Different PD-L1 Assays Reveal Distinct Immunobiology and Clinical Outcomes in Urothelial Cancer.

Testing for PD-L1 expression by immunohistochemistry (IHC) is used to predict immune checkpoint blockade (ICB) benefit but has performed inconsistently in urothelial cancer (UC) clinical trials. Different approaches are used for PD-L1 IHC. We analyzed paired PD-L1 IHC data on UC samples using the SP142 and 22C3 assays from the phase 3 IMvigor130 trial and found discordant findings summarized by four phenotypes: PD-L1 positive by both assays (PD-L1 double positive; PD-L1DP), PD-L1 positive by the SP142 assay only (SP142 single positive; SP142SP), PD-L1 positive by the 22C3 assay only (22C3 single positive; 22C3SP), and PD-L1 negative by both assays double negative (PD-L1 double negative; PD-L1DN).

A Threshold Technique Study to Understand Patient Preference for Smooth Versus Textured Breast Implants.

Background: Breast implant surfaces are categorized as smooth or textured. Compared with smooth implants, textured surface implants have a higher risk of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) but may have a lower risk of capsular contracture (CC). This study aimed to quantify whether survey respondents would be willing to accept a higher risk of BIA-ALCL in exchange for the potential reported benefits of textured breast implants.

Influence of forage-to-concentrate ratio on the effects of a radiata pine bark extract on methane production and fermentation using the rumen simulation technique.

Climate change and food safety standards have intensified research into plant-based compounds as alternatives to dietary supplements in animal feed. These compounds can reduce enteric methane (CH) emissions and the formation of ruminal ammonia. This study investigated the effects of radiata pine bark extract (PBE) supplementation on CH production, ruminal fermentation parameters, and nutrient disappearance using the rumen simulation technique in diets with different forage-to-concentrate (F:C) ratios.

Glutathione, Vitamin C, and Cysteine Use in Autistic Children With Disruptive Behavior: A Double-Blind, Placebo-Controlled Crossover Pilot Study.

Objective: Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social communication differences and restricted interests. One proposed biologic mechanism underlying ASD is oxidative stress, leading to the clinical use of glutathione based on anecdotal reports of improved behavior in autistic children. In this pilot study, we tested this observation using a randomized clinical trial format to collect preliminary data on glutathione safety and efficacy.

The bright and dark side of blue-enriched light on sleep and activity in older adults.

Low indoor light in urban housing can disrupt health and wellbeing, especially in older adults who experience reduced light sensitivity and sleep/circadian disruptions with natural aging. While controlled studies suggest that enhancing indoor lighting may alleviate the negative effects of reduced light sensitivity, evidence for this to be effective in the real world is lacking. This study investigates the effects of two light conditions on actigraphic rest-activity rhythms and subjective sleep in healthy older adults (≥ 60 years) living at home.

A novel approach to expedite evidence to impact in pre-eclampsia: co-developed policy labs in Zambia and Sierra Leone.

Pre-eclampsia is a leading cause of maternal and neonatal mortality; 30,000 pre-eclampsia-related maternal deaths occur annually, with 70% in Sub-Saharan Africa (SSA) and 16% in South Asia. We have shown that early, accurate detection of hypertension combined with planned early delivery in women with late preterm pre-eclampsia significantly reduces stillbirth and severe maternal hypertension. We describe co-development and delivery of policy labs, working with The Policy Institute (King's College London), and local stakeholders in Sierra Leone and Zambia, to expedite integration of new knowledge into pre-eclampsia care pathways, to improve care for women and babies with the worst outcomes.

Neurodevelopmental outcomes in children exposed in utero to dolutegravir- or efavirenz-based ART.

Objective: To examine the impact of in utero exposure to dolutegravir (DTG)- or efavirenz (EFV)-based antiretroviral treatment (ART) on child neurodevelopmental (ND) outcomes.

Design: Prospective cohort design, enrolling 3 cohorts of 2-year-olds: children HIV-negative born to mothers with HIV (CHEU) receiving either DTG-based or EFV-based 3-drug ART during pregnancy, and children born to mothers without HIV (CHUU).

Methods: Primary child ND outcomes were assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) and compared between cohorts using generalized estimating equation models adjusted for confounders.

Sustainable nanomaterials: the role of Cyrene in optimising carbon nanotubes dispersion and filtration efficiency.

This study focuses on the fabrication and characterisation of single-walled carbon nanotube (SWCNT) buckypapers and polyethersulfone (PES) flat-sheet membranes using Cyrene, aiming toevaluate its efficacy as a green solvent for these applications. Pristine SWCNTs were dispersed inCyrene without surfactants and compared to N-Methyl-2-pyrrolidone (NMP) dispersions. Buckypapers were fabricated from these dispersions and characterised using Scanning ElectronMicroscopy (SEM), Atomic Force Microscopy (AFM), and infrared spectroscopy.

Cost-Effectiveness of Breast Cancer Screening Using Digital Mammography in Canada.

Importance: Evolving breast cancer treatments have led to improved outcomes but carry a substantial financial burden. The association of treatment costs with the cost-effectiveness of screening mammography is unknown.

Objective: To determine the cost-effectiveness of population-based breast cancer screening in the context of current treatment standards.

Quorum sensing signals of the grapevine crown gall bacterium, sp. Rr2-17: use of inducible expression and polymeric resin to sequester acyl-homoserine lactones.

Background: A grapevine crown gall tumor strain, sp. strain Rr2-17 was previously reported to accumulate copious amounts of diverse quorum sensing signals during growth. Genome sequencing identified a single luxI homolog in strain Rr2-17, suggesting that it may encode for a AHL synthase with broad substrate range, pending functional validation.

