Characterization of bleeding in thrombotic thrombocytopenic purpura in the precaplacizumab era: a retrospective nationwide analysis.

Background: The addition of caplacizumab to immune thrombotic thrombocytopenia (iTTP) treatment options has led to a renewed interest in characterizing the epidemiology and risk factors for bleeding in iTTP. Limited data exist on the bleeding risk in iTTP due to systemic underreporting in earlier cohorts.

Objectives: To describe the incidence, patterns, and predictors of bleeding in hospitalized iTTP patients independent of caplacizumab use.

Consensus Recommendations for the Management of Neurosarcoidosis: A Delphi Survey of Experts Across the United States.

Background And Objectives: Neurosarcoidosis poses a diagnostic and management challenge due to its rarity, phenotypic variability, and lack of randomized controlled studies to guide treatment selection. Recommendations for management based on expert opinion are useful in clinical practice and provide a framework for designing prospective studies.

Methods: In this Delphi survey study, specialists with experience in managing patients with neurosarcoidosis were invited to anonymously complete 2 surveys about key elements of evaluation, diagnosis, treatment, monitoring, and long-term management of neurosarcoidosis.

An Integrative, Non-Pharmacological Pain Management Approach In Severe Lumbar Spine Degeneration: A Case Report.

Introduction: Chronic low back pain (CLBP), or low back pain lasting greater than 12 weeks, is a prevalent condition that profoundly impacts the quality of life in affected individuals. Traditional treatments - such as physical therapy, medications, injections, minimally invasive procedures, and surgery - often prove ineffective in a considerable number of cases, particularly when utilized as singular modalities. Given the complex biopsychosocial nature of CLBP, a multi-modality approach tailored to each patients' unique needs is essential.

Temporal Trends in Parkinson's Disease Related Mortality from 1999-2020: A National Analysis.

Introduction: Parkinson's disease (PD) is the most common neurodegenerative movement disorder and is associated with significant disability. The prevalence is rising, and studies have reported potential sex and race disparities in patient outcomes. Data about the demographic trends in PD-related mortality in the United States (US) is limited.

Proximity based proteomics reveals Git1 as a regulator of Smoothened signaling.

The GPCR-like protein Smoothened (Smo) plays a pivotal role in the Hedgehog (Hh) pathway. To initiate Hh signaling, active Smo binds to and inhibits the catalytic subunit of PKA in the primary cilium, a process facilitated by G protein-coupled receptor kinase 2 (Grk2). However, the precise regulatory mechanisms underlying this process, as well as the events preceding and following Smo activation, remain poorly understood.

Kinetic analysis of strand invasion during meiosis reveals similar rates of sister- and homolog-directed repair.

Meiotic chromosome segregation requires reciprocal exchanges between the parental chromosomes (homologs). Exchanges are formed via tightly-regulated repair of double-strand DNA breaks (DSBs). However, since repair intermediates are mostly quantified in fixed images, our understanding of the mechanisms that control the progression of repair remains limited.

Low-Cost Silicon from Natural Sand with Tunable Oxygen Content and Its Effects on the Electrochemical Properties of Lithium-Ion Battery Anodes.

Silicon (Si) is recognized as a promising anode material for lithium-ion batteries (LIBs). However, the significant volume expansion during lithiation poses a make-or-break challenge for the commercial adoption of silicon as an anode. The solutions to mitigate the challenge often depend on processes that can increase costs for the LIB.

Enhanced Stability and Sensitivity for CA-125 Detection Under Microfluidic Shear Flow Using Polyethylene Glycol-Coated Biosensor.

The microfluidic-based point-of-care (POC) diagnostic tool has garnered significant interest in recent years, offering rapid and cost-effective disease detection. There is a growing trend toward integrating microfluidic platforms with biosensors, aligning lab-on-a-chip technologies with POC diagnostic devices. Despite numerous efforts to incorporate biosensors into microfluidic systems, researchers have performed very limited investigations on the stability of biomarker detection when biosensors operate under microfluidic shear flow conditions.

The extinction burst: Effects of reinforcement magnitude.

The extinction burst is an increase in an operant behavior early in the transition to extinction. A matching-law-based quantitative theory suggests that it results from the elimination of competition from reinforcement-related behavior that accompanies the transition to extinction. This experiment examined the effects of reinforcement magnitude on the extinction burst with rats.

CD11c-Expressing Microglia Are Transient, Driven by Interactions With Apoptotic Cells.

Microglia, the parenchymal macrophage of the central nervous system, serve crucial remodeling functions throughout development. Microglia are transcriptionally heterogenous, suggesting that distinct microglial states confer discrete roles. Currently, little is known about how dynamic these states are, the cues that promote them, or how they impact microglial function.

Proteasome inhibition enhances oncolytic reovirus therapy in multiple myeloma independently of its direct cytotoxic effects.

Background: Reovirus (RV) is an oncolytic virus with natural tropism for cancer cells. We previously showed that RV administration in multiple myeloma (MM) patients was safe, but disease control associated with viral replication in the cancer cells was not observed. The combination with proteasome inhibitors (PIs) has shown to enhance RV therapeutic activity, but the mechanisms of action have not been fully elucidated.

Proposed resources required for a comprehensive program for CCT CHD imaging.

