Cerebral Microbleeds and Amyloid Pathology Estimates From the Amyloid Biomarker Study.

Importance: Baseline cerebral microbleeds (CMBs) and APOE ε4 allele copy number are important risk factors for amyloid-related imaging abnormalities in patients with Alzheimer disease (AD) receiving therapies to lower amyloid-β plaque levels.

Objective: To provide prevalence estimates of any, no more than 4, or fewer than 2 CMBs in association with amyloid status, APOE ε4 copy number, and age.

Design, Setting, And Participants: This cross-sectional study used data included in the Amyloid Biomarker Study data pooling initiative (January 1, 2012, to the present [data collection is ongoing]).

Depressive Symptoms and Amyloid Pathology.

Importance: Depressive symptoms are associated with cognitive decline in older individuals. Uncertainty about underlying mechanisms hampers diagnostic and therapeutic efforts. This large-scale study aimed to elucidate the association between depressive symptoms and amyloid pathology.

Clinical Phenotype and Prognosis of Asymptomatic Patients With Transthyretin Cardiac Amyloid Infiltration.

Importance: Patients with transthyretin (ATTR) cardiac amyloid infiltration are increasingly diagnosed at earlier disease stages with no heart failure (HF) symptoms and a wide range of cardiac amyloid infiltration.

Objective: To characterize the clinical phenotype and natural history of asymptomatic patients with ATTR cardiac amyloid infiltration.

Design, Setting, And Participants: This cohort study analyzed data of all patients at 12 international centers for amyloidosis from January 1, 2008, through December 31, 2023.

Dual ligand functionalized pH-sensitive liposomes for metastatic breast cancer treatment: and assessment.

This research demonstrates the design and development of a novel dual-targeting, pH-sensitive liposomal (pSL) formulation of 5-Fluorouracil (5-FU), , (5-FU-iRGD-FA-pSL) to manage breast cancer (BC). The motivation to explore this formulation is to overcome the challenges of systemic toxicity and non-specific targeting of 5-FU, a conventional chemotherapeutic agent. The proposed formulation also combines folic acid (FA) and iRGD peptides as targeting ligands to enhance tumor cell specificity and penetration, while the pH-sensitive liposomes ensure the controlled drug release in the acidic tumor microenvironment.

Nonpharmacological Childhood Obesity Management in Denmark Reduces Steatotic Liver Disease and Obesity.

Steatotic liver disease (SLD) represents a multisystem disease and is a common complication of childhood obesity. We studied fat content at the abdominal level (liver, subcutaneous, and visceral) and the response to childhood obesity management. In this retrospective longitudinal study, 8-18-year-olds with a body mass index (BMI) z-score above 1.

The Cu site in particulate methane monooxygenase may be used to produce hydrogen peroxide.

Particulate methane monooxygenase (pMMO) is the most efficient of the two groups of enzymes that can hydroxylate methane. The enzyme is membrane bound and therefore hard to study experimentally. For that reason, there is still no consensus regarding the location and nature of the active site.

CpG island methylator phenotype classification improves risk assessment in pediatric T-cell Acute Lymphoblastic Leukemia.

Current intensive treatment of pediatric T-cell acute lymphoblastic leukemia (T-ALL) has substantial side-effects, highlighting a need for novel biomarkers to improve risk stratification. Canonical biomarkers such as genetics and immunophenotype are largely not used in pediatric T-ALL stratification. This study aimed to validate the prognostic relevance of DNA methylation CpG island methylator phenotype (CIMP) risk stratification in two pediatric T-ALL patient cohorts: the Nordic NOPHO ALL2008 T-ALL study cohort (n=192) and the Dutch DCOG ALL-10/ALL-11 validation cohorts (n=156).

Immunogenicity of the 9-valent human papillomavirus vaccine: Post hoc analysis from five phase 3 studies.

Post hoc analyses of 9-valent human papillomavirus (9vHPV) vaccine immunogenicity were conducted in five Phase 3 studies that enrolled males. Month 7 antibody geometric mean titers (GMTs) after three 9vHPV vaccine doses were analyzed in 10,024 males/females aged 16-26 years from studies 001 (NCT00543543), 002 (NCT00943722), 003 (NCT01651949), and 020 (NCT02114385). Covariates considered were age, gender, sexual orientation, region of residence, and race.