Carbidopa and ZnCarbidopa Induce Reductive Stress in MDA-MB-231 Cells.

The redox imbalance, caused by depletion or generation of reactive oxygen species (ROS), is a key mechanism by which metal complexes exert anticancer effects. Carbidopa has shown the ability to inhibit the MDA-MB-231 cell line, a highly aggressive triple-negative human breast adenocarcinoma, by inducing reductive stress. The metal complex of carbidopa with zinc (ZnCarbi) was designed to modify carbidopa's structure and exhibited increased cytotoxicity against MDA-MB-231 cells.

Clinical and cost-effectiveness of first contact physiotherapy for musculoskeletal disorders in primary care: the FRONTIER, mixed method realist evaluation.

Background: First-contact physiotherapists assess and diagnose patients with musculoskeletal disorders, determining the best course of management without prior general practitioner consultation.

Objectives: The primary aim was to determine the clinical and cost-effectiveness of first-contact physiotherapists compared with general practitioner-led models of care.

Design: Mixed-method realist evaluation of effectiveness and costs, comprising three main phases: A United Kingdom-wide survey of first contact physiotherapists.

A liberalized diet does not improve caloric intake during neutropenia in patients undergoing hematopoietic stem cell transplants: A prospective randomized controlled trial.

Background: The neutropenic diet has been a long-standing approach to preventing infection in patients with hematopoietic stem cell transplants (HSCTs), although data on its efficacy are inconclusive and its restrictive nature might contribute to harm by reducing dietary intake in this patient population who typically experiences poor oral intake. The aim was to determine if a liberalized diet (LD), in comparison with a neutropenic hospital diet (ND), would improve energy intake and lessen weight loss during neutropenia in patients with HSCTs.

Methods: A randomized controlled trial was conducted in a single-center HSCT/hematologic malignancy unit.

Phase II Study of Defactinib (VS6063) in Patients With Tumors With Loss: Results From the NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol U.

Purpose: The NCI-MATCH trial assigned patients with solid tumors, lymphomas, or multiple myeloma to targeted therapies on the basis of identified genetic alterations from tumor biopsies. In preclinical models, ()-inactivated tumors display sensitivity to focal adhesion kinase (FAK) inhibition. The EAY131-U subprotocol evaluated the efficacy of defactinib, a FAK inhibitor, in patients with -altered tumors.

Glucocorticoid dosing and implications for vaccination: Evolution of global definitions.

Despite widespread adoption of "high-dose" glucocorticoid definitions across international immunisation guidelines (i.e., prednisone-equivalent dosing >20 mg/day, or >2 mg/kg/day in children), the rationale remains unclear.

Using Polarization to Increase Contrast of Water OH Raman Scattering Relative to Fluorescence of Dissolved Organic Matter.

Environmental fluorescence measurements sometimes use water Raman scattering as an internal standard to compensate for path length, lensing effects, and turbidity. Fluorescent dissolved organic matter (FDOM) in water may interfere strongly with the measurement of this reference. However, fluorescence in fluid solution is largely unpolarized, while the OH stretching Raman band of water is always strongly polarized.

Phase II Study of Sunitinib in Tumors With Mutations: Results From the NCI MATCH ECOG-ACRIN Trial (EAY131) Subprotocol V.

Purpose: The NCI-MATCH study is a tumor-agnostic platform trial enrolling patients to targeted therapies on the basis of genomic alterations. Subprotocol V investigated sunitinib in patients with tumors harboring - mutations.

Methods: EAY131-V, is an open-label, single-arm, phase II study.

A new wave of Mesoamerican bumblebees? Revising the weisi-complex to reject numts and pseudospecies (Apidae: Bombus).

COI-barcode-like sequences appear to show substantially more species diversity among Mesoamerican bumblebees than had been reported previously from morphological studies. Closer examination shows that some of this apparent diversity may be pseudospecies (groups falsely misinterpreted as separate species), often supported by paralogous 'numts' (nuclear copies of mitochondrial sequences). For the well-sampled weisi-complex, we seek to filter out pseudogenes in order to use the orthologous COI-barcode sequences for identifying estimates of evolutionary relationships and likely species' gene coalescents for candidate species.

Discovery of Gene Fusions in Driver-Negative Cancer Samples From the National Cancer Institute-Molecular Analysis for Therapy Choice Screening Cohort.

Purpose: The National Cancer Institute-Molecular Analysis for Therapy Choice (NCI-MATCH) trial was implemented to identify actionable genetic alterations across cancer types and enroll patients accordingly onto treatment arms, irrespective of tumor histology. Using multiplex polymerase chain reaction (PCR) next-generation sequencing, NCI-MATCH genotyped 5,540 patients, discovering gene fusions in 202/5,540 tumors (3.65%).

SHIV remission in macaques with early treatment initiation and ultra long-lasting antiviral activity.

Studies in SIV-infected macaques show that the virus reservoir is particularly refractory to conventional suppressive antiretroviral therapy (ART). We posit that optimized ART regimens designed to have robust penetration in tissue reservoirs and long-lasting antiviral activity may be advantageous for HIV or SIV remission. Here we treat macaques infected with RT-SHIV with oral emtricitabine/tenofovir alafenamide and long-acting cabotegravir/rilpivirine without (n = 4) or with (n = 4) the immune activator vesatolimod after the initial onset of viremia.

Diary- and actigraphy-estimated nighttime sleep during the perinatal period: A multimethod study.

Accurate estimation of perinatal sleep is important for informing future research and multigenerational health interventions. We compared diary- and actigraphy-estimated sleep parameters during pregnancy and postpartum. We informed our interpretation of these analyses with participants' feedback about these sleep estimation methods.