CEP162 deficiency causes human retinal degeneration and reveals a dual role in ciliogenesis and neurogenesis.

Defects in primary or motile cilia result in a variety of human pathologies, and retinal degeneration is frequently associated with these so-called ciliopathies. We found that homozygosity for a truncating variant in CEP162, a centrosome and microtubule-associated protein required for transition zone assembly during ciliogenesis and neuronal differentiation in the retina, caused late-onset retinitis pigmentosa in 2 unrelated families. The mutant CEP162-E646R*5 protein was expressed and properly localized to the mitotic spindle, but it was missing from the basal body in primary and photoreceptor cilia.

The expression of chirality in linked poly(thiophene)s.

Conjugated polymers have demonstrated to express chirality, for instance, by strong circular dichroism (CD). However, the shape and intensity of the spectra can be quite different and are very difficult to predict. Molecular irregularity, star-shapes, and linking polymers have demonstrated to affect the CD, often in a positive way.

Early life adversity: Epigenetic regulation underlying drug addiction susceptibility.

Drug addiction is a leading cause of disability worldwide, with more than 70,000 Americans dying from drug overdose in 2019 alone. While only a small percentage of chronic drug users escalate to drug addiction, little is understood on the precise mechanisms of this susceptibility. Early life adversity is causally relevant to adult psychiatric disease and may contribute to the risk of addiction.

Phase I study of novel SYK inhibitor TAK-659 (mivavotinib) in combination with R-CHOP for front-line treatment of high-risk diffuse large B-cell lymphoma.

: TAK-659, a novel oral SYK inhibitor, has demonstrated efficacy in heavily pretreated diffuse large B-cell lymphoma (DLBCL). We report results of a phase I single-institution escalation study of front-line treatment with R-CHOP and TAK-659 in treatment-naïve high-risk DLBCL. : Patients with high-risk DLBCL were treated with R-CHOP for 1 cycle, followed by combined R-CHOP and TAK-659 for an additional five cycles, with TAK-659 dosing escalated from 60 mg, to 80 mg, to 100 mg daily, based on a 3 + 3 design.

When Global Becomes Virtual: A Survey of Virtual Global Health Education Activities During the COVID-19 Pandemic Among Pediatric Educators.

Background: During the COVID-19 pandemic, global health education activities were disrupted. Transitioning to virtual options has allowed educators and trainees to continue global health education and partnerships, though the acceptability and implementation of this transition is unknown.

Objective: To evaluate current and planned virtual global health education activities (VGHEAs) of a group of US global health educators during the COVID-19 pandemic and to assess perceived benefits and challenges of VGHEAs.

Understanding Disparities in Receipt of Complex Gastrointestinal Cancer Surgery at a Small Geographic Scale.

Objective: To define neighborhood-level disparities in the receipt of complex cancer surgery.

Background: Little is known about the geographic variation of receipt of surgery among patients with complex gastrointestinal (GI) cancers, especially at a small geographic scale.

Methods: This study included individuals diagnosed with 5 invasive, nonmetastatic, complex GI cancers (esophagus, stomach, pancreas, bile ducts, liver) from the Ohio Cancer Incidence Surveillance System during 2009 and 2018.

MR-linac daily semi-automated end-to-end quality control verification.

Purpose: Adaptive radiation therapy (ART) on the integrated Elekta Unity magnetic resonance (MR)-linac requires routine quality assurance to verify delivery accuracy and system data transfer. In this work, our objective was to develop and validate a novel automated end-to-end test suite that verifies data transfer between multiple software platforms and quantifies the performance of multiple machine subcomponents critical to the ART process.

Methods: We designed and implemented a software tool to quantify the MR and megavoltage (MV) isocenter coincidence, treatment couch positioning consistency, isocenter shift accuracy for the adapted plan as well as the MLC and jaw position accuracy following the beam aperture adaptation.

