Development of MAPT S305 mutation human iPSC lines exhibiting elevated 4R tau expression and functional alterations in neurons and astrocytes.

Due to the importance of 4R tau (with four microtubule-binding-repeat domains) in the pathogenicity of primary tauopathies, it has been challenging to model these diseases in induced pluripotent stem cell (iPSC)-derived neurons, which express very low levels of 4R tau. To address this, we have developed a panel of isogenic iPSC lines carrying MAPT splice-site mutations, S305S, S305I, or S305N, derived from four different donors. All mutations significantly increase 4R tau expression in iPSC neurons and astrocytes.

A chemically induced, room temperature, single source precursor to CuS (covellite) nanomaterials: synthesis and reactivity of [Cu(SCNHBz)].

Addition of two equivalents of NaSCNHBz to CuSO affords the yellow diamagnetic coordination polymer [Cu(SCNHBz)] (1), resulting from intramolecular electron-transfer and concomitant formation of the thiourea, (BzNH)CS. 1 reacts with PPh and 1,1'-bis(diphenylphosphino)ferrocene (dppf) in CHCl to give monomeric [Cu(κ-SCNHBz)(PPh)] (2) and [Cu(κ-SCNHBz)(κ-dppf)] (3), respectively, both of which have been crystallographically characterised. While 1 is thermally stable in dimethylsulfoxide (DMSO) up to 70 °C, addition of BuNH to 1 leads to its rapid decomposition to afford CuS (covellite) nanomaterials; indeed in neat BuNH, covellite formation is rapid at room temperature.

F-FDG-PET/MR imaging to monitor disease activity in large vessel vasculitis.

Disease-monitoring in large vessel vasculitis (LVV) is challenging. Simultaneous F-fluorodeoxyglucose positron emission tomography with magnetic resonance imaging (PET/MRI) provides functional assessment of vascular inflammation alongside high-definition structural imaging with a relatively low burden of radiation exposure. Here, we investigate the ability of PET/MRI to monitor LVV disease activity longitudinally in a prospective cohort of patients with active LVV.

Conducting an objective structured clinical examination under COVID-restricted conditions.

Background: The administration of performance assessments during the coronavirus disease of 2019 (COVID-19) pandemic posed many challenges, especially for examinations employed as part of certification and licensure. The National Assessment Collaboration (NAC) Examination, an Objective Structured Clinical Examination (OSCE), was modified during the pandemic. The purpose of this study was to gather evidence to support the reliability and validity of the modified NAC Examination.

Choroidalyzer: An Open-Source, End-to-End Pipeline for Choroidal Analysis in Optical Coherence Tomography.

Purpose: To develop Choroidalyzer, an open-source, end-to-end pipeline for segmenting the choroid region, vessels, and fovea, and deriving choroidal thickness, area, and vascular index.

Methods: We used 5600 OCT B-scans (233 subjects, six systemic disease cohorts, three device types, two manufacturers). To generate region and vessel ground-truths, we used state-of-the-art automatic methods following manual correction of inaccurate segmentations, with foveal positions manually annotated.

Designing a touchless physical examination for a virtual Objective Structured Clinical Examination.

Purpose: Given the COVID-19 pandemic, many Objective Structured Clinical Examinations (OSCEs) have been adapted to virtual formats without addressing whether physical examination maneuvers can or should be assessed virtually. In response, we developed a novel touchless physical examination station for a virtual OSCE and gathered validity evidence for its use.

Methods: We used a touchless physical examination OSCE station pilot-tested in a virtual OSCE in which Internal Medicine residents had to verbalize their approach to the physical examination, interpret images and videos of findings provided upon request, and make a diagnosis.

Evolving better solvate electrolytes for lithium secondary batteries.

The overall performance of lithium batteries remains unmatched to this date. Decades of optimisation have resulted in long-lasting batteries with high energy density suitable for mobile applications. However, the electrolytes used at present suffer from low lithium transference numbers, which induces concentration polarisation and reduces efficiency of charging and discharging.

Choroidal and retinal thinning in chronic kidney disease independently associate with eGFR decline and are modifiable with treatment.

