Enhanced Vitamin C Delivery: A Systematic Literature Review Assessing the Efficacy and Safety of Alternative Supplement Forms in Healthy Adults.

Vitamin C is an antioxidant and is essential for immune function and infection resistance. Supplementation is necessary when a sufficient amount of vitamin C is not obtained through the diet. Alternative formulations of vitamin C may enhance its bioavailability and retention over traditional ascorbic acid.

iDIA-QC: AI-empowered data-independent acquisition mass spectrometry-based quality control.

Quality control (QC) in mass spectrometry (MS)-based proteomics is mainly based on data-dependent acquisition (DDA) analysis of standard samples. Here, we collect 2754 files acquired by data independent acquisition (DIA) and paired 2638 DDA files from mouse liver digests using 21 mass spectrometers across nine laboratories over 31 months. Our data demonstrate that DIA-based LC-MS/MS-related consensus QC metrics exhibit higher sensitivity compared to DDA-based QC metrics in detecting changes in LC-MS status.

Transferrin Saturation, Serum Iron, and Ferritin in Heart Failure: Prognostic Significance and Proteomic Associations.

Background: Iron deficiency (ID) is currently defined as a serum ferritin level <100 or 100 to 299 ng/mL with transferrin saturation (TSAT) <20%. Serum ferritin and TSAT are currently used to define absolute and functional ID. However, individual markers of iron metabolism may be more informative than current arbitrary definitions of ID.

Population Pharmacokinetics of Epcoritamab Following Subcutaneous Administration in Relapsed or Refractory B Cell Non-Hodgkin Lymphoma.

Background And Objectives: Epcoritamab is a CD3xCD20 bispecific antibody approved for the treatment of adults with different types of relapsed or refractory (R/R) B cell non-Hodgkin lymphoma (B-NHL) after ≥ 2 lines of systemic therapy. Here we report the first results from a population pharmacokinetic model-based analysis using data from 2 phase 1/2 clinical trials (EPCORE NHL-1, NCT03625037 and EPCORE NHL-3, NCT04542824) evaluating epcoritamab in patients with R/R B-NHL.

Methods: Plasma concentration-time data included 6819 quantifiable pharmacokinetic samples from 327 patients with R/R B-NHL.

DNA methylation-based predictors of metabolic traits in Scottish and Singaporean cohorts.

Exploring the molecular correlates of metabolic health measures may identify their shared and unique biological processes and pathways. Molecular proxies of these traits may also provide a more objective approach to their measurement. Here, DNA methylation (DNAm) data were used in epigenome-wide association studies (EWASs) and for training epigenetic scores (EpiScores) of six metabolic traits: body mass index (BMI), body fat percentage, waist-hip ratio, and blood-based measures of glucose, high-density lipoprotein cholesterol, and total cholesterol in >17,000 volunteers from the Generation Scotland (GS) cohort.

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.

Use of Cannabis-Based Medical Products for Pediatric Health Conditions: A Systematic Review of the Recent Literature.

Introduction: Cannabis policy is rapidly changing in the USA and across the globe, with 24 states legalizing cannabis for adult use and 38 states making medical cannabis available for those with qualified conditions. Building on prior evidence, we reviewed the recently published literature (from the past 5 years) focused on the treatment effects of naturally derived medical cannabis products within the pediatric population.

Methods: We conducted a systematic literature review of three electronic databases using MeSH terms and free-text.

Surveillance, Epidemiology, and End Results Data Show Increasing Rates of Distant-Stage Breast Cancer at Presentation in U.S. Women.

Background The incidence of distant-stage (metastatic) breast cancer at initial presentation has increased significantly in U.S. women under 40 years of age, but no clear trend in older women has been reported.

Leveraging a Separation of States Method for Relative Binding Free Energy Calculations in Systems with Trapped Waters.

Methods for calculating the relative binding free energy (RBFE) between ligands to a target protein are gaining importance in the structure-based drug discovery domain, especially as methodological advances and automation improve accuracy and ease of use. In an RBFE calculation, the difference between the binding affinities of two ligands to a protein is calculated by transforming one ligand into another, in the protein-ligand complex, and in solvent. Alchemical binding free energy calculations are often used for such ligand transformations.

Tumor-derived cyclooxygenase-2 fuels hypothalamic inflammation.

Hypothalamic inflammation often coincides with cancer and cachexia-anorexia. Prior work established the significance of tumor-derived inflammatory factors in triggering hypothalamic inflammation, yet the precise mechanisms remained elusive. Here, we demonstrate that prostaglandin E2 (PGE2), produced in the tumor via cyclooxygenase-2 (COX-2), plays a pivotal role in this context.

Optimizing Anti-Myelin-Associated Glycoprotein and IgM-Gammopathy Testing for Neuropathy Treatment Evaluation.

Background And Objectives: Patients with typical anti-myelin-associated glycoprotein (anti-MAG) neuropathy have IgM-gammopathy, mimic distal chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and are treatment resistant. Anti-MAG patients go unrecognized when IgM-gammopathy is undetected or with atypical phenotypes. We investigated an optimal anti-MAG titration cutoff for excluding CIDP and the impact of IgM-gammopathy detection on neuropathy treatment evaluation without anti-MAG antibodies.

Development of an Automated Triage System for Longstanding Dizzy Patients Using Artificial Intelligence.

Objective: To report the first steps of a project to automate and optimize scheduling of multidisciplinary consultations for patients with longstanding dizziness utilizing artificial intelligence.

Study Design: Retrospective case review.

Setting: Quaternary referral center.

