Antitumor efficacy of intermittent low-dose erlotinib plus sulindac via MHC upregulation and remodeling of the immune cell niche.

A previously reported clinical trial in familial adenomatous polyposis (FAP) patients treated with erlotinib plus sulindac (ERL + SUL) highlighted immune response/interferon-γ signaling as a key pathway. In this study, we combine intermittent low-dose ERL ± SUL treatment in the polyposis in rat colon (Pirc) model with mechanistic studies on tumor-associated immune modulation. At clinically relevant doses, short-term (16 weeks) and long-term (46 weeks) ERL ± SUL administration results in near-complete tumor suppression in Pirc colon and duodenum (p < 0.

Characterising symptomatic substates in individuals on the psychosis continuum: a hidden Markov modelling approach.

Background: To improve early intervention and personalise treatment for individuals early on the psychosis continuum, a greater understanding of symptom dynamics is required. We address this by identifying and evaluating the movement between empirically derived attenuated psychotic symptomatic substates-clusters of symptoms that occur within individuals over time.

Methods: Data came from a 90-day daily diary study evaluating attenuated psychotic and affective symptoms.

Associations of Device-Measured Physical Activity and Sedentary Time With Neural Responses to Visual Food Cues in Adults: A Functional Magnetic Resonance Imaging Study.

Self-reported physical activity is associated with lower brain food cue responsiveness in reward-related regions, but relationships utilizing objective physical activity measurement tools have not been explored. This cross-sectional study examined whether device-measured moderate-to-vigorous intensity physical activity and sedentary time are related to neural responses to visual food cues using functional magnetic resonance imaging. Fifty-one healthy adults (30 men, 21 women; mean ± SD: age 26 ± 6 years; body mass index 24.

Conceptualizing and Measuring Violence: A Feminist Critical Measurement Analysis of Gender-Based Violence Research in a Government Policy-Based Setting.

Feminist methodological advances in gender-based violence research have yet to be comprehensively integrated into policy-based research. This article discusses methodological concerns identified when reviewing the UK government's public consultation for its 2021 Tackling Violence Against Women and Girls Strategy. We apply intersectional feminist perspectives and critical measurement analysis, and discuss two areas of methodological concern: issues with conceptualizations of violence, and issues with the measurement of public experiences, attitudes, and opinions, and implications for the accuracy of the survey.

Hepatitis C virus transmission among people who inject drugs in rural United States: mathematical modeling study using stochastic agent-based network simulation (AJE-00824-2024).

People who inject drugs (PWID) account for the majority of hepatitis C virus (HCV) infections in the United States. The injection-equipment-sharing network likely plays an important role in shaping the dynamics of HCV transmission. Recognizing the emerging HCV epidemic in rural communities, we developed an agent-based network simulation model of HCV transmission via injection-equipment-sharing and used data on rural PWID networks to inform model parameterization and calibration.

Clinician differences in attitudes and perceptions on the use of long-acting injectable antipsychotic agents in treating patients with schizophrenia: results from the US DECIDE survey.

Background: Long-acting injectable antipsychotics (LAIs) reduce relapses in schizophrenia; however, most clinicians reserve LAIs for nonadherence with oral antipsychotics (OAs) or severe disease.

Methods: US psychiatric clinicians were surveyed regarding their schizophrenia management practices and use of LAIs. Respondents were grouped by LAI use (high [≥ 31% of patients using LAIs], low [≤ 14% using LAIs]; mid not analyzed) and mindset based on their response to "Which of the following best fits the current way you view your use of [LAIs] for your patients with schizophrenia?"

Results: Respondents (n = 380) were distributed across LAI use (106 high, 130 low) and mindset (123 early-use, 88 severity-reserved, 113 adherence-reserved, 56 LAI-hesitant) subgroups.

Knowledge and practices of regional and rural general practitioners in the identification and management of intimate partner and family violence: a mixed methods study in Western Australia.

