Development and Characterization of a -Flp Mouse Model.

The use of genetically engineered tools, including combinations of Cre-LoxP and Flp-FRT systems, enable the interrogation of complex biology. Steroidogenic factor-1 (SF-1) is expressed in the ventromedial hypothalamic nucleus (VMH). Development of genetic tools, such as mice expressing Flp recombinase (Flp) in SF-1 neurons ( -Flp), will be useful for future studies that unravel the complex physiology regulated by the VMH.

Development and characterization of an Sf-1-Flp mouse model.

The use of genetically engineered tools, including combinations of Cre-LoxP and Flp-FRT systems, enable the interrogation of complex biology. Steroidogenic factor-1 (SF-1) is expressed in the ventromedial hypothalamic nucleus (VMH). Development of genetic tools, such as mice expressing Flp recombinase (Flp) in SF-1 neurons (Sf-1-Flp), will be useful for future studies that unravel the complex physiology regulated by the VMH.

Assessing a Community Partnership Addressing Food Security Among Older Adults During COVID-19.

For many vulnerable older adults, food access was disrupted during the COVID-19 pandemic. In Hawai'i, the Kūpuna (the Hawaiian word for elders) Food Security Coalition (KFSC) was formed in March 2020 to address this challenge, leveraging local and federal funding support. This case study presents information on coalition formation and success in addressing this emergency, as well as evaluation data on coalition functioning as assessed by the Collective Impact (CI) framework.

A third COVID-19 vaccine dose in kidney transplant recipients induces antibody response to vaccine and Omicron variants but shows limited Ig subclass switching.

Solid organ transplant recipients (SOTRs) suffer more frequent and more severe infections due to their compromised immune responses resulting from immunosuppressive treatments designed to prevent organ rejection. Pharmacological immunosuppression can adversely affect immune responses to vaccination. A cohort of kidney transplant recipients (KTRs) received their third dose of ancestral, monovalent COVID-19 vaccine in the context of a clinical trial and antibody responses to the vaccine strain, as well as two Omicron variants BA.

Clinical outcomes and management following progressive disease with anti-PD-(L)1 therapy in patients with advanced Merkel Cell Carcinoma.

Aim: Merkel Cell Carcinoma (MCC) is a rare skin cancer with a rising incidence worldwide. Anti-programmed death-1/ligand-1 (anti-PD-(L)1) therapies are effective for the treatment of advanced MCC. This study examines patterns of response / progression of advanced MCC to anti-PD-(L)1 therapies and describes subsequent management.

Precision in Liver Diagnosis: Varied Accuracy Across Subgroups and the Need for Variable Thresholds in Diagnosis of MASLD.

Background And Aims: The performance of non-invasive liver tests (NITs) is known to vary across settings and subgroups. We systematically evaluated whether the performance of three NITs in detecting advanced fibrosis in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) varies with age, sex, body mass index (BMI), type 2 diabetes mellitus (T2DM) status or liver enzymes.

Methods: Data from 586 adult LITMUS Metacohort participants with histologically characterised MASLD were included.

Predictors of mortality among sepsis patients transferred from a rural, low-volume ED to an urban, high-volume hospital.

Introduction: We investigated the extent to which demographic characteristics, clinical care aspects, and relevant biomarkers predicted sepsis-related mortality among patients transferred from a rural, low-volume emergency department (ED) to an urban, high-volume, level-2 trauma center.

Methods: We conducted an observational study among adult severe sepsis patients (N = 242) who, within a community-based regional healthcare system, presented to one of the four rural, low-volume EDs and were subsequently transferred to the urban, high-volume, level-2 trauma center, and were identified as septic at either location. We evaluated in-hospital and 30 days after discharge mortality.

Nurses' Workplace Violence Reporting Behaviours and Reasons for Not Formally Reporting: A Cross-Sectional Secondary Analysis.

Aim: To investigate predictors of nurses' reporting behaviours and their reasons for not formally reporting.

Background: Underreporting of workplace violence (WPV) among nurses contributes to gaps in WPV prevention measures, as it cannot be fully understood. WPV is classified according to its source (Type II: patients and visitors, Type III: coworkers) and forms (physical assault, threat of assault, emotional abuse, verbal sexual harassment and sexual assault).

LCoRL Regulates Growth and Metabolism.

Genome-wide association studies (GWAS) in humans and livestock have identified genes associated with metabolic traits. However, the causality of many of these genes on metabolic homeostasis is largely unclear due to a lack of detailed functional analyses. Here we report ligand-dependent corepressor-like (LCoRL) as a metabolic regulator for body weight and glucose homeostasis.

A Third COVID-19 Vaccine Dose in Kidney Transplant Recipients Induces Antibody Response to Vaccine and Omicron Variants but Shows Limited Ig Subclass Switching.

Unlabelled: Solid organ transplant recipients (SOTRs) suffer more frequent and more severe infections due to their compromised immune responses resulting from immunosuppressive treatments designed to prevent organ rejection. Pharmacological immunosuppression can adversely affect immune responses to vaccination. A cohort of kidney transplant recipients (KTRs) received their third dose of ancestral, monovalent COVID-19 vaccine in the context of a clinical trial and antibody responses to the vaccine strain, as well as to Omicron variants BA.

