Inhaled alpha-1 antitrypsin (AAT) restores lower respiratory tract protease-antiprotease homoeostasis and reduces inflammation in AAT-deficient individuals: a randomised phase 2 study.

Background: Alpha-1 antitrypsin (AAT)-deficient individuals have a greater risk for developing COPD than individuals with normal AAT levels.

Methods: This was a double-blind, randomised, parallel group, placebo-controlled trial to examine the safety and tolerability of "Kamada-AAT for Inhalation" (inhaled AAT) in subjects with AAT deficiency, and to explore its effect on AAT and biomarkers in the lung epithelial lining fluid (ELF). 36 patients with severe AAT deficiency were randomised 2:1 to receive 80 mg or 160 mg inhaled AAT or placebo once daily for 12 weeks.

Prepared, Protected, EmPowered (P3): Primary Results of a Randomized Controlled Trial Using a Social Networking, Gamification, and Coaching App to Promote Pre-exposure Prophylaxis (PrEP) Adherence for Sexual and Gender Minority (SGM) Youth Living in the United States.

The population-level reductions in HIV incidence attributed to pre-exposure prophylaxis (PrEP) have not been fully realized among sexual, gender, and racial/ethnic minority youth. P3 (Prepared, Protected, emPowered) is a comprehensive mobile application (app) intervention developed to support PrEP adherence through gamification, medication tracking, and social engagement. A randomized controlled trial was conducted with 246 young men who have sex with men (YMSM) and young transgender women who have sex with men (YTWMSM) currently on or planning to begin PrEP.

Delayed Separation of Kaplan-Meier Curves is Commonly Observed in Studies of Advanced/Metastatic Solid Tumors Treated with Anti-PD-(L)1 Therapy: Systematic Review and Meta-Analysis.

Background: Immune checkpoint inhibitor (ICI) Kaplan-Meier (KM) curves often show delayed survival benefit followed by long-term survival in a subgroup of patients. Such outcomes can violate the proportional hazards assumption, leading to a loss of statistical power.

Objective: We aimed to determine common trends in delayed separation to inform future ICI clinical trials.

Perspectives and Factors Related to Pre-exposure Prophylaxis Use Among Young Men Who Have Sex With Men in the United States: A Mixed-Methods Study on the Role of History of PrEP Use.

This study quantitatively examined factors related to young men who have sex with men (YMSM)'s decisions to use pre-exposure prophylaxis (PrEP) by their history of PrEP use and qualitatively elicited their perspectives on PrEP options. Higher proportions of YMSM who had never used (vs. ever used) PrEP considered the following factors as important in their decisions to use PrEP: (a) Returning to PrEP follow-up visits ( p = .

Association of serum biomarkers with radiographic knee osteoarthritis, knee pain and function in a young, male, trauma-exposed population - Findings from the ADVANCE study.

Objective: The ArmeD SerVices TrAuma RehabilitatioN OutComE (ADVANCE) study is investigating long-term combat-injury outcomes; this sub-study aims to understand the association of osteoarthritis (OA) biomarkers with knee radiographic OA (rOA), pain and function in this high-risk population for post-traumatic OA.

Design: ADVANCE compares combat-injured participants with age, rank, deployment and job-role frequency-matched uninjured participants. Post-injury immunoassay-measured serum biomarkers, knee radiographs, Knee Injury and Osteoarthritis Outcome Scale, and six-minute walk tests are reported.

Nuclear RNA: a transcription-dependent regulator of chromatin structure.

Although the majority of RNAs are retained in the nucleus, their significance is often overlooked. However, it is now becoming clear that nuclear RNA forms a dynamic structure through interacting with various proteins that can influence the three-dimensional structure of chromatin. We review the emerging evidence for a nuclear RNA mesh or gel, highlighting the interplay between DNA, RNA and RNA-binding proteins (RBPs), and assessing the critical role of protein and RNA in governing chromatin architecture.

In vivo effect of LATE-NC on integrity of white matter connections to the hippocampus.

Introduction: TAR DNA-binding protein 43 (TDP-43) is a highly prevalent proteinopathy that is involved in neurodegenerative processes, including axonal damage. To date, no ante mortem biomarkers exist for TDP-43, and few studies have directly assessed its impact on neuroimaging measures utilizing pathologic quantification.

Methods: Ante mortem diffusion-weighted images were obtained from community-dwelling older adults.

Differential diagnosis of frontotemporal dementia subtypes with explainable deep learning on structural MRI.

Background: Frontotemporal dementia (FTD) represents a collection of neurobehavioral and neurocognitive syndromes that are associated with a significant degree of clinical, pathological, and genetic heterogeneity. Such heterogeneity hinders the identification of effective biomarkers, preventing effective targeted recruitment of participants in clinical trials for developing potential interventions and treatments. In the present study, we aim to automatically differentiate patients with three clinical phenotypes of FTD, behavioral-variant FTD (bvFTD), semantic variant PPA (svPPA), and nonfluent variant PPA (nfvPPA), based on their structural MRI by training a deep neural network (DNN).

