A novel label-free method to determine equilibrium dissociation constants of antibodies binding to cell surface proteins.

Solution-based affinity assays are used for the selection and characterization of proteins that could be developed into therapeutic molecules. However, these assays have limitations for cell-surface proteins as in most cases their purification requires detergent solubilization and are unlikely to assume conformations in solution that resemble their native states in cell membranes. This report describes a novel electrochemiluminescence-based method, called MSD-CAT, for the affinity analysis of antibodies binding to cell-surface receptors.

Informed Consent and Shared Decision-Making in Modern Medicine. Case-based Approach, Current Gaps and Practical Proposal.

Advances in personalized medicine and Systems Biology have introduced probabilistic models and error discovery to cardiovascular care, aiding disease prevention and procedural planning. However, clinical application faces cultural, technical, and methodological hurdles. Patient autonomy remains essential, with shared decision-making (SDM) gaining importance in managing complex cardiovascular treatment options.

Biochemical, structural, and cellular characterization of S-but-3-yn-2-ylglycine as a mechanism-based covalent inactivator of the flavoenzyme proline dehydrogenase.

The mitochondrial flavoenzymes proline dehydrogenase (PRODH) and hydroxyproline dehydrogenase (PRODH2) catalyze the first steps of proline and hydroxyproline catabolism, respectively. The enzymes are targets for chemical probe development because of their roles in cancer cell metabolism (PRODH) and primary hyperoxaluria (PRODH2). Mechanism-based inactivators of PRODH target the FAD by covalently modifying the N5 atom, with N-propargylglycine (NPPG) being the current best-in-class of this type of probe.

Methods to Adjust for Confounding in Test-Negative Design COVID-19 Effectiveness Studies: Simulation Study.

Background: Real-world COVID-19 vaccine effectiveness (VE) studies are investigating exposures of increasing complexity accounting for time since vaccination. These studies require methods that adjust for the confounding that arises when morbidities and demographics are associated with vaccination and the risk of outcome events. Methods based on propensity scores (PS) are well-suited to this when the exposure is dichotomous, but present challenges when the exposure is multinomial.

Examining Mammalian facial behavior using Facial Action Coding Systems (FACS) and combinatorics.

There has been an increased interest in standardized approaches to coding facial movement in mammals. Such approaches include Facial Action Coding Systems (FACS), where individuals are trained to identify discrete facial muscle movements that combine to create a facial configuration. Some studies have utilized FACS to analyze facial signaling, recording the quantity of morphologically distinct facial signals a species can generate.

Genetic Services in Appalachia Conference Series.

This study examined the data generated as part of a seven-session webinar series that focused on genetics care provision in the medically underserved, rural Appalachian region and examined how these services have adapted to challenging practice environments. Barriers and facilitators to care in our region were considered. Data included a baseline survey of registrants, transcripts of sessions, and feedback about sessions.

Transaxillary endovascular aortic aneurysm repair using a reverse mounted Gore Excluder endograft for a patient with abdominal aortic aneurysm and severe iliofemoral occlusive disease.

Adverse iliofemoral anatomy represents a unique challenge for endovascular aortic aneurysm repair (EVAR). This report describes a transaxillary EVAR in a patient with severe iliofemoral occlusive disease and an infrarenal aortic aneurysm. A reversely mounted Gore Excluder graft was advanced and deployed in the infrarenal aorta using the left axillary artery.

Generative artificial intelligence in graduate medical education.

Generative artificial intelligence (GenAI) is rapidly transforming various sectors, including healthcare and education. This paper explores the potential opportunities and risks of GenAI in graduate medical education (GME). We review the existing literature and provide commentary on how GenAI could impact GME, including five key areas of opportunity: electronic health record (EHR) workload reduction, clinical simulation, individualized education, research and analytics support, and clinical decision support.

Rare variants in PRKCI cause Van der Woude syndrome and other features of peridermopathy.

Van der Woude syndrome (VWS) is an autosomal dominant disorder characterized by lower lip pits and orofacial clefts (OFCs). With a prevalence of approximately 1 in 35,000 live births, it is the most common form of syndromic clefting and may account for ~2% of all OFCs. The majority of VWS is attributed to genetic variants in IRF6 (~70%) or GRHL3 (~5%), leaving up to 25% of individuals with VWS without a molecular diagnosis.

Motor network reorganization associated with rTMS-induced writing improvement in writer's cramp dystonia.

Background: Writer's cramp (WC) dystonia is an involuntary movement disorder with distributed abnormalities in the brain's motor network. Prior studies established the potential for repetitive transcranial magnetic stimulation (rTMS) to either premotor cortex (PMC) or primary somatosensory cortex (PSC) to modify symptoms. However, clinical effects have been modest with limited understanding of the neural mechanisms hindering therapeutic advancement of this promising approach.

A novel TERT variant associated with a telomere biology disorder and challenges in variant classification.

Telomere biology disorders (TBDs) are inherited conditions associated with multisystem manifestations. We describe clinical and functional characterisation of a novel TERT variant. Whole-genome sequencing was performed along with single length analysis ().

Re-evaluation of mastodon material from Oregon and Washington, USA, Alberta, Canada, and Hidalgo and Jalisco, Mexico.

The presence of at least two contemporaneous Pleistocene mastodon taxa in North America ( and ) invites re-examination of specimens at the geographic margins of each species in order to determine range boundaries, overlaps, and fluctuations. Third molars from Oregon in the United States, as well as from Hidalgo and Jalisco in Mexico, were found to be morphologically consistent with . Washington in the United States includes a number of specimens that could not be confidently assigned to either taxon.

