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Temporal Sequence associated with Post-Mortem Autolysis from the Computer mouse button Retina.
Cell clustering is one of the most important and commonly performed tasks in single-cell RNA sequencing (scRNA-seq) data analysis. An important step in cell clustering is to select a subset of genes (referred to as 'features'), whose expression patterns will then be used for downstream clustering. A good set of features should include the ones that distinguish different cell types, and the quality of such set could have a significant impact on the clustering accuracy. All existing scRNA-seq clustering tools include a feature selection step relying on some simple unsupervised feature selection methods, mostly based on the statistical moments of gene-wise expression distributions. In this work, we carefully evaluate the impact of feature selection on cell clustering accuracy. In addition, we develop a feature selection algorithm named FEAture SelecTion (FEAST), which provides more representative features. We apply the method on 12 public scRNA-seq datasets and demonstrate that using features selected by FEAST with existing clustering tools significantly improve the clustering accuracy.
Palliative care is a care option considered appropriate for those with heart failure, but is uncommon partially due to a lack of timely identification of those needing palliative care. A standard mechanism that triggers which heart failure patients should receive palliative care is not available. The Gold Standards Framework (GSF) identifies those needing palliative care but has not been investigated with heart failure patients.

To describe palliative care provided in the community and determine whether the GSF can identify heart failure patients in need of palliative care.

Descriptive study. A total of 252 heart failure patients in the community completed a demographic characteristics questionnaire, the Edmonton symptom assessment scale-revised and the Minnesota living with heart failure questionnaire. Clinical data were collected from the medical chart and the primary physician completed the GSF prognostic indicator guidance.

Participants had a mean age of 76.9 years (standard deviation 10.9), most at New York Heart Association level III (n=152, 60%). Fewer than half received pain medications (n=76, 30%), anxiolytics (n=35, 14%), antidepressants (n=64, 25%) or sleep medications (n=65, 26%). Eight patients spoke with a psychologist or psychologist (3%). Transmembrane Transporters inhibitor One had an advanced directive and 16 (6%) had a record of discussions with their family caregivers. Three (1%) had end-of-life discussions with their healthcare providers. Most healthcare providers responded 'no' to the 'surprise question' (n=160, 63%). Sensitivity and specificity of the gold standards framework was poor.

Few community dwelling heart failure patients received most aspects of palliative care. The gold standards framework was not a good indicator of those who should receive palliative care.
Few community dwelling heart failure patients received most aspects of palliative care. The gold standards framework was not a good indicator of those who should receive palliative care.
Frailty is an important consideration in the assessment of transcatheter aortic valve implantation patients. The documentation of a patient photograph to augment the objective measurement of frailty has been adopted by some transcatheter aortic valve implantation multidisciplinary (TAVI) programmes.

We used a prospective two-part multimethod study design. In part A, we examined the concordance between the Essential Frailty Toolset (EFT) and the score attributed by healthcare professionals based on visual rating of photographs using kappa estimates and linear regression. In part B, we conducted a content analysis qualitative study to elicit information about how the TAVI multidisciplinary team used photographs to form impressions about frailty.

Part A 94 healthcare professionals (registered nurses/allied health 65%; physicians 35%) rated 40 representative photographs (women 42.5%; mean age 83.4±7.5; mobility aid 40%) between 0 (robust) and 5 (very frail). The estimate of weighted kappa was 0.2575 (95% confidence interval 0.082-0.433), indicating fair agreement between median healthcare professional visual and EFT score, especially when the EFT was 1 or 4. There was significant discordance among raters (kappa estimate 0.110, 95% confidence interval 0.079-0.141). Age, sex and mobility aid did not have a significant effect on score discordance. Part B 12 members of the TAVI multidisciplinary team (registered nurses 27.5%; physicians 72.5%) were shown a series of six representative patient photographs. The following themes emerged from the data (a) looking at the outside; (b) thinking about the inside; (c) use but with caution; and (d) a better approach.

A patient photograph offers complementary information to the multimodality assessment of TAVI patients.
A patient photograph offers complementary information to the multimodality assessment of TAVI patients.Transcriptional enhanced associate domain (TEAD) is a family of transcription factors that plays a significant role during embryonic developmental processes, and its dysregulation is responsible for tumour progression. TEAD is considered as druggable targets in various diseases, namely cancer, cardiovascular diseases and neurodegenerative disorders. Previous structural studies revealed the importance of the central hydrophobic pocket of TEAD as a potential target for small-molecule inhibitors and demonstrated flufenamic acid (FLU) (a COX-2 enzyme inhibitor) to bind and inhibit TEAD2 functions. However, to date, no drug candidates that bind specifically to TEAD2 with high selectivity and efficacy have been developed or proposed. Within this framework, we present here a case study where we have identified potential TEAD2 inhibitor candidates by integrating multiple computational approaches. Among the candidates, the top two ranked compounds ZINC95969481 (LG1) which is a fused pyrazole derivative and ZINC05203789 (LG2), a fluorene derivative resulted in much favourable binding energy scores than the reference ligand, FLU. The drug likeliness of the best compounds was also evaluated in silico to ensure the bioavailability of these compounds particularly LG1 as compared to FLU thus providing a strong rationale for their development as leads against TEAD. Molecular dynamics simulations results highlighted the role of key residues contributing to favourable interactions in TEAD2-LG1 complex with much favourable interaction and binding free energy values with respect to the reference compound. Altogether, this study provides a starting platform to be more exploited by future experimental research towards the development of inhibitors against TEAD, a persuasive strategy for therapeutic intervention in cancer treatment.
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