Analytical Quality Evaluation of the Tox21 Compound Library.

The analytical quality of compounds subjected to high-throughput screening (HTS) impacts accurate interpretation of assay results, with poor quality samples potentially leading to false negatives or positives. The Tox21 "10K" library consists of over 8900 unique compounds, spanning a diverse landscape of environmental and pharmaceutical chemicals, posing opportunities and challenges for analytical quality control (QC) determinations. Tox21 sample plates stored in DMSO at ambient conditions for 0 (T0) and/or 4 months (T4), totaling more than 13K unique sample identifiers (Tox21 IDs), were subjected to various analyses, including liquid and gas chromatography mass spectrometry (LC-MS, GC-MS) and nuclear magnetic resonance (NMR).

Factors Associated with Persisting Post-Concussion Symptoms Among Collegiate Athletes and Military Cadets: Findings from the NCAA-DoD CARE Consortium.

Background: Persisting post-concussion symptoms (PPCS) is a condition characterized by prolonged recovery from a mild traumatic brain injury (mTBI) and compromised quality of life. Previous literature, on the basis of small sample sizes, concludes that there are several risk factors for the development of PPCS.

Objective: We seek to identify protective and risk factors for developing slow recovery or persisting post-concussion symptoms (PPCS) by analyzing medical history, contact sport level, setting, and the Sport Concussion Assessment Tool (SCAT) and Brief Symptom Inventory (BSI-18) assessments at baseline and post-injury.

Fusion Technologies for Image-Guided Robotic Interventions.

An image guided robot only becomes fully useful with integrated software leveraging image fusion. Image fusion is the process of registering and superimposing imaging data in the same coordinate space and can be helpful to image-guided robotic interventions. Effective percutaneous robotic procedures can utilize real-time image guidance and navigation which are powered by fusion technologies.

Endometriosis and autoimmunity.

Endometriosis is a female-specific chronic condition that affects 1 in 10 women and other individuals with a uterus worldwide with common symptoms that include pelvic pain and infertility. Reliable and effective non-invasive biomarkers for endometriosis do not exist, and therefore currently a diagnosis of endometriosis requires direct visualization of lesions at surgery. Similarly, few safe and effective management strategies exist for endometriosis, with hormonal interventions and surgery only providing temporary symptom control.

County socioeconomic status and premature mortality from cancer in the United States.

Introduction: There are consistent data demonstrating socioeconomic status (SES) is associated with cancer survivorship among older adults, but research on the relationship between area-level SES and risk of premature mortality from cancer remains not well understood. This study investigated the association between county-level SES and premature mortality from cancer.

Methods: Demographic characteristics and causes of death were ascertained from the national death certificate data for years 2016-2020.

How Should Clinicians Discuss Deprescribing with Caregivers of Older Adults Living with Dementia? A Qualitative Study.

Background: Preventive medications are potential targets for deprescribing in older adults with dementia as goals of care change from preventive to palliative. Yet, prescribers lack communication guidance to address deprescribing.

Objective: Using bisphosphonates as a case example, we sought to characterize and compare communication preferences of prescribers and family/informal caregivers regarding deprescribing.

Compensatory Swallowing Strategies Recommended in Oncology Practice: Practice Patterns and Relationship to Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) Grades.

Compensatory swallow strategies are recommended to improve swallow safety and efficiency; however, there is limited evidence on use in specific populations or their relationship to swallow study results. We sought to describe/explore strategy recommendations in an oncology practice and their relationship to Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) grades as a marker of clinical utility of the tool. This is a sub-study of a STARI-guided retrospective implementation evaluation at a single comprehensive cancer center.

Evolving Paradigms in the Treatment of Oligometastatic Pancreatic Ductal Adenocarcinoma.

Multiple randomized trials have suggested that the addition of comprehensive metastasis-directed therapy to best systemic therapy improves disease control and survival among patients with oligometastatic disease, even for histologies with a high propensity for rapid spread. Here, we review the growing literature supporting the oligometastatic paradigm in pancreatic ductal adenocarcinoma. We summarize key details from nascent institutional series and reflect on the recently reported phase II randomized EXTEND trial.

Longitudinal investigation of neurobiological changes across pregnancy.

Pregnancy is a period of profound biological transformation. However, we know remarkably little about pregnancy-related brain changes. To address this gap, we chart longitudinal changes in brain structure during pregnancy and explore potential mechanisms driving these changes.

Incomplete human reference genomes can drive false sex biases and expose patient-identifying information in metagenomic data.

As next-generation sequencing technologies produce deeper genome coverages at lower costs, there is a critical need for reliable computational host DNA removal in metagenomic data. We find that insufficient host filtration using prior human genome references can introduce false sex biases and inadvertently permit flow-through of host-specific DNA during bioinformatic analyses, which could be exploited for individual identification. To address these issues, we introduce and benchmark three host filtration methods of varying throughput, with concomitant applications across low biomass samples such as skin and high microbial biomass datasets including fecal samples.

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.

Mental health in children with and without ADHD: the role of physical activity and parental nativity.

Background: Physical activity (PA) can improve mental health, including anxiety/depression, in individuals with attention-deficit/hyperactivity disorder (ADHD) with minimal side effects, unlike pharmacotherapy that can result in significant side effects. However, the influence of PA on mental health among children with ADHD is understudied. Also, immigrants tend to have better mental health, but the influence of parental nativity on children's mental health is unknown.

A simple and highly efficient protocol for C-labeling of plant cell wall for structural and quantitative analyses via solid-state nuclear magnetic resonance.

