nearing the active-site possess functional importance. Here, to decipher the role of such residues in the activity and stability of VIM-2, the residues E146, D182, N210, S207, and D213 were selected through in-silico analyses and substituted with alanine using site-directed mutagenesis.

Emerging models to study competitive interactions within bacterial communities.

Within both abiotic and host environments, bacteria typically exist as diverse, multispecies communities and have crucial roles in human health, agriculture, and industry. In these communities, bacteria compete for resources, and these competitive interactions can shape the overall population structure and community function. Studying bacterial community dynamics requires experimental model systems that capture the different interaction networks between bacteria and their surroundings.

Clinical Outcomes With Immune Checkpoint Inhibitors in Patients With FGFR2/3, MTAP or ERBB2 Genomic Alterations in Advanced Urothelial Carcinoma.

Background: FGFR2/3, MTAP and ERBB2 genomic alterations have treatment targets in advanced urothelial carcinoma (aUC). These alterations may affect tumor microenvironment and outcomes with immune checkpoint inhibitors (ICIs) in aUC.

Patients And Methods: We identified patients with available genomic data in our multi-institution cohort of patients with aUC treated with ICI.

3D bioprinting: Advancing the future of food production layer by layer.

3D bioprinting is an advanced manufacturing technique that involves the precise layer-by-layer deposition of biomaterials, such as cells, growth factors, and biomimetic scaffolds, to create three-dimensional living structures. It essentially combines the complexity of biology with the principles of 3D printing, making it possible to fabricate complex biological structures with extreme control and accuracy. This review discusses how 3D bioprinting is developing as an essential step in the creation of alternative food such as cultured meat and seafood.

Allocation of Semaglutide According to Coronary Artery Calcium and BMI: Applying the SELECT Trial to MESA.

Background: Implementation of semaglutide weight loss therapy has been challenging due to drug supply and cost, underscoring a need to identify those who derive the greatest absolute benefit.

Objectives: Allocation of semaglutide was modeled according to coronary artery calcium (CAC) among individuals without diabetes or established atherosclerotic cardiovascular disease (CVD).

Methods: In this analysis, 3,129 participants in the MESA (Multi-Ethnic Study of Atherosclerosis) without diabetes or clinical CVD met body mass index criteria for semaglutide and underwent CAC scoring on noncontrast cardiac computed tomography.

Trajectories of breast density change over time and subsequent breast cancer risk: longitudinal study.

Objective: To identify clusters of women with similar trajectories of breast density change over four longitudinal assessments and to examine the association between these trajectories and the subsequent risk of breast cancer.

Design: Retrospective cohort study.

Setting: Data from the national breast cancer screening programme, which is embedded in the National Health Insurance Service database in Korea.

Issues and Limitations on the Road to Fair and Inclusive AI Solutions for Biomedical Challenges.

Objective: In this paper, we explore the correlation between performance reporting and the development of inclusive AI solutions for biomedical problems. Our study examines the critical aspects of bias and noise in the context of medical decision support, aiming to provide actionable solutions. Contributions: A key contribution of our work is the recognition that measurement processes introduce noise and bias arising from human data interpretation and selection.

Exploring the Inhibition of α-Carbonic Anhydrase by Sulfonamides: Insights into Potential Drug Targeting.

, the causative agent of toxoplasmosis, is a protozoan parasite capable of infecting a wide range of hosts, posing significant health risks, particularly to immunocompromised individuals and congenital transmission. Current therapeutic options primarily target the active tachyzoite stage but are limited by issues such as toxicity and incomplete efficacy. As a result, there is an urgent need for alternative therapies that can selectively target parasite-specific mechanisms critical for metabolic processes and host-parasite interactions.

Exploring Feed Digestibility and Broiler Performance in Response to Dietary Supplementation of .

This study evaluated the feed digestibility of diets including autotrophic in 252 male broilers (Ross 308), comparing unprocessed biomass (trial 1) and pulsed electric field (PEF) processed biomass (trial 2) at inclusion levels up to 20%. In trial 2, performance and meat color were also evaluated. Each trial included seven treatments (0%, 1%, 2%, 5%, 10%, 15%, and 20% (%/ on dry matter (DM)) ) with six replicates (three birds per replicate) per treatment.

Microvascular decompression: a contemporary update.

Background: Microvascular decompression (MVD) is the gold-standard surgical treatment for cranial nerve compression disorders, including trigeminal neuralgia (TN), hemifacial spasm (HFS), and glossopharyngeal neuralgia (GPN). This review synthesizes historical milestones, recent advances, and evolving techniques in MVD, with a primary focus on these conditions.

Methods: A comprehensive literature review was conducted using databases such as PubMed, SpringerLink, Google Scholar, BioMed Central, Scopus, and ScienceDirect.

Staging of prostate Cancer with ultra-fast PSMA-PET scans enhanced by AI.

Purpose: PSMA-PET is a reference standard examination for patients with prostate cancer, but even using recently introduced digital PET detectors image acquisition with standard field-of-view scanners is still in the range of 20 min. This may cause limited access to examination slots because of the growing demand for PSMA-PET. Ultra-fast PSMA-PET may enhance throughput but comes at the cost of poor image quality.

Sitravatinib in combination with nivolumab plus ipilimumab in patients with advanced clear cell renal cell carcinoma: a phase 1 trial.

We conducted a phase I trial to determine the optimal dose of triplet therapy with the tyrosine kinase inhibitor sitravatinib plus nivolumab plus ipilimumab in 22 previously untreated patients with advanced clear cell renal cell carcinoma. The primary endpoint was safety. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), 1-year survival probability, and sitravatinib pharmacokinetics.

Guidance on biomaterials for periodontal tissue regeneration: Fabrication methods, materials and biological considerations.

Regeneration of the multiple tissues and interfaces in the periodontal complex necessitates multidisciplinary evaluation to establish structure/function relationships. This article, an initiative of the Academy of Dental Materials, provides guidance for performing chemical, structural, and mechanical characterization of materials for periodontal tissue regeneration, and outlines important recommendations on methods of testing bioactivity, biocompatibility, and antimicrobial properties of biomaterials/scaffolds for periodontal tissue engineering. First, we briefly summarize periodontal tissue engineering fabrication methods.

ECM stiffness regulates lung fibroblast survival through RasGRF1 dependent signaling.

Extracellular matrix stiffness is one of the multiple mechanical signals that alters cellular behavior. During studies exploring the effect of matrix rigidity on lung fibroblast survival we discovered that enhanced survival on stiff substrates is dependent on elevated Ras activity, owing to the activation of the GEF, RasGRF1. Mechanistically, we found that the increased Ras activity lead to the activation of both the AKT and ERK pathways.