Loop engineering of enzymes to control their immobilization and ultimately fabricate more efficient heterogeneous biocatalysts.

Enzyme immobilization is indispensable for enhancing enzyme performance in various industrial applications. Typically, enzymes require specific spatial arrangements for optimal functionality, underscoring the importance of correct orientation. Despite well-known N- or C-terminus tailoring techniques, alternatives for achieving orientation control are limited.

Impacts of hnRNP A1 Splicing Inhibition on the Brain Remyelination Proteome.

Oligodendrocytes, the myelinating cells in the central nervous system, are implicated in several neurological disorders marked by dysfunctional RNA-binding proteins (RBPs). The present study aimed at investigating the role of hnRNP A1 in the proteome of the corpus callosum, prefrontal cortex, and hippocampus of a murine cuprizone-induced demyelination model. Right after the cuprizone insult, we administered an hnRNP A1 splicing activity inhibitor and analyzed its impact on brain remyelination by nanoESI-LC-MS/MS label-free proteomic analysis to assess the biological processes affected in these brain regions.

Amplifying Women's Voices in Menopause Research: The Importance of Inclusive Perspectives.

Menopause, a significant life transition for half the global population, intersects biological, cultural and social dimensions. Despite its universal occurrence, menopause research has historically been dominated by biomedical perspectives, often neglecting women's voices and diverse experiences. This article highlights the importance of including women's perspectives in menopause research to ensure relevance, accuracy and equity.

Achievement of HbA1c and weight targets in adults with type 2 diabetes on once weekly injectable glucagon-like peptide-1 receptor agonist therapy in UK primary care: A retrospective, real-world study.

Aims: Evaluate glycated haemoglobin (HbA1c) and weight changes after 6 months of once-weekly (QW) injectable glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in UK primary care.

Materials And Methods: Retrospective, non-interventional study, using the Clinical Practice Research Datalink Aurum primary care database, identified adults with type 2 diabetes (T2D) newly initiating a QW injectable GLP-1 RA between January 2020 and November 2021. Dual primary outcomes were proportion of patients with (1) HbA1c < 7% (<53 mmol/mol) and (2) weight loss categories (from 0% to 15+%) after 6 months of continuous GLP-1 RA therapy.

Evidence-Based Application of Natriuretic Peptides in the Evaluation of Chronic Heart Failure With Preserved Ejection Fraction in the Ambulatory Outpatient Setting.

Background: Plasma NT-proBNP (N-terminal pro-B-type natriuretic peptide) is commonly used to diagnose heart failure with preserved ejection fraction (HFpEF), but its diagnostic performance in the ambulatory/outpatient setting is unknown because previous studies lacked objective reference standards.

Methods: Among patients with chronic dyspnea, diagnosis of HFpEF or noncardiac dyspnea was determined conclusively by exercise catheterization in a derivation cohort (n=414), multicenter validation cohort 1 (n=560), validation cohort 2 (n=207), and a nonobese Japanese validation cohort 3 (n=77). Optimal NT-proBNP cut points for HFpEF rule out (optimizing sensitivity) and rule in (optimizing specificity) were derived and tested, stratified by obesity and atrial fibrillation.

Detection of clinically relevant variants in the gene below 10% allelic frequency: A multicenter study by ERIC, the European Research Initiative on CLL.

In chronic lymphocytic leukemia, the reliability of next-generation sequencing (NGS) to detect variants ≤10% allelic frequency (low-VAF) is debated. We tested the ability to detect 23 such variants in 41 different laboratories using their NGS method of choice. The sensitivity was 85.

Chronic enteropathy in dogs affects the quality of life in both dogs and their owners-are veterinarians proficient in handling the caregiver burden?

Introduction: Chronic disease is generally known to affect dogs' quality of life (QoL) as well as being associated with increased strain on their owners. Gastrointestinal (GI) disease is a common problem in companion animal practice, yet little is known about the QoL of dogs with chronic enteropathy (CE) and how their owners and veterinarians assess it.

Methods: The aim of this study was to explore: (i) how dog owners and veterinarians observed and evaluated QoL for dogs with chronic GI disease, (ii) how having a dog with CE affected the owner's QoL, and (iii) characteristics of the communication and relationship between the dog owner and veterinarian.