Background: Plant cell walls are made of a complex network of interacting polymers that play a critical role in plant development and responses to environmental changes. Thus, improving plant biomass and fitness requires the elucidation of the structural organization of plant cell walls in their native environment. The C-based multi-dimensional solid-state nuclear magnetic resonance (ssNMR) has been instrumental in revealing the structural information of plant cell walls through 2D and 3D correlation spectral analyses.

Quantification and prediction of human fetal (-)-Δ-tetrahydrocannabinol/(±)-11-OH-Δ-tetrahydrocannabinol exposure during pregnancy to inform fetal cannabis toxicity.

Prenatal cannabis use is associated with neurodevelopmental deficits, likely due to exposure to the psychoactive cannabinoid, (-)-Δ-tetrahydrocannabinol, and its active metabolite, (±)-11-OH-Δ-tetrahydrocannabinol. To determine causality, preclinical studies mimicking human fetal cannabinoid exposure must be conducted. Here we show cannabinoid concentrations across gestation in maternal plasma and paired fetal tissues in trimester 1 and 2 and maternal plasma and fetal umbilical venous plasma in trimester 3.

The 2024 American Association for Thoracic Surgery expert consensus document: Current standards in donor lung procurement and preservation.

Background: Donor lung procurement and preservation is critical for lung transplantation success. Unfortunately, the large variability in techniques impacts organ utilization rates and transplantation outcomes. Compounding this variation, recent developments in cold static preservation and new technological advances with machine perfusion have increased the complexity of the procedure.

Functional capacity at rehabilitation discharge predicts physical activity characteristics twenty-four weeks later for people with total knee arthroplasty: a secondary analysis of a randomized controlled trial.

Objective: To determine the association between performance-based and patient-reported functional capacity at the conclusion of 12-week rehabilitation with average daily step counts and peak walking cadence 38 weeks following total knee arthroplasty (TKA).

Design: Secondary analysis of an RCT.

Setting: Veterans Affairs Medical Center.

Long-term hemodynamic responses and reverse remodeling after pharmacotherapy in HFpEF versus HFrEF: a systematic review and meta-analysis.

The acute response to therapeutic afterload reduction differs between heart failure with preserved (HFpEF) versus reduced ejection fraction (HFrEF), with larger left ventricular (LV) stroke work augmentation in HFrEF compared to HFpEF. This may (partially) explain the neutral effect of HFrEF-medication in HFpEF. It is unclear whether such differences in hemodynamic response persist and/or differentially trigger reverse remodeling in case of long-term afterload reduction.

Light-Triggered Protease-Mediated Release of Actin-Bound Cargo from Synthetic Cells.

Synthetic cells offer a versatile platform for addressing biomedical and environmental challenges, due to their modular design and capability to mimic cellular processes such as biosensing, intercellular communication, and metabolism. Constructing synthetic cells capable of stimuli-responsive secretion is vital for applications in targeted drug delivery and biosensor development. Previous attempts at engineering secretion for synthetic cells have been confined to non-specific cargo release via membrane pores, limiting the spatiotemporal precision and specificity necessary for selective secretion.

Functional variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are associated with increased risk of colorectal cancer.

Background: Individuals with cystic fibrosis (CF; a recessive disorder) have an increased risk of colorectal cancer (CRC). Evidence suggests individuals with a single CFTR variant may also have increased CRC risk.

Methods: Using population-based studies (GECCO, CORECT, CCFR, and ARIC; 53 785 CRC cases and 58 010 controls), we tested for an association between the most common CFTR variant (Phe508del) and CRC risk.

Enriched phenotypes in rare variant carriers suggest pathogenic mechanisms in rare disease patients.

Background: The mechanistic pathways that give rise to the extreme symptoms exhibited by rare disease patients are complex, heterogeneous, and difficult to discern. Understanding these mechanisms is critical for developing treatments that address the underlying causes of diseases rather than merely the presenting symptoms. Moreover, the same dysfunctional series of interrelated symptoms implicated in rare recessive diseases may also lead to milder and potentially preventable symptoms in carriers in the general population.

Selective deficiency of mitochondrial respiratory complex I subunits Ndufs4/6 causes tumor immunogenicity.

Cancer cells frequently rewire their metabolism to support proliferation and evade immune surveillance, but little is known about metabolic targets that could increase immune surveillance. Here we show a specific means of mitochondrial respiratory complex I (CI) inhibition that improves tumor immunogenicity and sensitivity to immune checkpoint blockade (ICB). Targeted genetic deletion of either Ndufs4 or Ndufs6, but not other CI subunits, induces an immune-dependent growth attenuation in melanoma and breast cancer models.

Defective homologous recombination and genomic instability predict increased responsiveness to carbon ion radiotherapy in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is notably resistant to conventional chemotherapy and radiation treatment. However, clinical trials indicate that carbon ion radiotherapy (CIRT) with concurrent gemcitabine is effective for unresectable locally advanced PDAC. This study aimed to identify patient characteristics predictive of CIRT response.

SAMHD1 shapes deoxynucleotide triphosphate homeostasis by interconnecting the depletion and biosynthesis of different dNTPs.

SAMHD1 is a dNTPase that impedes replication of HIV-1 in myeloid cells and resting T lymphocytes. Here we elucidate the substrate activation mechanism of SAMHD1, which involves dNTP binding at allosteric sites and transient tetramerization. Our findings reveal that tetramerization alone is insufficient to promote dNTP hydrolysis; instead, the activation mechanism requires an inactive tetrameric intermediate with partially occupied allosteric sites.