Rethinking the residual approach: leveraging statistical learning to operationalize cognitive resilience in Alzheimer's disease.

Cognitive resilience (CR) describes the phenomenon of individuals evading cognitive decline despite prominent Alzheimer's disease neuropathology. Operationalization and measurement of this latent construct is non-trivial as it cannot be directly observed. The residual approach has been widely applied to estimate CR, where the degree of resilience is estimated through a linear model's residuals.

Short-term outcomes of mesh-suture repair in the treatment of ventral hernias: a single-center study.

Background: Defect closure with mesh suture is a novel technique for hernia repair. Originally described as the construction of lightweight macroporous polypropylene mesh strips as a suture material, it is now available as an FDA-approved product. Mesh suture better distributes tensile forces and reduces fascial tearing compared to traditional suture but requires less implanted material and tissue dissection compared to planar mesh.

International myeloma working group immunotherapy committee recommendation on sequencing immunotherapy for treatment of multiple myeloma.

T-cell redirecting therapy (TCRT), specifically chimeric antigen receptor T-cell therapy (CAR T-cells) and bispecific T-cell engagers (TCEs) represent a remarkable advance in the treatment of multiple myeloma (MM). There are several products available around the world and several more in development targeting primarily B-cell maturation antigen (BCMA) and G protein-coupled receptor class C group 5 member D (GRPC5D). The relatively rapid availability of multiple immunotherapies brings the necessity to understand how a certain agent may affect the safety and efficacy of a subsequent immunotherapy so MM physicians and patients can aim at optimal sequential use of these therapies.

The underlying mechanisms of the association of bone health with depression - an experimental study.

Background: Depression constitutes a risk factor for osteoporosis, but underlying molecular and cellular mechanisms are not fully understood. MiRNAs influence gene expression and are carried by extracellular vesicles (EV), affecting cell-cell communication.

Aims: (1) Identify the difference in miRNA expression between depressed patients and healthy controls; (2) Analyze associations of these miRNAs with bone turnover markers; (3) Analyze target genes of differentially regulated miRNAs and predict associated pathways regarding depression and bone metabolism.

An Algorithmic Overview of Advanced Pain Therapies: A Narrative Review.

Purpose Of Review: Quickly referenceable, streamlined, algorithmic approaches for advanced pain management are lacking for patients, trainees, non-pain specialists, and interventional specialists. This manuscript aims to address this gap by proposing a comprehensive, evidence-based algorithm for managing neuropathic, nociceptive, and cancer-associated pain. Such an algorithm is crucial for pain medicine education, offering a structured approach for patient care refractory to conservative management.

Roads to remission: evolving treatment concepts in type 2 inflammatory diseases.

Unlabelled: Non-communicable diseases (NCDs) characterised by type 2 inflammation, including asthma, allergic rhinitis, chronic rhinosinusitis with nasal polyps, atopic dermatitis, food allergies and eosinophilic esophagitis, are increasing in prevalence worldwide. Currently, there is a major paradigm shift in the management of these diseases, towards the concept of disease modification and the treatment goal remission, regardless of severity and age. Remission as a treatment goal in chronic inflammatory NCDs was first introduced in rheumatoid arthritis, and then adopted in other non-type 2 inflammatory diseases.

Interferon activation in bone marrow long-lived plasma cells in systemic lupus erythematosus.

While durable antibody responses from long-lived plasma cell (LLPC) populations are important for protection against pathogens, LLPC may be harmful if they produce antibodies against self-proteins or self-nuclear antigens as occurs in autoimmune diseases such as systemic lupus erythematosus (SLE). Thus, the elimination of autoreactive LLPC may improve the treatment of antibody-driven autoimmune diseases. However, LLPC remain a challenging therapeutic target.

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.

Safety, tolerability and therapeutic efficacy of anti-inflammatory drug pirfenidone in acute pancreatitis patients: Protocol for a randomized pilot clinical trial.

Background: Acute Pancreatitis (AP) is a formidable disease with significant morbidity, mortality and healthcare expenditure. There is an emergent need to develop therapeutic agents for this disease as there are no targeted therapies available. We have recently demonstrated that pirfenidone can significantly decrease the severity of AP in animal models.

Sex-specific effects on the heart from combined exposure to simulated galactic cosmic radiation and hindlimb unloading.

Future long duration space missions will expose astronauts to higher doses of galactic cosmic radiation (GCR) than those experienced on the international space station. Recent studies have demonstrated astronauts may be at risk for cardiovascular complications due to increased radiation exposure and fluid shift from microgravity. However, there is a lack of direct evidence on how the cardiovascular system is affected by GCR and microgravity since no astronauts have been exposed to exploratory mission relevant GCR doses.

Sleep variability and time to achieving pregnancy: findings from a pilot cohort study of women desiring pregnancy.

Objective: To determine whether chronodisruption is associated with achieving pregnancy.

Design: Pilot prospective cohort study.

