Impact of COVID-19 pandemic on physician-scientist trainees to faculty one year into the pandemic.

Purpose: Physician-scientists play a crucial role in advancing biomedical sciences. Proportionally fewer physicians are actively engaged in scientific pursuits, attributed to attrition in the training and retention pipeline. This national study evaluated the ongoing and longer-term impact of the COVID-19 pandemic on stress levels, research productivity, and optimism for physician-scientists at all levels of training.

Chemical Ligation-Mediated Total Synthesis of Corramycin.

The ligation-mediated total synthesis of corramycin, a myxobacterial natural product of the strain , is presented. The synthetic strategy included using two consecutive chemical ligations for a modular and efficient preparation. Finally, the synthesis employed a Ser/Thr ligation (STL) at a new ligation site combined with classical fragment coupling.

Mission Alliance Community Engagement Project: Exploring the Impact of COVID-19 on Social Isolation, Loneliness, Mental Health and Wellbeing in Veterans.

During the Coronavirus disease pandemic, many U.S. veterans with posttraumatic stress disorder (PTSD) experienced increased symptomology and worsened mental health and well-being due in part to social isolation and loneliness.

Impact of COVID-19 Pandemic on Physician-Scientist Trainees to Faculty One Year into the Pandemic.

Purpose: Physician-scientists play a crucial role in advancing biomedical sciences. Proportionally fewer physicians are actively engaged in scientific pursuits, attributed to attrition in the training and retention pipeline. This national study evaluated the ongoing and longer-term impact of the COVID-19 pandemic on research productivity for physician-scientists at all levels of training.

Impact of a reimbursement policy change on treatment with erenumab in migraine - a real-world experience from Germany.

Background: Monoclonal antibodies (mAbs) targeting the Calcitonin Gene-Related Peptide (CGRP) pathway are safe and effective treatments for migraine prevention. However, the high cost of these novel therapies has led to reimbursement policies requiring patients to try multiple traditional preventives before access. In Germany, a recent change in insurance policy significantly expanded coverage for the CGRP receptor mAb erenumab, enabling migraine patients who failed just one prior prophylactic medication to receive this mAb.

The role of the cerebellum in internet gaming disorder-A systematic review.

Recent studies increasingly highlight involvement of the cerebellum in drug craving and addiction. However, its exact role, that is, whether the cerebellum is a critical component of a brain network underlying addictive behaviour, or whether it rather is a facilitator or mediator, is still unclear. Findings concerning the newly recognized internet gaming disorder (IGD) suggest that changes in cerebellar connectivity and functioning are associated with behavioural/non-substance addiction.

Serum tau protein elevation in migraine: a cross-sectional case-control study.

Background: Migraine is a disorder associated with neuropeptide release, pain and inflammation. Tau protein has recently been linked to inflammatory diseases and can be influenced by neuropeptides such as CGRP, a key neurotransmitter in migraine. Here, we report serum concentrations of total-tau protein in migraine patients and healthy controls.

Near-death experiences are associated with rapid eye movement (REM) sleep intrusions in migraine patients, independent of migraine aura.

Background And Purpose: Migraine aura, near-death experiences (NDEs), and rapid eye movement (REM) sleep intrusions might share common mechanisms. Here, we investigated the prevalence of NDEs and REM sleep intrusions in people with migraine. We hypothesized that NDEs and REM sleep intrusions are more prevalent in migraine patients with aura than in those without.

Induced pluripotent stem cell line generated from a patient with differences in sex development (DSD) and multiple genetic variants including a large deletion in NR5A1.

The nuclear receptor subfamily 5, Group A, Member 1 (NR5A1) gene encodes steroidogenic factor 1 (SF1), which is necessary for development of steroid hormone-producing tissues including the gonad and adrenal gland. An induced pluripotent stem cell line (iPSC) LCHi002-B was generated from a participant with differences (disorders) of sex development (DSD) and multiple genetic variants including a large deletion in NR5A1, and three single nucleotide changes in DYNC2H1, PDE4D, and ZFPM2. The line presented typical morphology, expressed stem cell markers, differentiated into three germ layers, had normal karyotype, was mycoplasma-free, and carried mutations in NR5A1, DYNC2H1, PDE4D, and ZFPM2.

