Fluid flow impacts endothelial-monocyte interactions in a model of vascular inflammatory fibrosis.

The aberrant vascular response associated with tendon injury results in circulating immune cell infiltration and a chronic inflammatory feedback loop leading to poor healing outcomes. Studying this dysregulated tendon repair response in human pathophysiology has been historically challenging due to the reliance on animal models. To address this, our group developed the human tendon-on-a-chip (hToC) to model cellular interactions in the injured tendon microenvironment; however, this model lacked the key element of physiological flow in the vascular compartment.

A constitutive interferon-high immunophenotype defines response to immunotherapy in colorectal cancer.

Fewer than 50% of metastatic deficient mismatch repair (dMMR) colorectal cancer (CRC) patients respond to immune checkpoint inhibition (ICI). Identifying and expanding this patient population remains a pressing clinical need. Here, we report that an interferon-high immunophenotype locally enriched in cytotoxic lymphocytes and antigen-presenting macrophages is required for response.

The impacts of alien species on river bioassessment.

The extent of alien taxa impacts on river ecosystem health is unclear, but their frequency continues to rise. We investigated 1) the prevalence of including alien taxa in common bioindicators used in river bioassessment, 2) the effect of alien taxa on the richness and abundance of natives, and 3) whether including alien taxa in bioassessment tools increased their sensitivity to river degradation. In the 17 countries analyzed fish represented the greatest number of alien species (1726), followed by macrophytes (925), macroinvertebrates (556), and diatoms (7).

VeloxChem: GPU-Accelerated Fock Matrix Construction Enabling Complex Polarization Propagator Simulations of Circular Dichroism Spectra of G-Quadruplexes.

An automatic code generated C++/HIP/CUDA implementation of the (auxiliary) Fock, or Kohn-Sham, matrix construction for execution in GPU-accelerated hardware environments is presented. The module is developed as part of the quantum chemistry software package VeloxChem, employing localized Gaussian atomic orbitals. The performance and scaling characteristics are analyzed in view of the specific requirements for self-consistent field optimization and response theory calculations.

About bacteriophage tail terminator and tail completion proteins: structure of the proximal extremity of siphophage T5 tail.

Bacteriophages are viruses infecting bacteria. The vast majority of them bear a tail, allowing host recognition, cell wall perforation, and DNA injection into the host cytoplasm. Using electron cryo-microscopy (cryo-EM) and single particle analysis, we determined the organization of the tail proximal extremity of siphophage T5 that possesses a long flexible tail and solved the structure of its tail terminator protein p142 (TrP).

Navigating from cellular phenotypic screen to clinical candidate: selective targeting of the NLRP3 inflammasome.

The NLRP3 inflammasome plays a pivotal role in host defense and drives inflammation against microbial threats, crystals, and danger-associated molecular patterns (DAMPs). Dysregulation of NLRP3 activity is associated with various human diseases, making it an attractive therapeutic target. Patients with NLRP3 mutations suffer from Cryopyrin-Associated Periodic Syndrome (CAPS) emphasizing the clinical significance of modulating NLRP3.

Biohydrogen with negative CO emissions from municipal solid waste for decarbonising the public bus fleet. Application to the municipality of Madrid.

This study assesses the production potential, environmental impact, and economic viability of generating biohydrogen from biomethane obtained from the organic fraction of municipal solid waste (MSW) using steam methane reforming with carbon capture and storage (CCS). As the emissions are biogenic, CCS results in negative emissions. The methodology is based on a previously developed model, including techno-economic analysis based on the levelised cost of hydrogen (LCOH) and mobility (LCOM), and environmental assessment, focusing on production potential, cost estimates, and emissions impact.

Societal Discrimination, Vigilance, and Patient-Provider Relationships Among Perinatal Women: A Mixed Methods Study.

Introduction: In the United States, maternal mortality is high and patterned by race and socioeconomic status (SES). Patient-provider relationships and societal discrimination have been separately associated with poor maternal outcomes, but it is not clear how such mechanisms may be interrelated. Thus, the present study investigates how societal experiences of discrimination are associated with and manifest in patient-provider relationship quality among perinatal women.

Diversity, equity, and inclusion initiatives in the Medical Library Association: a look back at the last twenty-five years.

Over the past twenty-five years, the Medical Library Association (MLA) has pursued a range of diversity, equity, and inclusion (DEI) initiatives. This article, written by members of the 's Equity Advisory Group (EAG), outlines significant measures taken to raise awareness about specific concepts, opportunities, and challenges related to DEI among MLA members. Topics discussed include the impact of influential Black, Indigenous, and people of color (BIPOC) leaders, the establishment of DEI and social justice-focused membership communities, and specific initiatives led by various working groups and committees which have served to strengthen MLA's commitment to diversity, equity, and inclusion during the last three decades.