Adverse childhood experiences, cognitive functioning, depression, and anxiety in adulthood.

Background: Evidence suggests that adverse childhood experiences (ACEs) predict cognitive dysfunction, possibly through direct (e.g., brain structure/function changes) and indirect (e.

Comparing Self-Reported Running Distance and Pace With a Commercial Fitness Watch Data: Reliability Study.

Background: There is substantial evidence exploring the reliability of running distance self-reporting and GPS wearable technology, but there are currently no studies investigating the reliability of participant self-reporting in comparison to GPS wearable technology. There is also a critical sports science and medical research gap due to a paucity of reliability studies assessing self-reported running pace.

Objective: The purpose of this study was to assess the reliability of weekly self-reported running distance and pace compared to a commercial GPS fitness watch, stratified by sex and age.

Associations of Muscle Strength with Central Aspects of Pain: Data from the Knee Pain and Related Health in the Community (KPIC) Cohort.

Knee pain is associated with lower muscle strength, and both contribute to disability. Peripheral and central neurological mechanisms contribute to OA pain. Understanding the relative contributions of pain mechanisms to muscle strength might help future treatments.

The student patient alliance: development and formative evaluation of an initiative to support collaborations between patient and public involvement partners and doctoral students.

Background: While the integration of patient and public involvement (PPI) in clinical research is now widespread and recommended as standard practice, meaningful PPI in pre-clinical, discovery science research is more difficult to achieve. One potential way to address this is by integrating PPI into the training programmes of discovery science postgraduate doctoral students. This paper describes the development and formative evaluation of the Student Patient Alliance (SPA), a programme developed at the University of Birmingham that connects PPI partners with doctoral students.

Knee MRI biomarkers associated with structural, functional and symptomatic changes at least a year from ACL injury - A systematic review.

Introduction: Osteoarthritis (OA) results from various aetiologies, including joint morphology, biomechanics, inflammation, and injury. The latter is implicated in post-traumatic OA, which offers a paradigm to identify potential biomarkers enabling early identification and intervention. This review aims to describe imaging features associated with structural changes or symptoms at least one year following injury.

Osteoarthritis in the UK Armed Forces: a review of its impact, treatment and future research.

Within the UK Armed Forces, musculoskeletal injuries account for over half of all medical downgrades and discharges. Data from other Armed Forces show that osteoarthritis (OA), more common in military personnel, is likely to contribute to this, both in its primary form and following injury (post-traumatic OA, PTOA), which typically presents in the third or fourth decade. OA is not a progressive 'wear and tear' disease, as previously thought, but a heterogenous condition with multiple aetiologies and modulators, including joint damage, abnormal morphology, altered biomechanics, genetics, low-grade inflammation and dysregulated metabolism.

Social Determinants of Health: Associations Between Dichotomous Versus Dimensional Scores, Neuropsychological Test Performance, and Psychiatric Symptoms.

This study examined the utility of dichotomous versus dimensional scores across two measures of social determinants of health (SDOH) regarding their associations with cognitive performance and psychiatric symptoms in a mixed clinical sample of 215 adults referred for neuropsychological evaluation ( = 43.91, 53.5% male, 44.

Longitudinal Spatial Relationships Between Atrophy and Hypometabolism Across the Alzheimer's Disease Continuum.

Background: The A/T/N framework allows for the assessment of pathology-specific markers of MRI-derived structural atrophy and hypometabolism on 18FDG-PET. However, how these measures relate to each other locally and distantly across pathology-defined A/T/N groups is currently unclear.

Objective: To determine the regions of association between atrophy and hypometabolism in A/T/N groups both within and across time points.

Investigating the temporal pattern of neuroimaging-based brain age estimation as a biomarker for Alzheimer's Disease related neurodegeneration.

Neuroimaging-based brain-age estimation via machine learning has emerged as an important new approach for studying brain aging. The difference between one's estimated brain age and chronological age, the brain age gap (BAG), has been proposed as an Alzheimer's Disease (AD) biomarker. However, most past studies on the BAG have been cross-sectional.

Mobile Phone Ownership and Use Among Women Screening for Cervical Cancer in a Community-Based Setting in Western Kenya: Observational Study.

Background: Mobile phone ownership among women of reproductive age in western Kenya is not well described, and our understanding of its link with care-seeking behaviors is nascent. Understanding access to and use of mobile phones among this population as well as willingness to participate in mobile health interventions are important in improving and more effectively implementing mobile health strategies.

Objective: This study aims to describe patterns of mobile phone ownership and use among women attending cervical cancer screening and to identify key considerations for the use of SMS text message-guided linkage to treatment strategies and other programmatic implications for cervical cancer screening in Kenya.