Segmentation aware probabilistic phenotyping of single-cell spatial protein expression data.

Spatial protein expression technologies can map cellular content and organization by simultaneously quantifying the expression of >40 proteins at subcellular resolution within intact tissue sections and cell lines. However, necessary image segmentation to single cells is challenging and error prone, easily confounding the interpretation of cellular phenotypes and cell clusters. To address these limitations, we present STARLING, a probabilistic machine learning model designed to quantify cell populations from spatial protein expression data while accounting for segmentation errors.

Osteochondral Abnormalities on Three-Dimensional Ultrashort Echo Time MRI Scans Are Associated with Knee Cartilage Degradation.

Background The calcified cartilage layer and subchondral bone plate (SBP) contribute to osteoarthritis development. Three-dimensional (3D) ultrashort echo-time (UTE) MRI can help to evaluate calcified cartilage and SBP in various stages of cartilage degradation. Purpose To compare calcified cartilage and SBP abnormalities using 3D UTE MRI with cartilage degradation and osteochondral junction (OCJ) abnormalities observed at proton-density fast spin-echo with fat suppression (PDFS) MRI.

Efficient non-viral immune cell engineering using circular single-stranded DNA-mediated genomic integration.

The use of adeno-associated viruses (AAVs) as donors for homology-directed repair (HDR)-mediated genome engineering is limited by safety issues, manufacturing constraints and restricted packaging limits. Non-viral targeted genetic knock-ins rely primarily on double-stranded DNA (dsDNA) and linear single-stranded DNA (lssDNA) donors. dsDNA is known to have low efficiency and high cytotoxicity, while lssDNA is challenging for scaled manufacture.

Hospital-wide access to genomic data advanced pediatric rare disease research and clinical outcomes.

Boston Children's Hospital has established a genomic sequencing and analysis research initiative to improve clinical care for pediatric rare disease patients. Through the Children's Rare Disease Collaborative (CRDC), the hospital offers CLIA-grade exome and genome sequencing, along with other sequencing types, to patients enrolled in specialized rare disease research studies. The data, consented for broad research use, are harmonized and analyzed with CRDC-supported variant interpretation tools.

Arthroscopic Partial Repair of Large to Massive Rotator Cuff Tears Shows Clinical Outcomes and Survivorship at Minimum 10-Year Follow-Up Comparable to Those of Arthroscopic Complete Repair.

Purpose: To compare the survival rate (revision surgery) and clinical and radiologic outcomes of arthroscopic partial versus complete repair for large to massive rotator cuff tears over a minimum 10-year follow-up period.

Methods: We conducted a retrospective analysis of patients who underwent arthroscopic partial or complete repair of large to massive rotator cuff tears between 2008 and 2013, with minimum 10-year follow-up. Functional outcomes were measured using the visual analog scale pain score, Subjective Shoulder Value, American Shoulder and Elbow Surgeons score, University of California, Los Angeles shoulder score, and passive range of motion preoperatively and at the last follow-up.

MIMIC-BP: A curated dataset for blood pressure estimation.

Blood pressure (BP) is one of the most prominent indicators of potential cardiovascular disorders. Traditionally, BP measurement relies on inflatable cuffs, which is inconvenient and limit the acquisition of such important health-related information in general population. Based on large amounts of well-collected and annotated data, deep-learning approaches present a generalization potential that arose as an alternative to enable more pervasive approaches.

Simultaneous Analysis of 504 Pesticide Multiresidues in Crops Using UHPLC-QTOF at MS and MS Levels.

A robust analytical method was developed for the simultaneous detection of 504 pesticide multiresidues in various crops using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-QTOF). The method integrates both MS and MS levels through sequential window acquisition of all theoretical mass spectra (SWATH) analysis, allowing for accurate mass measurements and the construction of a spectral library to enhance pesticide residue identification. An evaluation of the method was carried out according to international standards, including the FAO guidelines and SANTE/11312/2021.

Device-Measured 24-Hour Movement Behaviors and Blood Pressure: A 6-Part Compositional Individual Participant Data Analysis in the ProPASS Consortium.

Background: Blood pressure (BP)-lowering effects of structured exercise are well-established. Effects of 24-hour movement behaviors captured in free-living settings have received less attention. This cross-sectional study investigated associations between a 24-hour behavior composition comprising 6 parts (sleeping, sedentary behavior, standing, slow walking, fast walking, and combined exercise-like activity [eg, running and cycling]) and systolic BP (SBP) and diastolic BP (DBP).

Malformations of Cortical Development: Updated Imaging Review.

Malformations of cortical development (MCD) are structural anomalies that disrupt the normal process of cortical development. Patients with these anomalies frequently present with seizures, developmental delay, neurologic deficits, and cognitive impairment, resulting in a wide spectrum of neurologic outcomes. The severity and type of malformation, in addition to the genetic pathways of brain development involved, contribute to the observed variability.

