Hastening Progress in Requires Studying Surrogates.

is an enigmatic human parasite that sickens thousands of people worldwide. The scarcity of research material and lack of any animal model or cell culture system slows research, denying the produce industry, epidemiologists, and regulatory agencies of tools that might aid diagnosis, risk assessment, and risk abatement. Fortunately, related species offer a strong foundation when used as surrogates to study parasites of this type.

Exploring the connection between work-family conflict and job burnout among Nigerian correctional staff.

Only one study among U.S. prison staff has explored the effects of work-family conflict and job burnout.

Using Deep Learning for Task and Tremor Type Classification in People with Parkinson's Disease.

Hand tremor is one of the dominating symptoms of Parkinson's disease (PD), which significantly limits activities of daily living. Along with medications, wearable devices have been proposed to suppress tremor. However, suppressing tremor without interfering with voluntary motion remains challenging and improvements are needed.

Segregation analysis of 17,425 population-based breast cancer families: Evidence for genetic susceptibility and risk prediction.

Rare pathogenic variants in known breast cancer-susceptibility genes and known common susceptibility variants do not fully explain the familial aggregation of breast cancer. To investigate plausible genetic models for the residual familial aggregation, we studied 17,425 families ascertained through population-based probands, 86% of whom were screened for pathogenic variants in BRCA1, BRCA2, PALB2, CHEK2, ATM, and TP53 via gene-panel sequencing. We conducted complex segregation analyses and fitted genetic models in which breast cancer incidence depended on the effects of known susceptibility genes and other unidentified major genes and a normally distributed polygenic component.

Real-Time Performance Assessment of High-Order Tremor Estimators Used in a Wearable Tremor Suppression Device.

The side effects and complications of traditional treatments for treating pathological tremor have led to a growing research interest in wearable tremor suppression devices (WTSDs) as an alternative approach. Similar to how the human brain coordinates the function of the human system, a tremor estimator determines how a WTSD functions. Although many tremor estimation algorithms have been developed and validated, whether they can be implemented on a cost-effective embedded system has not been studied; furthermore, their effectiveness on tremor signals with multiple harmonics has not been investigated.

Fascicles split or merge every ∼560 microns within the human cervical vagus nerve.

Vagus nerve stimulation (VNS) is Food and Drug Administration-approved for epilepsy, depression, and obesity, and stroke rehabilitation; however, the morphological anatomy of the vagus nerve targeted by stimulatation is poorly understood. Here, we used microCT to quantify the fascicular structure and neuroanatomy of human cervical vagus nerves (cVNs).We collected eight mid-cVN specimens from five fixed cadavers (three left nerves, five right nerves).

The SCRIPT trial: study protocol for a randomised controlled trial of a polygenic risk score to tailor colorectal cancer screening in primary care.

Background: Polygenic risk scores (PRSs) can predict the risk of colorectal cancer (CRC) and target screening more precisely than current guidelines using age and family history alone. Primary care, as a far-reaching point of healthcare and routine provider of cancer screening and risk information, may be an ideal location for their widespread implementation.

Methods: This trial aims to determine whether the SCRIPT intervention results in more risk-appropriate CRC screening after 12 months in individuals attending general practice, compared with standard cancer risk reduction information.

Using EHR Data to Identify Patient Frailty and Risk for ICU Transfer.

The predictive properties of four definitions of a frailty risk score (FRS) constructed using combinations of nursing flowsheet data, laboratory tests, and ICD-10 codes were examined for time to first intensive care unit (ICU) transfer in medical-surgical inpatients ≥50 years of age. Cox regression modeled time to first ICU transfer and Schemper-Henderson explained variance summarized predictive accuracy of FRS combinations. Modeling by age group and controlling for sex, all FRS measures significantly predicted time to first ICU transfer.

Preliminary Assessment of the Safety of a Fault-Tolerant Control-based Wearable Tremor Suppression Glove.

