Characterizing substructure via mixture modeling in large-scale genetic summary statistics.

Genetic summary data are broadly accessible and highly useful, including for risk prediction, causal inference, fine mapping, and incorporation of external controls. However, collapsing individual-level data into summary data, such as allele frequencies, masks intra- and inter-sample heterogeneity, leading to confounding, reduced power, and bias. Ultimately, unaccounted-for substructure limits summary data usability, especially for understudied or admixed populations.

The sarcoma ring trial: a case-based analysis of inter-center agreement across 21 German-speaking sarcoma centers.

Purpose: The management of soft tissue sarcoma (STS) at reference centers with specialized multidisciplinary tumor boards (MTB) improves patient survival. The German Cancer Society (DKG) certifies sarcoma centers in German-speaking countries, promoting high standards of care. This study investigated the variability in treatment recommendations for localized STS across different German-speaking tertiary sarcoma centers.

Measurements of neurite extension and nucleokinesis in an iPSC-derived model system following microtubule perturbation.

In neurons, patterns of different microtubule types are essential for neurite extension and nucleokinesis. Cellular model systems such as rodent primary cultures and induced pluripotent stem cells (iPSC)-derived neurons have provided key insights into how these patterns are created and maintained through the action of microtubule-associated proteins, motor proteins, and regulatory enzymes. iPSC-derived models show tremendous promise but lack benchmarking and validation relative to rodent primary cultures.

CCAFE: Estimating Case and Control Allele Frequencies from GWAS Summary Statistics.

Methods involving summary statistics in genetics can be quite powerful but can be limited in utility. For instance, many post-hoc analyses of disease studies require case and control allele frequencies (AFs), which are not always published. We present two frameworks to derive case and control AFs from GWAS summary statistics using the odds ratio, case and control sample sizes, and either the total (case and control aggregated) AF or standard error (SE).

Clinical Interventions Following Escalations from a Continuous Respiratory Monitoring Service in Patients With Chronic Obstructive Pulmonary Disease.

Background: Continuous respiratory monitoring can support integrated care for chronic obstructive pulmonary disease (COPD) patients, by coupling them with remote clinical personnel who triage patients in coordination with their health care providers. When deploying such services, there remains uncertainty surrounding outcomes when at-risk patients are proactively identified and escalated for provider evaluation. This study presents findings from a service deployed in a real-world COPD cohort by analyzing the clinical interventions made during in-person and telehealth pulmonary outpatient visits following remote escalations.

Unraveling the role of local ablative therapies for patients with metastatic soft tissue sarcoma - A retrospective multicenter study of the Bavarian university hospitals.

Background: Local ablative therapies (LAT) are increasingly used in patients with metastatic soft tissue sarcoma (STS), yet evidence-based standards are lacking. This study aimed to assess the impact of LAT on survival of metastatic STS patients and to identify prognostic factors.

Methods: In this retrospective multicenter study, 246 STS patients with metastatic disease who underwent LAT on tumor board recommendation between 2017 and 2021 were analyzed.

Optogenetic control of kinesin-1, -2, -3 and dynein reveals their specific roles in vesicular transport.

Each cargo in a cell employs a unique set of motor proteins for its transport. To dissect the roles of each type of motor, we developed optogenetic inhibitors of endogenous kinesin-1, -2, -3 and dynein motors and examined their effect on the transport of early endosomes, late endosomes, and lysosomes. While kinesin-1, -3, and dynein transport vesicles at all stages of endocytosis, kinesin-2 primarily drives late endosomes and lysosomes.

Quantifying abnormal alveolar microstructure in cystic fibrosis lung disease via hyperpolarized Xe diffusion MRI.

Rationale: Cystic Fibrosis (CF) progresses through recurrent infection and inflammation, causing permanent lung function loss and airway remodeling. CT scans reveal abnormally low-density lung parenchyma in CF, but its microstructural nature remains insufficiently explored due to clinical CT limitations. To this end, diffusion-weighted Xe MRI is a non-invasive and validated measure of lung microstructure.

Pulsed electric field effect on acrylamide reduction and quality attributes of continuous-style Lamoka potato chips.

Potato chips are a popular snack, well-liked because of their texture-flavor combination. Potato chips are made by frying slices of potato in vegetable oil to achieve a crispy texture. Frying potato slices initiates the Maillard reaction, resulting in chemical changes that enhance taste, color, and texture, but also undesired acrylamides, which are suspected carcinogens.

Characterizing substructure via mixture modeling in large-scale genetic summary statistics.

Genetic summary data are broadly accessible and highly useful including for risk prediction, causal inference, fine mapping, and incorporation of external controls. However, collapsing individual-level data into groups masks intra- and inter-sample heterogeneity, leading to confounding, reduced power, and bias. Ultimately, unaccounted substructure limits summary data usability, especially for understudied or admixed populations.

The types and numbers of kinesins and dyneins transporting endocytic cargoes modulate their motility and response to tau.

Organelles and vesicular cargoes are transported by teams of kinesin and dynein motors along microtubules. We isolated endocytic organelles from cells at different stages of maturation and reconstituted their motility along microtubules in vitro. We asked how the sets of motors transporting a cargo determine its motility and response to the microtubule-associated protein tau.

Continuous Flow with Reagent Injection on an Inlaid Microfluidic Platform Applied to Nitrite Determination.

A continuous flow with reagent injection method on a novel inlaid microfluidic platform for nitrite determination has been successfully developed. The significance of the high-frequency monitoring of nutrient fluctuations in marine environments is crucial for understanding our impacts on the ecosystem. Many in-situ systems face limitations in high-frequency data collection and have restricted deployment times due to high reagent consumption.