Subjects: One hundred eighty-three women desiring pregnancy were recruited from the local community of an academic medical center located in the Midwest and provided sleep information between February 1, 2015, and November 30, 2017.

Future directions in the evaluation and management of newly diagnosed metastatic cancer.

There is a much debate regarding optimal selection in patients with metastatic cancer who should undergo local treatment (surgery or radiation treatment) to the primary tumor and/or metastases. Additionally, the optimal treatment of newly diagnosed metastatic cancer is largely unclear. Current prognostication systems to best inform these clinical scenarios are limited, as all metastatic patients are grouped together as having Stage IV disease without further incorporation of patient and disease-specific covariates that significantly impact patient outcomes.

Mobilize the Troops! Military Involvement in the History of Testicular Cancer.

This review examines the historical evolution of testicular cancer (TCa) treatment, emphasizing the transformative impact of World War II. Prior to the war, cases of more than 50 testicular tumors were exceedingly rare. The mobilization of American troops, especially after the German Blitz, resulted in widespread military health screenings, leading to a surge in incidental TCa diagnoses during the 1940s.

The influence of genotype on the natural history of types 1 - 3 spinal muscular atrophy.

The severity of spinal muscular atrophy (SMA) is inversely correlated with the number of survival of motor neuron 2 (SMN2) copies an individual has. This observational, retrospective analysis of natural history data included untreated individuals with a genetic diagnosis of types 1-3 SMA and stratified disease-related characteristics by SMN2 copy number. The outcomes investigated were time to: death, permanent ventilation, respiratory support, feeding support, scoliosis surgery, and achievement and loss of motor milestones.

Evaluating Clinician Experience in Health Care Transition: Results From Six Health Systems.

Purpose: There is a paucity of evidence examining clinician experiences with structured health-care transition (HCT) programs. Among HCT Learning Collaborative participants, this study describes clinician experiences with implementation of a structured HCT process: Got Transition's 6 Core Elements.

Methods: Representative members from 6 health systems designed a survey to collect clinician feedback regarding HCT and demographic and practice information.

Fluid flow impacts endothelial-monocyte interactions in a model of vascular inflammatory fibrosis.

The aberrant vascular response associated with tendon injury results in circulating immune cell infiltration and a chronic inflammatory feedback loop leading to poor healing outcomes. Studying this dysregulated tendon repair response in human pathophysiology has been historically challenging due to the reliance on animal models. To address this, our group developed the human tendon-on-a-chip (hToC) to model cellular interactions in the injured tendon microenvironment; however, this model lacked the key element of physiological flow in the vascular compartment.

Apixaban versus aspirin for stroke prevention in people with subclinical atrial fibrillation and a history of stroke or transient ischaemic attack: subgroup analysis of the ARTESiA randomised controlled trial.

Background: People with subclinical atrial fibrillation are at increased risk of stroke, albeit to a lesser extent than those with clinical atrial fibrillation, leading to an ongoing debate regarding the benefit of anticoagulation in these individuals. In the ARTESiA trial, the direct-acting oral anticoagulant apixaban reduced stroke or systemic embolism compared with aspirin in people with subclinical atrial fibrillation, but the risk of major bleeding was increased with apixaban. In a prespecified subgroup analysis of ARTESiA, we tested the hypothesis that people with subclinical atrial fibrillation and a history of stroke or transient ischaemic attack, who are known to have an increased risk of recurrent stroke, would show a greater benefit from oral anticoagulation for secondary stroke prevention compared with those without a history of stroke or transient ischaemic attack.

Intranasal oxytocin for apathy in people with frontotemporal dementia (FOXY): a multicentre, randomised, double-blind, placebo-controlled, adaptive, crossover, phase 2a/2b superiority trial.

Background: No treatments exist for apathy in people with frontotemporal dementia. Previously, in a randomised double-blind, placebo-controlled, dose-finding study, intranasal oxytocin administration in people with frontotemporal dementia improved apathy ratings on the Neuropsychiatric Inventory over 1 week and, in a randomised, double-blind, placebo-controlled, crossover study, a single dose of 72 IU oxytocin increased blood-oxygen-level-dependent signal in limbic brain regions. We aimed to determine whether longer treatment with oxytocin improves apathy in people with frontotemporal dementia.

Hidradenitis suppurativa.

Hidradenitis suppurativa is a chronic inflammatory disease characterised by painful, deep-seated nodules, abscesses, and draining tunnels in the skin of axillary, inguinal, genitoanal, or inframammary areas. In recent years, the body of knowledge in hidradenitis suppurativa has advanced greatly. This disorder typically starts in the second or third decade of life.

The Anatomy of Gossip: Dissecting Dynamics and Impacts in Surgical Residency.

Background: Gossip, defined by social scientists as "evaluative talk about an absent third party," is anecdotally pervasive yet poorly understood in surgical residency programs. Gossip is known to have both positive and negative impacts. This study sought to deconstruct the role of gossip in surgical residency and evaluate its impact through the lens of surgical residents.