Ramp sequence may explain synonymous variant association with Alzheimer's disease in the Paired Immunoglobulin-like Type 2 Receptor Alpha ().

Background: Synonymous variant () in the Paired Immunoglobulin-like Type 2 Receptor Alpha () gene was previously associated with decreased risk for Alzheimer's disease (AD) in genome-wide association studies, but its biological impact is largely unknown.

Objective: We hypothesized that decreases mRNA and protein levels by destroying a ramp of slowly translated codons at the 5' end of .

Methods: We assessed predicted effects on through quantitative polymerase chain reactions (qPCR) and enzyme-linked immunosorbent assays (ELISA) using Chinese hamster ovary (CHO) cells.

Quantifying Metagenomic Strain Associations from Microbiomes with Anpan.

Genetic and genomic variation among microbial strains can dramatically influence their phenotypes and environmental impact, including on human health. However, inferential methods for quantifying these differences have been lacking. Strain-level metagenomic profiling data has several features that make traditional statistical methods challenging to use, including high dimensionality, extreme variation among samples, and complex phylogenetic relatedness.

Engineering of CRISPR-Cas PAM recognition using deep learning of vast evolutionary data.

CRISPR-Cas enzymes must recognize a protospacer-adjacent motif (PAM) to edit a genomic site, significantly limiting the range of targetable sequences in a genome. Machine learning-based protein engineering provides a powerful solution to efficiently generate Cas protein variants tailored to recognize specific PAMs. Here, we present Protein2PAM, an evolution-informed deep learning model trained on a dataset of over 45,000 CRISPR-Cas PAMs.

Development of a Paper-Based Disposal Thin-Film Solid-Phase Microextraction Tool for the Quantification of Environmentally Hazardous 4-Chlorophenol in Water.

The presence of chlorinated compounds in water resources presents various environmental and health risks. Therefore, there is a precise need to develop a potential technique for fast and efficient monitoring of chlorinated contaminants in water due to environmental protection and regulation compliance. Here, we designed a paper-based thin-film solid-phase microextraction (TF-SPME) patch to estimate 4-chlorophenol (4-CRP), a widely known environmentally hazardous pollutant in water samples.

Enhanced Stability and Sensitivity for CA-125 Detection Under Microfluidic Shear Flow Using Polyethylene Glycol-Coated Biosensor.

The microfluidic-based point-of-care (POC) diagnostic tool has garnered significant interest in recent years, offering rapid and cost-effective disease detection. There is a growing trend toward integrating microfluidic platforms with biosensors, aligning lab-on-a-chip technologies with POC diagnostic devices. Despite numerous efforts to incorporate biosensors into microfluidic systems, researchers have performed very limited investigations on the stability of biomarker detection when biosensors operate under microfluidic shear flow conditions.

Utilization of Staging Laparoscopy for Patients With Gastric Cancer in Ukraine.

Background: The use of advanced diagnostic methods, such as high-resolution CT or PET-CT scans, are limited in low and middle-income countries (LMICs). In gastric cancer, occult peritoneal disease may be present in up to 20% of cases, limiting the benefits of surgical resection. Accurate staging of gastric cancer is essential to ensure optimal patient management and prevent undue morbidity from unnecessary surgery.

Autonomous Self-Healing Magnetoelectric I-Skin from Self-Bonded Deep Eutectic Polymer.

Next-generation ionic skin (i-skin) should be self-healing and self-powered, promoting its development toward lightweight, miniaturization, compact, and portable designs. Previously reported self-powered i-skin mostly either lack the ability to self-repair damaged parts or only have self-healing capabilities some components, falling short of achieving complete device self-healability. In this work, a self-bonding strategy is presented to obtain an all-polymerizable deep eutectic solvent (PDES) magnetoelectric i-skin (MIS) that simultaneously achieves self-powering and full-device autonomous self-healability.

Novel use of ultrasound-guided high-intensity focused ultrasound (HIFU) may enable the neuroablation of the sacroiliac joint in a swine model: a feasibility study.

Background: Sacroiliac joint (SIJ) dysfunction accounts for the etiology of pain in 15%-30% of low back pain cases. Some patients with conservative treatment-refractory SIJ dysfunction undergo radiofrequency (RF) ablation of the SIJ for prolonged pain relief. This procedure involves placing up to 12 RF probes in what is an invasive, resource-intensive, and time-consuming process.

Assessment and treatment considerations for patients with colorectal liver metastases: AHPBA consensus guideline and update for surgeons.

Background: Colorectal cancer most commonly metastasizes to the liver. While various treatment strategies have been developed, surgical management of these patients has vital implications on the prognosis and survival of this group of patients. There remains a need for a consensus guideline regarding the surgical evaluation and management of patients with colorectal liver metastases (CRLM).

The renin-angiotensin-aldosterone system and salt sensitivity of blood pressure offer new insights in obesity phenotypes.

Objective: Individuals who have metabolically healthy overweight/obesity (MHOO) do not have cardiometabolic complications despite an elevated BMI. Renin-angiotensin-aldosterone system (RAAS) activation and salt sensitivity of blood pressure (SSBP) are cardiovascular disease (CVD) risks, which are increased in individuals with higher BMI values. Little is known about the differences in RAAS activation and SSBP between MHOO and metabolically unhealthy overweight/obesity (MUOO) phenotypes.

Coffee Consumption, Additive Use, and Risk of Type 2 Diabetes- Results from Three Large Prospective US Cohort Studies.

Background: Consumption of coffee has been consistently associated with lower risk of type 2 diabetes (T2D). However, it is unknown whether the use of additives may modify the association.

