Ca and Nε-lysine acetylation regulate the CALR-ATG9A interaction in the lumen of the endoplasmic reticulum.

The acetylation of autophagy protein 9 A (ATG9A) in the lumen of the endoplasmic reticulum (ER) by ATase1 and ATase2 regulates the induction of reticulophagy. Analysis of the ER-specific ATG9A interactome identified calreticulin (CALR), an ER luminal Ca-binding chaperone, as key for ATG9A activity. Specifically, if acetylated, ATG9A is sequestered by CALR and prevented from engaging FAM134B and SEC62.

Opportunities and challenges of using generative AI to personalize educational assessment.

In line with the positive effects of personalized learning, personalized assessments are expected to maximize learner motivation and engagement, allowing learners to show what they truly know and can do. Considering the advances in Generative Artificial Intelligence (GenAI), in this perspective article, we elaborate on the opportunities of integrating GenAI into personalized educational assessments to maximize learner engagement, performance, and access. We also draw attention to the challenges of integrating GenAI into personalized educational assessments regarding its potential risks to the assessment's core values of validity, reliability, and fairness.

Pancreatic cancer screening is effective in individuals at risk with predisposing germline gene variants, but not in gene variant-negative familial pancreatic cancer families.

Objective: To evaluate the diagnostic yield of pancreatic cancer screening in individuals at risk (IAR) from familial pancreatic cancer (FPC) families with respect to the presence or absence of pathogenic germline variants predisposing to pancreatic adenocarcinoma (PDAC).

Design: In a 20 years period, IAR from FPC families were enrolled in a prospective screening program of the national case collection for FPC of Germany, including magnet resonance imaging (MRI) and endoscopic ultrasound (EUS). The diagnostic yield was analyzed regarding significant pancreatic lesions such as PDAC, high-grade pancreatic-intraepithelial-neoplasia (PanIN3) and intraductal-papillary-mucinous-neoplasia (IPMN) with high-grade dysplasia.

Mesenteric fibrosis in patients with small intestinal neuroendocrine tumors is associated with enrichment of alpha-smooth muscle actin-positive fibrosis and COMP-expressing stromal cells.

Neuroendocrine tumors of the small intestine (SI-NETs) often develop lymph node metastasis (LNM)-induced mesenteric fibrosis (MF). MF can cause intestinal obstruction as well as ischemia and render surgical resection technically challenging. The underlying pathomechanisms of MF are still not well understood.

Financial strain and the health and well-being of college students during the COVID-19 pandemic.

This study examined the associations between COVID-19-related financial strain and the stress, mental health, physical health symptoms, and health behaviors of American university students. Online data were collected from 485 participants between May 2020 and March 2021. Participants were majority female and majority white.

Responses to pathogen exposure in sentinel juvenile fall-run Chinook salmon in the Sacramento River, CA.

This study investigated how the deployment of juvenile Chinook salmon in ambient river conditions and the subsequent exposure to and infection by pathogens was associated with the changes in the expression of genes involved in immune system functioning, general stress and host development. Juvenile fish were deployed in sentinel cages for 21 days in the Sacramento River, CA, USA. Gill, kidney and intestinal tissue were sampled at 0, 7, 14 and 21 days post-deployment.

High expression of insulinoma-associated protein 1 (INSM1) distinguishes colorectal mixed and pure neuroendocrine carcinomas from conventional adenocarcinomas with diffuse expression of synaptophysin.

Complementary to synaptophysin and chromogranin A, insulinoma-associated protein 1 (INSM1) has emerged as a sensitive marker for the diagnosis of neuroendocrine neoplasms. Since there are no comparative data regarding INSM1 expression in conventional colorectal adenocarcinomas (CRCs) and colorectal mixed adenoneuroendocrine carcinomas/neuroendocrine carcinomas (MANECs/NECs), we examined INSM1 in a large cohort of conventional CRCs and MANECs/NECs. In conventional CRC, we put a special focus on conventional CRC with diffuse expression of synaptophysin, which carry the risk of being misinterpreted as a MANEC or a NEC.

Characteristics of familial pancreatic cancer families with additional colorectal carcinoma.

