One size does not fit all: revising traditional paradigms for assessing accuracy of QSAR models used for virtual screening.

Traditional best practices for quantitative structure activity relationship (QSAR) modeling recommend dataset balancing and balanced accuracy (BA) as the key desired objective of model development. This study explores the value of the conventional norms in the context of using QSAR models for virtual screening of modern large and ultra-large chemical libraries. For this increasingly common task, we now recommend the use of models with the highest positive predictive value (PPV) built on imbalanced training sets as preferred virtual screening tools.

Two-year outcomes using fast-acting sub-perception therapy for spinal cord stimulation: results of a real-world multicenter study in the United States.

Background: Fast-acting Sub-perception Therapy (FAST) is a novel spinal cord stimulation (SCS) modality delivering paresthesia-free pain relief. Our study evaluated the longer-term, real-world impact of FAST on chronic pain.

Research Design And Methods: As part of a multicenter, real-world, consecutive case series, we retrospectively identified patients who used FAST-SCS and analyzed their data.

Why and how should we simulate platform trials? Learnings from EU-PEARL.

Background: Platform trials are innovative clinical trials governed by a master protocol that allows for the evaluation of multiple investigational treatments that enter and leave the trial over time. Interest in platform trials has been steadily increasing over the last decade. Due to their highly adaptive nature, platform trials provide sufficient flexibility to customize important trial design aspects to the requirements of both the specific disease under investigation and the different stakeholders.

The effects of admission hyperglycemia and diabetes mellitus on mechanical thrombectomy outcomes: A systematic review and meta-analysis.

Background: The impact of certain comorbidities on mechanical thrombectomy (MT) outcomes remains largely unexplored. Diabetes mellitus (DM) and admission hyperglycemia have been associated with poor clinical outcomes for patients treated with MT. In this study, we sought to investigate the effects of DM and admission hyperglycemia on MT outcomes.

Association Between Social Determinants of Health and Concussion Among High School Students in the United States.

We examined the association between social determinants of health and the likelihood of sustaining a concussion among adolescents. Participants in this cross-sectional study were 7164 high school students who completed the 2021 Adolescent Behaviors and Experiences Survey (52.7% girls; mean age = 16.

Intra-arterial lidocaine administration of lidocaine in middle meningeal artery for short-term treatment of subarachnoid hemorrhage-related headaches.

Background And Purpose: We report short- and intermediate-term effects on headaches with intra-arterial injection of lidocaine in the middle meningeal artery in patients with severe headaches associated with subarachnoid hemorrhage.

Methods: We treated seven patients with intra-arterial lidocaine in doses up to 50 mg in each middle meningeal artery via a microcatheter bilaterally (except in one patient). We recorded the maximum intensity of headache (graded by 11-point numeric rating scale) prior to procedure and every day for the next 10 days or discharge, whichever came first.

Impact of Treatment With Trifluridine/Tipiracil in Combination With Bevacizumab on Health-Related Quality of Life and Performance Status in Refractory Metastatic Colorectal Cancer: An Analysis of the Phase III SUNLIGHT Trial.

Background: The efficacy of trifluridine/tipiracil (FTD/TPI) + bevacizumab compared to FTD/TPI for treatment of refractory metastatic colorectal cancer (mCRC) was demonstrated in the SUNLIGHT trial. This analysis of SUNLIGHT investigated the impact of treatment with FTD/TPI + bevacizumab on patient quality of life (QoL) and Eastern Cooperative Oncology Group performance status (ECOG PS).

Methods: Questionnaires (EORTC QLQ-C30 and EQ-5D-5L) and ECOG PS assessments were conducted at baseline and on Day 1 of each treatment cycle.

Metabolomics signatures of serotonin reuptake inhibitor (escitalopram), serotonin norepinephrine reuptake inhibitor (duloxetine) and cognitive-behavioral therapy on key neurotransmitter pathways in major depressive disorder.

