Papillary and ductal patterns of mesonephric-like adenocarcinomas are often overlooked: a retrospective revaluation of over 1000 endometrial carcinomas.

Aims: Mesonephric-like adenocarcinoma (MLA) of the endometrium is often a diagnostic challenge, due to its morphological resemblance to other more common Müllerian neoplasms. This study aimed to retrospectively identify overlooked MLA in a large endometrial carcinoma cohort, using a combination of immunohistochemistry (IHC), morphology and KRAS sequencing.

Methods And Results: IHC was conducted on 1094 endometrial carcinomas, identifying 16 potential MLA cases based on GATA3+ and/or TTF1+ and ER- staining patterns, which subsequently underwent detailed histological review, KRAS sequencing and ProMisE molecular classification.

A short review of application of near-infrared spectroscopy (NIRS) for the assessment of microvascular post-occlusive reactive hyperaemia (PORH) in skeletal muscle.

Near-infrared spectroscopy (NIRS) is an optical technique that can be used to non-invasively interrogate haemodynamic changes within skeletal muscle. It can be combined with a short (3-5 min) arterial cuff-occlusion to quantify post-occlusive reactive hyperaemia (PORH). This technique has utility in tracking changes in vascular health in relation to exercise, disease progression or treatment efficacy.

Validation and clinical performance of a single test, DNA based endometrial cancer molecular classifier.

Objectives: We have previously shown that DNA based, single test molecular classification by next generation sequencing (NGS) (Proactive Molecular risk classifier for Endometrial cancer (ProMisE) NGS) is highly concordant with the original ProMisE classifier and maintains prognostic value in endometrial cancer. Our aim was to validate ProMisE NGS in an independent cohort and assess the performance of ProMisE NGS in real world clinical practice to address if there were any practical challenges or learning points for implementation.

Methods: We evaluated DNA extracted from an external research cohort of 211 endometrial cancer cases diagnosed in 2016 from Germany, Switzerland, and Austria, across seven European centers, comparing standard molecular classification (NGS for status, immunohistochemistry for mismatch repair and p53) with ProMisE NGS (NGS for and microsatellite instability assay) for concordance metrics and Kaplan-Meier survival statistics across molecular subtypes.

Polypharmacy in elective lumbar spinal surgery for degenerative conditions with 24-month follow-up.

We sought to identify long-term associations of medical complications and healthcare utilization related to polypharmacy following spinal surgery for degenerative lumbar pathology. The IBM MarketScan dataset was used to select patients who underwent spinal surgery for degenerative lumbar pathology with 2-year follow-up. Regression analysis compared two matched cohorts: those with and without polypharmacy.

Targeting CLK3 with Covalent Inhibitors: A Novel Strategy for Malaria Treatment.

Malaria still causes over 600,000 deaths annually, with rising resistance to frontline drugs by increasing this number each year. New medicines with novel mechanisms of action are, therefore, urgently needed. In this work, we solved the cocrystal structure of the essential malarial kinase CLK3 with the reversible inhibitor TCMDC-135051 (), enabling the design of covalent inhibitors targeting a unique cysteine residue (Cys368) poorly conserved in the human kinome.

Identifying and modeling the impact of neonicotinoid exposure on honey bee colony profit.

Pollination by the European honey bee, Apis mellifera, is essential for the production of many crops, including highbush blueberries (Vaccinum corymbosum). To understand the impact of agrochemicals (specifically, neonicotinoids, a class of synthetic, neurotoxic insecticides) on these pollinators, we conducted a field study during the blueberry blooms of 2020 and 2021 in British Columbia (B.C.

Pollen foraging mediates exposure to dichotomous stressor syndromes in honey bees.

Recent declines in the health of honey bee colonies used for crop pollination pose a considerable threat to global food security. Foraging by honey bee workers represents the primary route of exposure to a plethora of toxins and pathogens known to affect bee health, but it remains unclear how foraging preferences impact colony-level patterns of stressor exposure. Resolving this knowledge gap is crucial for enhancing the health of honey bees and the agricultural systems that rely on them for pollination.

Peripheral Ca2.2 Channels in the Skin Regulate Prolonged Heat Hypersensitivity during Neuroinflammation.

Neuroinflammation can lead to chronic maladaptive pain affecting millions of people worldwide. Neurotransmitters, cytokines, and ion channels are implicated in neuroimmune cell signaling, but their roles in specific behavioral responses are not fully elucidated. Voltage-gated Ca2.

Deep-sea ecosystems of the Indian Ocean >1000 m.

The Indian Ocean is the third largest of the world's oceans, accounting for ~20 % of the global marine realm. It is geomorphologically complex, hosting a wide variety of ecosystems across basins, trenches, seamounts, ridges, and fracture zones. While modern exploration has contributed significantly to our knowledge of its coastal ecosystems, deeper waters (>1000 m) remain relatively unknown despite accounting for over 90 % of its total area.

Pseudomyxoma peritonei arising from mature ovarian teratoma, a rare entity: Report of six cases and review of current literature.