In patients with chronic kidney disease (CKD), there is an unmet need for novel biomarkers that reliably track kidney injury, demonstrate treatment-response, and predict outcomes. Here, we investigate the potential of retinal optical coherence tomography (OCT) to achieve these ends in a series of prospective studies of patients with pre-dialysis CKD (including those with a kidney transplant), patients with kidney failure undergoing kidney transplantation, living kidney donors, and healthy volunteers. Compared to health, we observe similar retinal thinning and reduced macular volume in patients with CKD and in those with a kidney transplant.

Implicit versus explicit first impressions in performance-based assessment: will raters overcome their first impressions when learner performance changes?

First impressions can influence rater-based judgments but their contribution to rater bias is unclear. Research suggests raters can overcome first impressions in experimental exam contexts with explicit first impressions, but these findings may not generalize to a workplace context with implicit first impressions. The study had two aims.

An Open-Source Deep Learning Algorithm for Efficient and Fully Automatic Analysis of the Choroid in Optical Coherence Tomography.

Purpose: To develop an open-source, fully automatic deep learning algorithm, DeepGPET, for choroid region segmentation in optical coherence tomography (OCT) data.

Methods: We used a dataset of 715 OCT B-scans (82 subjects, 115 eyes) from three clinical studies related to systemic disease. Ground-truth segmentations were generated using a clinically validated, semiautomatic choroid segmentation method, Gaussian Process Edge Tracing (GPET).

Evaluation of an Automated Choroid Segmentation Algorithm in a Longitudinal Kidney Donor and Recipient Cohort.

Purpose: To evaluate the performance of an automated choroid segmentation algorithm in optical coherence tomography (OCT) data using a longitudinal kidney donor and recipient cohort.

Methods: We assessed 22 donors and 23 patients requiring renal transplantation over up to 1 year posttransplant. We measured choroidal thickness (CT) and area and compared our automated CT measurements to manual ones at the same locations.

Improving School Environments for Preventing Sexual Violence Among LGBTQ+ Youth.

Background: Sexual violence (SV) is a serious public health concern, and lesbian, gay, bisexual, transgender, queer and questioning (LGBTQ+) youth report higher rates than their heterosexual and cisgender peers. This qualitative study aimed to understand LGBTQ+ students' perspectives on how middle and high school environments can better prevent and address SV.

Methods: In partnership with a school-based LGBTQ+ support group in Washington State, we recruited 31 LGTBQ+ students ages 13-18 for virtual interviews (n = 24) and for providing text-based answers to interview questions (n = 7).

Widespread habitat loss and redistribution of marine top predators in a changing ocean.

The Northwest Atlantic Ocean and Gulf of Mexico are among the fastest warming ocean regions, a trend that is expected to continue through this century with far-reaching implications for marine ecosystems. We examine the distribution of 12 highly migratory top predator species using predictive models and project expected habitat changes using downscaled climate models. Our models predict widespread losses of suitable habitat for most species, concurrent with substantial northward displacement of core habitats >500 km.

On the Use of Triarylsilanols as Catalysts for Direct Amidation of Carboxylic Acids.

Triarylsilanols have been reported as the first silicon-centered molecular catalysts for direct amidation of carboxylic acids with amines as identified after a screen of silanols, silanediols, disiloxanediols, and incompletely condensed silsesquioxanes as potential homogeneous catalysts. Subsequent synthesis and testing of various electronically differentiated triarylsilanols have identified tris(-haloaryl)silanols as more active than the parent triarylsilanol, where the bromide congener is found to be the most active. Catalyst decomposition can be observed by NMR methods, but RPKA methods reveal that product inhibition is operative, where tertiary amides are more inhibitory than secondary amides.

Trace Minerals Nutrition in Goats.

This article is an overview of trace mineral nutrition, disease association with dietary inadequacy of trace minerals, and the associated diseases in goats. The trace minerals most commonly associated with deficiency-related diseases encountered in clinical veterinary medicine, Copper, Zinc, and Selenium, are discussed in greater detail than those less commonly associated with diseases. However, Cobalt, Iron, and Iodine are also discussed.

Experience of introducing an electronic health records station in an objective structured clinical examination to evaluate medical students’ communication skills in Canada: a descriptive study.