Metabolomics provides powerful tools that can inform about heterogeneity in disease and response to treatments. In this exploratory study, we employed an electrochemistry-based targeted metabolomics platform to assess the metabolic effects of three randomly-assigned treatments: escitalopram, duloxetine, and Cognitive-Behavioral Therapy (CBT) in 163 treatment-naïve outpatients with major depressive disorder. Serum samples from baseline and 12 weeks post-treatment were analyzed using targeted liquid chromatography-electrochemistry for metabolites related to tryptophan, tyrosine metabolism and related pathways.

Decoding the blueprint of receptor binding by filoviruses through large-scale binding assays and machine learning.

Evidence suggests that bats are important hosts of filoviruses, yet the specific species involved remain largely unidentified. Niemann-Pick C1 (NPC1) is an essential entry receptor, with amino acid variations influencing viral susceptibility and species-specific tropism. Herein, we conducted combinatorial binding studies with seven filovirus glycoproteins (GPs) and NPC1 orthologs from 81 bat species.

CDK2 activity crosstalk on the ERK kinase translocation reporter can be resolved computationally.

The mitogen-activated protein kinase (MAPK) pathway integrates growth factor signaling through extracellular signal-regulated kinase (ERK) to control cell proliferation. To study ERK dynamics, many researchers use an ERK activity kinase translocation reporter (KTR). Our study reveals that this ERK KTR also partially senses cyclin-dependent kinase 2 (CDK2) activity, making it appear as if ERK activity rises as cells progress through the cell cycle.

Pain severity contributes to worse outcomes in opioid use disorder recovery than pain status.

Background: Opioid use disorder (OUD) continues to pose a significant challenge to public health in the United States. Chronic pain and OUD are highly comorbid conditions, yet few studies have examined the relative associations of pain status and severity toward multidimensional OUD recovery outcomes (e.g.

Community-Partnered Training in Trauma-Informed Primary Care for Patients Experiencing Reentry From Incarceration: A Pilot Training Study.

Introduction/objectives: Patients returning to the community from incarceration (ie, reentry) are at heightened risk of experiencing trauma when interacting with the healthcare system. Healthcare professionals may not recognize patients' trauma reactions or know how to effectively respond. This paper describes the development and pilot evaluation of a single-session training to prepare primary care teams to deliver trauma-informed care (TIC) to patients experiencing reentry.

Olaparib as treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency: Phase 2 LIGHT study final overall survival analysis.

Background: LIGHT (oLaparib In HRD-Grouped Tumor types; NCT02983799) prospectively evaluated olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer (PSROC) assigned to cohorts by known BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD-positive non-BRCAm, and HRD-negative. At the primary analysis, olaparib treatment demonstrated activity across all cohorts, with greatest efficacy in terms of objective response rate and progression-free survival observed in the g/sBRCAm cohorts. The authors report final overall survival (OS).

Rheumatic Heart Disease Burden in Africa and the Need to Build Robust Infrastructure.

Rheumatic heart disease (RHD) is an important public health problem in Africa. Mapping the epidemiology of RHD involves elucidating its geographic distribution, temporal trends, and demographic characteristics. The prevalence of RHD in Africa varies widely, with estimates ranging from 2.

PREVENT and Pooled Cohort Equations in Mortality Risk Prediction: National Health and Nutrition Examination Survey.

Background: The Predicting Risk of CVD Events (PREVENT) equations were developed to address limitations of the Pooled Cohort Equations (PCEs) in predicting atherosclerotic cardiovascular disease (ASCVD) risk. The comparative effectiveness of the PREVENT equations versus the PCEs in predicting mortality risk remains unknown.

Objectives: The purpose of this study was to compare the risk discrimination value of the PREVENT equations with the PCEs for predicting mortality.

Acylglycerol kinase inhibits macrophage anti-tumor activity via limiting mtDNA release and cGAS-STING-type I IFN response.

