Control of striatal circuit development by the chromatin regulator .

The pathophysiology of neurodevelopmental disorders involves vulnerable neural populations, including striatal circuitry, and convergent molecular nodes, including chromatin regulation and synapse function. Despite this, how epigenetic regulation regulates striatal development is understudied. Recurrent de novo mutations in are associated with intellectual disability and autism.

Programmed shape transformations in cell-laden granular composites.

Tissues form during development through mechanical compaction of their extracellular matrix (ECM) and shape morphing, processes that result in complex-shaped structures that contribute to tissue function. While observed in vivo, control over these processes in vitro to understand both tissue development and guide tissue formation has remained challenging. Here, we use combinations of mesenchymal stromal cell spheroids and hydrogel microparticles (microgels) with varied hydrolytic stability to fabricate programmable and dynamic granular composites that control compaction and tissue formation over time.

Biologically relevant integration of transcriptomics profiles from cancer cell lines, patient-derived xenografts, and clinical tumors using deep learning.

Cell lines and patient-derived xenografts are essential to cancer research; however, the results derived from such models often lack clinical translatability, as they do not fully recapitulate the complex cancer biology. Identifying preclinical models that sufficiently resemble the biological characteristics of clinical tumors across different cancers is critically important. Here, we developed MOBER, Multi-Origin Batch Effect Remover method, to simultaneously extract biologically meaningful embeddings while removing confounder information.

Targeting uPAR with an antibody-drug conjugate suppresses tumor growth and reshapes the immune landscape in pancreatic cancer models.

Antibody-drug conjugates (ADCs) hold promise to advance targeted therapy of pancreatic ductal adenocarcinoma (PDAC), where the desmoplastic tumor stroma challenges effective treatment. Here, we explored the urokinase plasminogen activator receptor (uPAR) as a candidate ADC target in PDAC, harnessing its massive tumoral and stromal expression in this stroma-dense tumor. We generated a site-specific ADC offering high-affinity, cross-species reactivity, and efficient internalization of the anti-uPAR monoclonal antibody, FL1, carrying a potent anthracycline derivative (PNU-158692).

Concordance of non-invasive plasma cell-free DNA with invasive diagnostics for diagnosis of invasive fungal disease.

Background: Mold plasma cell-free DNA (cfDNA) PCR is a promising non-invasive diagnostic modality for early diagnosis of invasive mold disease (IMD) in immunocompromised patients. Although mold cfDNA PCR has been shown to be highly accurate, the value of invasive procedures to collect specimens for conventional fungal diagnostics following plasma cfDNA testing remains unclear.

Methods: This retrospective single-center cohort study included patients with mold plasma cfDNA PCR performed 7 days before or 2 days after invasive specimen collection.

Skeletal and Adipose Manifestations of Stress in a Contemporary Pediatric Sample.

Introduction: Adverse experiences leading to physiological disruptions (stress) in early life produce cascade effects on various biological systems, including the endocrine and metabolic systems, which, in turn, shape the developing skeletal system. To evaluate the effects of stress on adipose and skeletal tissues, we examine the relationship between skeletal indicators of stress (porotic hyperostosis [PH] and cribra orbitalia [CO]), bone mineral density (BMD), vertebral neural canal (VNC) diameters, and adipose tissue distribution in a contemporary pediatric autopsy sample.

Methods: Data is from 702 (409 males, 293 females) individuals from a pediatric (0.

Neurodegeneration: 2024 update.

This review highlights a collection of both diverse and highly impactful studies published in the previous year selected by the author from the neurodegenerative neuropathology literature. As with previous reviews in this series, the focus is, to the best of my ability, to highlight human tissue-based experimentation most relevant to experimental and clinical neuropathologists. A concerted effort was made to balance the selected studies across neurodegenerative disease categories, approaches, and methodologies to capture the breadth of the research landscape.

The Gendered Impact of the COVID-19 Pandemic on Employment in Argentina: The Mediating Role of the Public vs. Private Sectors.