Objective: To study the association between coffee consumption and risk of T2D by considering the addition of sugar, artificial sweeteners, cream or a non-dairy coffee whitener.

Accuracy, Effectiveness, and Safety of Robot-Assisted MRI-Guided Laser Interstitial Thermal Therapy for Treatment of Drug-Resistant Epilepsy: A Systematic Review and Meta-Analysis.

Objectives: Robotic-assisted laser interstitial thermal therapy (LITT) is a minimally invasive method for ablating seizure foci and has gained prominence in epilepsy treatment. The use of robotic guidance in these procedures can minimize errors in probe placement, potentially leading to better clinical outcomes. In this meta-analysis, we assessed the accuracy, safety, and effectiveness of robot-assisted LITT for drug-resistant epilepsy.

Skeletal muscle adiposity, coronary microvascular dysfunction, and adverse cardiovascular outcomes.

Background And Aims: Skeletal muscle (SM) fat infiltration, or intermuscular adipose tissue (IMAT), reflects muscle quality and is associated with inflammation, a key determinant in cardiometabolic disease. Coronary flow reserve (CFR), a marker of coronary microvascular dysfunction (CMD), is independently associated with body mass index (BMI), inflammation and risk of heart failure, myocardial infarction, and death. The relationship between SM quality, CMD, and cardiovascular outcomes is not known.

Mild autonomous cortisol secretion in patients with aldosterone-producing adenoma and risk for cardiac remodeling and diastolic dysfunction.

Background: Mild autonomous cortisol secretion (MACS) is common in adrenal adenomas, including patients with primary aldosteronism (PA) with aldosterone-producing adenomas (APA). This study investigated the impact of MACS on cardiac remodeling and diastolic dysfunction in patients with APA.

Methods: We prospectively enrolled 483 patients with APA.

Preventing unrestricted and unmonitored AI experimentation in healthcare through transparency and accountability.

The integration of large language models (LLMs) into electronic health records offers potential benefits but raises significant ethical, legal, and operational concerns, including unconsented data use, lack of governance, and AI-related malpractice accountability. Sycophancy, feedback loop bias, and data reuse risk amplifying errors without proper oversight. To safeguard patients, especially the vulnerable, clinicians must advocate for patient-centered education, ethical practices, and robust oversight to prevent harm.

Predicting metabolite response to dietary intervention using deep learning.

Due to highly personalized biological and lifestyle characteristics, different individuals may have different metabolite responses to specific foods and nutrients. In particular, the gut microbiota, a collection of trillions of microorganisms living in the gastrointestinal tract, is highly personalized and plays a key role in the metabolite responses to foods and nutrients. Accurately predicting metabolite responses to dietary interventions based on individuals' gut microbial compositions holds great promise for precision nutrition.

International Expert-Based Consensus Definition, Classification Criteria, and Minimum Data Elements for Osteoradionecrosis of the Jaw: An Inter-Disciplinary Modified Delphi Study.

Purpose: Osteoradionecrosis of the jaw (ORNJ) is a severe iatrogenic disease characterized by bone death after radiation therapy (RT) to the head and neck. With over 9 published definitions and at least 16 classification systems, the true incidence and severity of ORNJ are obscured by lack of a standard for disease definition and severity assessment, leading to inaccurate estimation of incidence, reporting ambiguity, and likely under-diagnosis worldwide. This study aimed to achieve consensus on an explicit definition and phenotype of ORNJ and related precursor states through data standardization to facilitate effective diagnosis, monitoring, and multidisciplinary management of ORNJ.

Oral vancomycin treatment alters levels of indole derivatives and secondary bile acids modulating the expression of mTOR pathway genes in astrocytes during EAE.

Astrocytes play important roles in the central nervous system (CNS) during health and disease. Prior studies have shown that gut commensal-derived indole derivatives as well as secondary bile acids modulate astrocyte function during the late stage of EAE (recovery phase). Here we showed that administering vancomycin to mice starting during the early stage of EAE improved disease recovery, an effect that is mediated by the gut microbiota.

Consistent direction despite wavering policy: reductions in resident physician extended duration shifts over 20 years.

We examined data from 17,498 physicians-in-training who reported on 92,662 months of work over a 20 year study interval that included three major revisions to work hour limits. Extended duration shifts (≥24 hours; EDS) are much less common than they used to be. On average, first-year resident physicians (PGY1s) currently work a total of 4 EDS per year and 3 EDS per month during months in which any EDS are worked.

HER2DX in HER2-positive inflammatory breast cancer: correlative insights and comparative analysis with noninflammatory breast cancers.

Background: The HER2DX assay predicts long-term prognosis and pathologic complete response (pCR) in patients with early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving neoadjuvant systemic therapy but has not been evaluated in inflammatory breast cancer (IBC).

Patients And Methods: HER2DX was analyzed in baseline biopsy tissues from 23 patients with stage III HER2-positive IBC on a phase II trial (NCT01796197) treated with neoadjuvant trastuzumab, pertuzumab, and paclitaxel (THP). To assess the assay's predictive accuracy for pCR in IBC, clinical-pathological features and outcomes from this IBC cohort were compared with 156 patients with stage III HER2-positive non-IBC from four different cohorts.

A Targeted Feedback Framework to Move the Needle on Operative Feedback.

Objective: Actionable and impactful feedback remains a perpetual challenge in medical education despite extensive efforts to improve the feedback process. A feedback framework was adapted from a validated model and tailored to a single residency program. The purpose of this study was to evaluate the impact of the new feedback framework on the quantity and quality of perioperative feedback amongst surgical residents.