Familial pancreatic cancer (FPC) is a rare hereditary tumor entity with broad phenotypic heterogeneity, including colorectal carcinoma (CRC) in some families. The underlying factors for this co-occurrence are still not well evaluated. FPC families in the National Case Collection of Familial Pancreatic Cancer with an additional occurrence of CRC were analyzed regarding the phenotype, genotype and recommendation for a clinical screening program.

Multidisciplinary Approach to Improve Human Immunodeficiency Virus and Syphilis Testing Rates in Emergency Departments.

Background: Best practice guidelines recommend that patients at risk for sexually transmitted infections (STIs), such as gonorrhea (GC) and chlamydia, should also be tested for human immunodeficiency virus (HIV) and syphilis. This prospective quality assurance study aimed to increase HIV and syphilis testing rates in emergency departments (EDs) across the Cleveland Clinic Health System from January 1, 2020 through January 1, 2022.

Methods: A multidisciplinary team of emergency medicine, infectious diseases, pharmacy, and microbiology personnel convened to identify barriers to HIV and syphilis testing during ED encounters at which GC/chlamydia were tested.

Self-Regulation and Relaxation-Based Interventions for Adults With Traumatic Brain Injury (2013-2020).

Systematic Review Briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association's Evidence-Based Practice Program. Each Systematic Review Brief summarizes the evidence on a theme related to a systematic review topic. This Systematic Review Brief presents findings from the systematic review on self-regulation and relaxation-based interventions to improve psychosocial outcomes for people with traumatic brain injury.

Education and Skills Training Interventions for Adults With Traumatic Brain Injury (TBI) (Dates of Review: 2013-2020).

Systematic Review Briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association's Evidence-Based Practice Program. Each Systematic Review Brief summarizes the evidence on a theme related to a systematic review topic. This Systematic Review Brief presents findings from the systematic review on education and skills training interventions that address psychosocial, behavioral, and emotional skills for people with traumatic brain injury (TBI).

Physical Activity Interventions for Adults With Traumatic Brain Injury (2013-2020).

Systematic Review Briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association's Evidence-Based Practice Program. Each Systematic Review Brief summarizes the evidence on a theme related to a systematic review topic. This Systematic Review Brief presents findings from the systematic review on physical activity interventions to improve psychosocial outcomes for people with traumatic brain injury.

Cognitive Behavioral Therapy Interventions for Adults With Traumatic Brain Injury (2013-2020).

Systematic Review Briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association's Evidence-Based Practice Program. Each Systematic Review Brief summarizes the evidence on a theme related to a systematic review topic. This Systematic Review Brief presents findings from the systematic review on interventions that address psychosocial, behavioral, and emotional skills for people with traumatic brain injury (TBI).

Goal- and Client-Directed Interventions for Adults With Traumatic Brain Injury (2013-2020).

Systematic Review Briefs provide a summary of the findings from systematic reviews developed in conjunction with the American Occupational Therapy Association's Evidence-Based Practice Program. Each Systematic Review Brief summarizes the evidence on a theme related to a systematic review topic. This Systematic Review Brief presents findings from the systematic review on goal- and client-directed interventions to improve psychosocial outcomes for people with traumatic brain injury.

Frequency and Prognostic Significance of Intertumoural Heterogeneity in Multifocal Jejunoileal Neuroendocrine Tumours.

Background: A recent study found that multifocal jejunoileal neuroendocrine tumors (SI-NETs) are genetically unrelated synchronous neoplasms. So far, it is unclear if this finding of synchronous independent neoplasms is mirrored by heterogeneity of key morphological parameters of SI-NETs and how it affects patient survival.

Methods: We separately assessed WHO grade (based on the Ki-67 index), expression of basal diagnostic markers (synaptophysin/chromogranin A/CDX2/serotonin), SSTR2a, and the contexture of the immunogenic microenvironment in 146 separate tumors from 28 patients with multifocal SI-NETs and correlated the results with clinicopathological factors and survival.

Putative transcription antiterminator RfaH contributes to Erwinia amylovora virulence.

The gram-negative bacterium Erwinia amylovora causes fire blight disease of apple and pear trees. The exopolysaccharide amylovoran and lipopolysaccharides are essential E. amylovora virulence factors.

