ESAT-6 protein suppresses allograft rejection by inducing CD4Foxp3 regulatory T cells through IκBα/cRel pathway.

Background: Maintenance immunosuppression is required for suppression of alloimmunity or allograft rejection. However, continuous use of immunosuppressants may lead to various side effects, necessitating the use of alternative immunosuppressive drugs. The early secreted antigenic target of 6 kDa (ESAT-6) is a virulence factor and immunoregulatory protein of mycobacterium tuberculosis (Mtb), which alters host immunity through dually regulating development or activation of various immune cells.

Atacama Large Aperture Submillimeter Telescope (AtLAST) science: Probing the transient and time-variable sky.

The study of transient and variable events, including novae, active galactic nuclei, and black hole binaries, has historically been a fruitful path for elucidating the evolutionary mechanisms of our universe. The study of such events in the millimeter and submillimeter is, however, still in its infancy. Submillimeter observations probe a variety of materials, such as optically thick dust, which are hard to study in other wavelengths.

Effects of vitamin D supplementation on cardiac biomarkers: Results from the STURDY trial.

Objectives: In observational studies, older adults with low serum vitamin D levels are at higher risk of cardiovascular disease (CVD), but randomized trials have failed to demonstrate reduction in CVD risk from vitamin D supplementation, possibly because the doses of vitamin D supplements tested were too low. Our objective was to determine if higher doses of vitamin D supplementation reduce high-sensitivity cardiac troponin (hs-cTnI) and N-terminal pro-b-type natriuretic peptide (NT-proBNP), markers of subclinical CVD.

Methods: The Study to Understand Fall Reduction and Vitamin D in You (STURDY) was a double-blind, randomized, response-adaptive trial that tested the effects of 4 doses of vitamin D3 supplementation (200, 1000, 2000, 4000 IU/day) on fall risk among older adults with low serum 25-hydroxyvitamin D concentrations (10-29 ng/mL).

Coronavirus Disease 2019 (COVID-19) Real World Data Infrastructure: A Big-Data Resource for Study of the Impact of COVID-19 in Patient Populations With Immunocompromising Conditions.

Background: We developed a United States-based real-world data resource to better understand the continued impact of the coronavirus disease 2019 (COVID-19) pandemic on immunocompromised patients, who are typically underrepresented in prospective studies and clinical trials.

Methods: The COVID-19 Real World Data infrastructure (CRWDi) was created by linking and harmonizing de-identified HealthVerity medical and pharmacy claims data from 1 December 2018 to 31 December 2023, with severe acute respiratory syndrome coronavirus 2 virologic and serologic laboratory data from major commercial laboratories and Northwell Health; COVID-19 vaccination data; and, for patients with cancer, 2010 to 2021 National Cancer Institute Surveillance, Epidemiology, and End Results registry data.

Results: The CRWDi contains 4 cohorts: patients with cancer; patients with rheumatic diseases receiving pharmacotherapy; noncancer solid organ and hematopoietic stem cell transplant recipients; and people from the general population including adults and pediatric patients.

Integrated SegFlow, µSIA, and UPLC for Online Sialic Acid Quantitation of Glycoproteins Directly from Bioreactors.

This study emphasizes the critical importance of closely monitoring and controlling the sialic acid content in therapeutic glycoproteins, including EPO, interferon-γ, Orencia, Enbrel, and others, as the level of sialylation directly impacts their pharmacokinetics (PK), immunogenicity, potency, and overall clinical performance due to its influence on protein clearance via hepatic asialoglycoprotein receptors (ASGPR). The ASGPR recognizes and binds to glycoproteins exposed to terminal galactose or N-acetylgalactosamine residues, leading to receptor-mediated endocytosis. Recent studies have demonstrated that sialylation of O-linked glycan plays a role in protecting against macrophage galactose lectin (MGL)-mediated clearance.

Multisensory naturalistic decoding with high-density diffuse optical tomography.

Significance: Decoding naturalistic content from brain activity has important neuroscience and clinical implications. Information about visual scenes and intelligible speech has been decoded from cortical activity using functional magnetic resonance imaging (fMRI) and electrocorticography, but widespread applications are limited by the logistics of these technologies.

Aim: High-density diffuse optical tomography (HD-DOT) offers image quality approaching that of fMRI but with the silent, open scanning environment afforded by optical methods, thus opening the door to more naturalistic research and applications.

