Notes

agReg-SNPdb: The Repository involving Regulatory SNPs pertaining to Garden Canine Species.
4 (SD ± 2.4) and 18.1 (SD ± 3.5), respectively. There were 14 STARD items that demonstrated an adherence of 75%.Conclusion The dichotomous distribution of adherence to the STARD statement by DAS investigated demonstrates that areas of deficient reporting may be present and require attention to ensure complete and transparent reporting in the future.Brainstem median raphe (MR) neurons expressing the serotonergic regulator gene Pet1 send collateralized projections to forebrain regions to modulate affective, memory-related, and circadian behaviors. Some Pet1 neurons express a surprisingly incomplete battery of serotonin pathway genes, with somata lacking transcripts for tryptophan hydroxylase 2 (Tph2) encoding the rate-limiting enzyme for serotonin [5-hydroxytryptamine (5-HT)] synthesis, but abundant for vesicular glutamate transporter type 3 (Vglut3) encoding a synaptic vesicle-associated glutamate transporter. Genetic fate maps show these nonclassical, putatively glutamatergic Pet1 neurons in the MR arise embryonically from the same progenitor cell compartment-hindbrain rhombomere 2 (r2)-as serotonergic TPH2+ MR Pet1 neurons. Well established is the distribution of efferents en masse from r2-derived, Pet1-neurons; unknown is the relationship between these efferent targets and the specific constituent source-neuron subgroups identified as r2-Pet1Tph2-highemical identity with distant cell bodies in the brainstem raphe. The results are significant because they suggest that disparate neuronal subsystems derive from Pet1+ precursor cells of the embryonic progenitor compartment rhombomere 2 (r2). Of these r2-Pet1 neuronal subsystems, one appears largely serotonergic, as expected given expression of the serotonergic regulator PET1, and projects to the olfactory bulb, thalamus, and suprachiasmatic nucleus. Another expresses VGLUT3, suggesting principally glutamate transmission, and projects to the hippocampus, septum, and cortex. Some r2-Pet1 boutons-those that are VGLUT3+ or VGLUT3+/5-HT+ co-positive-comprise "baskets" encasing interneurons, suggesting that they control local networks perhaps with differential kinetics via glutamate versus serotonin signaling. Results inform brain organization and circuit nodes for therapeutic consideration.Studies have found that anterior temporal lobe (ATL) is critical for detailed knowledge of object categories, suggesting that it has an important role in semantic memory. However, in addition to information about entities, such as people and objects, semantic memory also encompasses information about places. We tested predictions stemming from the PMAT model, which proposes there are distinct systems that support different kinds of semantic knowledge an anterior temporal (AT) network, which represents information about entities; and a posterior medial (PM) network, which represents information about places. We used representational similarity analysis to test for activation of semantic features when human participants viewed pictures of famous people and places, while controlling for visual similarity. Anlotinib inhibitor We used machine learning techniques to quantify the semantic similarity of items based on encyclopedic knowledge in the Wikipedia page for each item and found that these similarity models accurately predict hums known about whether these regions preferentially represent semantic knowledge about specific people and places. We used machine learning techniques to develop a model of semantic similarity based on information available from Wikipedia, validating the model against similarity ratings from human participants. Using our computational model, we found that semantic knowledge about people and places is represented in distinct anterior temporal and posterior medial brain networks, respectively. We further found that hippocampus, an important memory center, represented semantic knowledge for both types of stimuli.The androgen receptor (AR) is the key oncogenic driver of prostate cancer, and despite implementation of novel AR targeting therapies, outcomes for metastatic disease remain dismal. There is an urgent need to better understand androgen-regulated cellular processes to more effectively target the AR dependence of prostate cancer cells through new therapeutic vulnerabilities. Transcriptomic studies have consistently identified lipid metabolism as a hallmark of enhanced AR signaling in prostate cancer, yet the relationship between AR and the lipidome remains undefined. Using mass spectrometry-based lipidomics, this study reveals increased fatty acyl chain length in phospholipids from prostate cancer cells and patient-derived explants as one of the most striking androgen-regulated changes to lipid metabolism. Potent and direct AR-mediated induction of ELOVL fatty acid elongase 5 (ELOVL5), an enzyme that catalyzes fatty acid elongation, was demonstrated in prostate cancer cells, xenografts, and clinical tumors. Assessment of mRNA and protein in large-scale data sets revealed ELOVL5 as the predominant ELOVL expressed and upregulated in prostate cancer compared with nonmalignant prostate. ELOVL5 depletion markedly altered mitochondrial morphology and function, leading to excess generation of reactive oxygen species and resulting in suppression of prostate cancer cell proliferation, 3D growth, and in vivo tumor growth and metastasis. Supplementation with the monounsaturated fatty acid cis-vaccenic acid, a direct product of ELOVL5 elongation, reversed the oxidative stress and associated cell proliferation and migration effects of ELOVL5 knockdown. Collectively, these results identify lipid elongation as a protumorigenic metabolic pathway in prostate cancer that is androgen-regulated, critical for metastasis, and targetable via ELOVL5. SIGNIFICANCE This study identifies phospholipid elongation as a new metabolic target of androgen action that is critical for prostate tumor metastasis.Signaling between cancer and nonmalignant (stromal) cells in the tumor microenvironment (TME) is a key to tumor progression. Here, we deconvoluted bulk tumor transcriptomes to infer cross-talk between ligands and receptors on cancer and stromal cells in the TME of 20 solid tumor types. This approach recovered known transcriptional hallmarks of cancer and stromal cells and was concordant with single-cell, in situ hybridization and IHC data. Inferred autocrine cancer cell interactions varied between tissues but often converged on Ephrin, BMP, and FGFR-signaling pathways. Analysis of immune checkpoints nominated interactions with high levels of cancer-to-immune cross-talk across distinct tumor types. Strikingly, PD-L1 was found to be highly expressed in stromal rather than cancer cells. Overall, our study presents a new resource for hypothesis generation and exploration of cross-talk in the TME. SIGNIFICANCE This study provides deconvoluted bulk tumor transcriptomes across multiple cancer types to infer cross-talk in the tumor microenvironment.Gastric cancer is the third most lethal cancer worldwide, and evaluation of the genomic status of gastric cancer cells has not translated into effective prognostic or therapeutic strategies. We therefore hypothesize that outcomes may depend on the tumor microenvironment (TME), in particular, cancer-associated fibroblasts (CAF). However, very little is known about the role of CAFs in gastric cancer. To address this, we mapped the transcriptional landscape of human gastric cancer stroma by microdissection and RNA sequencing of CAFs from patients with gastric cancer. A stromal gene signature was associated with poor disease outcome, and the transcription factor heat shock factor 1 (HSF1) regulated the signature. HSF1 upregulated inhibin subunit beta A and thrombospondin 2, which were secreted in CAF-derived extracellular vesicles to the TME to promote cancer. Together, our work provides the first transcriptional map of human gastric cancer stroma and highlights HSF1 and its transcriptional targets as potential diagnostic and therapeutic targets in the genomically stable tumor microenvironment. SIGNIFICANCE This study shows how HSF1 regulates a stromal transcriptional program associated with aggressive gastric cancer and identifies multiple proteins within this program as candidates for therapeutic intervention. GRAPHICAL ABSTRACT http//cancerres.aacrjournals.org/content/canres/81/7/1639/F1.large.jpg.A quality improvement (QI) scheme was launched in 2017, covering a large group of 25 general practices working with a deprived registered population. The aim was to improve the measurable quality of care in a population where type 2 diabetes (T2D) care had previously proved challenging. A complex set of QI interventions were co-designed by a team of primary care clinicians and educationalists and managers. These interventions included organisation-wide goal setting, using a data-driven approach, ensuring staff engagement, implementing an educational programme for pharmacists, facilitating web-based QI learning at-scale and using methods which ensured sustainability. This programme was used to optimise the management of T2D through improving the eight care processes and three treatment targets which form part of the annual national diabetes audit for patients with T2D. With the implemented improvement interventions, there was significant improvement in all care processes and all treatment targets for patients with diabetes. Achievement of all the eight care processes improved by 46.0% (p less then 0.001) while achievement of all three treatment targets improved by 13.5% (p less then 0.001). The QI programme provides an example of a data-driven large-scale multicomponent intervention delivered in primary care in ethnically diverse and socially deprived areas.
In nursing homes, 25%-75% of antibiotic days of treatment are inappropriate or unnecessary and are often continued for longer durations than necessary. In Ontario, physicians can receive a provincial audit and feedback report that provides individualised, confidential, data about their antibiotic prescribing. Objectives of this study were to explore antibiotic prescribing of nursing home physicians and the influence of the report.