Background: Pseudomyxoma peritonei (PMP) is a clinical syndrome characterised by intraperitoneal accumulation of mucus due to mucinous neoplasia. It is a rare condition affecting 1-2 per million individuals per year. The majority of PMP arises from a ruptured mucinous appendiceal tumour, with infrequent occurrences from other primary gastrointestinal tumours and mucinous ovarian tumours.

Machine Learning-Assisted Near-Infrared Spectral Fingerprinting for Macrophage Phenotyping.

Spectral fingerprinting has emerged as a powerful tool that is adept at identifying chemical compounds and deciphering complex interactions within cells and engineered nanomaterials. Using near-infrared (NIR) fluorescence spectral fingerprinting coupled with machine learning techniques, we uncover complex interactions between DNA-functionalized single-walled carbon nanotubes (DNA-SWCNTs) and live macrophage cells, enabling phenotype discrimination. Utilizing Raman microscopy, we showcase statistically higher DNA-SWCNT uptake and a significantly lower defect ratio in M1 macrophages compared to M2 and naive phenotypes.

Submarine canyon development controlled by slope failure and oceanographic process interactions.

The southeastern Australian margin hosts a series of submarine canyons. Although the origin and evolution of canyons within the northwestern segment of the margin is relatively well studied, their quantitative morphology, interaction with longshore drift currents and slope failure remain poorly understood in the southeastern region. In this study, high-resolution bathymetry and 3D seismic reflection datasets revealed five main submarine canyons present in the central offshore Otway Basin.

Near-infrared spectroscopy (NIRS) assessment of skeletal muscle oxidative capacity: a comparison of results from short long exercise protocols and reproducibility in non-athletic adults.

Background: Near-infrared spectroscopy (NIRS) provides a non-invasive, cost-effective method for assessing skeletal muscle oxidative capacity when combined with a short exercise protocol and arterial occlusions. However, the impact of different exercise protocols and reproducibility of the method in non-athletic adults have not previously been assessed.

Methods: Young, non-athletic adults (YA) were invited to perform a short duration, fast frequency contraction (SF) exercise protocol and a long duration slow frequency (LS) contraction protocol, combined with NIRS measurements and arterial occlusions to assess skeletal muscle oxidative capacity.

Peripheral Ca2.2 channels in skin regulate prolonged heat hypersensitivity during neuroinflammation.

Neuroinflammation can lead to chronic maladaptive pain affecting millions of people worldwide. Neurotransmitters, cytokines, and ion channels are implicated in neuro-immune cell signaling but their roles in specific behavioral responses are not fully elucidated. Voltage-gated Ca2.

A review of adaptive equipment and technology for exercise and sports activities for people with disabilities.

Individuals with disabilities face psychological, environmental, and resource-related barriers to participating in exercise and sports. The lack of participation in exercise observed in the disability community poses great concern to this population's health. This review discusses commercially available adaptive equipment and technology for exercise and sports that help people with disabilities circumvent barriers to exercise.

Brain-age prediction: Systematic evaluation of site effects, and sample age range and size.

Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model.

AI-based histopathology image analysis reveals a distinct subset of endometrial cancers.

Endometrial cancer (EC) has four molecular subtypes with strong prognostic value and therapeutic implications. The most common subtype (NSMP; No Specific Molecular Profile) is assigned after exclusion of the defining features of the other three molecular subtypes and includes patients with heterogeneous clinical outcomes. In this study, we employ artificial intelligence (AI)-powered histopathology image analysis to differentiate between p53abn and NSMP EC subtypes and consequently identify a sub-group of NSMP EC patients that has markedly inferior progression-free and disease-specific survival (termed 'p53abn-like NSMP'), in a discovery cohort of 368 patients and two independent validation cohorts of 290 and 614 from other centers.

'It was never about me': A qualitative inquiry into the experiences of psychological support and perceived support needs of family caregivers of people with high-grade glioma.

Background: Family caregivers of people with high-grade glioma often report high rates of psychological distress, which has been attributed to the unique aspects of the disease and onerous care demands. Clinical practice guidelines advocate for caregiver support from diagnosis through to end-of-life and bereavement. Yet, research has identified that caregivers' support needs are often overlooked.

A general algorithm for consensus 3D cell segmentation from 2D segmented stacks.

Cell segmentation is the fundamental task. Only by segmenting, can we define the quantitative spatial unit for collecting measurements to draw biological conclusions. Deep learning has revolutionized 2D cell segmentation, enabling generalized solutions across cell types and imaging modalities.

Interleukin-1α links peripheral Ca2.2 channel activation to rapid adaptive increases in heat sensitivity in skin.

Neurons have the unique capacity to adapt output in response to changes in their environment. Within seconds, sensory nerve endings can become hypersensitive to stimuli in response to potentially damaging events. The underlying behavioral response is well studied, but several of the key signaling molecules that mediate sensory hypersensitivity remain unknown.

Honey bee stressor networks are complex and dependent on crop and region.

Honey bees play a major role in crop pollination but have experienced declining health throughout most of the globe. Despite decades of research on key honey bee stressors (e.g.