Explainable deep learning and virtual evolution identifies antimicrobial peptides with activity against multidrug-resistant human pathogens.

Artificial intelligence (AI) is a promising approach to identify new antimicrobial compounds in diverse microbial species. Here we developed an AI-based, explainable deep learning model, EvoGradient, that predicts the potency of antimicrobial peptides (AMPs) and virtually modifies peptide sequences to produce more potent AMPs, akin to in silico directed evolution. We applied this model to peptides encoded in low-abundance human oral bacteria, resulting in the virtual evolution of 32 peptides into potent AMPs.

Recombinant Thrombomodulin Domain 1 Modulates Macrophage Polarization and Enhances Healing in Corneal Alkali Burns.

Purpose: Corneal alkali burns are severe ocular injuries characterized by intense inflammation, tissue damage, and vision impairment, with current treatments often insufficient in restoring corneal function and clarity. This study aimed to evaluate the therapeutic effects of recombinant thrombomodulin domain 1 (rTMD1) in the treatment of corneal alkali burns, focusing on its impact on inflammation, tissue repair, fibrosis, and neovascularization.

Methods: A murine model of corneal alkali burn was utilized to investigate the therapeutic potential of rTMD1.

Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B.

Background: Xalnesiran, a small interfering RNA molecule that targets a conserved region of the hepatitis B virus (HBV) genome and silences multiple HBV transcripts, may have efficacy, with or without an immunomodulator, in patients with chronic HBV infection.

Methods: We conducted a phase 2, multicenter, randomized, controlled, adaptive, open-label platform trial that included the evaluation of 48 weeks of treatment with xalnesiran at a dose of 100 mg (group 1), xalnesiran at a dose of 200 mg (group 2), xalnesiran at a dose of 200 mg plus 150 mg of ruzotolimod (group 3), xalnesiran at a dose of 200 mg plus 180 μg of pegylated interferon alfa-2a (group 4), or a nucleoside or nucleotide analogue (NA) alone (group 5) in participants with chronic HBV infection who had virologic suppression with NA therapy. The primary efficacy end point was hepatitis B surface antigen (HBsAg) loss (HBsAg level, <0.

Heat-Killed subsp. 557 Extracts Protect Chondrocytes from Osteoarthritis Damage by Reducing Inflammation: An In Vitro Study.

Background: Osteoarthritis (OA) is a chronic condition characterized by joint pain and disability, driven by excessive oxidative stress and inflammatory cytokine production in chondrocytes, resulting in cell death and cartilage matrix breakdown. Our previous study showed that in monosodium iodoacetate (MIA)-induced OA rats, oral administration of heat-killed subsp. 557 (LDL557) could significantly decrease OA progression.

The Influence of Extra-Ribosomal Functions of Eukaryotic Ribosomal Proteins on Viral Infection.

The eukaryotic ribosome is a large ribonucleoprotein complex consisting of four types of ribosomal RNA (rRNA) and approximately 80 ribosomal proteins (RPs), forming the 40S and 60S subunits. In all living cells, its primary function is to produce proteins by converting messenger RNA (mRNA) into polypeptides. In addition to their canonical role in protein synthesis, RPs are crucial in controlling vital cellular processes such as cell cycle progression, cellular proliferation, differentiation, DNA damage repair, genome structure maintenance, and the cellular stress response.

Human respiratory organoids sustained reproducible propagation of human rhinovirus C and elucidation of virus-host interaction.

The lack of a robust system to reproducibly propagate HRV-C, a family of viruses refractory to cultivation in standard cell lines, has substantially hindered our understanding of this common respiratory pathogen. We sought to develop an organoid-based system to reproducibly propagate HRV-C, and characterize virus-host interaction using respiratory organoids. We demonstrate that airway organoids sustain serial virus passage with the aid of CYT387-mediated immunosuppression, whereas nasal organoids that more closely simulate the upper airway achieve this without any intervention.

An antibody cocktail targeting two different CD73 epitopes enhances enzyme inhibition and tumor control.

CD73, an ectoenzyme responsible for adenosine production, is often elevated in immuno-suppressive tumor environments. Inhibition of CD73 activity holds great promise as a therapeutic strategy for CD73-expressing cancers. In this study, we have developed a therapeutic anti-human CD73 antibody cocktail, HB0045.

Global Fatty Degeneration Index on Preoperative Magnetic Resonance Imaging Predicts Early Postoperative Shoulder Stiffness at 3 Months After Primary Rotator Cuff Repair.