All physicians who received a personalised
report from Ontario Health (Quality) (OH(Q)) in January 2019 (n=361) were eligible to participate in semistructured telephone interviews that were recorded then transcribed verbatim. Recruitment emails were sent from OH(Q) until saturation of ideas. Analysis was conducted by two team members inductively, then deductively using the theoretical domains framework, a comprehensive, theory-informed framework to classify determinants of specific behaviours.

Interviews were conducted with n=18 physicians; 78% (n=14) were men, practising fmed approach is being used to inform upcoming versions of existing audit and feedback initiatives. Appealing to the role that prescribers see themselves offers a unique opportunity to encourage desired changes, such as providing tools for physicians to be Educators and facilitating, particularly medical directors, to be Change drivers.We report our experience in using virtual technology in our emergency department (ED) to meet communication needs of our patients who have limited English proficiency (LEP) during the COVID-19 pandemic. Our project aim was to improve communication between our ED staff and patients who have LEP. Specifically, our primary aim was to eliminate the use of healthcare staff as ad hoc interpreters by 50% in our ED by using virtual medical interpreters within 2 months. To achieve our goal, several strategies were employed. First, we assessed the need for interpreters in our ED by tracking the number of times our nursing staff is pulled away from their nursing role to help other staff as an ad hoc interpreter. Second, a patient survey was conducted to understand their thoughts and needs for interpretation in the ED. Third, we developed strategies in improving access to interpreters in our ED. During the COVID-19 pandemic, we conducted a trial of using 'Interpreter on Wheels' (IOW) in our ED. In a 2-month period, we had 477 virtual interpretation encounters totaling 4123 interpretation minutes of IOW usage.
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