Malignant Peripheral Nerve Sheath Tumors of the Brachial Plexus: A Single-Center Experience on Diagnosis, Management, and Outcomes.

Introduction: The incidence of malignant peripheral nerve sheath tumors (MPNSTs) is 0.001%. Commonly, MPNST arise in neurofibromatosis; however, they can occur sporadically, de novo or from a preexisting neurofibroma.

A novel electron source for a compact x-ray tube for microbeam radiotherapy with very high dose rates.

Microbeam radiotherapy (MRT) is a novel concept in radiation oncology with arrays of alternating micrometer-wide high-dose peaks and low-dose valleys. Preclinical experiments have shown a lower normal tissue toxicity for MRT with similar tumor control rates compared to conventional radiotherapy. A promising candidate for the demanded compact radiation source is the line-focus x-ray tube.

Liver Endothelium Microenvironment Promotes HER3-mediated Cell Growth in Pancreatic Ductal Adenocarcinoma.

~90% metastatic pancreatic ductal adenocarcinoma (mPDAC) occurs in the liver, and the 5-year survival rate for patients with mPDAC is only at 3%. The liver has a unique endothelial cell (EC)-rich microenvironment, and preclinical studies showed that ECs promote cancer cell survival pathways by secreting soluble factors in a paracrine fashion in other types of cancer. However, the effects of liver ECs on mPDAC have not been elucidated.

The challenge of estimating the direct and indirect effects of COVID-19 interventions - Toward an integrated economic and epidemiological approach.

Decisions on public health measures to contain a pandemic are often based on parameters such as expected disease burden and additional mortality due to the pandemic. Both pandemics and non-pharmaceutical interventions to fight pandemics, however, produce economic, social, and medical costs. The costs are, for example, caused by changes in access to healthcare, social distancing, and restrictions on economic activity.

Distinct features in adult polyglucosan body disease: a case series.

Adult polyglucosan body disease (APBD) is caused by bi-allelic pathogenic variants in GBE1 and typically shows middle age onset urinary symptoms followed by progressive gait disturbances and possibly cognitive decline. Here we present a Belgian cohort of four patients from three families showing both classical and atypical signs of APBD. By clinical phenotyping, detailed neuroimaging of both central nervous system and skeletal muscle, genetic and biochemical testing, we confront our findings with the classical presentation of adult polyglucosan body disease and emphasize the importance of a multidisciplinary approach when diagnosing these patients.

Multiple Negative Fecal Immunochemical Tests Reduce Risk of Advanced Neoplasia in a Colonoscopy Surveillance Program.

Background & Aims: In above-average-risk individuals undergoing colonoscopy-based surveillance for colorectal cancer (CRC), screening with fecal immunochemical tests (FIT) between colonoscopies might facilitate personalization of surveillance intervals. Because a negative FIT is associated with a reduced risk for CRC, we examined the relationship between number of rounds of negative FIT and risk for advanced neoplasia in individuals undergoing surveillance colonoscopy.

Methods: We conducted a retrospective cohort study on 4021 surveillance intervals in 3369 individuals (50-74 years), who had completed a 2-sample FIT between colonoscopies, from 1 to 4 rounds at 1-2 yearly intervals, each with a negative result (<20 μg hemoglobin/g feces).

Systemic thrombolytic and ultrasound-assisted catheter-directed thrombolysis for treatment of acute pulmonary embolism: a 7-year, multicenter experience.

Treatment of acute pulmonary embolism (PE) varies based upon risk stratification and ranges from outpatient oral anticoagulation to emergency surgical embolectomy. Patients with high-risk PE can be considered for systemic thrombolytic (ST) based upon guideline recommendations, but intermediate-risk PE does not currently have strong evidence to guide primary reperfusion strategies via thrombolytic administration. Ultrasound-assisted catheter-directed thrombolysis (USAT) is an alternative reperfusion option to ST but is not currently recommended as first line in any key guidelines due to limited available evidence.