Behavioural interventions targeting the prevention and treatment of young children's mental health problems in low- and middle-income countries: a scoping review.

Background: Globally, 10% of children and adolescents live with mental health problems and often lack high-quality care. Over 80% of people facing mental health issues reside in low- and middle-income countries (LMICs). Failing to address children's mental health may prolong these challenges into adulthood, impeding their chances for a healthy life.

Pandemic preparedness in Vietnam: a review of health system resilience and areas for improvement.

In this viewpoint, we explore Vietnam's health system vulnerabilities and its national response to the COVID-19 pandemic, as well as critical areas of health system resilience, including health financing, workforce distribution, information systems, and governance. While Vietnam achieved early success through strong governance and mass vaccination campaigns, the pandemic revealed weaknesses in resource procurement, workforce imbalance, and limitations of its health information system. There are challenges in ensuring the rapid disbursement of financial resources and reliance on imported medical supplies, which delayed response times.

Cultural foundations of global health: a critical examination of universal child feeding recommendations.

There has been a rising call to decolonize global health so that it more fully includes the concerns, knowledge, and research from people all over the world. This endeavor can only succeed, we argue, if we also recognize that much of established global health doctrine is rooted in Euro-American beliefs, values, and practice rather than being culturally neutral. This paper examines the cultural biases of child feeding recommendations as a case in point.

Balancing the risks: continuous vs. interrupted anticoagulation during TAVI - what does the evidence say?

Anticoagulation therapy is a critical component of post-transcatheter aortic valve implantation (TAVI) management, aimed at reducing the risk of thromboembolic events and mortality. This review examines the efficacy of continuous versus interrupted anticoagulation strategies in TAVI patients, focusing on mortality, stroke rates, and composite events. A literature review was conducted, analyzing recent studies that evaluate the impact of different anticoagulation regimens on clinical outcomes in TAVI patients.

Emerging targets of α-synuclein spreading in α-synucleinopathies: a review of mechanistic pathways and interventions.

α-Synucleinopathies constitute a spectrum of neurodegenerative disorders, including Parkinson's disease (PD), Lewy body dementia (LBD), Multiple System Atrophy (MSA), and Alzheimer's disease concurrent with LBD (AD-LBD). These disorders are unified by a pathological hallmark: aberrant misfolding and accumulation of α-synuclein (α-syn). This review delves into the pivotal role of α-syn, the key agent in α-synucleinopathy pathophysiology, and provides a survey of potential therapeutics that target cell-to-cell spread of pathologic α-syn.

Salt-in-presalt electrolyte solutions for high-potential non-aqueous sodium metal batteries.

Room-temperature non-aqueous sodium metal batteries are viable candidates for cost-effective and safe electrochemical energy storage. However, they show low specific energy and poor cycle life as the use of conventional organic-based non-aqueous electrolyte solutions enables the formation of interphases that cannot prevent degradations at the positive and negative electrodes. Here, to promote the formation of inorganic NaF-rich interphases on both negative and positive electrodes, we propose the salt-in-presalt (SIPS) electrolyte formulation strategy.

Clinical spectrum of positional downbeat nystagmus: a diagnostic approach.

Positional downbeat nystagmus (pDBN) is a common finding in dizzy patients, with etiologies ranging from benign paroxysmal positional vertigo (BPPV) to central vestibular lesions. Although peripheral pDBN often presents with distinct clinical features that differentiate it from BPPV, diagnosing its etiology can be challenging. A thorough clinical evaluation, including the physical characteristics of the nystagmus, response to positional maneuvers, and neurological findings, is often sufficient to diagnose conditions that provoke pDBN such as anterior canal BPPV, atypical posterior canal BPPV, and central causes.

Oncocytoma: a rare neoplasm of the caruncle.

Oncocytoma is a rare benign neoplasm of the glandular tissue, most commonly found in the caruncle of the eye. These lesions have an excellent prognosis and have not been reported to recur after resection from the caruncle. Given the wide range of differentials and potential for malignancy, excision and histopathological examination are recommended to establish the diagnosis and guide proper treatment.

Computational Nuclear Oncology Toward Precision Radiopharmaceutical Therapies: Ethical, Regulatory, and Socioeconomic Dimensions of Theranostic Digital Twins.

