Kremen1 regulates the regenerative capacity of support cells and mechanosensory hair cells in the zebrafish lateral line.

Mechanosensory hair cells in the inner ear mediate the sensations of hearing and balance, and in the specialized lateral line sensory system of aquatic vertebrates, the sensation of water movement. In mammals, hair cells lack the ability to regenerate following damage, resulting in sensory deficits. In contrast, non-mammalian vertebrates, such as zebrafish, can renew hair cells throughout their lifespan.

Determining the impact of vaccination on SARS-CoV-2 RT-PCR cycle threshold values and infectious viral titres.

Background: As the COVID-19 pandemic continues, efforts to better understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral shedding and transmission in both unvaccinated and vaccinated populations remain critical to informing public health policies and vaccine development. The utility of using real time RT-PCR cycle threshold values (C values) as a proxy for infectious viral litres from individuals infected with SARS-CoV-2 is yet to be fully understood. This retrospective observational cohort study compares quantitative infectious viral litres derived from a focus-forming viral titre assay with SARS-CoV-2 RT-PCR C values in both unvaccinated and vaccinated individuals infected with the Delta strain.

Electronic alerts for ambulatory patients with atrial fibrillation not prescribed anticoagulation: A randomized, controlled trial (AF-ALERT2).

Background: Despite widely available risk stratification tools, safe and effective anticoagulants, and guideline recommendations, anticoagulation for stroke prevention in atrial fibrillation (AF) is under-prescribed in ambulatory patients. To assess the impact of alert-based computerized decision support (CDS) on anticoagulation prescription in ambulatory patients with AF and high-risk for stroke, we conducted this randomized controlled trial.

Methods: Patients with AF and CHADSVASc score ≥ 2 who were not prescribed anticoagulation and had a clinic visit at Brigham and Women's Hospital were enrolled.

Peer-led team learning in an undergraduate biology course: Impacts on recruitment, retention, and imposter phenomenon.

Objectives: The data presented in this note were collected during a multi-year project conducted in the context of large-enrollment introductory biology course at a large private R-1 research institution in the Northeastern United States. The project aimed to examine the impact of Peer-Led Team Learning (PLTL) on the recruitment and retention of marginalized groups in Science, Technology, Engineering, and Mathematics (STEM) majors. While several results from the project have been published, additional data of interest have yet to be reported.

Trends in management and outcomes of pulmonary embolism with a multidisciplinary response team.

Multidisciplinary pulmonary embolism (PE) response teams have garnered widespread adoption given the complexities of managing acute PE and provide a platform for assessment of trends in therapy and outcomes. We describe temporal trends in PE management and outcomes following the deployment of such a team. All consecutive patients managed by our multidisciplinary PE response team activated by the Emergency Department were included over a 5-year calendar period.

Patients with myeloproliferative neoplasms and COVID-19 have increased rates of arterial thrombosis.

Background: Both coronavirus disease-2019 (COVID-19) and myeloproliferative neoplasms (MPNs) are associated with systemic inflammation and risk of thrombosis. Risk of thrombosis in patients with COVID with and without MPNs has not been extensively studied.

Methods: Retrospective cohort study of 44 patients with MPNs and 1114 patients without MPNs positive for SARS-COV-2.

Divergent Genetic Regulation of Nitric Oxide Production between C57BL/6J and Wild-Derived PWD/PhJ Mice Controls Postactivation Mitochondrial Metabolism, Cell Survival, and Bacterial Resistance in Dendritic Cells.

Dendritic cell (DC) activation is characterized by sustained commitment to glycolysis that is a requirement for survival in DC subsets that express inducible NO synthase () due to NO-mediated inhibition of mitochondrial respiration. This phenomenon primarily has been studied in DCs from the classic laboratory inbred mouse strain C57BL/6J (B6) mice, where DCs experience a loss of mitochondrial function due to NO accumulation. To assess the conservation of NO-driven metabolic regulation in DCs, we compared B6 mice to the wild-derived genetically divergent PWD/PhJ (PWD) strain.

Extended-Duration Low-Intensity Apixaban to Prevent Recurrence in Patients with Provoked Venous Thromboembolism and Enduring Risk Factors: Rationale and Design of the HI-PRO Trial.

Patients with acute venous thromboembolism (VTE) in the setting of transient provoking factors are typically treated with short-term anticoagulation. However, the risk of recurrence may be increased in the presence of enduring risk factors. In such patients, the optimal duration of treatment remains uncertain.

Impact of Atrial Fibrillation on In-Hospital Mortality and Stroke in Acute Aortic Syndromes.

Background: Acute aortic syndromes may present with a number of cardiovascular complications, including atrial fibrillation. We assessed the prevalence of atrial fibrillation in patients presenting with acute aortic syndromes and evaluated atrial fibrillation's association with in-hospital mortality and stroke.

Methods: Consecutive patients with acute aortic syndromes admitted to a single tertiary care center from January 2015 to March 2020 were included.

Registry of Arterial and Venous Thromboembolic Complications in Patients With COVID-19.

Background: Cardiovascular complications, including myocardial infarction, ischemic stroke, and pulmonary embolism, represent an important source of adverse outcomes in coronavirus disease-2019 (COVID-19).

Objectives: To assess the frequency of arterial and venous thromboembolic disease, risk factors, prevention and management patterns, and outcomes in patients with COVID-19, the authors designed a multicenter, observational cohort study.

Methods: We analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through our Mass General Brigham integrated health network.

The meiotic driver utilizes controlled protein aggregation to generate selective cell death.

