A humanized anti-MSLN×4-1BB bispecific antibody exhibits potent antitumour activity through 4-1BB signaling activation and fc function without systemic toxicity.

Background: Agonistic monoclonal antibodies targeting 4-1BB/CD137 have shown preclinical promise, but their clinical development has been limited by severe liver toxicity or limited efficacy. Therefore, a safe and efficient immunostimulatory molecule is urgently needed for cancer immunotherapy.

Methods: A novel anti-MSLN×4-1BB bispecific antibody (bsAb) was generated via antibody engineering, and its affinity and activity were detected via enzyme-linked immunosorbent assay (ELISA), flow cytometry, and T-cell activation and luciferase reporter assays.

Exploring the General Acceptability and User Experience of a Digital Therapeutic for Cognitive Training in a Singaporean Older Adult Population: Qualitative Study.

Background: Singapore's large aging population poses significant challenges for the health care system in managing cognitive decline, underscoring the importance of identifying and implementing effective interventions. Cognitive training delivered remotely as a digital therapeutic (DTx) may serve as a scalable and accessible approach to overcoming these challenges. While previous studies indicate the potential of cognitive training as a promising solution for managing cognitive decline, understanding the attitudes and experiences of older adults toward using such DTx platforms remains relatively unexplored.

Insights into age-related osteoporosis from senescence-based preclinical models and human accelerated aging paradigms.

Preclinical models of age-related osteoporosis have been developed based on the accumulation and clearance of senescent cells. The former include animal models based on telomere dysfunction and focal radiation; the latter based on genetic and pharmacological targeting (i.e.

The telomere connection between aging and cancer: The burden of replication stress and dysfunction.

Aging is a complex process that affects individuals at the molecular, cellular, tissue, and systemic levels, arising from the cumulative effects of damage and diminished repair mechanisms. This process leads to the onset of age-related diseases, including cancer, which exhibits increased incidence with age. Telomeres, the protective caps at chromosome ends, play a crucial role in genome stability and are closely connected with aging and age-related disorders.

Comparing analog and 3D measurements of vertical dimension in edentulous subjects.

Objective: This study aimed to explore the feasibility and reliability of measuring the vertical dimension of occlusion/rest (OVD/RVD) on 3D facial scans of edentulous patients.

Methods: Nineteen edentulous participants rehabilitated with complete removable dental prostheses (CDs) participated in this study. Analog measurements (control) were obtained directly on the face for each participant with the jaws positioned at the rest position (without CDs, RVD) and at central occlusion (OVD), between the facial landmarks: Glabella (G) and Soft Pogonion (SP), Pronasale (PN) and SP, and Subnasale (SN) and SP.

Baseline characteristics of patients in the Chinese Bronchiectasis Registry (BE-China): a multicentre prospective cohort study.

Background: Bronchiectasis is a disease with a global impact, but most published data come from high-income countries. We aimed to describe the clinical characteristics of patients with bronchiectasis in China.

Methods: The Chinese Bronchiectasis Registry (BE-China) is a prospective, observational cohort enrolling patients from 111 hospitals in China.

Effectiveness of Synchronous Postdischarge Contacts on Health Care Use and Patient Satisfaction : A Systematic Review and Meta-analysis.

Background: Postdischarge contacts (PDCs) after hospitalization are common practice, but their effectiveness in reducing use of acute care after discharge remains unclear.

Purpose: To assess the effects of PDC on 30-day emergency department (ED) visits, 30-day hospital readmissions, and patient satisfaction.

Data Sources: MEDLINE, Embase, and CINAHL searched from 2012 to 25 May 2023.

Longitudinal FDG-PET Metabolic Change Along the Lewy Body Continuum.

Importance: Although 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) is a well-established cross-sectional biomarker of brain metabolism in dementia with Lewy bodies (DLB), the longitudinal change in FDG-PET has not been characterized.

Objective: To investigate longitudinal FDG-PET in prodromal DLB and DLB, including a subsample with autopsy data, and report estimated sample sizes for a hypothetical clinical trial in DLB.

Design, Setting, And Participants: Longitudinal case-control study with mean (SD) follow-up of 3.

East Asia and the Pacific Surveillance Metrics and History of the COVID-19 Pandemic: Updated Epidemiological Assessment.

Background: This study updates the COVID-19 pandemic surveillance in East Asia and the Pacific we first conducted in 2020 with two additional years of data for the region.

Objective: First, we measure whether there was an expansion or contraction of the pandemic in East Asia and the Pacific region when the World Health Organization (WHO) declared the end of the COVID-19 public health emergency of international concern on May 5, 2023. Second, we use dynamic and genomic surveillance methods to describe the dynamic history of the pandemic in the region and situate the window of the WHO declaration within the broader history.

Prevalence and type of removable prostheses manufactured in dental laboratories in Switzerland over the last 10 years.

Due to effective preventive measures and advanced techniques in operative dentistry, tooth loss occurs later in life and implant restorations have become a common solution for replacement of missing teeth. Therefore, the use of removable dental prostheses (RDPs) is expected to decline over time. This study aims to evaluate the expected decrease in the production of RDPs in Swiss dental laboratories over the past decade.

Do We Have Sufficient Evidence to Derive Innovative Approaches to Assessing Unmet Need, Delivering Education on Bladder and Bowel Continence Health, and Providing a Better Environment for Joint Decision-Making? ICI-RS 2024.

