TDP43 autoregulation gives rise to dominant negative isoforms that are tightly controlled by transcriptional and post-translational mechanisms.

The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation.

Adherence to institutional stroke alert criteria in an academic adult emergency department population.

Background: Timely recognition of acute ischemic stroke (AIS) is essential to identify patients who may be eligible for acute intervention. Protocols to streamline systems-based care, such as "stroke alerts" in the emergency department (ED) can safely reduce time-to-care while enhancing safety. However, clinician adherence to stroke alert criteria is poorly described.

DLK-dependent axonal mitochondrial fission drives degeneration after axotomy.

Currently there are no effective treatments for an array of neurodegenerative disorders to a large part because cell-based models fail to recapitulate disease. Here we develop a reproducible human iPSC-based model where laser axotomy causes retrograde axon degeneration leading to neuronal cell death. Time-lapse confocal imaging revealed that damage triggers an apoptotic wave of mitochondrial fission proceeding from the site of injury to the soma.

Widespread occurrence of benzimidazole resistance single nucleotide polymorphisms in the canine hookworm, Ancylostoma caninum, in Australia.

Canine hookworm (Ancylostoma caninum), a gastrointestinal nematode of domestic dogs, principally infects the small intestine of dogs and has the potential to cause zoonotic disease. In greyhounds and pet dogs in the USA, A. caninum has been shown to be resistant to multiple anthelmintics.

African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in GBA1.

Recently, an African ancestry-specific Parkinson disease (PD) risk signal was identified at the gene encoding glucocerebrosidase (GBA1). This variant ( rs3115534 -G) is carried by ~50% of West African PD cases and imparts a dose-dependent increase in risk for disease. The risk variant has varied frequencies across African ancestry groups but is almost absent in European and Asian ancestry populations.

Development and results of a novel emergency medicine residency research immersion program.

Creating a sustainable residency research program is necessary to develop a sustainable research pipeline, as highlighted by the recent Society for Academic Emergency Medicine 2024 Consensus Conference. We sought to describe the implementation of a novel, immersive research program for first-year emergency medicine residents. We describe the curriculum development, rationale, implementation process, and lessons learned from the implementation of a year-long research curriculum for first-year residents.

Prognostic Significance of PD-L1 Expression on Circulating Myeloid-Derived Suppressor Cells in NSCLC Patients Treated with Anti-PD-1/PD-L1 Checkpoint Inhibitors.

Even though anti-PD-1/PD-L1 immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) have improved survival, a high percentage of patients still do not respond to ICIs. Myeloid-derived suppressor cells (MDSCs) are circulating cells that express PD-L1 and can infiltrate and proliferate in the tumor microenvironment, inducing immunosuppression. By evaluating changes in PD-L1 expression of live peripheral blood MDSCs, we are able to define a new PD-L1 index, useful in predicting ICI escape in NSCLC patients before initiating anti-PD-1/PD-L1 immunotherapy.

Correction: Cu(i) diimine complexes as immobilised antibacterial photosensitisers operating in water under visible light.

[This corrects the article DOI: 10.1039/D0MA00642D.].

A Modified Transgluteal Approach Sparing Abductor Function in Total Hip Arthroplasty Results in a Low Postoperative Dislocation Rate: A Retrospective Study of Short- and Long-Term Outcomes.

Background A modified transgluteal approach in total hip arthroplasty (THA) can be utilized to preserve abductor muscle function and reduce dislocation rate. We present a study evaluating outcomes for a modified transgluteal approach using a validated patient-reported outcome measure (PROM) tool, the Oxford Hip Score (OHS). Methods This was a retrospective single-centre study over a four-year period.

Structure-activity relationships and pharmacokinetic evaluation of L-cystine diamides as L-cystine crystallization inhibitors for cystinuria.

Cystinuria is a rare genetic disorder characterized by defective l-cystine reabsorption from the renal proximal tubule, resulting in abnormally high concentrations of L-cystine and subsequent l-cystine crystallization and stone formation in urine. l-Cystine diamides have shown great promise as inhibitors of l-cystine crystallization. The free α-amino groups in l-cystine diamides have previously been shown to be necessary for l-cystine crystallization inhibitory activity.

Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer's disease.

Background: Variants of the gene triggering receptor expressed on myeloid cells-2 (TREM2) increase the risk of Alzheimer's disease (AD) and other neurodegenerative disorders. Signaling by TREM2, an innate immune receptor expressed by microglia, is thought to enhance phagocytosis of amyloid beta (Aβ) and other damaged proteins, promote microglial proliferation, migration, and survival, and regulate inflammatory signaling. Thus, TREM2 activation has potential to alter the progression of AD.