Assessment of Mosaicism and Detection of Cryptic Alleles in CRISPR/Cas9-Engineered Neurofibromatosis Type 1 and Mutant Porcine Models Reveals Overlooked Challenges in Precision Modeling of Human Diseases.

Genome editing in pigs has been made efficient, practical, and economically viable by the CRISPR/Cas9 platform, representing a promising new era in translational modeling of human disease for research and preclinical development of therapies and devices. Porcine embryo microinjection provides a universally available, efficient option over somatic-cell nuclear transfer, but requires that critical considerations be made in genotypic validation of the models that routinely go unaddressed. Accurate validation of genotypes is especially important when modeling genetic disorders, such as neurofibromatosis type 1 (NF1) that exhibits complex genotype-phenotypic relationships.

Cultural differences in stress and affection following social support receipt.

Culturally appropriate social support predicts better psychological outcomes. Motivation for providing social support may vary cross-culturally, with more independent cultures valuing self-esteem and more interdependent cultures valuing closeness. Participants in the U.

TGFβ2 and TGFβ3 mediate appropriate context-dependent phenotype of rat valvular interstitial cells.

This study focused on characterizing the potential mechanism of valvular toxicity caused by TGFβ receptor inhibitors (TGFβRis) using rat valvular interstitial cells (VICs) to evaluate early biological responses to TGFβR inhibition. Three TGFβRis that achieved similar exposures in the rat were assessed. Two dual TGFβRI/-RII inhibitors caused valvulopathy, whereas a selective TGFβRI inhibitor did not, leading to a hypothesis that TGFβ receptor selectivity may influence the potency of valvular toxicity.

High-throughput digitization of analog human echocardiography data.

Echocardiographic imaging has been acquired in historical longitudinal cohorts of cardiovascular disease. Many cohorts were established prior to digital recording of echocardiography, and thus have preserved their archival imaging on Video Home System (VHS) tapes. These tapes require large physical storage space, are affected by physical degradation, and cannot be analyzed using modern digital techniques.

Dynamic regulation of CTCF stability and sub-nuclear localization in response to stress.

The nuclear protein CCCTC-binding factor (CTCF) has diverse roles in chromatin architecture and gene regulation. Functionally, CTCF associates with thousands of genomic sites and interacts with proteins, such as cohesin, or non-coding RNAs to facilitate specific transcriptional programming. In this study, we examined CTCF during the cellular stress response in human primary cells using immune-blotting, quantitative real time-PCR, chromatin immunoprecipitation-sequence (ChIP-seq) analysis, mass spectrometry, RNA immunoprecipitation-sequence analysis (RIP-seq), and Airyscan confocal microscopy.

Virulence Genetics of an Erwinia amylovora Putative Polysaccharide Transporter Family Member.

The Gram-negative enterobacterium causes fire blight disease in apple and pear trees. Lipopolysaccharides and the exopolysaccharide amylovoran are essential virulence factors. We found that mutations in disrupted amylovoran production and virulence in apple fruits and tree shoots and that the deletion of suppressed the mutant phenotype.

COVID-19: a primer for the rheumatologist: management of patients and care settings.

Purpose Of Review: There are currently many unanswered questions surrounding the management of patients with immune-mediated inflammatory diseases during the COVID-19 pandemic and several 'rapid' guidelines have been released, although are subject to be updated and changed in the near future. The purpose of this review is to discuss the approach to management of patients with immune-mediated diseases during the COVID-19 pandemic.

Recent Findings: At present, there is little evidence to suggest an increased risk of COVID-19 infection or its complications in patients with immune-mediated diseases or associated with conventional or biologic disease modifying antirheumatic drugs; however, glucocorticoid use does appear to have negative associations.

Clostridium septicum-infected aortic aneurysm or graft is a deadly diagnosis.

Background: Clostridium septicum is an anaerobic, motile, spore-forming, toxin-producing gram-positive bacillus that can lead to rapidly progressive gas gangrene due to the release of alpha toxin. Aortic aneurysm secondary to C. septicum infection is a rare condition with 60 cases reported in the literature; however, we have recently treated several patients with the condition in our large tertiary care and aortic center.