Single-cell RNA sequencing reveals melanoma cell state-dependent heterogeneity of response to MAPK inhibitors.

Background: Melanoma is a heterogeneous cancer influenced by the plasticity of melanoma cells and their dynamic adaptations to microenvironmental cues. Melanoma cells transition between well-defined transcriptional cell states that impact treatment response and resistance.

Methods: In this study, we applied single-cell RNA sequencing to interrogate the molecular features of immunotherapy-naive and immunotherapy-resistant melanoma tumours in response to ex vivo BRAF/MEK inhibitor treatment.

A qualitative exploration of the pathway to diagnosis and treatment of cutaneous squamous cell carcinoma of the head and neck with perineural spread.

Background: Perineural spread (PNS) is associated with a poor prognosis in cutaneous squamous cell carcinoma of the head and neck (cSCCHN). Hence, investigating facilitators and barriers of early diagnosis and treatment of PNS in cSCCHN may improve outcomes.

Methods: Patients were recruited from an institutional database.

Circulating tumour DNA dynamics predict recurrence in stage III melanoma patients receiving neoadjuvant immunotherapy.

Background: Neoadjuvant therapy improves recurrence-free survival (RFS) in resectable stage III cutaneous melanoma. However, accurately predicting individual recurrence risk remains a significant challenge. We investigated circulating tumour DNA (ctDNA) as a biomarker for recurrence in measurable stage IIIB/C melanoma patients undergoing neoadjuvant immunotherapy.

AC-ASPECTS, ACh-ASPECTS, and H-ASPECTS: new imaging scales to assess territorial and total cerebral hemispheric ischemic injury.

Background: The extent of ischemic injury in acute stroke is assessed in clinical practice using the Acute Stroke Prognosis Early CT Score (ASPECTS) rating system. However, current ASPECTS semi-quantitative topographic scales assess only the middle cerebral artery (MCA) (original ASPECTS) and posterior cerebral (PC-ASPECTS) territories. For treatment decision-making in patients with anterior cerebral artery (ACA) occlusions and internal carotid artery (ICA) occlusions with large ischemic cores, measures of all hemispheric regions are desirable.

Participant Assessment of an Alternative Flexible Congregate Nutrition Meal Program for Older Adults.

Congregate Nutrition Services have long been a pillar of public health assistance, championing the independence and community engagement of older Americans. The advent of COVID-19, however, restricted access to these services due to the closure of physical locations. In response, Lanakila Meals on Wheels initiated a virtual congregate meal program, Kūpuna U, in collaboration with community partners in Honolulu County.

3-Hydroxykynurenine targets kainate receptors to promote defense against infection.

Bacterial infection involves a complex interaction between the pathogen and host where the outcome of infection is not solely determined by pathogen eradication. To identify small molecules that promote host survival by altering the host-pathogen dynamic, we conducted an in vivo chemical screen using zebrafish embryos and found that treatment with 3-hydroxykynurenine (3-HK) protects from lethal bacterial infection. 3-HK, a metabolite produced through host tryptophan metabolism, has no direct antibacterial activity but enhances host survival by restricting bacterial expansion in macrophages through a systemic mechanism that targets kainate-sensitive glutamate receptors.

Diagnostic accuracy of non-invasive tests to screen for at-risk MASH-An individual participant data meta-analysis.

Background & Aims: There is a need to reduce the screen failure rate (SFR) in metabolic dysfunction-associated steatohepatitis (MASH) clinical trials (MASH+F2-3; MASH+F4) and identify people with high-risk MASH (MASH+F2-4) in clinical practice. We aimed to evaluate non-invasive tests (NITs) screening approaches for these target conditions.

Methods: This was an individual participant data meta-analysis for the performance of NITs against liver biopsy for MASH+F2-4, MASH+F2-3 and MASH+F4.

RNAi mediated silencing of STAT3/PD-L1 in tumor-associated immune cells induces robust anti-tumor effects in immunotherapy resistant tumors.

Malignant tumors are often associated with an immunosuppressive tumor microenvironment (TME), rendering most of them resistant to standard-of-care immune checkpoint inhibitors (CPIs). Signal transducer and activator of transcription 3 (STAT3), a ubiquitously expressed transcription factor, has well-defined immunosuppressive functions in several leukocyte populations within the TME. Since the STAT3 protein has been challenging to target using conventional pharmaceutical modalities, we investigated the feasibility of applying systemically delivered RNA interference (RNAi) agents to silence its mRNA directly in tumor-associated immune cells.

Quality and Accessibility of Home Assessment mHealth Apps for Community Living: Systematic Review.

Background: Home assessment is a critical component of successful home modifications, enabling individuals with functional limitations to age in place comfortably. A high-quality home assessment tool should facilitate a valid and reliable assessment involving health care and housing professionals, while also engaging and empowering consumers and their caregivers who may be dealing with multiple functional limitations. Unlike traditional paper-and-pencil assessments, which require extensive training and expert knowledge and can be alienating to consumers, mobile health (mHealth) apps have the potential to engage all parties involved, empowering and activating consumers to take action.