ProBDNF as a Myokine in Skeletal Muscle Injury: Role in Inflammation and Potential for Therapeutic Modulation of p75.

Brain-derived neurotropic factor (BDNF) is expressed by skeletal muscle as a myokine. Our previous work showed that the active precursor, proBDNF, is the predominant form of BDNF expressed in skeletal muscle, and that following skeletal muscle injury, proBDNF levels are significantly increased. However, the function of the muscle-derived proBDNF in injury-induced inflammation has yet to be fully understood.

Cochlear Mechanics Are Preserved After Inner Ear Delivery of Gold Nanoparticles.

Novel therapeutic delivery systems and delivery methods to the inner ear are necessary to treat hearing loss and inner ear disorders. However, numerous barriers exist to therapeutic delivery into the bone-encased and immune-privileged environment of the inner ear and cochlea, which makes treating inner ear disorders challenging. Nanoparticles (NPs) are a type of therapeutic delivery system that can be engineered for multiple purposes, and posterior semicircular canal (PSCC) infusion is a method to directly deposit them into the cochlea.

Automated Detection and Differentiation of Stanford Type A and Type B Aortic Dissections in CTA Scans Using Deep Learning.

Background/objectives: To develop and validate a model system using deep learning algorithms for the automatic detection of type A aortic dissection (AD), and differentiate it from normal and type B AD patients.

Methods: In this retrospective study, a deep learning model is developed, based on aortic computed tomography angiography (CTA) scans of 498 patients using training, validation and test sets of 398, 50 and 50 patients, respectively. An independent test set of 316 patients is used to validate and evaluate its performance.

Diagnostic evaluation and management of recurrent urinary tract infections in the spinal cord injury population - a retrospective evaluation at a tertiary care center.

Study Design: Retrospective review.

Objectives: While most individuals with spinal cord injury (SCI) are expected to have 1-2 urinary tract infections (UTIs) per year, there is a subset with higher incidence. We evaluate our practice to characterize common causes of recurrent UTIs, hypothesizing that more frequent infections typically have addressable risk factors.

Seasonal changes of mélange thickness coincide with Greenland calving dynamics.

Iceberg calving is a major contributor to Greenland's ice mass loss. Ice mélange, tightly packed sea ice and icebergs, has been hypothesized to buttress the calving fronts. However, quantifying the mélange buttressing force from field observations remains a challenge.

Host-microbe multiomic profiling identifies distinct COVID-19 immune dysregulation in solid organ transplant recipients.

Coronavirus disease 2019 (COVID-19) poses significant risks for solid organ transplant recipients, who have atypical but poorly characterized immune responses to infection. We aim to understand the host immunologic and microbial features of COVID-19 in transplant recipients by leveraging a prospective multicenter cohort of 86 transplant recipients age- and sex-matched with 172 non-transplant controls. We find that transplant recipients have higher nasal SARS-CoV-2 viral abundance and impaired viral clearance, and lower anti-spike IgG levels.

Increased local DNA methylation disorder in AMLs with DNMT3A-destabilizing variants and its clinical implication.

The mechanistic link between the complex mutational landscape of de novo methyltransferase DNMT3A and the pathology of acute myeloid leukemia (AML) has not been clearly elucidated so far. Motivated by a recent discovery of the significance of DNMT3A-destabilizing mutations (DNMT3A) in AML, we here investigate the common characteristics of DNMT3A AML methylomes through computational analyses. We present that methylomes of DNMT3A AMLs are considerably different from those of DNMT3A AMLs in that they exhibit increased intratumor DNA methylation heterogeneity in bivalent chromatin domains.

Mutations in Necroptosis-Related Genes Reported in Breast Cancer: A Cosmic and Uniport Database-Based Study.

Breast cancer (BC) now holds the top position as the primary reason of cancer-related fatalities worldwide, overtaking lung cancer. BC is classified into diverse categories depending on histopathological type, hormone receptor status, and gene expression profile, with ongoing evolution in their classifications. Cancer initiates and advances when there is a disruption in cell death pathways.

Late development of sensory thresholds for horizontal relative disparity in human visual cortex in the face of precocial development of thresholds for absolute disparity.

Immaturities exist at multiple levels of the developing human visual pathway, starting with immaturities in photon efficiency and spatial sampling in the retina and on through immaturities in early and later stages of cortical processing. Here we use Steady-State Visual Evoked Potentials (SSVEPs) and controlled visual stimuli to determine the degree to which sensitivity to horizontal retinal disparity is limited by the visibility of the monocular half-images, the ability to encode absolute disparity or the ability to encode relative disparity. Responses were recorded from male and female human participants at average ages of 5.

Thoracic Surgery Outcomes Research Network (ThORN) Consensus Document on Defining a High Quality Wedge Resection for Early Stage Lung Cancer.

With the publication of CALGB 140503, an increase in wedge resections for small, peripheral non-small cell lung cancer is expected; however, a relative paucity of data exists as to what defines a high quality oncologic wedge resection. The Thoracic Surgery Outcomes Research Network (ThORN), through expert discussion, guided by review of what limited data does exist, and through use of a modified Delphi process, provides these consensus statements defining an oncologically sound, high quality wedge resection. The statements are classified into five categories: 1) Preoperative Considerations 2) Technical Aspects 3) Lymph Node Assessment 4) Margin Assessment and 5) Tissue Handling by Pathology.

Design and implementation of an action plan for justice, equity, diversity, and inclusion within the Clinical Genome Resource.

