Understanding Disenfranchised Grief in a Post-COVID-19 World-A Pilot Study of Advanced Practice Registered Nurses in Palliative Care.

Disenfranchised grief is a form of grief that remains unacknowledged and unsupported. Building on Doka's foundational concept of disenfranchised grief, the guiding framework for this pilot project was the Knowledge to Action framework. This study is a quantitative cross-sectional web-based survey, which included a validated questionnaire: the Witnessing Disenfranchised Grief Scale.

Medication non-adherence: reflecting on two decades since WHO adherence report and setting goals for the next twenty years.

Background: Non-adherence to medication remains a persistent and significant challenge, with profound implications for patient outcomes and the long-term sustainability of healthcare systems. Two decades ago, the World Health Organization (WHO) dedicated its seminal report to adherence to long-term therapies, catalysing notable changes that advanced both research and practice in medication adherence. The aim of this paper was to identify the most important progress made over the last 2 decades in medication adherence management and to initiate a discussion on future objectives, suggesting priority targets for the next 20 years.

Generalized Fused Lasso for Treatment Pooling in Network Meta-Analysis.

This work develops a generalized fused lasso (GFL) approach to fitting contrast-based network meta-analysis (NMA) models. The GFL method penalizes all pairwise differences between treatment effects, resulting in the pooling of treatments that are not sufficiently different. This approach offers an intriguing avenue for potentially mitigating biases in treatment rankings and reducing sparsity in networks.

Act for the Future of Community Pharmacy.

Community pharmacies serve as a vital gateway to primary care and public health, offering face-to-face pharmacist expert care to assure safe and effective medication use. However, they are disappearing at an alarming rate, with 20-30% of all community pharmacy locations projected to close within the next year. The objective of this commentary is to highlight the critical need for systemic reforms and collective action within our profession to address the unique challenges faced by community pharmacies, ensuring their sustainability and continued role in providing essential healthcare services for patients.

A 12-Year Analysis of Demand and Supply for Hand Surgery Training in the United States.

Introduction: The consistent recruitment of quality applicants is critical to the integrity of the US surgical workforce. This study assesses the demand and supply for hand surgery training in the US.

Methods: This was a cross-sectional analysis of US hand surgery fellowship applicants from 2012 to 2023.

Type 1 interferons promote Staphylococcus aureus nasal colonization by inducing phagocyte apoptosis.

Staphylococcus aureus is an important human commensal which persistently colonizes up to 30% of the human population, predominantly within the nasal cavity. The commensal lifestyle of S. aureus is complex, and the mechanisms underpinning colonization are not fully understood.

Matching-Adjusted Indirect Comparison of the Efficacy and Safety of Erdafitinib vs Enfortumab Vedotin in Patients with Locally Advanced Metastatic Urothelial Carcinoma.

For patients with locally advanced or metastatic urothelial carcinoma (la/mUC), prognosis is poor and effective treatment options are limited. Erdafitinib is an oral fibroblast growth factor receptor (FGFR) kinase inhibitor approved by the FDA for the treatment of adults with la/mUC harboring FGFR alterations whose disease progressed following at least 1 prior line of therapy, including a PD-1 or PD-L(1) inhibitor, based on the phase 3, randomized THOR trial (NCT03390504, Cohort 1). To compare the efficacy and safety of erdafitinib vs enfortumab vedotin-ejfv (EV) in the absence of head-to-head comparison via an anchored matching-adjusted indirect comparison (MAIC).

A systematic review and network meta-analysis of psychological, psychosocial, pharmacological, physical and combined treatments for adults with a new episode of depression.

Background: Various effective treatments for depression exist. We aimed to identify the most effective first-line treatments for new episodes of less and more severe depression (defined by depression scale cut-off scores), to update NICE guidance on the management of Depression in Adults in England.

Methods: Systematic review and network meta-analysis of randomised controlled trials (RCTs) published up to June 2020 (PROSPERO registration number CRD42019151328).

Employing Metadynamics to Predict the Membrane Partitioning of Carboxy-2-Azirine Natural Products.

Natural products containing the carboxy-2-azirine moiety are an exciting target for investigation due to their broad-spectrum antimicrobial activity and new chemical space they afford for novel therapeutic development. The carboxy-2-azirine moiety, including those appended to well-characterized chemical scaffolds, is understudied, which creates a challenge for understanding potential modes of inhibition. In particular, some known natural product carboxy-2-azirines have long hydrophobic tails, which could implicate them in membrane-associated processes.

LTβR Agonism Promotes Antitumor Immune Responses via Modulation of the Tumor Microenvironment.

The presence of high endothelial venules (HEV) and tertiary lymphoid structures (TLS) in solid tumors is correlated with favorable prognosis and better responses to immune checkpoint blockade in many cancer types. Elucidation of the molecular mechanisms underlying intratumoral HEV and TLS formation and their contribution to antitumor responses may facilitate the development of improved treatment strategies. Lymphotoxin β receptor (LTβR) signaling is a critical regulator of lymph node organogenesis and can cooperate with antiangiogenic and immune checkpoint blockade treatment to augment tumor-associated HEV formation.

Molecular mechanism of distinct chemokine engagement and functional divergence of the human Duffy antigen receptor.

The Duffy antigen receptor is a seven-transmembrane (7TM) protein expressed primarily at the surface of red blood cells and displays strikingly promiscuous binding to multiple inflammatory and homeostatic chemokines. It serves as the basis of the Duffy blood group system in humans and also acts as the primary attachment site for malarial parasite Plasmodium vivax and pore-forming toxins secreted by Staphylococcus aureus. Here, we comprehensively profile transducer coupling of this receptor, discover potential non-canonical signaling pathways, and determine the cryoelectron microscopy (cryo-EM) structure in complex with the chemokine CCL7.