Meiotic drivers are parasitic loci that force their own transmission into greater than half of the offspring of a heterozygote. Many drivers have been identified, but their molecular mechanisms are largely unknown. The gene is a meiotic driver in that uses a poison-antidote mechanism to selectively kill meiotic products (spores) that do not inherit .

Development and Validation of WeCares, a Survey Instrument to Assess Hospitalized Patients' and Family Members' "Willingness to Engage in Your Care and Safety".

Background: Patient engagement is recognized as a method to improve care quality and safety. A research team developed WeCares (Willingness to Engage in Your Care and Safety), a survey instrument assessing patients' and families' engagement in the safety of their care during their hospital stay. The objective of this study is to establish the preliminary construct validity and internal consistency of WeCares.

Glycogen Metabolism Supports Early Glycolytic Reprogramming and Activation in Dendritic Cells in Response to Both TLR and Syk-Dependent CLR Agonists.

Dendritic cells (DCs) increase their metabolic dependence on glucose and glycolysis to support their maturation, activation-associated cytokine production, and T-cell stimulatory capacity. We have previously shown that this increase in glucose metabolism can be initiated by both Toll-like receptor (TLR) and C-type lectin receptor (CLR) agonists. In addition, we have shown that the TLR-dependent demand for glucose is partially satisfied by intracellular glycogen stores.

Unique Patient-Reported Hospital Safety Concerns With Online Tool: MySafeCare.

Background: Hospitalized patients and their care partners have valuable and unique perspectives of the medical care they receive. Direct and real-time reporting of patients' safety concerns, though limited in the acute care setting, could provide opportunities to improve patient care.

Methods: We implemented the MySafeCare (MSC) application on six acute care units for 18 months as part of a patient-centered health information technology intervention to promote engagement and safety in the acute care setting.

Syk-dependent glycolytic reprogramming in dendritic cells regulates IL-1β production to β-glucan ligands in a TLR-independent manner.

Dendritic cells (DCs) activated via TLR ligation experience metabolic reprogramming, in which the cells are heavily dependent on glucose and glycolysis for the synthesis of molecular building blocks essential for maturation, cytokine production, and the ability to stimulate T cells. Although the TLR-driven metabolic reprogramming events are well documented, fungal-mediated metabolic regulation via C-type lectin receptors such as Dectin-1 and Dectin-2 is not clearly understood. Here, we show that activation of DCs with fungal-associated β-glucan ligands induces acute glycolytic reprogramming that supports the production of IL-1β and its secretion subsequent to NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome activation.

Regulation of Dendritic Cell Immune Function and Metabolism by Cellular Nutrient Sensor Mammalian Target of Rapamycin (mTOR).

Dendritic cell (DC) activation is characterized by an acute increase in glucose metabolic flux that is required to fuel the high anabolic rates associated with DC activation. Inhibition of glycolysis significantly attenuates most aspects of DC immune effector function including antigen presentation, inflammatory cytokine production, and T cell stimulatory capacity. The cellular nutrient sensor mammalian/mechanistic Target of Rapamycin (mTOR) is an important upstream regulator of glycolytic metabolism and plays a central role in coordinating DC metabolic changes and immune responses.

MYBPC3 truncation mutations enhance actomyosin contractile mechanics in human hypertrophic cardiomyopathy.

Rationale: Truncation mutations in the MYBPC3 gene, encoding for cardiac myosin-binding protein C (MyBP-C), are the leading cause of hypertrophic cardiomyopathy (HCM). Whole heart, fiber and molecular studies demonstrate that MyBP-C is a potent modulator of cardiac contractility, but how these mutations contribute to HCM is unresolved.

Objectives: To readdress whether MYBPC3 truncation mutations result in loss of MyBP-C content and/or the expression of truncated MyBP-C from the mutant allele and determine how these mutations effect myofilament sliding in human myocardium.

Peer-Led Team Learning Helps Minority Students Succeed.

Active learning methods have been shown to be superior to traditional lecture in terms of student achievement, and our findings on the use of Peer-Led Team Learning (PLTL) concur. Students in our introductory biology course performed significantly better if they engaged in PLTL. There was also a drastic reduction in the failure rate for underrepresented minority (URM) students with PLTL, which further resulted in closing the achievement gap between URM and non-URM students.

Implementation of the peer-led team-learning instructional model as a stopgap measure improves student achievement for students opting out of laboratory.

In entry-level university courses in science, technology, engineering, and mathematics fields, students participating in associated laboratory sessions generally do better than those who have no related lab classes. This is a problem when, for various reasons, not enough lab sections can be offered for students and/or when students opt out of optional available lab courses. Faced with such a situation, this study evaluated the efficacy of the peer-led team-learning (PLTL) instructional model as a potential method for narrowing the achievement gap among undergraduate students electing not to enroll in an optional laboratory component of an introductory biology course.

Peer led team learning in introductory biology: effects on peer leader critical thinking skills.

This study evaluated hypothesized effects of the Peer-Led Team Learning (PLTL) instructional model on undergraduate peer leaders' critical thinking skills. This investigation also explored peer leaders' perceptions of their critical thinking skills. A quasi-experimental pre-test/post-test with control group design was used to determine critical thinking gains in PLTL/non-PLTL groups.

Fbxw7 regulates Notch to control specification of neural precursors for oligodendrocyte fate.

Background: In the developing vertebrate nervous system elevated levels of Notch signaling activity can block neurogenesis and promote formation of glial cells. The mechanisms that limit Notch activity to balance formation of neurons and glia from neural precursors are poorly understood.

Results: By screening for mutations that disrupt oligodendrocyte development in zebrafish we found one allele, called vu56, that produced excess oligodendrocyte progenitor cells (OPCs).