Purpose: There is limited literature related to the assessment of electronic medical record (EMR)-related competencies. To address this gap, this study explored the feasibility of an EMR objective structured clinical examination (OSCE) station to evaluate medical students’ communication skills by psychometric analyses and standardized patients’ (SPs) perspectives on EMR use in an OSCE.

Methods: An OSCE station that incorporated the use of an EMR was developed and pilot-tested in March 2020.

Development of MAPT S305 mutation models exhibiting elevated 4R tau expression, resulting in altered neuronal and astrocytic function.

Due to the importance of 4R tau in the pathogenicity of primary tauopathies, it has been challenging to model these diseases in iPSC-derived neurons, which express very low levels of 4R tau. To address this problem we have developed a panel of isogenic iPSC lines carrying the splice-site mutations S305S, S305I or S305N, derived from four different donors. All three mutations significantly increased the proportion of 4R tau expression in iPSC-neurons and astrocytes, with up to 80% 4R transcripts in S305N neurons from as early as 4 weeks of differentiation.

Building use-inspired species distribution models: Using multiple data types to examine and improve model performance.

Species distribution models (SDMs) are becoming an important tool for marine conservation and management. Yet while there is an increasing diversity and volume of marine biodiversity data for training SDMs, little practical guidance is available on how to leverage distinct data types to build robust models. We explored the effect of different data types on the fit, performance and predictive ability of SDMs by comparing models trained with four data types for a heavily exploited pelagic fish, the blue shark (Prionace glauca), in the Northwest Atlantic: two fishery dependent (conventional mark-recapture tags, fisheries observer records) and two fishery independent (satellite-linked electronic tags, pop-up archival tags).

Patients with sporadic FTLD exhibit similar increases in lysosomal proteins and storage material as patients with FTD due to GRN mutations.

Loss of function progranulin (GRN) mutations are a major autosomal dominant cause of frontotemporal dementia (FTD). Patients with FTD due to GRN mutations (FTD-GRN) develop frontotemporal lobar degeneration with TDP-43 pathology type A (FTLD-TDP type A) and exhibit elevated levels of lysosomal proteins and storage material in frontal cortex, perhaps indicating lysosomal dysfunction as a mechanism of disease. To investigate whether patients with sporadic FTLD exhibit similar signs of lysosomal dysfunction, we compared lysosomal protein levels, transcript levels, and storage material in patients with FTD-GRN or sporadic FTLD-TDP type A.

Integrated Proteomics to Understand the Role of Neuritin (NRN1) as a Mediator of Cognitive Resilience to Alzheimer's Disease.

The molecular mechanisms and pathways enabling certain individuals to remain cognitively normal despite high levels of Alzheimer's disease (AD) pathology remain incompletely understood. These cognitively normal people with AD pathology are described as preclinical or asymptomatic AD (AsymAD) and appear to exhibit cognitive resilience to the clinical manifestations of AD dementia. Here we present a comprehensive network-based approach from cases clinically and pathologically defined as asymptomatic AD to map resilience-associated pathways and extend mechanistic validation.

Does allowing access to electronic differential diagnosis support threaten the reliability of a licensing exam?

Introduction: Newer electronic differential diagnosis supports (EDSs) are efficient and effective at improving diagnostic skill. Although these supports are encouraged in practice, they are prohibited in medical licensing examinations. The purpose of this study is to determine how using an EDS impacts examinees' results when answering clinical diagnosis questions.

A Case Report of Hypotension and Methemoglobinemia Associated With Gunshot Residue Poisoning: Nitrite-Induced Methemoglobinemia.

A patient with gunshots within inches of the skin developed intraoperative vasodilatory hypotension and methemoglobinemia, both recognized consequences of nitrite poisoning. A 1- mg/kg dose of methylene blue transiently and partially reversed methemoglobinemia, but the color of the methylene blue faded rapidly, consistent with bleaching of methylene blue by nitrite in vivo. Methylene blue did not raise blood pressure, consistent with inhibition of nitric oxide (NO) synthase.

Endothelin blockade prevents the long-term cardiovascular and renal sequelae of acute kidney injury in mice.

Acute kidney injury (AKI) is common and associated with increased risks of cardiovascular and chronic kidney disease. Causative molecular/physiological pathways are poorly defined. There are no therapies to improve long-term outcomes.