A Tetravalent Bispecific Antibody Selectively Inhibits Diverse FGFR3 Oncogenic Variants.

The receptor tyrosine kinase FGFR3 is frequently mutated in bladder cancer and is a validated therapeutic target. Although pan-FGFR tyrosine kinase inhibitors (TKI) have shown clinical efficacy, toxicity and acquired resistance limit the benefit of these agents. While antibody-based therapeutics can offer superior selectivity than TKIs, conventional ligand-blocking antibodies are usually ineffective inhibitors of constitutively active receptor tyrosine kinases.

Feasibility of Indirect Treatment Comparisons Between Niraparib Plus Abiraterone Acetate and Other First-Line Poly ADP-Ribose Polymerase Inhibitor Treatment Regimens for Patients with BRCA1/2 Mutation-Positive Metastatic Castration-Resistant Prostate Cancer.

Introduction: Poly(ADP-ribose) polymerase inhibitors (PARPi) are a novel option to treat patients with metastatic castration-resistant prostate cancer (mCRPC). Niraparib plus abiraterone acetate and prednisone (AAP) is indicated for BRCA1/2 mutation-positive mCRPC. Niraparib plus AAP demonstrated safety and efficacy in the phase 3 MAGNITUDE trial (NCT03748641).

Discharged from the emergency department following hospital-presented self-harm: referral patterns and risk of repeated self-harm.

Background: Presentation to the emergency department (ED) with self-harm provides an important opportunity for intervention.

Aims: To investigate characteristics and self-harm repetition risk of those discharged from the ED without a referral for mental health-related aftercare.

Method: Data on consecutive self-harm presentations to EDs for the years 2013-2019 (n = 55,770) were obtained from the National Self-Harm Registry Ireland.

An Association between OXPHOS-Related Gene Expression and Malignant Hyperthermia Susceptibility in Human Skeletal Muscle Biopsies.

Malignant hyperthermia (MH) is a pharmacogenetic condition of skeletal muscle that manifests in hypermetabolic responses upon exposure to volatile anaesthetics. This condition is caused primarily by pathogenic variants in the calcium-release channel RYR1, which disrupts calcium signalling in skeletal muscle. However, our understanding of MH genetics is incomplete, with no variant identified in a significant number of cases and considerable phenotype diversity.

Optimized Bags of Artificial Neural Networks Can Predict the Viability of Organisms Exposed to Nanoparticles.

Prediction of organismal viability upon exposure to a nanoparticle in varying environments─as fully specified at the molecular scale─has emerged as a useful figure of merit in the design of engineered nanoparticles. We build on our earlier finding that a bag of artificial neural networks (ANNs) can provide such a prediction when such machines are trained with a relatively small data set (with ca. 200 examples).

How a Canadian federal organization integrated synoptic reporting and quality improvement tools to drive a national learning health system in cancer surgery.

Accurate and complete surgical and pathology reports are the cornerstone of treatment decisions and cancer care excellence. Synoptic reporting is a process for reporting specific data elements in a specific format in surgical and pathology reports. Since 2007, the Canadian Partnership Against Cancer has led the implementation of synoptic reporting mechanisms across multiple cancer disease sites and jurisdictions across Canada.

Development of a universal method for vibrational analysis of the terminal alkyne C≡C stretch.

The terminal alkyne C≡C stretch has a large Raman scattering cross section in the "silent" region for biomolecules. This has led to many Raman tag and probe studies using this moiety to study biomolecular systems. A computational investigation of these systems is vital to aid in the interpretation of these results.

Perilunate Dislocations: Reduction and Stabilization.

Background: The all-dorsal scapholunate reconstruction technique is indicated for the treatment of scapholunate injuries in cases in which the carpus is reducible and there is no arthrosis present. The goal of this procedure is to reconstruct the torn dorsal portion of the scapholunate ligament in order to stabilize the scaphoid and lunate.

Description: A standard dorsal approach to the wrist, extending from the third metacarpal distally to the distal radioulnar joint, is utilized.

Prevalence of food insecurity among caregivers of young children during the COVID-19 pandemic in Ireland.

Our objectives were to explore the prevalence of food insecurity in primary caregivers of young children in Ireland and to compare two tools for measuring food insecurity during the COVID-19 crisis. A cross-sectional online survey was conducted among caregivers of children aged <2 years in Ireland in May/June 2020. Relevant survey questions were closed-ended using two established tools for measuring food poverty/insecurity; the Irish Food Poverty Indicator and the Food Insecurity Experience Scale, developed by the Food and Agriculture Organization.

Weight change following diagnosis with psychosis: a retrospective cohort study in Greater Manchester, UK.

Introduction: Weight gain in the months/years after diagnosis/treatment of severe enduring mental illness (SMI) is a major predictor of future diabetes, dysmetabolic profile and increased risk of cardiometabolic diseases. There is limited data on the longer-term profile of weight change in people with a history of SMI and how this may differ between individuals. We here report a retrospective study on weight change over the 5 years following an SMI diagnosis in Greater Manchester UK, an ethnically and culturally diverse community, with particular focus on comparing non-affective psychosis (NAP) vs affective psychosis (AP) diagnoses.

Cytoneme signaling provides essential contributions to mammalian tissue patterning.

During development, morphogens pattern tissues by instructing cell fate across long distances. Directly visualizing morphogen transport in situ has been inaccessible, so the molecular mechanisms ensuring successful morphogen delivery remain unclear. To tackle this longstanding problem, we developed a mouse model for compromised sonic hedgehog (SHH) morphogen delivery and discovered that endocytic recycling promotes SHH loading into signaling filopodia called cytonemes.