Purpose: To determine whether the fatty infiltration of rotator cuff muscles, as measured by magnetic resonance imaging (MRI) preoperatively and assessed using the Goutallier fatty degeneration index (GFDI), can predict early postoperative shoulder stiffness (POSS) after rotator cuff repair (RCR).

Methods: This retrospective longitudinal cohort study included patients who underwent primary RCR, had available medical records, and underwent MRI before RCR between November 2012 and July 2022. Patients were excluded on the basis of the following criteria: (1) preoperative shoulder stiffness, (2) additional procedures (e.

A New Marine Epizoic Diatom, Ceratanaulus alaris sp. nov. (Bacillariophyceae), From Guangxi Zhuang Autonomous Region, the Southwest Coast of China.

Diatoms (Bacillariophyceae) are diverse and abundant microalgae, and many of them are found in marine intertidal environments. Here, we present a new marine epizoic diatom isolated from Euspira gilva Philippi in intertidal area of Beihai city, Guangxi Zhuang Autonomous Region, named Ceratanaulus alaris L.J.

Development and Validation of a Nomogram Based on Multiparametric MRI for Predicting Lymph Node Metastasis in Endometrial Cancer: A Retrospective Cohort Study.

Rationale And Objectives: To develop a radiomics nomogram based on clinical and magnetic resonance features to predict lymph node metastasis (LNM) in endometrial cancer (EC).

Materials And Methods: We retrospectively collected 308 patients with endometrial cancer (EC) from two centers. These patients were divided into a training set (n=155), a test set (n=67), and an external validation set (n=86).

Radiomics of Periprostatic Fat and Tumor Lesion Based on MRI Predicts the Pathological Upgrading of Prostate Cancer from Biopsy to Radical Prostatectomy.

Rationale And Objectives: To assess the predictive value of MRI-based radiomics of periprostatic fat (PPF) and tumor lesions for predicting Gleason score (GS) upgrading from biopsy to radical prostatectomy (RP) in prostate cancer (PCa).

Methods: A total of 314 patients with pathologically confirmed prostate cancer (PCa) after radical prostatectomy (RP) were included in the study. The patients were randomly assigned to the training cohort (n = 157) and the validating cohort (n = 157) in a 1:1 ratio.

A Systematic Method to Detect Next-Generation Sequencing-Based Microsatellite Instability in Plasma Cell-Free DNA: plasmaMSI.

Microsatellite instability (MSI) detection using tumor tissue is a well-established prognostic and predictive biomarker for certain types of cancers. However, tumor tissue samples are less convenient to obtain than blood plasma samples. The main challenge facing next-generation sequencing-based MSI detection in blood plasma samples is the ultralow signal/noise ratio in plasma cell-free DNA (cfDNA).

Data-driven discovery of cell-type-directed network-correcting combination therapy for Alzheimer's disease.

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder characterized by heterogeneous molecular changes across diverse cell types, posing significant challenges for treatment development. To address this, we introduced a cell-type-specific, multi-target drug discovery strategy grounded in human data and real-world evidence. This approach integrates single-cell transcriptomics, drug perturbation databases, and clinical records.

Suite of Biochemical and Cell-Based Assays for the Characterization of Kirsten Rat Sarcoma (KRAS) Inhibitors and Degraders.

KRAS is an important oncogenic driver which is mutated in numerous cancers. Recent advances in the selective targeting of KRAS mutants via small molecule inhibitors and targeted protein degraders have generated an increase in research activity in this area in recent years. As such, there is a need for new assay platforms to profile next generation inhibitors which improve on the potency and selectivity of existing drug candidates, while evading the emergence of resistance.

Four-component protein nanocages designed by programmed symmetry breaking.

Four, eight or twenty C3 symmetric protein trimers can be arranged with tetrahedral, octahedral or icosahedral point group symmetry to generate closed cage-like structures. Viruses access more complex higher triangulation number icosahedral architectures by breaking perfect point group symmetry, but nature appears not to have explored similar symmetry breaking for tetrahedral or octahedral symmetries. Here we describe a general design strategy for building higher triangulation number architectures starting from regular polyhedra through pseudosymmetrization of trimeric building blocks.

Editorial Commentary: Thoughtful Application of Artificial Intelligence Technique Improves Diagnostic Accuracy and Supportive Clinical Decision-Making.

Medical research within areas of deep learning, particularly in computer vision for medical imaging, has shown promise over the past decade with an increasing volume of technical papers published in orthopaedics related to imaging artificial intelligence (AI). However, as more tools and models are developed and deployed, it is easy for clinicians to get overwhelmed with the different types of models, leaving "artificial intelligence" as an empty buzzword where true value can be unclear. As with surgery, the techniques of deep learning require thoughtful application and cannot follow a one-size-fits-all approach as different problems require differential levels of technical complexity with model application.