This study examines the COVID-19 pandemic's immediate and long-term impact on Argentina's labor market with a focus on gender disparities and the mediating role of the public vs. private sectors. Using household survey data, we assess men and women's employment trends before, during, and after the pandemic.

Design and validation of cell-based potency assays for frataxin supplementation treatments.

Friedreich's ataxia (FRDA) is a multisystem, autosomal recessive disorder caused by mutations in the frataxin () gene. As FRDA is considered an FXN deficiency disorder, numerous therapeutic approaches in development or clinical trials aim to supplement FXN or restore endogenous expression. These include gene therapy, protein supplementation, genome editing or upregulation of transcription.

Insecticides may facilitate the escape of weeds from biological control.

Background: Preventative pesticide seed treatments (hereafter preventative pest management or PPM) are common corn and soybean treatments, and often include both fungicides and neonicotinoid insecticides. While PPM is intended to protect crops from soil-borne pathogens and early season insect pests, these seed treatments may have detrimental effects on biological control of weed seeds by insects.

Methods: Here, in two 3-year corn-soy rotations in Pennsylvania USA, we investigated a PPM approach to insect management compared to an integrated pest management approach (IPM) and a "no (insect) pest management" (NPM) control.

The Complete Inpatient Record Using Comprehensive Electronic Data (CIRCE) project: A team-based approach to clinically validated, research-ready electronic health record data.

Introduction: The rapid adoption of electronic health record (EHR) systems has resulted in extensive archives of data relevant to clinical research, hospital operations, and the development of learning health systems. However, EHR data are not frequently available, cleaned, standardized, validated, and ready for use by stakeholders. We describe an in-progress effort to overcome these challenges with cooperative, systematic data extraction and validation.

Using gaming to prepare health professional students to practice systems thinking.

Background: Healthcare professionals face numerous challenges regarding the delivery of care. Creating solutions to these challenges is imperative to improve the quality and safety of care to positively impact patient outcomes. However, health professional students rarely receive formal training regarding systems thinking during didactic components of their professional training.

Robotic-Assistance in Total Hip Arthroplasty Is Associated With Decreased Dislocation Rates.

Background: As the use of robotics in total hip arthroplasty (THA) continues to gain popularity, differences in clinical outcomes when compared to manual techniques have remained unclear. This study aimed to compare postoperative complications between patients undergoing robotic-assisted techniques and manual THA for primary osteoarthritis at 90 days, 1 year, and 2 years.

Methods: Using an all-payer national database, we identified 405,048 patients who underwent either robotic-assisted or manual THA for primary osteoarthritis.

Concomitant Pulmonary and Biliary Manifestations of Ulcerative Colitis: A Case Report.

Ulcerative colitis can present with extra-intestinal manifestations, including interstitial lung disease and primary sclerosing cholangitis. When pulmonary symptoms precede gastrointestinal, diagnosis can be challenging. Consideration of Ulcerative colitis in patients with unexplained lung and hepatic pathology is crucial, as a failure of timely intervention can lead to multiorgan complications.

Cortical windows for implant and cement removal during revision total elbow arthroplasty.

Background: Revision total elbow arthroplasty (rTEA) remains a technically challenging procedure with potential for substantial morbidity. Cases involving excessively long cement mantles, removal of well-fixed implants or infected revisions requiring complete cement removal introduce additional technical challenges. Our purpose was to describe the outcomes, results, and complications associated with the use of cortical windows in rTEA.

Improved patient reported outcomes with knotless double-row rotator cuff repair with and without lateral row biceps tenodesis at 2- and 5-years.

Background: The purpose of this study is to report outcomes of an arthroscopic knotless double-row (DR) rotator cuff repair (RCR) technique at 2- and 5- years postoperatively, and to compare clinical outcomes in patients undergoing knotless DR RCR with incorporated lateral row biceps tenodesis (LRT) vs. those without LRT.