Discovery of 6,7-Dihydropyrazolo[1,5-]pyrazin-4(5)-one Derivatives as mGluR Negative Allosteric Modulators with Activity in a Rodent's Model of Cognition.

Allosteric modulators of the metabotropic group II receptors, mGluR and mGluR, have been widely explored due to their ability to modulate cognitive and neurological functions in mood disorders, although none have been approved yet. In our search for new and selective mGluR negative allosteric modulators (NAMs), series of 6,7-dihydropyrazolo[1,5-]pyrazin-4(5)-one derivatives were identified from our published series of 1,3,5-trisubstituted pyrazoles. SAR evolution of the initial hit resulted in 100-fold improvement in the mGluR NAM potency and subsequent selection of compound based on its overall profile, including selectivity and ADMET properties.

Latine perspectives on the impact of family, perceptions of medication, health systems, incarceration, and housing on accessing opioid agonist therapy: A thematic analysis.

Introduction: Opioid-related overdose deaths rates among Latine individuals are increasing rapidly and, in Massachusetts, have exceeded rates among non-Hispanic White individuals. Yet Latine individuals are less likely to receive opioid agonist therapies (OAT) methadone and buprenorphine, which have been demonstrated to prevent opioid deaths. Amid climbing Latine overdose rates, we lack qualitative data from Spanish-speaking people who use opioids about their views on and access to OAT.

Skin and systemic inflammation in adults with atopic dermatitis before and after whole-body topical betamethasone 17-valerate 0.1% or tacrolimus 0.1% treatment: A randomized controlled study.

Background: Atopic dermatitis (AD) is mainly driven by type 2 inflammation and often treated with topical agents. Studies comparing differences in biomarkers between these treatments are lacking.

Objectives: The aim of this study was to evaluate the effects of topical betamethasone 17-valerate 0.

Late-Stage C()-C() Diversification via Nickel Oxidative Addition Complexes.

Herein, we describe nickel oxidative addition complexes (Ni-OACs) of drug-like molecules as a platform to rapidly generate lead candidates with enhanced C() fraction. The potential of Ni-OACs to access new chemical space has been assessed not only in C()-C() couplings but also in additional bond formations without recourse to specialized ligands and with improved generality when compared to Ni-catalyzed reactions. The development of an automated diversification process further illustrates the robustness of Ni-OACs, thus offering a new gateway to expedite the design-make-test-analyze (DMTA) cycle in drug discovery.

Acceptance and commitment therapy versus cognitive behavioral therapy for insomnia: A randomized controlled trial.

Objective: To compare the effectiveness of an acceptance and commitment therapy (ACT)-based protocol and cognitive behavior therapy (CBT) for insomnia in adults.

Method: The participants comprised 227 adults with insomnia. They were randomized to six weekly group sessions consisting of acceptance and commitment therapy for insomnia (n = 76), cognitive behavioral therapy for insomnia (n = 76), or waitlist (WL; n = 75).

Exploring the Telephone Call Experience of Patients with Non-English Language Preference in Primary Care vs. Specialty.

Background: Latine people, comprising 18.5% of the US population, constitute the largest ethnic minority group, with nearly one-third self-identifying as having non-English language preference (NELP). Despite the importance of the telephone in health care access, there is limited understanding of how NELP patients navigate telephone calls with primary and specialty care clinics.

Homopolymer switches mediate adaptive mutability in mismatch repair-deficient colorectal cancer.

Mismatch repair (MMR)-deficient cancer evolves through the stepwise erosion of coding homopolymers in target genes. Curiously, the MMR genes MutS homolog 6 (MSH6) and MutS homolog 3 (MSH3) also contain coding homopolymers, and these are frequent mutational targets in MMR-deficient cancers. The impact of incremental MMR mutations on MMR-deficient cancer evolution is unknown.

Short-term effects of fine particulate matter from biomass combustion and Saharan dust intrusions on emergency hospital admissions due to mental and behavioural disorders, anxiety and depression in Spain.

Climate change is affecting both the frequency and scale of wildfires, as well as the increase in the number of days with Saharan dust intrusions. Traditionally, studies have focused on the extent to which the increase in fine particulate matter (PM) has had an impact on cardio-respiratory diseases, but (apart from PM) not on how the meteorological and pollution conditions in these situations affect other diseases, such as those linked to mental health. This study therefore sought to ascertain how daily mean PM, PM , NO, O concentrations and daily maximum temperature in heat waves influence daily emergency hospital admissions in Spain caused by mental and behavioural disorders, depression and anxiety on days with PM from biomass combustion and/or Saharan dust intrusions, as compared to days without such conditions, across the period 2009-2018.