Major Publications in the Critical Care Pharmacotherapy Literature: 2021.

Unlabelled: To summarize the most impactful articles relevant to the pharmacotherapy of critically ill adult patients published in 2021.

Data Source: PubMed/MEDLINE.

Study Selection: Randomized controlled trials, prospective studies, or systematic review/meta-analyses of adult critical care patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2021, and December 31, 2021.

Design and Rationale of Routine ltrasoud Gudance for ascular Accss fo Cardiac Procedure: Randomized Tria (UNIVERSAL).

Background: A significant limitation of femoral artery access for cardiac interventions is the increased risk of vascular complications and bleeding compared to radial access. Ultrasound (US)-guided femoral access may reduce major vascular complications and bleeding. We aim to determine whether routinely using US guidance for femoral arterial access for coronary angiography or intervention will reduce leeding cademic esearch onsortium (BARC) 2, 3, or 5 bleeding or major vascular complications.

Adjuvant -Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial.

Purpose: This randomized, open-label trial compared the efficacy and safety of adjuvant -paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430).

Methods: We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to -paclitaxel (125 mg/m) + gemcitabine (1,000 mg/m) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles.

Shared control versus traded control in driving: a debate around automation pitfalls.

A major question in human-automation interaction is whether tasks should be traded or shared between human and automation. This work presents reflections-which have evolved through classroom debates between the authors over the past 10 years-on these two forms of human-automation interaction, with a focus on the automated driving domain. As in the lectures, we start with a historically informed survey of six pitfalls of automation: (1) Loss of situation and mode awareness, (2) Deskilling, (3) Unbalanced mental workload, (4) Behavioural adaptation, (5) Misuse, and (6) Disuse.

Prognostic value of left ventricular global constructive work in patients with cardiac amyloidosis.

Purpose: The aim of the present study was to evaluate the role of ejection fraction (EF), left ventricular (LV) global longitudinal strain (LVGLS) and global constructive work (GCW) as prognostic variables in patients with cardiac amyloidosis (CA).

Methods: CA patients were retrospectively identified between 2015 and 2021 at a tertiary care hospital. Comprehensive clinical, biochemical, and imaging evaluation including two-dimensional (2D) echocardiography with myocardial work (MW) analysis was performed.

Genomic diversity of populations from different regions of the human stomach.

Individuals infected with harbor unique and diverse populations of quasispecies, but diversity between and within different regions of the human stomach and the process of bacterial adaptation to each location are not yet well understood. We applied whole-genome deep sequencing to characterize the within- and between-stomach region genetic diversity populations from paired antrum and corpus biopsies of 15 patients, along with single biopsies from one region of an additional 3 patients, by scanning allelic diversity. We combined population deep sequencing with more conventional sequencing of multiple single colony isolates from individual biopsies to generate a unique dataset.

Neutrophil degranulation, NETosis and platelet degranulation pathway genes are co-induced in whole blood up to six months before tuberculosis diagnosis.

Mycobacterium tuberculosis (M.tb) causes tuberculosis (TB) and remains one of the leading causes of mortality due to an infectious pathogen. Host immune responses have been implicated in driving the progression from infection to severe lung disease.

DNA Authentication and Chemical Analysis of Mushrooms Reveal Widespread Misdeterminations in Fungaria and Inconsistencies in Metabolites.

The mushroom genus is best known as the core group of psychoactive mushrooms, yet basic information on their diversity, taxonomy, chemistry, and general biology is still largely lacking. In this study, we reexamined 94 fungarium specimens, representing 18 species, by DNA barcoding, evaluated the stability of psilocybin, psilocin, and their related tryptamine alkaloids in 25 specimens across the most commonly vouchered species (Psilocybe cubensis, Psilocybe cyanescens, and Psilocybe semilanceata), and explored the metabolome of cultivated . Our data show that, apart from a few well-known species, the taxonomic accuracy of specimen determinations is largely unreliable, even at the genus level.