Methods: All primary RCR surgeries were performed by a single surgeon at a single institution using a knotless transosseous equivalent (TOE) technique.

Left Atrial Papillary Fibroelastoma Mimicking Myxoma.

Papillary fibroelastomas (PFEs) followed by cardiac myxomas (CM) are the 2 most common primary benign cardiac tumors. Although typically asymptomatic, they can manifest with nonspecific symptoms such as dyspnea and dizziness or more acute manifestations such as embolic events. We describe an unusual location of a PFE typically seen with a CM.

Extracavitary Cardiac Calcific Amorphous Tumors Compressing Biventricular Outflow Tracts.

Extracavitary cardiac calcific amorphous tumors/masses are extremely rare. We present a case report of a 62-year-old man with end-stage renal disease who presented with extracavitary cardiac calcific amorphous tumors/masses compressing the biventricular outflow tracts, resulting in hemodynamic compromise and progressive limitation of activities. The patient was successfully treated with surgery, with complete resolution of symptoms and markedly improved quality of life.

TEER for SAM of the Mitral Valve and Flail Posterior Mitral Leaflet: 1-Clip Solution.

Transcatheter edge-to-edge repair (TEER) is approved for patients with symptomatic severe mitral regurgitation (MR) who are deemed inoperable or at high surgical risk with life expectancy of more than 1 year, but has also been used off-label in patients with hypertrophic obstructive cardiomyopathy (HOCM) for symptomatic relief who are not candidates for septal reduction therapy. An 83-year-old woman with decompensated heart failure was found to have HOCM with systolic anterior motion of the mitral valve and a large P2 flail segment with ruptured cords. TEER was performed resulting in mild MR and resolution of the prior left ventricular outflow tract gradient.

NET Models Meeting 2024 white paper: the current state of neuroendocrine tumour research models and our future aspirations.

Current models for the study of neuroendocrine tumours (NETs) are severely limited. While (e.g.

Response to induction chemotherapy modifies the effect of conventional prognostic factors in high-risk neuroblastoma: A report from the Children's Oncology Group.

Background: Response to induction chemotherapy has been shown to predict outcome in patients with high-risk neuroblastoma (HR-NB), with those achieving a complete response (CR) having superior outcomes.

Methods: We evaluated whether conventional prognostic factors remain prognostic in subsets of patients defined by response to induction. 1244 Patients from four COG high-risk trials were included.

Progressive anterior segment involvement of an infant with corneoscleral juvenile xanthogranuloma refractory to topical steroids.

Purpose: To report a case of corneoscleral juvenile xanthogranuloma (JXG) with progressive anterior segment involvement refractory to topical steroids.

Observations: A 4-month-old male was referred for a new-onset subconjunctival lesion in the right eye. He was found to have a thickened, yellow corneoscleral lesion and hyphema, presumed to be ocular JXG.

Advances in moyamoya disease: pathogenesis, diagnosis, and therapeutic interventions.

Moyamoya disease (MMD) is a type of cerebrovascular disease characterized by occlusion of the distal end of the internal carotid artery and the formation of collateral blood vessels. Over the past 20 years, the landscape of research on MMD has significantly transformed. In this review, we provide insights into the pathogenesis, diagnosis, and therapeutic interventions in MMD.

Integrated Business and Engineering Educational Experience for Medical Students in the Development of Pediatric Medical Devices.

Background: There are few opportunities in undergraduate medical education that provide formal training in engineering and scientific innovation. Institutions have sought to address student-specific career goals through combined degree programs such as the Medical Scientist Training Program and MD/MBA. However, only a small percentage of medical students pursue these additional degrees.

A clinical audit on the utilization of group O-negative red cells and the lesson learnt.

Background: Ideal blood inventory management involves guaranteeing maximal availability of blood while minimizing wastage. Benchmark for the guidance of O (Rh) D-negative red blood cells (ONEG RBCs) is not widely available. In this study, we aimed to identify the areas of improvement in blood center inventory of ONEG RBCs through a clinical audit.