The dynamics of capillary flow in an open-channel system featuring trigger valves.

Trigger valves are fundamental features in capillary-driven microfluidic systems that stop fluid at an abrupt geometric expansion and release fluid when there is flow in an orthogonal channel connected to the valve. The concept was originally demonstrated in closed-channel capillary circuits. We show here that trigger valves can be successfully implemented in open channels.

The Cryo-EM structure of human CD163 bound to haptoglobin-hemoglobin reveals molecular mechanisms of hemoglobin scavenging.

CD163, a macrophage-specific receptor, plays a critical role in scavenging hemoglobin released during hemolysis, protecting against oxidative effects of heme iron. In the bloodstream, hemoglobin is bound by haptoglobin, leading to its immediate endocytosis by CD163. While haptoglobin's structure and function are well understood, CD163's structure and its interaction with the haptoglobin-hemoglobin complex have remained elusive.

Cerebellar-driven cortical dynamics can enable task acquisition, switching and consolidation.

The brain must maintain a stable world model while rapidly adapting to the environment, but the underlying mechanisms are not known. Here, we posit that cortico-cerebellar loops play a key role in this process. We introduce a computational model of cerebellar networks that learn to drive cortical networks with task-outcome predictions.

NOS inhibition sensitizes metaplastic breast cancer to PI3K inhibition and taxane therapy via c-JUN repression.

Metaplastic breast cancer (MpBC) is a highly chemoresistant subtype of breast cancer with no standardized therapy options. A clinical study in anthracycline-refractory MpBC patients suggested that nitric oxide synthase (NOS) inhibitor NG-monomethyl-l-arginine (L-NMMA) may augment anti-tumor efficacy of taxane. We report that NOS blockade potentiated response of human MpBC cell lines and tumors to phosphoinositide 3-kinase (PI3K) inhibitor alpelisib and taxane.

Intensification of future subsurface marine heatwaves in an eddy-resolving model.

A shift in depth range enables marine organisms to adapt to marine heatwaves (MHWs). Subsurface MHWs could limit this pathway, yet their response to climate warming remains unclear. Here, using an eddy-resolving Earth system model forced under a high emission scenario, we project a robust global increase in subsurface MHWs driven by rising subsurface mean temperatures and enhanced temperature variability.

PSCA-targeted BPX-601 CAR T cells with pharmacological activation by rimiducid in metastatic pancreatic and prostate cancer: a phase 1 dose escalation trial.

Here we report results of a phase 1 multi-institutional, open-label, dose-escalation trial (NCT02744287) of BPX-601, an investigational autologous PSCA-directed GoCAR-T® cell product containing an inducible MyD88/CD40 ON-switch responsive to the activating dimerizer rimiducid, in patients with metastatic pancreatic (mPDAC) or castration-resistant prostate cancer (mCRPC). Primary objectives were to evaluate safety and tolerability and determine the recommended phase 2 dose/schedule (RP2D). Secondary objectives included the assessment of efficacy and characterization of the pharmacokinetics of rimiducid.

Induced Chirality in QDs Using Thermoresponsive Elastin-like Polypeptides.

Circular dichroism (CD) spectroscopy has emerged as a potent tool for probing chiral small-molecule ligand exchange on natively achiral quantum dots (QDs). In this study, we report a novel approach to identifying QD-biomolecule interactions by inducing chirality in CdS QDs using thermoresponsive elastin-like polypeptides (ELPs) engineered with C-terminal cysteine residues. Our method is based on a versatile two-step ligand exchange process starting from monodisperse oleate-capped QDs in nonpolar media and proceeding through an easily accessed achiral glycine-capped QD intermediate.

Non-Cell-Based Extracorporeal Artificial Liver Systems: Historic Perspectives, Approaches and Mechanisms, Current Applications, and Challenges.

Background: Liver disease is a growing burden. Transplant organs are scarce. Extracorporeal liver support systems (ELSS) are a bridge to transplantation for eligible patients.