How might members of a large, multi-institutional research and resource consortium foster justice, equity, diversity, and inclusion as central to its mission, goals, governance, and culture? These four principles, often referred to as JEDI, can be aspirational-but to be operationalized, they must be supported by concrete actions, investments, and a persistent long-term commitment to the principles themselves, which often requires self-reflection and course correction. We present here the iterative design process implemented across the Clinical Genome Resource (ClinGen) that led to the development of an action plan to operationalize JEDI principles across three major domains, with specific deliverables and commitments dedicated to each. Active involvement of consortium leadership, buy-in from its members at all levels, and support from NIH program staff at pivotal stages were essential to the success of this effort.

Direct visualization of electric-field-stimulated ion conduction in a potassium channel.

Understanding protein function would be facilitated by direct, real-time observation of chemical kinetics in the atomic structure. The selectivity filter (SF) of the K channel provides an ideal model, catalyzing the dehydration and transport of K ions across the cell membrane through a narrow pore. We used a "pump-probe" method called electric-field-stimulated time-resolved X-ray crystallography (EFX) to initiate and observe K conduction in the NaK2K channel in both directions on the timescale of the transport process.

Sociodemographic differences in modes of cannabis use among pregnant individuals in Northern California.

Background: The potential risks of prenatal cannabis use may vary depending on how cannabis is administered, but little is known about modes of prenatal cannabis use. This study characterized prevalence and sociodemographic correlates of modes of prenatal cannabis use in California.

Methods: This cross-sectional study included patients with pregnancies between January 1, 2021 and December 31, 2022 in a large healthcare system (3507 pregnancies [3454 individuals]) who self-reported prenatal cannabis use and mode of use (smoke, vape, edibles, dabs, and topicals) during universal screening at entrance to prenatal care.

Primary intrarenal hemangioma - A series of 39 cases.

Intrarenal hemangiomas lack concise clinicopathologic information, due to the predominance of single case reports and inclusion of other vascular neoplasms and hemangiomas of perirenal, hilar, and renal vein origin. Herein, in this multi-institutional study we evaluate clinicopathologic features of 39 intrarenal hemangiomas. The median age was 62 years (range = 27-94 years; 2:1 male to female ratio), with left-sided predominance (left = 21, right = 13; one case was bilateral).

Intraoperative Anesthetic Care During Emergent/Urgent Craniotomy or Craniectomy for Intracranial Hypertension or Herniation: A Systematic Review.

This systematic review aimed to identify and describe best practice for the intraoperative anesthetic management of patients undergoing emergent/urgent decompressive craniotomy or craniectomy for any indication. The PubMed, Scopus, EMBASE, and Cochrane databases were searched for articles related to urgent/emergent craniotomy/craniectomy for intracranial hypertension or brain herniation. Only articles focusing on intraoperative anesthetic management were included; those investigating surgical or intensive care unit management were excluded.

Across the firewall: Foreign media's role in shaping Chinese social media narratives on the Russo-Ukrainian War.

There is a widespread perception that China's digital censorship distances its people from the global internet, and the Chinese Communist Party, through state-controlled media, is the main gatekeeper of information about foreign affairs. Our analysis of narratives about the Russo-Ukrainian War circulating on the Chinese social media platform Weibo challenges this view. Comparing narratives on Weibo with 8.

Energy-poverty-inequality SDGs: A large-scale household analysis and forecasting in China.

Affordable and clean energy, eliminating poverty, and reducing inequality are important goals of the United Nations Sustainable Development Goals (SDGs). This paper examines the role of access to clean cooking fuels in promoting income growth and reducing income inequality. Using data from Chinese households, we show that a 10% increase in the adoption of clean cooking fuels would result in an increase in total annual household income of US$37 billion nationwide.

Pseudogap in electron-doped cuprates: Strong correlation leading to band splitting.

The pseudogap phenomena have been a long-standing mystery of the cuprate high-temperature superconductors. The pseudogap in the electron-doped cuprates has been attributed to band folding due to antiferromagnetic (AFM) long-range order or short-range correlation. We performed an angle-resolved photoemission spectroscopy study of the electron-doped cuprates PrLaCeCuO showing spin-glass, disordered AFM behaviors, and superconductivity at low temperatures and, by measurements with fine momentum cuts, found that the gap opens on the unfolded Fermi surface rather than the AFM Brillouin zone boundary.

Mechanism-guided engineering of a minimal biological particle for genome editing.

The widespread application of genome editing to treat and cure disease requires the delivery of genome editors into the nucleus of target cells. Enveloped delivery vehicles (EDVs) are engineered virally derived particles capable of packaging and delivering CRISPR-Cas9 ribonucleoproteins (RNPs). However, the presence of lentiviral genome encapsulation and replication proteins in EDVs has obscured the underlying delivery mechanism and precluded particle optimization.

Voices of Nanomedicine: Blueprint Guidelines for Collaboration in Addressing Global Unmet Medical Needs.

The "" under this Perspective underline the importance of interdisciplinary collaboration and partnerships across several disciplines, such as medical science and technology, medicine, bioengineering, and computational approaches, in bridging the gap between research, manufacturing, and clinical applications. Effective communication is key to bridging team gaps, enhancing trust, and resolving conflicts, thereby fostering teamwork and individual growth toward shared goals. Drawing from the success of the COVID-19 vaccine development, we advocate the application of similar collaborative models in other complex health areas such as nanomedicine and biomedical engineering.

Donor Regulatory T-Cell Therapy to Prevent Graft-Versus-Host Disease.

Allogeneic hematopoietic cell transplantation (HCT) is a curative therapy limited by graft-versus-host disease (GVHD). In preclinical studies and early-phase clinical studies enrichment of donor regulatory T cells (Tregs) appears to prevent GVHD and promote healthy immunity.We enrolled 44 patients on an open-label, single-center, phase 2 efficacy study investigating if a precision selected and highly purified Treg cell therapy manufactured from donor mobilized peripheral blood improves one-year GVHD-free relapse free survival (GRFS) after myeloablative conditioning (trial NCT01660607).