The advent of wearable tremor suppression de-vices (WTSDs) has provided a promising alternative approach for parkinsonian tremor management, especially for individuals whose tremors are not managed by conventional treatment options. Currently, research in WTSDs has shown successful results with a tremor suppression ratio of up to 99 %; however, the user safety of WTSDs has not been properly considered, especially in the occurrence of unexpected events, such as faults and disturbances. In this study, a fault-tolerant control system was developed and integrated into the control system of a WTSD for the first time.

Prenatal genetic testing 1: screening tests.

Purpose Of Review: Prenatal genetic testing can be divided into two categories: screening and diagnostic. This article will focus on reviewing prenatal genetic screening tests.

Recent Findings: Cell-free DNA (cfDNA) is a new prenatal genetic screening test with a high degree of accuracy for identifying certain genetic conditions like trisomy 21, 18, and 13.

Prenatal genetic testing 2: diagnostic tests.

Purpose Of Review: Prenatal genetic testing can be divided into two categories: screening and diagnosis. Prenatal genetic screening tests are used to assess carrier status or as a fetal risk assessment for a particular genetic disorder [1]. Prenatal genetic diagnostic testing is used to diagnose particular genetic conditions with as much certainty as possible [1,2].

S-nitroso-L-cysteine stereoselectively blunts the adverse effects of morphine on breathing and arterial blood gas chemistry while promoting analgesia.

S-nitrosothiols exert multiple effects on neural processes in the central and peripheral nervous system. This study shows that intravenous infusion of S-nitroso-L-cysteine (SNO-L-CYS, 1 μmol/kg/min) in anesthetized male Sprague Dawley rats elicits (a) sustained increases in minute ventilation, via increases in frequency of breathing and tidal volume, (b) a decrease in Alveolar-arterial (A-a) gradient, thus improving alveolar gas-exchange, (c) concomitant changes in arterial blood-gas chemistry, such as an increase in pO and a decrease in pCO, (d) a decrease in mean arterial blood pressure (MAP), and (e) an increase in tail-flick (TF) latency (antinociception). Infusion of S-nitroso-D-cysteine (SNO-D-CYS, 1 μmol/kg/min, IV), did not elicit similar responses, except for a sustained decrease in MAP equivalent to that elicited by SNO-L-CYS.

Alcohol-associated liver disease predicts increased post-liver transplant opioid use.

Background: Alcohol-associated liver disease (ALD) is a rising indication for liver transplantation (LT). Prolonged opioid use after LT leads to increased graft loss and mortality. The aim is to determine if patients transplanted with a primary diagnosis of ALD had higher risk of post-LT opioid use (p-LTOU) compared to non-ALD patients.

Investigating disparity in access to Australian clinical genetic health services for Aboriginal and Torres Strait Islander people.

Globally, there is a recognised need that all populations should be able to access the benefits of genomics and precision medicine. However, achieving this remains constrained by a paucity of data that quantifies access to clinical genomics, particularly amongst Indigenous populations. Using administrative data from clinical genetic health services across three Australian jurisdictions (states/territories), we investigate disparities in the scheduling and attendance of appointments among Aboriginal and/or Torres Strait Islander people, compared to non-Indigenous people.

A validation of models for prediction of pathogenic variants in mismatch repair genes.

Purpose: Models used to predict the probability of an individual having a pathogenic homozygous or heterozygous variant in a mismatch repair gene, such as MMRpro, are widely used. Recently, MMRpro was updated with new colorectal cancer penetrance estimates. The purpose of this study was to evaluate the predictive performance of MMRpro and other models for individuals with a family history of colorectal cancer.

Analysis of the distribution of vagal afferent projections from different peripheral organs to the nucleus of the solitary tract in rats.

Anatomical tracing studies examining the vagal system can conflate details of sensory afferent and motor efferent neurons. Here, we used a serotype of adeno-associated virus that transports retrogradely and exhibits selective tropism for vagal afferents, to map their soma location and central termination sites within the nucleus of the solitary tract (NTS). We examined the vagal sensory afferents innervating the trachea, duodenum, stomach, or heart, and in some animals, from two organs concurrently.