Background: Cardiac Computed Tomography (CCT) is increasingly used for evaluation of congenital heart disease (CHD) in patients of all ages. Pediatric and adult congenital heart disease (ACHD) surgical programs require high quality CCT imaging as part of the multimodality imaging support expected of comprehensive care centers. Despite these expectations, there are no benchmarks or defined programmatic elements specific to the performance of CCT in patients with CHD.

Radiotherapy toxicities: mechanisms, management, and future directions.

For over a century, radiotherapy has revolutionised cancer treatment. Technological advancements aim to deliver high doses to tumours with increased precision while minimising off-target effects to organs at risk. Despite advancements such as image-guided, high-precision radiotherapy delivery, long-term toxic effects on healthy tissues remain a great clinical challenge.

Economic inequality, intergenerational mobility, and life expectancy.

This study explores the mediating role of intergenerational mobility (IM) in the relationship between economic inequality and population health in the United States, focusing on life expectancy. Using multilevel structural equation modeling across state and commuting zone (CZ) levels for both genders, we find that economic inequality indices, except for the top 1 percent's income share, adversely affect life expectancy through absolute and relative mobility. Specifically, economic inequality reduces life expectancy more significantly through absolute mobility, especially among males and lower-income groups, with nuanced impacts observed across different geographic levels.

Comparison of Postoperative Antibiotic Protocols for Pediatric Complicated Appendicitis: A Western Pediatric Surgery Research Consortium Study.

Background: There is no consensus on the appropriate duration of postoperative antibiotics for complicated appendicitis in children. Commonly used antibiotic endpoints include normalization of white blood cell count (WBC) or completion of a minimum number of prespecified treatment days. We compared clinical outcomes resulting from varying postoperative antibiotic protocols for complicated appendicitis in children.

Heterozygous Eif4nif1 Stop Gain Mice Replicate the Primary Ovarian Insufficiency Phenotype in Women.

We created the c.1286C>G stop-gain mutation found in a family with primary ovarian insufficiency (POI) at age 30 years. The Eif4enif1 C57/Bl6 transgenic mouse model contained a floxed exon 10-19 cassette with a conditional knock-in cassette containing the c.

Symptom Documentation in Unstructured Palliative Care Notes of Children and Adolescents With Cancer.

Context: Children and adolescents with cancer experiencing complex symptoms can benefit from subspeciality palliative care. However, standardized methods of symptom documentation by pediatric palliative care teams are lacking. Understanding current approaches to symptom documentation will inform next steps to optimize symptom support.

A study of internal structure validity for the American board of surgery in training examination.

Background: As principles of competency-based medical education are implemented into graduate medical education [GME] programs, it is imperative that the assessments employed are reliable and valid. Internal structure is a core component of validity evidence that has been under studied. In this study, we examined elements of the internal structure for the American Board of Surgery In-Training Examination [ABSITE].

Glass Ceiling.

Fifty-five word stories have proven a useful reflective tool across medicine. This short piece details an episode in which 'leadership' came up short. Leadership has to make itself present.

Predicting fall parameters from infant skull fractures using machine learning.

When infants are admitted to the hospital with skull fractures, providers must distinguish between cases of accidental and abusive head trauma. Limited information about the incident is available in such cases, and witness statements are not always reliable. In this study, we introduce a novel, data-driven approach to predict fall parameters that lead to skull fractures in infants in order to aid in determinations of abusive head trauma.

Data-Driven Equation-Free Dynamics Applied to Many-Protein Complexes: The Microtubule Tip Relaxation.

Microtubules (MTs) constitute the largest components of the eukaryotic cytoskeleton and play crucial roles in various cellular processes, including mitosis and intracellular transport. The property allowing MTs to cater to such diverse roles is attributed to dynamic instability, which is coupled to the hydrolysis of GTP (guanosine-5'-triphosphate) to GDP (guanosine-5'-diphosphate) within the β-tubulin monomers. Understanding the equilibrium dynamics and the structural features of both GDP- and GTP-complexed MT tips, especially at an all-atom level, remains challenging for both experimental and computational methods because of their dynamic nature and the prohibitive computational demands of simulating large, many-protein systems.

Hybrid Bilayer Interfaces within Reversed-Phase Chromatographic Silica Formed by Self-Assembly of Long-Chain Primary Alcohols.

Modification of silica interfaces by covalent attachment of functional ligands is a primary means of controlling the interfacial chemistry of porous silicas used in separations, environmental cleanup, and biosensing. Recently, modification of hydrophobic, -alkyl-silane-functionalized interfaces has been achieved through self-assembly of zwitterionic phospholipids or mixed-charged surfactants to form "hybrid bilayers", producing interfaces that mimic lipid-bilayer partitioning and provide shape-selective partitioning of aromatic hydrocarbons. Charged headgroups, however, introduce electrostatic interactions that strongly influence the retention of ionizable solutes and require careful control over pH and ionic strength in the solution phase.

High-Value Care Education in the USA: Lessons from a National Value Curriculum for Resident and Fellow Physicians.

Purpose: Physicians are estimated to be responsible for more than 50% of national healthcare costs and hold the greatest potential to improve value by orchestrating quality-driven programs to reduce unnecessary practices and variability. A physician's ability to practice cost-conscious care has been linked to their training, underscoring the importance of integrating cost-conscious practice into training.

Methods: The High Value Practice Academic Alliance was formed to help advance the value-improvement work of individual institutions through a national organization.