Background: General Practitioners (GPs) are well placed to identify and assist patients experiencing intimate partner violence (IPV) and family violence (FV). However, patients experiencing IPV/FV can be under-detected or inadequately assisted when GPs do not have the necessary confidence, knowledge, attitudes or skills for this. Given the high rates of IPV/FV in the Australian regional setting where this study was conducted, this investigation explored the confidence, knowledge, attitudes and practices of local GPs in identifying and managing patients who are experiencing IPV/FV.

VDAC2 and Bak scarcity in liver mitochondria enables targeting hepatocarcinoma while sparing hepatocytes.

Differences between normal tissues and invading tumors that allow tumor targeting while saving normal tissue are much sought after. Here we show that scarcity of VDAC2, and the consequent lack of Bak recruitment to mitochondria, renders hepatocyte mitochondria resistant to permeabilization by truncated Bid (tBid), a Bcl-2 Homology 3 (BH3)-only, Bcl-2 family protein. Increased VDAC2 and Bak is found in most human liver cancers and mitochondria from tumors and hepatic cancer cell lines exhibit VDAC2- and Bak-dependent tBid sensitivity.

ROSAH syndrome presenting with recurrent vitreous hemorrhage: a multimodal imaging study.

Background: ROSAH syndrome is an autosomal dominant systemic disease featuring etinal dystrophy, ptic nerve edema, plenomegaly, nhidrosis and migrainous eadache. Ocular manifestation of ROSAH syndrome can simulate posterior uveitis, vasculitis, generalized retinal dystrophy and neuroretinitis.

Purpose: To report a case of a 17-year-old female presenting with recurrent vitreous hemorrhage on a background of dental anomalies and anhidrosis.

Designing a method to test the efficacy of different sanitizers for use in rubber footbaths as applied to dairy manufacturing.

This study designed an in vitro model to test the efficacies of footbath sanitizers for use in dairy processing plants. Efficacies of selected sanitizers for inactivation of mixed-cocktail, dairy-relevant Gram-negative bacteria in model footbaths, in the presence of milk residues, were measured over 7 days against attached and planktonic populations by plate counting and calculating log reductions achieved. A simplified practical table ranked the most to least effective sanitizers.

A Scoping Review of Interventions Designed to Increase Behavioural Health Service Engagement.

Background: A documented underutilization of behavioural health interventions with known efficacy for treating psychological disorders exists. Thus, engagement enhancement approaches (EEAs) exist to help increase individuals' use of behavioural health interventions. EEAs target a range of barriers to treatment; therefore, a wide variety of approaches exist.

Engineering mtDNA deletions by reconstituting end joining in human mitochondria.

Recent breakthroughs in the genetic manipulation of mitochondrial DNA (mtDNA) have enabled precise base substitutions and the efficient elimination of genomes carrying pathogenic mutations. However, reconstituting mtDNA deletions linked to mitochondrial myopathies remains challenging. Here, we engineered mtDNA deletions in human cells by co-expressing end-joining (EJ) machinery and targeted endonucleases.

Exploring relationships between household crowding and health in two First Nations communities.

Lasting results of federal government influence for housing on-reserve include challenges with housing quantity and quality. Some First Nations communities face distressing housing shortages and household crowding. This study used a cross-sectional survey and the Canadian National Occupancy Standard definition of crowding to explore how household crowding affects health of people living on-reserve.

Implementation of Integrated Patient-Reported outcome collection in outpatient cranial neurosurgical Practice: Results of qualitative interviews.

Objective: Patient Reported Outcome Measures (PROMs) quantify the patient's quality of life and symptom burden. This study assesses the implementation of an automated PROM-capture system in an outpatient cranial neurosurgery clinic.

Methods: We conducted both quantitative and qualitative analyses of the implementation of a PROM tool in a single-center, dedicated brain tumor neurosurgery clinic.

A randomized controlled feasibility trial of a single-session metacognitive training intervention for reducing eating disorder risk factors.

This study investigates the feasibility and preliminary evidence for the efficacy of a single-session online metacognitive training (MCT-ED) among a population considered to be at-risk of developing an eating disorder. A total of  = 95 participants with high weight concerns were randomised to an MCT-ED condition ( = 43) or a waitlist control condition ( = 52). Participants completed measures of body image flexibility, perfectionism, weight and shape concerns and mood at baseline, post-treatment (one-week post-baseline), and 3-months post-treatment.