: Tumor associated macrophages (TAMs) are critical components in regulating the immune statuses of the tumor microenvironments. Although TAM has been intensively studied, it is unclear how mitochondrial proteins such as AGK regulate the TAMs' function. : We investigated the AGK function in TAMs using macrophage-specific deficient mice with B16 and LLC syngeneic tumor models.

Transcriptomic Analysis Identifies Disease Severity and Therapeutic Response in Psoriasis.

Abnormalities in gene expression profiles characterize patients with inflammatory skin diseases, including psoriasis, and changes may reflect the action of specific therapeutic agents. To examine this, gene expression analysis of psoriatic skin was assessed by Gene Set Variation Analysis using informative gene modules, and longitudinal data were analyzed to assess the impact of various treatments. Ridge penalized logistic regression was employed to derive a transcriptomic score.

Impact of Sports on Female Growth and Pubertal Development: A Cohort Study.

Introduction The participation of women in sports is increasing, and the rising training demands may impact growth and pubertal development. High-intensity sports are often linked to delayed growth and bone maturation due to energy deficits and intense regimens. These factors may increase the risk of injury and musculoskeletal issues.

Design concepts for advanced-technology intraocular lenses [Invited].

An intraocular lens (IOL) replaces the natural crystalline lens during cataract surgery, and although the vast majority of implants have simple optics, "advanced technology" IOLs have multifocal and extended depth of focus (EDOF) properties. Optical concepts are evaluated here, with image contrast, focal range, and unwanted visual phenomena being the primary concerns. Visual phenomena with earlier bifocal diffractive lenses led to alternative diffractive designs (trifocals, etc.

Fine particulate matter from burning oil and gas and associated neurological symptoms among Deepwater Horizon oil spill cleanup workers.

Burning and flaring of oil and gas following the 2010 Deepwater Horizon (DWH) oil spill generated high airborne concentrations of fine particulate matter (PM). Neurological effects of PM have been previously reported, but this relationship has received limited attention in the context of oil spills. We evaluated associations between burning-related PM and prevalence of self-reported neurological symptoms during, and 1-3 years after, the DWH disaster cleanup.

First-line pembrolizumab-axitinib versus sunitinib in metastatic RCC: subgroup analysis of patients enrolled in the phase 3 KEYNOTE-426 in Eastern Asia.

Background: The phase 3 open-label KEYNOTE-426 study demonstrated that first-line pembrolizumab plus axitinib improved overall survival (OS) and progression-free survival (PFS) versus sunitinib for metastatic renal cell carcinoma (mRCC) in a global population. This subgroup analysis investigated the efficacy and safety of pembrolizumab-axitinib versus sunitinib in patients enrolled in KEYNOTE-426 in East Asia (Japan, South Korea, and Taiwan).

Methods: Adults with clear cell mRCC were randomly assigned 1:1 to receive intravenous pembrolizumab 200 mg every 3 weeks with oral axitinib 5 mg twice daily or oral sunitinib 50 mg once daily (4 weeks on/2 weeks off).

A conceptual model for advanced/metastatic gastric or gastroesophageal junction cancer: a review of qualitative studies and results from patient interviews.

Background: Despite approvals of new first-line immunotherapies for advanced/metastatic gastric cancer/gastroesophageal junction cancer (aGC/GEJC), patients' median survival is around 14 months and their health-related quality of life (HRQoL) is affected by disease-related symptoms and treatment-related side effects. Using a targeted literature review (TLR) and patient interviews, this study identified disease- and treatment-related concepts that are important to patients with aGC/GEJC and their HRQoL.

Methods: A TLR was conducted to identify primary qualitative studies from 2018 to 2021 on patients' experiences with aGC/GEJC.

Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study.

In the MAIA study (median follow-up, 56.2 months), daratumumab plus lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival (PFS) and overall survival versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). In this post hoc analysis of clinically important subgroups in MAIA (median follow-up, 64.