Quantitative Pathologic Analysis of Digitized Images of Colorectal Carcinoma Improves Prediction of Recurrence-Free Survival.

Background & Aims: To examine whether quantitative pathologic analysis of digitized hematoxylin and eosin slides of colorectal carcinoma (CRC) correlates with clinicopathologic features, molecular alterations, and prognosis.

Methods: A quantitative segmentation algorithm (QuantCRC) was applied to 6468 digitized hematoxylin and eosin slides of CRCs. Fifteen parameters were recorded from each image and tested for associations with clinicopathologic features and molecular alterations.

Digital Interventions Supporting Self-care in People With Type 2 Diabetes Across Greater Manchester (Greater Manchester Diabetes My Way): Protocol for a Mixed Methods Evaluation.

Background: Type 2 Diabetes (T2D) is common, with a prevalence of approximately 7% of the population in the United Kingdom. The quality of T2D care is inconsistent across the United Kingdom, and Greater Manchester (GM) does not currently achieve the National Institute for Health and Care Excellence treatment targets. Barriers to delivery of care include low attendance and poor engagement with local T2D interventions, which tend to consist of programs of education delivered in traditional, face-to-face clinical settings.

What can We Learn From High-Performing Screening Programs to Increase Bowel Cancer Screening Participation in Australia?

Background: Colorectal cancer (CRC) is the second most diagnosed cancer in men and women and second most common cause of cancer death in Australia; Australia's CRC incidence and mortality are among the world's highest. The Australian National Bowel Cancer Screening Program began in 2006; however, only 33% of those approached for the first time by the Program between 2018 and 2019 returned the kit. Of the 5.

Disparities in dermatology AI performance on a diverse, curated clinical image set.

An estimated 3 billion people lack access to dermatological care globally. Artificial intelligence (AI) may aid in triaging skin diseases and identifying malignancies. However, most AI models have not been assessed on images of diverse skin tones or uncommon diseases.

Development and profiling of mGlu NAMs with a range of saturable inhibition of agonist responses in vitro.

We describe here a series of metabotropic glutamate receptor 7 (mGlu) negative allosteric modulators (NAMs) with a saturable range of activity in inhibiting responses to an orthosteric agonist in two distinct in vitro pharmacological assays. The range of inhibition among compounds in this scaffold provides highly structurally related ligands with differential degrees of receptor blockade that can be used to understand inhibitory efficacy profiles in native tissue or in vivo.

Cloning and expression of a cDNA coding for Eimeria acervulina 25 kDa protein associated with oocyst and sporocyst walls.

The purpose of this study was to characterize a gene named EAH 00033530 identified by RNAseq analysis of sporulating Eimeria acervulina oocysts and its encoded protein. Quantitative RT-PCR analysis revealed peak expression of EAH 00033530 mRNA early (3-6 h) in sporulation followed by downregulation at 12-24 h. The gene for EAH 00033530 was expressed in Escherichia coli as a 70 kDa polyHis fusion protein (rEAH 00033530).

Colocalized targeting of TGF-β and PD-L1 by bintrafusp alfa elicits distinct antitumor responses.

Background: Bintrafusp alfa (BA) is a bifunctional fusion protein designed for colocalized, simultaneous inhibition of two immunosuppressive pathways, transforming growth factor-β (TGF-β) and programmed death-ligand 1 (PD-L1), within the tumor microenvironment (TME). We hypothesized that targeting PD-L1 to the tumor by BA colocalizes the TGF-β trap (TGF-βRII) to the TME, enabling it to sequester TGF-β in the tumor more effectively than systemic TGF-β blockade, thereby enhancing antitumor activity.

Methods: Multiple technologies were used to characterize the TGF-β trap binding avidity.