Stress and stiffness as predictors of shear wave velocity in peripheral nerve.

Shear wave elastography (SWE) is a promising non-invasive indicator for diagnosing peripheral neuropathy. Emerging validation studies using ultrasound-based measures of shear wave velocity (SWV) in other biological tissues, such as muscle, demonstrate there is a concern of whether SWE is an accurate measure of tensile stress or stiffness. Distinguishing between these two parameters and their relationship with SWV is crucial if SWE is to be used as a biomarker for peripheral neuropathies, where changes in mechanical properties are known to occur.

A cross-sectional survey analysis of patient and family knowledge, confidence, and perceived barriers to reporting patient deterioration.

Background: The knowledge, confidence, and skills of healthcare consumers to identify acute clinical deterioration and appropriately escalate concerns remain largely undetermined. This gap is despite the widespread international introduction of consumer escalation systems intended to provide patients and family an avenue to escalate their concerns if worried about deterioration in their own or relative's condition during a hospital stay.

Aim: To explore patient and family knowledge of acute clinical deterioration, and their confidence and perceived barriers to escalating their concerns.

Enrichment of Microbial DNA in Plasma to Improve Pathogen Detection in Sepsis: A Pilot Study.

Background: Diagnosis of sepsis and timely identification of pathogens in critically ill patients remains challenging. Plasma metagenomic sequencing to detect microbial cell-free DNA (mDNA) has shown promise, but low abundance of mDNA in plasma limits sensitivity and necessitates high sequencing depth. mDNA is shorter and more fragmented than human cell-free DNA.

Improving Respite Outcomes for Caregivers: Who Benefits and Under What Conditions?

Alzheimer's disease and related dementias (ADRD) pose a substantial caregiving burden in the United States, yet efforts to improve caregiver well-being have seen mixed results. We ask whether an app-based intervention ( = 143) to prioritize can substantially improve the caregiving experience, and whether these benefits are moderated by (1) caregiver demographics and (2) conditions of the caregiving situation (such as baseline impairment). Constructing curvilinear growth models to assess changes over a 20-week period, we find significant improvements in the positive aspects of caregiving (PAC).

Revealing correlation mechanisms through nonorthogonal multiconfiguration self-consistent field calculations.

The presence of spin and spatial symmetry breaking upon variational optimization of mean-field wavefunctions is known to be an indicator of nondynamical electron correlation. However, a single mean-field wavefunction may not have sufficient flexibility to flag the correlated orbital space where there are multiple correlation mechanisms present. In such situations, there are multiple nearly degenerate self-consistent field solutions that describe different correlation mechanisms, but it is often not possible to know a priori when such situations will occur or if sufficient solutions have been obtained.

Late pandemic COVID-19 positivity at the time of thrombectomy is associated with poor outcomes and tandem carotid pathology.

Objectives: COVID-19 is an independent risk factor for ischemic stroke. Studies from early in the pandemic show increased rates of unfavorable recanalization, poor outcomes, and mortality in patients who were COVID-19 positive at the time of mechanical thrombectomy. However, there are currently no studies examining these parameters during the later pandemic when circulating variants were less virulent.

Mixed methods evaluation of a digital resource to build students' skills in ASsessing cardiovascular risk, MOtivating change, and SUStaining a healthier lifestyle in themselves and others- ASMOSUS: a study protocol.

Background: Cardiovascular disease (CVD) is a prevalent cause of morbidity and mortality globally. Nurses and nursing students are in an optimum role to assess, manage and promote lifestyle changes associated with CVD risk. Patients and service users are more likely to adopt these changes if the person delivering the information embodies this lifestyle themselves.

How to stop being surprised by unprecedented weather.

We see unprecedented weather causing widespread impacts across the world. In this perspective, we provide an overview of methods that help anticipate unprecedented weather hazards that can contribute to stop being surprised. We then discuss disaster management and climate adaptation practices, their gaps, and how the methods to anticipate unprecedented weather may help build resilience.