Perforation of the Septal Perforators: A Case Series and Proposed Management Paradigm.

Septal artery perforations are an uncommon complication of percutaneous coronary intervention. Unlike epicardial vessels, septal perforations do not result in pericardial effusions but rather produce septal haematomas. While most can be managed expectantly, a small proportion requires active management to prevent rapid haematoma expansion resulting in compromise of right ventricular filling and 'dry tamponade'.

A systematic review and meta-analysis of bovine tuberculosis occurrence and burden in Bangladesh, 1970-2023.

We aimed to estimate the overall apparent prevalence, true prevalence, and the spatial, temporal, and test-specific burden of bovine tuberculosis in Bangladesh. PubMed, Web of Science, Scopus, Google Scholar, and BanglaJOL were searched for bovine tuberculosis publications in Bangladesh from 1 January 1970 to 23 June 2023. Of 142 articles screened, systematic review and meta-analysis were performed on 22 (15.

Hydrogen-bonded frameworks for conformational analysis of reactive substrates.

Guanidinium organosulfonate (GS) hydrogen-bonded host frameworks were used to trap α-halopropiophenones and α-halocyclooctanones to determine their molecular structure by single crystal X-ray diffraction. The majority of encapsulated guest molecules adopted conformations expected from computational analysis and stereochemical outcomes of Grignard reactions.

Advances in the Computational Assessment of Disturbed Coronary Flow and Wall Shear Stress: A Contemporary Review.

Coronary artery blood flow is influenced by various factors including vessel geometry, hemodynamic conditions, timing in the cardiac cycle, and rheological conditions. Multiple patterns of disturbed coronary flow may occur when blood flow separates from the laminar plane, associated with inefficient blood transit, and pathological processes modulated by the vascular endothelium in response to abnormal wall shear stress. Current simulation techniques, including computational fluid dynamics and fluid-structure interaction, can provide substantial detail on disturbed coronary flow and have advanced the contemporary understanding of the natural history of coronary disease.

Facet-Dependent Lethality of a Contact Insecticide Crystal.

The activity of crystalline contact insecticides relies on the extraction of surface molecules by insect tarsi upon contact. Most crystals are inherently anisotropic, and surface molecules on symmetry independent faces are expected to have different free energies. The facet-dependent bioavailability and associated efficacy of insect lethality have not been investigated, however.

A proposed method for identifying Interfacility transfers in Medicare claims data.

Objective: To develop a method of consistently identifying interfacility transfers (IFTs) in Medicare Claims using patients with ST-Elevation Myocardial Infarction (STEMI) as an example.

Data Sources/study Setting: 100% Medicare inpatient and outpatient Standard Analytic Files and 5% Carrier Files, 2011-2020.

Study Design: Observational, cross-sectional comparison of patient characteristics between proposed and existing methods.

New insights into coordination-cage based catalysis.

This review article summarises work from the author's group on catalysis using coordination cages over the (approximate) period 2018-2024. Recent insights discussed include (i) the general mechanism of catalysis, which involves co-location of reaction partners using orthogonal interactions involving the cage cavity (neutral hydrophobic substrates) and the surface anion-based reaction partners; (ii) the role of the cage exterior surface in facilitating catalysis in some cases; (iii) quantitative analysis of anion-binding to the cage surface, as a complement to measurement of binding constants of neutral guests inside the cavity; (iv) a new type of redox-based catalysis using reactive oxygen species, which are generated by reaction of oxidants such as HO and HSO with Co(II)/Co(III) redox couples in the cage superstructure. Collectively the results discussed provide signficant new possibilities for further exploration of catalysis using supramolecular assemblies.

Coordination-cage binding and catalysed hydrolysis of organophosphorus chemical warfare agent simulants.

The use of organophosphorus chemical warfare agents still remains an ongoing global threat. Here we investigate the binding of small-molecule organic guests including phosphate esters, sulfonate esters, carbonate esters and a sulfite ester - some of which act as simulants for organophosphorus chemical warfare agents - in the cavity of a water-soluble coordination cage. For several of these guest species, binding constants in the range 10 to 10 M were determined in water/DMSO (98 : 2 v/v) solution, through a combination of fluorescence and H NMR spectroscopy, and subsequent fitting of titration data to a 1 : 1 binding isotherm model.