Integrating dynamical modeling and phylogeographic inference to characterize global influenza circulation.

Global seasonal influenza circulation involves a complex interplay between local (seasonality, demography, host immunity) and global factors (international mobility) shaping recurrent epidemic patterns. No studies so far have reconciled the two spatial levels, evaluating the coupling between national epidemics, considering heterogeneous coverage of epidemiological, and virological data, integrating different data sources. We propose a novel-combined approach based on a dynamical model of global influenza spread (GLEAM), integrating high-resolution demographic, and mobility data, and a generalized linear model of phylogeographic diffusion that accounts for time-varying migration rates.

Sunset Sign Due to Intraventricular Tension Pneumocephalus: A Key Clue to Evaluating Delayed Emergence After General Anesthesia.

Prompt emergence from general anesthesia is crucial after neurosurgical procedures, such as craniotomies, to facilitate timely neurological evaluation for identification of intraoperative complications. Delayed emergence can be caused by residual anesthetics, metabolic imbalances, and intracranial pathology, for which an eye examination can provide early diagnostic clues. The sunset sign (or setting sun sign), characterized by a downward deviation of the eyes, can be an early indicator of raised intracranial pressure (ICP) or midbrain compression, as is commonly observed in states of hydrocephalus or periaqueductal or tectal plate dysfunction.

Durvalumab and tremelimumab in patients with advanced rare cancer: a multi-centre, non-blinded, open-label phase II basket trial.

Background: Dual inhibition of cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed death ligand 1 (PD-L1) has been shown to be an effective treatment strategy in many cancers. We sought to determine the objective response rate of combination durvalumab (D) plus tremelimumab (TM) in parallel cohorts of patients with carefully selected rare cancer types in which these agents had not previously been evaluated in phase II trials and for which there was clinical or biological rationale for dual immune checkpoint inhibitor therapy to be active.

Methods: We designed a multi-centre, non-blinded, open-label phase II basket trial with each of the following 8 rare cancers considered a separate phase II trial: salivary carcinoma, carcinoma of unknown primary (CUP) with tumour infiltrating lymphocytes and/or expressing PD-L1, mucosal melanoma, acral melanoma, osteosarcoma, undifferentiated pleomorphic sarcoma, clear cell carcinoma of the ovary (CCCO) or squamous cell carcinoma of the anal canal (SCCA).

Optimizing immunogenicity and product presentation of a SARS-CoV-2 subunit vaccine composition: effects of delivery route, heterologous regimens with self-amplifying RNA vaccines, and lyophilization.

Introduction: Dozens of vaccines have been approved or authorized internationally in response to the ongoing SARS-CoV-2 pandemic, covering a range of modalities and routes of delivery. For example, mucosal delivery of vaccines via the intranasal (i.n.

Impact of steroid-sparing immunosuppressive agents on tumor outcome in the context of cancer immunotherapy with highlight on melanoma: a systematic literature review and meta-analysis.

Background: The impact of steroid-sparing immunosuppressive agents (SSIAs) for immune-related adverse events (irAEs) on tumor outcome is not well-known. This systematic review evaluates tumor outcomes for corticosteroid (CS) monotherapy versus CS with SSIA (CS-SSIA) for irAE treatment with a focus on melanoma.

Methods: Search was conducted through 1/5/23 using PubMed, Embase, Cochrane CENTRAL, and Web of Science.

Fibroblasts modulate epithelial cell behavior within the proliferative niche and differentiated cell zone within a human colonic crypt model.

Colonic epithelium is situated above a layer of fibroblasts that provide supportive factors for stem cells at the crypt base and promote differentiation of cells in the upper crypt and luminal surface. To study the fibroblast-epithelial cell interactions, an crypt model was formed on a shaped collagen scaffold with primary epithelial cells growing above a layer of primary colonic fibroblasts. The crypts possessed a basal stem cell niche populated with proliferative cells and a differentiated, nondividing cell zone at the luminal crypt end.