Computational nuclear oncology for precision radiopharmaceutical therapy (RPT) is a new frontier for theranostic treatment personalization. A key strategy relies on the possibility to incorporate clinical, biomarker, image-based, and dosimetric information in theranostic digital twins (TDTs) of patients to move beyond a one-size-fits-all approach. The TDT framework enables treatment optimization by real-time monitoring of the real-world system, simulation of different treatment scenarios, and prediction of resulting treatment outcomes, as well as facilitating collaboration and knowledge sharing among health care professionals adopting a harmonized TDT.

PET Quantification in Healthy Humans of Cyclooxygenase-2, a Potential Biomarker of Neuroinflammation.

Cyclooxygenase-2 (COX-2) is present in a healthy brain at low densities but can be markedly upregulated by excitatory input and by inflammogens. This study evaluated the sensitivity of the PET radioligand [C]-6-methoxy-2-(4-(methylsulfonyl)phenyl)--(thiophen-2-ylmethyl)pyrimidin-4-amine ([C]MC1) to detect COX-2 density in a healthy human brain. The specificity of [C]MC1 was confirmed using lipopolysaccharide-injected rats and transgenic mice expressing the human gene, with 120-min baseline and blocked scans using COX-1 and COX-2 selective agents.

Leveraging mRNA technology for antigen based immuno-oncology therapies.

The application of messenger RNA (mRNA) technology in antigen-based immuno-oncology therapies represents a significant advancement in cancer treatment. Cancer vaccines are an effective combinatorial partner to sensitize the host immune system to the tumor and boost the efficacy of immune therapies. Selecting suitable tumor antigens is the key step to devising effective vaccinations and amplifying the immune response.

Worldwide epidemiology of paediatric multiple sclerosis: data from the Multiple Sclerosis International Federation Atlas of MS, third edition.

Background: Limited data are available on the global rates of paediatric multiple sclerosis. Here, we report on the estimated worldwide prevalence of paediatric MS.

Methods: We included paediatric prevalence data in 2020-2022 (Multiple Sclerosis International Federation Atlas of MS) and the prevalence of child neurologists (International Child Neurology Association).

Discovery of Orally Available Prodrugs of Itaconate and Derivatives.

Itaconate, an endogenous immunomodulator from the tricarboxylic acid (TCA) cycle, shows therapeutic effects in various disease models, but is highly polar with poor cellular permeability. We previously reported a novel, topical itaconate derivative, SCD-153, for the treatment of alopecia areata. Here, we present the discovery of orally available itaconate derivatives for systemic and skin disorders.

Nail Unit Melanoma Treated with Mohs Micrographic Surgery: Technique, Local Recurrence Rate, and Surgical Outcomes.

Background: Nail unit melanoma (NUM) is increasingly treated with digit-sparing surgery, but few published case series describe Mohs micrographic surgery (MMS) for NUM.

Objective: To describe the surgical technique, local recurrence rates, and reconstruction method for a large series of NUM treated with MMS using MART-1 immunostaining.

Methods: Biopsy-proven NUM treated with MMS-MART-1 were identified from a prospectively maintained database (2008-2023).

How Do Clinicians Use Quotations in Goals of Care Notes?

Background: Quoting patients in electronic medical record (EMR) notes is controversial. Quotations may be used to promote accuracy in documentation. However they also may be used to cast skepticism on patient speech.

Use of Harms trabeculotome to assist failed microcatheter advancement during trabeculotomy in primary congenital glaucoma.

We report the use of the Harms trabeculotome to facilitate 360° microcatheter advancement during illuminated microcatheter-assisted circumferential trabeculotomy (IMCT) ab externo in a 3-month-old infant with bilateral primary congenital glaucoma who required repeat surgery. The illuminated microcatheter was advanced 270°, from 9 to 6 o'clock; however, a focal blockage occurred, and, despite viscodilation, further advancement was not possible. The surgeon introduced a right Harms trabeculotome in the opposite direction, counterclockwise through the same scleral flap.

Impact of Subsequent Fellowship on Urology Chief Resident Case Log Volumes.

Objective: To characterize the impact of subsequent fellowship on the case log experience of trainees throughout their residency and specifically their chief resident year.

Materials And Methods: Urology resident case logs from 2010 to 2022 were obtained from 13 institutions for total residency and chief years. Five categorized index procedures were included for analysis: General Urology; Endourology; Reconstructive Urology; Urologic Oncology; and Pediatric Urology.