Systematic Review of Granulomatous Invasive Fungal Sinusitis Management.

Objectives: Granulomatous invasive fungal sinusitis (GIFS) affects immunocompetent individuals. There is ongoing debate over whether surgery, antifungal medication, or a combined approach is the best treatment. This article summarizes reports about GIFS and its management.

A 5-year single-center review of seropositivity in kidney transplant candidates in Central Texas.

Introduction: is a soil-transmitted helminth that can lead to life-threatening hyperinfection in transplant recipients. Targeted screening based on social history alone may preclude a large proportion of seropositive patients. Our institution implemented universal screening for kidney transplant candidates.

Body mass index and sleep disorders after moderate-to-severe traumatic brain injury - a national TBI model systems study.

Objective: To examine the relationship between body mass index (BMI), newly developed sleep disorders and functional outcome after moderate-to-severe traumatic brain injury (msTBI).

Methods: Retrospective data from the TBI Model Systems National Database was analyzed, focusing on the independent association between BMI, sleep disorder diagnosis, and functional outcome as measured by the Extended Glasgow Outcome Scale (GOSE) at 1-year post-injury. Linear and logistic regression were used.

Electrophysiological Characterization of Monoolein-Fatty Acid Bilayers.

Understanding the evolution of protocells, primitive compartments that distinguish self from nonself, is crucial for exploring the origin of life. Fatty acids and monoglycerides have been proposed as key components of protocell membranes due to their ability to self-assemble into bilayers and vesicles capable of nutrient exchange. In this study, we investigate the electrophysiological properties of planar bilayers composed of monoglyceride and fatty acid mixtures, using a droplet interface bilayer system.

Building a Culture of Health Through Leader-Inspired Nutrition.

The balance of operational readiness and maintaining a healthy recruitment force presents increasing challenges within the DoD. Chronic preventable diseases, such as overweight and obesity, along with musculoskeletal injuries, are threats to recruitment and retention. Novel approaches are needed and leaders are in a unique position to serve a key role in influencing nutrition readiness.

'This modern Cinderella': Railway Queens, mass media, and British civic culture, 1925-75.

Between 1925 and 1975, the British railway industry elected beauty queens from the daughters of employees. Focusing upon the Railway Queens, this article will reveal the importance of beauty queens as 'civic celebrities', a novel role for public figures that emerged between the wars and helped to sustain a vibrant civic culture across the early to mid-twentieth century. It combined the traditional ceremonial function of 'civic' representative with the modern consumerist ethos of media 'celebrity'.

Exploring the Implementation of Cognitive Screening in First-Episode Psychosis Settings: The CogScreen Implementation Study.

Aim: Accurate and appropriate cognitive screening can significantly enhance early psychosis care, yet no screening tools have been validated for the early psychosis population and little is known about current screening practices, experiences, or factors that may influence implementation. CogScreen is a hybrid type 1 study aiming to validate two promising screening tools with young people with first episode psychosis (primary aim) and to understand the context for implementing cognitive screening in early psychosis settings (secondary aim). This protocol outlines the implementation study, which aims to explore the current practices, acceptability, feasibility and determinants of cognitive screening in early psychosis settings from the perspective of key stakeholders.

Interprofessional and Inter-Organisational Collaboration in the COVID-19 Vaccination Programme: Lessons From North Central London.

Aim: To discuss inter-organisational collaboration in the context of the successful COVID-19 vaccination programme in North Central London (NCL).

Design: An action research study in 2023-2024.

Methods: Six action research cycles used mixed qualitative methods.

Extremely early initiation of vasopressors might not decrease short-term mortality for adults with septic shock: a systematic review and meta-analysis.

Background: The optimal timing for initiating vasopressor therapy in patients with septic shock remains unclear. This study aimed to assess the impact of early versus late vasopressor initiation on clinical outcomes.

Methods: A systematic review and meta-analysis were conducted by searching PubMed, Embase, and Cochrane databases.

Global impact of 10- and 13-valent pneumococcal conjugate vaccines on pneumococcal meningitis in all ages: the PSERENADE project.

Background: Pneumococcal conjugate vaccines (PCVs) introduced in childhood national immunization programs lowered vaccine-type invasive pneumococcal disease (IPD), but replacement with non-vaccine-types persisted throughout the PCV10/13 follow-up period. We assessed PCV10/13 impact on pneumococcal meningitis incidence globally.

Methods: The number of cases with serotyped pneumococci detected in cerebrospinal fluid and population denominators were obtained from surveillance sites globally.

Benefits of Duplex Ultrasound Surveillance of infra-inguinal bypass grafts and institutional costs of graft failure: a retrospective single-centre study.

Objective: The Achilles' heel of infrainguinal bypass grafts (IIBG) is restenosis. Duplex ultrasound (DUS) surveillance is commonly undertaken to identify restenosis allowing intervention for graft salvage. We report the impact of DUS surveillance on patient outcomes alongside healthcare-associated costs.

A novel POT1-TPD presentation: A germline pathogenic POT1 variant discovered in a patient with newly diagnosed posterior fossa ependymoma.

Introduction: POT1 tumor predisposition (POT1-TPD) is an autosomal dominant disorder characterized by increased lifetime malignancy risk. Melanoma, angiosarcoma, and chronic lymphocytic leukemia are the most frequently reported malignancies [1]. Protection of telomeres protein 1 (POT1) is part of the shelterin protein complex to maintain/protect telomeres [2].