Bacterial synergies amplify nitrogenase activity in diverse systems.

Endophytes are microbes living within plant tissue, with some having the capacity to fix atmospheric nitrogen in both a free-living state and within their plant host. They are part of a diverse microbial community whose interactions sometimes result in a more productive symbiosis with the host plant. Here, we report the co-isolation of diazotrophic endophytes with synergistic partners sourced from two separate nutrient-limited sites.

Factors Associated with Pediatric Drowning-Associated Lung Injury.

Objective: To identify risk factors for clinically-important drowning-associated lung injury (ciDALI) in children.

Study Design: This was a cross-sectional study of children (0 through18 years) who presented to 32 pediatric emergency departments (EDs) from 2010 through 2017. We reviewed demographics, comorbidities, prehospital data, chest radiographs reports, and ED course from emergency medical services, medical, and fatality records.

A reliability generalization meta-analysis of the internal consistency and test-retest reliability of the pre-sleep arousal scale (PSAS).

Purpose: The Pre-Sleep Arousal Scale (PSAS) is a self-report tool for assessing cognitive and somatic arousal before sleep. While the English version is well-validated, research on translations is limited. This meta-analysis examines PSAS translations' internal consistency and reliability.

Unveiling the Longitudinal Journey: 3-Year Follow-up of Women with MINOCA and INOCA in a Specialized Heart Centre.

Background: Myocardial infarction with no obstructive coronary arteries (MINOCA), and ischemia with no obstructive coronary arteries (INOCA), are female-predominant conditions; clinical trials are lacking to guide medical management for the common underlying vasomotor etiologies. Data on long-term outcomes of (M)INOCA patients following attendance at a women's heart centre (WHC) are lacking.

Methods: Women diagnosed with MINOCA (n = 51) or INOCA (n = 112) were prospectively followed for 3 years at the Leslie Diamond WHC (LDWHC) in Vancouver.

Multivariate analysis on the structure-activity parameters for nano CuO-catalyzed reduction reactions.

Understanding the origin of enhanced catalytic activity is critical to heterogeneous catalyst design. This is especially important for non-noble metal-based catalysts, notably metal oxides, which have recently emerged as viable alternatives for numerous thermal catalytic processes. For thermal catalytic reduction/hydrogenation using metal oxide nanoparticles, enhanced catalytic performance is typically attributed to increased surface area and oxygen vacancies.

Adaptation of a HIV Prevention Mobile App for Transmasculine People: A Pilot Acceptability and Feasibility Study.

Purpose: Using a community-engaged approach, we adapted a human immunodeficiency virus (HIV) prevention smartphone app, Transpire, to meet the HIV and sexually transmitted infection (STI) prevention needs of transgender men and other transmasculine people. We conducted a pilot study to assess the feasibility and acceptability of the app among participants in two cities in the southeastern United States.

Methods: Participants were recruited online and through community partners.

Organization Theory for Implementation Science (OTIS): reflections and recommendations.

Organizations exert influence on the implementation of evidence-based practices and other innovations that are independent of the influence of organizations' individual constituents. Despite their influence, nuanced explanations of organizations' influence remain limited in implementation science. Organization theories are uniquely suited to offer insights and explain organizational influences on implementation.

Pulmonary Embolism: Webcast June 13 2024.

This 61-minute webcast features a conversation about "Pulmonary Embolism"-the focus of Issue 20.3. Hosted by the issue's editors, the discussion engages the authors on emerging themes and lessons learned while researching and writing the articles.

Considerations for the Treatment of Sexual and Gender Minority Individuals in Colon and Rectal Surgery.

Sexual and gender minorities (SGMs) experience critical barriers to health care access and have unique health care needs that are often overlooked. Given the rise in individuals identifying as lesbian, gay, bisexual, transgender, and queer, colorectal surgeons are likely to care for increasing numbers of such individuals. Here, we discuss key barriers to health care access and research among SGM populations and outline approaches to address these barriers in clinical practice.