Principles of paralog-specific targeted protein degradation engaging the C-degron E3 KLHDC2.

PROTAC® (proteolysis-targeting chimera) molecules induce proximity between an E3 ligase and protein-of-interest (POI) to target the POI for ubiquitin-mediated degradation. Cooperative E3-PROTAC-POI complexes have potential to achieve neo-substrate selectivity beyond that established by POI binding to the ligand alone. Here, we extend the collection of ubiquitin ligases employable for cooperative ternary complex formation to include the C-degron E3 KLHDC2.

Expression, purification and characterization of non-heme iron-dependent mono-oxygenase OzmD in oxazinomycin biosynthesis.

Oxazinomycin is a C-nucleoside natural product characterized by a 1,3-oxazine ring linked to ribose via a C-C glycosidic bond. Construction of the 1,3-oxazine ring depends on the activity of OzmD, which is a mononuclear non-heme iron-dependent enzyme from a family of enzymes that contain a domain of unknown function (DUF) 4243. OzmD catalyzes an unusual oxidative ring rearrangement of a pyridine derivative that releases cyanide as a by-product in the final stage of oxazinomycin biosynthesis.

Progression of Heart Failure in People with Type 2 Diabetes in Germany: An Analysis Using German Health Insurance Claims Data.

Individuals with type 2 diabetes (T2D) show high risk of heart failure (HF). Left ventricular ejection fraction is a major factor for disease progression. In Germany, no recent longitudinal data are available.

Small-molecule GSDMD agonism in tumors stimulates antitumor immunity without toxicity.

Gasdermin-mediated inflammatory cell death (pyroptosis) can activate protective immunity in immunologically cold tumors. Here, we performed a high-throughput screen for compounds that could activate gasdermin D (GSDMD), which is expressed widely in tumors. We identified 6,7-dichloro-2-methylsulfonyl-3-N-tert-butylaminoquinoxaline (DMB) as a direct and selective GSDMD agonist that activates GSDMD pore formation and pyroptosis without cleaving GSDMD.

MRI Predicts Residual Disease and Outcomes in Watch-and-Wait Patients with Rectal Cancer.

Background MRI plays a crucial role in restaging locally advanced rectal cancer treated with total neoadjuvant therapy (TNT); however, prospective studies have not evaluated its ability to accurately select patients for nonoperative management. Purpose To evaluate the ability of restaging MRI to predict oncologic outcomes and identify imaging features associated with residual disease (RD) after TNT. Materials and Methods This was a secondary analysis of the Organ Preservation in Rectal Adenocarcinoma (OPRA) trial, which randomized participants from April 2014 to March 2020 with stages II or III rectal adenocarcinoma to undergo either induction or consolidation TNT.

The Improving Effects of Probiotic-Added Pollen Substitute Diets on the Gut Microbiota and Individual Health of Honey Bee ( L.).

Honey bee ( L.) health is crucial for honey bee products and effective pollination, and it is closely associated with gut bacteria. Various factors such as reduced habitat, temperature, disease, and diet affect the health of honey bees by disturbing the homeostasis of the gut microbiota.

Higher Risk of Mental Illness in Patients With Diagnosed and Untreated Unruptured Intracranial Aneurysm: Findings From a Nationwide Cohort Study.

Background: We aimed to investigate the association between a diagnosis of untreated unruptured intracranial aneurysms (UIAs) and the development of mental illness.

Methods: This retrospective, propensity-score-matched cohort study was based on the nationwide South Korean database. The UIA diagnosis group included participants newly diagnosed with UIA between 2011 and 2019.

Incidence and Progression of Diabetic Retinopathy After Cataract Surgery: A Systematic Review and Meta-Analysis.

Purpose: The impact of cataract surgery on diabetic retinopathy (DR) in patients with diabetes mellitus (DM) remains uncertain. This study aimed to investigate the incidence and progression of DR in patients with DM who underwent cataract surgery.

Design: Meta-analysis.

Trimethylamine -Oxide and Related Gut Microbe-Derived Metabolites and Incident Heart Failure Development in Community-Based Populations.

Background: Growing evidence indicates that trimethylamine -oxide, a gut microbial metabolite of dietary choline and carnitine, promotes both cardiovascular disease and chronic kidney disease risk. It remains unclear how circulating concentrations of trimethylamine -oxide and its related dietary and gut microbe-derived metabolites (choline, betaine, carnitine, γ-butyrobetaine, and crotonobetaine) affect incident heart failure (HF).

Methods: We evaluated 11 768 participants from the Cardiovascular Health Study and the Multi-Ethnic Study of Atherosclerosis with serial measures of metabolites.