In vivo evidence for cell body loss in cortical lesions in people with multiple sclerosis.

Objective: To quantify alterations in soma and neurite density imaging measures within and surrounding cortical lesions in people with multiple sclerosis using in vivo high-gradient diffusion MRI.

Methods: In this cross-sectional study, 41 people with multiple sclerosis and 34 age- and sex-matched healthy controls underwent 3 T high-gradient diffusion MRI. Cortical lesions were segmented on artificial intelligence-enabled double inversion recovery images.

Growth Hormone-Releasing Peptide 2 May Be Associated With Decreased M1 Macrophage Production and Increased Histologic and Biomechanical Tendon-Bone Healing Properties in a Rat Rotator Cuff Tear Model.

Purpose: To explore the potential of growth hormone-releasing peptide 2 (GHRP-2) for tendon-bone healing in a rat rotator cuff tear (RCT) model.

Methods: The impact of GHRP-2 on M1 macrophage polarization in vitro was determined using real-time polymerase chain reaction, Western blot, and immunofluorescence staining. GHRP-2 was then applied in a rat RCT model, and the healing of the tendon-bone interface was systemically evaluated by histologic staining, radiologic assessments, gait analysis, and biomechanical tests.

Evaluating the Use of Environmental and Polygenic Risk Scores to Inform Colorectal Cancer Risk-Based Surveillance Intervals.

Introduction: United States Multi-Society Task Force colonoscopy surveillance intervals are based solely on adenoma characteristics, without accounting for other risk factors. We investigated whether a risk model including demographic, environmental, and genetic risk factors could individualize surveillance intervals under an "equal management of equal risks" framework.

Methods: Using 14,069 individuals from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had a diagnostic colonoscopy following an abnormal flexible sigmoidoscopy, we modeled the risk of colorectal cancer, considering the diagnostic colonoscopy finding, baseline risk factors (e.

Accurate Intramyocardial Hemorrhage Assessment with Fast, Free-running, Cardiac Quantitative Susceptibility Mapping.

Purpose To evaluate the performance of a high-dynamic-range quantitative susceptibility mapping (HDR-QSM) cardiac MRI technique to detect intramyocardial hemorrhage (IMH) and quantify iron content using phantom and canine models. Materials and Methods A free-running whole-heart HDR-QSM technique for IMH assessment was developed and evaluated in calibrated iron phantoms and 14 IMH female canine models. IMH detection and iron content quantification performance of this technique was compared with the conventional iron imaging approaches, R2*(1/T2*) maps, using measurements from ex vivo imaging as the reference standard.

Comparative Evaluation of Clinical-MRI, Radiomics, and Integrated Nomogram Models for Preoperative Prediction of Placenta Accreta Spectrum.

Rationale And Objectives: The escalating incidence of placental accreta spectrum (PAS), a pregnancy complication, underscores the need for accurate prenatal diagnosis to guide optimal management strategies. This study aims to develop, validate, and compare various prenatal PAS prediction models integrating clinical data, MRI signs, and radiomics signatures.

Materials And Methods: A cohort comprising 111 patients (72 with PAS and 39 without, denoted as N-PAS) served as the training set, while another 47 patients (33 PAS and 14 N-PAS) constituted the validation set.

Deep Learning Algorithms for Breast Cancer Detection in a UK Screening Cohort: As Stand-alone Readers and Combined with Human Readers.

Background Deep learning (DL) algorithms have shown promising results in mammographic screening either compared to a single reader or, when deployed in conjunction with a human reader, compared with double reading. Purpose To externally validate the performance of three DL algorithms as mammographic screen readers in an independent UK data set. Materials and Methods Three commercial DL algorithms (DL-1, DL-2, and DL-3) were retrospectively investigated from January 2022 to June 2022 using consecutive full-field digital mammograms collected at two UK sites during 1 year (2017).

Plasma Glial Fibrillary Acid Protein and Phosphorated Tau 181 Association with Presynaptic Density-Dependent Tau Pathology at F-SynVesT-1 Brain PET Imaging.

Background Synaptic loss is an important factor in Alzheimer disease (AD); however, blood assays that conveniently and rapidly reflect changes in synaptic density are lacking. Purpose To correlate multiple potential synaptic blood markers with synaptic density measured using F-SynVesT-1, a fluorine 18 (F)-labeled radiotracer, brain PET and to explore the independent associations between these markers and synaptic density. Materials and Methods This prospective study included 50 cognitively unimpaired (mean age, 65.