Arthroscopic Primary Repair of Proximally Based Anterior Cruciate Ligament Tear With Augmentation and All-Epiphyseal Fixation.

Arthroscopic anterior cruciate ligament (ACL) reconstruction has been the gold standard of care for ACL injuries for many years. Recently, there has been growing literature and interest in arthroscopic primary ACL repair in select patients with predominantly proximally based ACL tears. This Technical Note demonstrates a surgical technique that offers an efficient minimally invasive and physeal-sparing anatomic ACL repair with all-inside internal brace augmentation that in the short term has offered good results for our patients.

Intact NOX2 in T Cells Mediates Pregnancy-Induced Renal Damage in Dahl SS Rats.

Background: Hypertensive disorders of pregnancy are associated with increased risk for cardiovascular disease, renal disease, and mortality. While the exact mechanisms remain unclear, T cells and reactive oxygen species have been implicated in its pathogenesis. We utilized Dahl salt-sensitive (SS), SS (Dahl SS CD247 knockout rat; lacking T cells), and SS (Dahl SS p67 [NOX2 (NADPH [nitcotinamide adenine dinucleotide phosphate] oxidase 2)] knockout rat; lacking NOX2) rats to investigate these mechanisms in primigravida and multigravida states.

DNAm scores for serum GDF15 and NT-proBNP levels associate with a range of traits affecting the body and brain.

Background: Plasma growth differentiation factor 15 (GDF15) and N-terminal proB-type natriuretic peptide (NT-proBNP) are cardiovascular biomarkers that associate with a range of diseases. Epigenetic scores (EpiScores) for GDF15 and NT-proBNP may provide new routes for risk stratification.

Results: In the Generation Scotland cohort (N ≥ 16,963), GDF15 levels were associated with incident dementia, ischaemic stroke and type 2 diabetes, whereas NT-proBNP levels were associated with incident ischaemic heart disease, ischaemic stroke and type 2 diabetes (all P < 0.

Progression independent of relapse activity can be predicted by passively acquired tapping speed through a smartphone for 1 month: A prospective study.

Background: Tapping speed (TS) correlates with baseline disability scales in people with multiple sclerosis (pwMS).

Objective: The study aimed to address if progression independent of relapse activity (PIRA) could be predicted by first-month measurement of TS.

Methods: Prospective study including pwMS in one referral MS center.

Association Between False-Positive Results and Return to Screening Mammography in the Breast Cancer Surveillance Consortium Cohort.

Background: False-positive results on screening mammography may affect women's willingness to return for future screening.

Objective: To evaluate the association between screening mammography results and the probability of subsequent screening.

Design: Cohort study.

High Survival Rate and Satisfaction at More Than 11-Year Follow-Up After Hip Arthroscopy for Femoroacetabular Impingement Syndrome: Impact of Preoperative Functional Scores, Osteoarthritis, and Chondrolabral Junction Damage on Failure.

Purpose: To investigate the survival and durability of clinical improvements after hip arthroscopy (HA) for femoroacetabular impingement syndrome (FAIS) at a minimum of 10-year follow-up.

Methods: Data from patients who underwent HA for FAIS between March 2003 and May 2012 were collected and retrospectively reviewed. Patients who underwent evaluation at a minimum 10-year follow-up, assessed according to the Hip Outcome Score (HOS)-Activities of Daily Living, HOS-Sport-Specific Subscale, and Non-arthritic Hip Score, were included.

Androgen receptor pathway inhibitors and taxanes in metastatic prostate cancer: an outcome-adaptive randomized platform trial.

ProBio is the first outcome-adaptive platform trial in prostate cancer utilizing a Bayesian framework to evaluate efficacy within predefined biomarker signatures across systemic treatments. Prospective circulating tumor DNA and germline DNA analysis was performed in patients with metastatic castration-resistant prostate cancer before randomization to androgen receptor pathway inhibitors (ARPIs), taxanes or a physician's choice control arm. The primary endpoint was the time to no longer clinically benefitting (NLCB).

Performance of Supplemental US Screening in Women with Dense Breasts and Varying Breast Cancer Risk: Results from the Breast Cancer Surveillance Consortium.

Background It is unclear whether breast US screening outcomes for women with dense breasts vary with levels of breast cancer risk. Purpose To evaluate US screening outcomes for female patients with dense breasts and different estimated breast cancer risk levels. Materials and Methods This retrospective observational study used data from US screening examinations in female patients with heterogeneously or extremely dense breasts conducted from January 2014 to October 2020 at 24 radiology facilities within three Breast Cancer Surveillance Consortium (BCSC) registries.

Benchmarking Quantum Mechanical Levels of Theory for Valence Parametrization in Force Fields.

A wide range of density functional methods and basis sets are available to derive the electronic structure and properties of molecules. Quantum mechanical calculations are too computationally intensive for routine simulation of molecules in the condensed phase, prompting the development of computationally efficient force fields based on quantum mechanical data. Parametrizing general force fields, which cover a vast chemical space, necessitates the generation of sizable quantum mechanical data sets with optimized geometries and torsion scans.

Development of covalent chemogenetic K channel activators.

K potassium channels regulate excitability by affecting cellular resting membrane potential in the brain, cardiovascular system, immune cells, and sensory organs. Despite their important roles in anesthesia, arrhythmia, pain, hypertension, sleep, and migraine, the ability to control K function remains limited. Here, we describe a chemogenetic strategy termed CATKLAMP (covalent activation of TREK family K channels to clamp membrane potential) that leverages the discovery of a K modulator pocket site that reacts with electrophile-bearing derivatives of a TREK subfamily small-molecule activator, ML335, to activate the channel irreversibly.