Identification of genomic loci regulating platelet plasminogen activator inhibitor-1 in mice.

Background: Plasminogen activator inhibitor-1 (PAI-1, Serpine1) is an important circulating fibrinolysis inhibitor. PAI-1 exists in 2 pools, packaged within platelet α-granules and freely circulating in plasma. Elevated plasma PAI-1 levels are associated with cardiovascular disease.

El Niño and other climatic drivers of epidemic malaria in Ethiopia: new tools for national health adaptation plans.

Background: Ethiopia has a history of climate related malaria epidemics. An improved understanding of malaria-climate interactions is needed to inform malaria control and national adaptation plans.

Methods: Malaria-climate associations in Ethiopia were assessed using (a) monthly climate data (1981-2016) from the Ethiopian National Meteorological Agency (NMA), (b) sea surface temperatures (SSTs) from the eastern Pacific, Indian Ocean and Tropical Atlantic and (c) historical malaria epidemic information obtained from the literature.

Differences in gonadal tissue cryopreservation practices for differences of sex development across regions in the United States.

Objective: Some individuals with differences of sex development (DSD) conditions undergo medically indicated prophylactic gonadectomy. Gonads of individuals with DSD can contain germ cells and precursors and patients interested in future fertility preservation and hormonal restoration can participate in DSD-specific research protocols to cryopreserve this tissue. However, it is unclear how many providers or institutions offer gonadal tissue cryopreservation (GTC) and how widespread GTC for DSD is across the United States (US).

Platelet tissue factor pathway inhibitor-α dampens cardiac thrombosis and associated fibrosis in mice.

Background: Tissue factor pathway inhibitor (TFPI) is the primary inhibitor of events initiating the blood coagulation pathway. Tfpi mice die during embryonic development. The absence of protease-activated receptor (PAR) 4, the major thrombin receptor on mouse platelets, rescues Tfpimice to adulthood.

Change of CGRP Plasma Concentrations in Migraine after Discontinuation of CGRP-(Receptor) Monoclonal Antibodies.

Discontinuation of treatment with monoclonal antibodies (mAb) targeting the Calcitonin Gene-Related Peptide (CGRP) pathway leads to an increase in migraine frequency. We aimed to assess changes in free and total CGRP plasma concentrations after the discontinuation of CGRP(-receptor) mAbs. This prospective analysis included 59 patients with migraine (n = 25 erenumab, n = 25 galcanezumab, n = 9 fremanezumab) who discontinued mAbs after ≥8 months of treatment.

Diet-induced obesity results in impaired oral tolerance induction.

Introduction: Obesity increases the risk of several diseases, such as type 2 diabetes mellitus and cardiovascular disease. Obesity also affects the immune system. When dietary lipids are transported via the lymphatics, they pass the mesenteric lymph nodes (mLNs).

Simultaneous dynamic glucose-enhanced (DGE) MRI and fiber photometry measurements of glucose in the healthy mouse brain.

Glucose is the main energy source in the brain and its regulated uptake and utilization are important biomarkers of pathological brain function. Glucose Chemical Exchange Saturation Transfer (GlucoCEST) and its time-resolved version Dynamic Glucose-Enhanced MRI (DGE) are promising approaches to monitor glucose and detect tumors, since they are radioactivity-free, do not require C labeling and are is easily translatable to the clinics. The main principle of DGE is clear.

Genetic analysis of human RNA binding motif protein 48 (RBM48) reveals an essential role in U12-type intron splicing.

U12-type or minor introns are found in most multicellular eukaryotes and constitute ∼0.5% of all introns in species with a minor spliceosome. Although the biological significance for the evolutionary conservation of U12-type introns is debated, mutations disrupting U12 splicing cause developmental defects in both plants and animals.

Ubiquitin profiling of lysophagy identifies actin stabilizer CNN2 as a target of VCP/p97 and uncovers a link to HSPB1.

Lysosomal membrane permeabilization (LMP) is an underlying feature of diverse conditions including neurodegeneration. Cells respond by extensive ubiquitylation of membrane-associated proteins for clearance of the organelle through lysophagy that is facilitated by the ubiquitin-directed AAA-ATPase VCP/p97. Here, we assessed the ubiquitylated proteome upon acute LMP and uncovered a large diversity of targets and lysophagy regulators.