Context: Improved continence outcomes are reliant on identification of unmet need, education delivery, and shared decision-making. The evidence base on which to derive innovative approaches in these areas was unclear.

Methods: A debate held at the International Consultation on Incontinence-Research Society meeting, held in Bristol in June 2024, considered ways to improve research requirements to advance these areas.

Dietary Interventions in Heart Failure With Preserved Ejection Fraction: A Scoping Review.

Patients with heart failure with preserved ejection fraction (HFpEF) are burdened by multiple diet-sensitive comorbidities, including obesity and malnutrition. Despite this, a low percentage of patients with HFpEF have been enrolled in dietary intervention trials in heart failure and few dietary interventions have been conducted in HFpEF exclusively. This scoping review will examine available evidence regarding dietary interventions in patients with HFpEF, highlight existing gaps in knowledge, and discuss emerging dietary therapies in this population.

Corticosteroid therapy and long-term outcomes in patients with cardiac sarcoidosis stratified by left ventricular ejection fraction.

Aims: This study aimed to investigate the relationship between corticosteroid therapy and long-term outcomes in patients with cardiac sarcoidosis, stratified by left ventricular ejection fraction (LVEF) at diagnosis.

Methods And Results: This study conducted a analysis of the ILLUstration of the Management and prognosIs of JapaNese PATiEnts with Cardiac Sarcoidosis, a retrospective multicentre registry. Cardiac sarcoidosis was diagnosed based on the 2016 Japanese Circulation Society and 2014 Heart Rhythm Society criteria.

Early career psychiatrists' perceptions of and training experience in electroconvulsive therapy: A cross-sectional survey across Europe.

Background: Electroconvulsive therapy (ECT) is a safe and effective treatment for several major psychiatric conditions, including treatment-resistant depression, mania, and schizophrenia; nevertheless, its use remains controversial. Despite its availability in some European countries, ECT is still rarely used in others. This study aims to investigate the experiences and attitudes of early career psychiatrists (ECPs) across Europe towards ECT and to examine how their exposure to ECT influences their perceptions.

Frailty index predicts adverse short- and long-term outcomes in older adults with rib fractures.

Background: Older adults with rib fractures pose an increasing clinical and financial burden on healthcare. Identifying and addressing the increased risk of adverse outcomes has been a key objective in geriatric co-management of surgical patients. The Comprehensive Geriatric Assessment-based Frailty Index (FI-CGA) is a useful predictor of complications and mortality in older adults, but its value in rib fracture management remains unclear.

Point of view: Challenges in implementation of new immunotherapies for Alzheimer's disease.

The advancement of disease-modifying treatments (DMTs) for Alzheimer's disease (AD), along with the approval of three amyloid-targeting therapies in the US and several other countries, represents a significant development in the treatment landscape, offering new hope for addressing this once untreatable chronic progressive disease. However, significant challenges persist that could impede the successful integration of this class of drugs into clinical practice. These challenges include determining patient eligibility, appropriate use of diagnostic tools and genetic testing in patient care pathways, effective detection and monitoring of side effects, and improving the healthcare system's readiness by engaging both primary care and dementia specialists.

Informal care for people with dementia in Europe.

Introduction: Informal care estimates for use in health-economic models are lacking. We aimed to estimate the association between informal care time and dementia symptoms across Europe.

Methods: A secondary analysis was performed on 13,529 observations in 5,369 persons from 9 European pooled cohort or trial studies in community-dwelling persons with dementia.

Genetic predisposition to high circulating levels of interleukin 6 and risk for Alzheimer's disease. Discovery and replication.

Importance: Aging is accompanied by immune dysregulation, which has been implicated in Alzheimer's disease (AD) pathogenesis. Individuals who are genetically predisposed to elevated levels of proinflammatory mediators might be at increased risk for AD.

Objective: To investigate whether genetic propensity for higher circulating levels of interleukin 6 (IL-6) is associated with AD risk.

Implementation of patient-reported outcome dashboards within the electronic health record to support shared decision-making in serious chronic illness.

Background: Attending to patient-reported outcomes (PROs) using data visualisation dashboards could enhance shared decision-making (SDM) and care delivery for serious chronic illnesses. However, few studies have evaluated real-world strategies and resulting implementation outcomes of PRO dashboards.

Method: From June 2020 to January 2022, we implemented an electronic health record (EHR)-integrated PRO dashboard for advanced cancer and chronic kidney disease.

Delayed primacy recall in AVLT is associated with medial temporal tau PET burden in cognitively unimpaired adults.

Background: Alzheimer's disease (AD) can be diagnosed by in vivo abnormalities of amyloid-β plaques (A) and tau accumulation (T) biomarkers. Previous studies have shown that analyses of serial position performance in episodic memory tests, and especially, delayed primacy, are associated with AD pathology even in individuals who are cognitively unimpaired. The earliest signs of cortical tau pathology are observed in medial temporal lobe (MTL) regions, yet it is unknown if serial position markers are also associated with early tau load in these regions.

Granting Permission: Toward Embracing Grief.

Grief, unavoidable and often excruciating, is rarely sufficiently acknowledged or supported in Western society. It is not granted to exist without barriers. By considering and evaluating grief experiences through the lens of their access to , clinicians can collectively imagine and promote inclusivity in grief.