Exoskeleton Training for Spinal Cord Injury Neuropathic Pain (ExSCIP): Protocol for a Phase 2 Feasibility Randomised Trial.

Background: Following Spinal Cord Injury (SCI), 53% of people develop neuropathic pain (NP). NP can be more debilitating than other consequences of SCI, and a persistent health issue. Pharmacotherapies are commonly recommended for NP management in SCI, although severe pain often remains refractory to these treatments in many sufferers.

Performance of the 1 h oral glucose tolerance test in predicting type 2 diabetes and association with impaired β-cell function in Asians: a national prospective cohort study.

Background: Postprandial glucose concentration 1-h (1 h-PG) after an oral glucose tolerance test (OGTT) has similar or superior performance to 2 h-PG in predicting type-2 diabetes mellitus (T2DM) in several populations, and is simpler to obtain in clinical practice. However, studies in Asians are scarce. We investigated the utility of elevated baseline 1 h-PG in predicting T2DM incidence within three years, and its relationship with β-cell function in 1250 non-diabetic Asian participants.

VACCIMEL, an allogeneic melanoma vaccine, efficiently triggers T cell immune responses against neoantigens and alloantigens, as well as against tumor-associated antigens.

VACCIMEL is a therapeutic cancer vaccine composed of four irradiated allogeneic human melanoma cell lines rationally selected to cover a wide range of melanoma tumor-associated antigens (TAA). We previously demonstrated that vaccination in the adjuvant setting prolonged the distant-metastasis-free survival of cutaneous melanoma patients and that T cells reactive to TAA and the patient's private neoantigens increased during treatment. However, immune responses directed to vaccine antigens that may arise from VACCIMEL's somatic mutations and human polymorphisms remain unexplored.

Ethics of Procuring and Using Organs or Tissue from Infants and Newborns for Transplantation, Research, or Commercial Purposes: Protocol for a Bioethics Scoping Review.

Unlabelled: Since the inception of transplantation, it has been crucial to ensure that organ or tissue donations are made with valid informed consent to avoid concerns about coercion or exploitation. This issue is particularly challenging when it comes to infants and younger children, insofar as they are unable to provide consent. Despite their vulnerability, infants' organs and tissues are considered valuable for biomedical purposes due to their size and unique properties.

Cross-cultural adaptation and validation of the Spanish version of the Prevent for Work questionnaire.

Background: Musculoskeletal pain represents an increase in medical expenses due to disability and decreased quality of life among workers. Various biopsychosocial factors contribute to the development of persistent and disabling musculoskeletal pain. The Prevent for Work questionnaire (P4Wq) intended to analyze these factors.

Regulatory problems and developmental psychopathology within the first 2 years of living-a nested in cohort population-based study.

Background: Infancy regulatory problems (RP) of sleep, feeding and eating, and excessive crying are thought to play a key role in the development of psychopathology in childhood, but knowledge of the early trajectories is limited.

Objective: To explore RP at ages 8-11 months and the associations with mental health problems at 1½ years, and assess the influences of maternal mental health problems and relationship problems.

Methods: RP was explored in a nested in-cohort sample ( = 416) drawn from a community-based cohort ( = 2,973).

Complications during chest tube drainage for iatrogenic pneumothorax.

Background: Iatrogenic pneumothorax is a common complication of diagnostic and therapeutic pulmonary procedures. New guidelines on primary spontaneous pneumothorax suggest ambulatory approaches may be suitable. However, guidance on iatrogenic pneumothorax occurring in patients with impaired lung function, increased age, comorbidity and frailty is lacking, and the safety profile of ambulatory management is not known.

Detecting respiratory impairment in newly diagnosed rheumatoid arthritis by MRC dyspnoea scale and microfibrillar-associated protein 4.

Objectives: To evaluate the Medical Research Council (MRC) dyspnoea scale and serum Microfibrillar-associated protein 4 (MFAP4) levels for the detection of respiratory impairment in newly diagnosed rheumatoid arthritis (RA).

Methods: Patients underwent blood tests, pulmonary function tests (PFT) and dyspnoea assessment using the MRC scale. Respiratory impairment was defined as a diffusion capacity of the lungs for carbon monoxide (DLCO) <80% predicted or FEV1/FVC <70%.