Zinc Supplementation Initiated Prior to or During Pregnancy Modestly Impacted Maternal Status and High Prevalence of Hypozincemia in Pregnancy and Lactation: The Women First Preconception Maternal Nutrition Trial.

Background: Data regarding effects of small-quantity-lipid-based nutrient supplements (SQ-LNS) on maternal serum zinc concentrations (SZC) in pregnancy and lactation are limited.

Objectives: The objectives of this study were to evaluate the effect of preconception compared with prenatal zinc supplementation (compared with control) on maternal SZC and hypozincemia during pregnancy and early lactation in women in low-resource settings, and assess associations with birth anthropometry.

Methods: From ∼100 women/arm at each of 3 sites (Guatemala, India, and Pakistan) of the Women First Preconception Maternal Nutrition trial, we compared SZC at 12- and 34-wk gestation (n = 651 and 838, respectively) and 3-mo postpartum (n = 742) in women randomly assigned to daily SQ-LNS containing 15 mg zinc from ≥3 mo before conception (preconception, arm 1), from ∼12 wk gestation through delivery (early pregnancy, arm 2) or not at all (control, arm 3).

Decades Delayed in Diagnosis: Hidradenitis Suppurativa and a Review of Barriers to Care.

We present a case of a 40-year-old female seen on the inpatient general surgery service in consultation for a suspected abdominal wall abscess or seroma. The history and examination were consistent with a diagnosis of hidradenitis suppurativa. The patient had a 25-year history of similar lesions present since her teenage years, not properly investigated and diagnosed, despite presenting with symptoms in multiple clinic and hospital settings since disease onset.

Cell surface β-lactamase recruitment: A facile selection to identify protein-protein interactions.

Protein-protein interactions (PPIs) are central to many cellular processes, and the identification of novel PPIs is a critical step in the discovery of protein therapeutics. Simple methods to identify naturally existing or laboratory evolved PPIs are therefore valuable research tools. We have developed a facile selection that links PPI-dependent β-lactamase recruitment on the surface of Escherichia coli with resistance to ampicillin.

mini-MED: study protocol for a randomized, multi-intervention, semi-controlled feeding trial of a Mediterranean-amplified vs. habitual Western dietary pattern for the evaluation of food-specific compounds and cardiometabolic health.

Background: Diet is among the most influential lifestyle factors impacting chronic disease risk. Nutrimetabolomics, the application of metabolomics to nutrition research, allows for the detection of food-specific compounds (FSCs) that can be used to connect dietary patterns, such as a Mediterranean-style (MED) diet, to health. This validation study is based upon analyses from a controlled feeding MED intervention, where our team identified FSCs from eight foods that can be detected in biospecimens after consumption and may therefore serve as food intake biomarkers.

Laboratory Evolution of Metalloid Reductase Substrate Recognition and Nanoparticle Product Size.

Glutathione reductase-like metalloid reductase (GRLMR) is an enzyme that reduces selenodiglutathione (GS-Se-SG), forming zerovalent Se nanoparticles (SeNPs). Error-prone polymerase chain reaction was used to create a library of ∼10,000 GRLMR variants. The library was expressed in BL21 in liquid culture with 50 mM of SeO present, under the hypothesis that the enzyme variants with improved GS-Se-SG reduction kinetics would emerge.

A Novel Acetone Sensor for Body Fluids.

Ketones are well-known biomarkers of fat oxidation produced in the liver as a result of lipolysis. These biomarkers include acetoacetic acid and β-hydroxybutyric acid in the blood/urine and acetone in our breath and skin. Monitoring ketone production in the body is essential for people who use caloric intake deficit to reduce body weight or use ketogenic diets for wellness or therapeutic treatments.

More than 30 Years of POSSUM: Are Scoring Systems Still Relevant Today for Colorectal Surgery?

Background: The Physiological and Operative Severity Score for the enUmeration of Mortality and Morbidity (POSSUM) weights the patient's individual health status and the extent of the surgical procedure to estimate the probability of postoperative complications and death of general surgery patients. The variations Portsmouth-POSSUM (P-POSSUM) and colorectal POSSUM (CR-POSSUM) were developed for estimating mortality in patients with low perioperative risk and for patients with colorectal carcinoma, respectively. The aim of the present study was to evaluate the significance of POSSUM, P-POSSUM, and CR-POSSUM in two independent colorectal cancer cohorts undergoing surgery, with an emphasis on laparoscopic procedures.

Salmon Food-Specific Compounds and Their Metabolites Increase in Human Plasma and Are Associated with Cardiometabolic Health Indicators Following a Mediterranean-Style Diet Intervention.

Background: Nutrimetabolomics allows for the comprehensive analysis of foods and human biospecimens to identify biomarkers of intake and begin to probe their associations with health. Salmon contains hundreds of compounds that may provide cardiometabolic benefits.

Objectives: We used untargeted metabolomics to identify salmon food-specific compounds (FSCs) and their predicted metabolites that were found in plasma after a salmon-containing Mediterranean-style (MED) diet intervention.

C3 glomerulopathy in a patient with a history of post-infectious glomerulonephritis.

Post-infectious glomerulonephritis (PIGN) is an immune complex mediated glomerular injury occurring because of an infection, most commonly with group A beta-hemolytic streptococcus in children. C3 glomerulopathy (C3G) is a distinct clinicopathological entity occurring secondary to dysregulation of alternate complement pathway encompassing both C3 glomerulonephritis (C3GN) and dense deposit disease (DDD). While most patients with PIGN attain complete remission with normalized complement levels by 6-8 weeks after presentation, patients with C3G continue to have hypocomplementemia with high rates of progressive kidney disease.