119 research outputs found

    DeepMood: Modeling Mobile Phone Typing Dynamics for Mood Detection

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    The increasing use of electronic forms of communication presents new opportunities in the study of mental health, including the ability to investigate the manifestations of psychiatric diseases unobtrusively and in the setting of patients' daily lives. A pilot study to explore the possible connections between bipolar affective disorder and mobile phone usage was conducted. In this study, participants were provided a mobile phone to use as their primary phone. This phone was loaded with a custom keyboard that collected metadata consisting of keypress entry time and accelerometer movement. Individual character data with the exceptions of the backspace key and space bar were not collected due to privacy concerns. We propose an end-to-end deep architecture based on late fusion, named DeepMood, to model the multi-view metadata for the prediction of mood scores. Experimental results show that 90.31% prediction accuracy on the depression score can be achieved based on session-level mobile phone typing dynamics which is typically less than one minute. It demonstrates the feasibility of using mobile phone metadata to infer mood disturbance and severity.Comment: KDD 201

    New Ultra-minimally Invasive Surgical Treatment for Benign Prostatic Hyperplasia: A Systematic Review and Analysis of Comparative Outcomes

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    Context: Benign prostatic hyperplasia (BPH) associated with lower urinary tract symptoms (LUTS) is diagnosed in up to 80% of men during their lifetime. Several novel ultra-minimally invasive surgical treatments (uMISTs) for BPH/benign prostatic obstruction (BPO) have become available over the past 5 yr. Objective: To evaluate the perioperative and functional outcomes of recently introduced uMISTs for BPH/BPO, including Urolift, Rezūm, temporary implantable nitinol device, prostatic artery embolization (PAE), and intraprostatic injection. Evidence acquisition: A systematic literature search was conducted in December 2020 using Medline (via PubMed), Embase (via Ovid), Scopus, and Web of Science (registered on PROSPERO as CRD42021225014). The search strategy used PICO criteria and article selection was conducted in accordance with the PRISMA guidelines. The risk of bias and the quality of the articles included were assessed. A dedicated data extraction form was used to collect the data of interest. Pooled and cumulative analyses were performed to compare perioperative and functional outcomes between study groups. A random-effects model using the DerSimonian and Laird method was used to evaluate heterogeneity. Stata version 15.0 software was used for all statistical analyses. Evidence synthesis: The initial electronic search identified 3978 papers, of which 48 ultimately met the inclusion criteria and were included in the analysis. Pooled analysis revealed a uMIST benefit in terms of International Prostate Symptom Score (IPSS; −9.81 points, 95% confidence interval [CI] −11.37 to −8.25 at 1 mo; −13.13 points, 95% CI −14.98 to −11.64 at 12 mo), maximum flow rate (from +3.66 ml/s, 95% CI 2.8–4.5 to +4.14 ml/s, 95% CI 0.72–7.56 at 12 mo), and postvoid residual volume (−10.10 ml, 95% CI −27.90 to 7.71 at 12 mo). No negative impact was observed on scores for the International Index of Erectile Function-5, Male Sexual Health Questionnaire-Ejaculatory Dysfunction bother and function scales (overall postintervention change in pooled median score of 1.88, 95% CI 1.34–2.42 at the start of follow-up; and 1.04, 95% CI 0.28–1.8 after 1 yr), or the IPSS-Quality of Life questionnaire. Conclusions: Novel uMISTs can yield fast and effective relief of LUTS without affecting patient quality of life. Only Rezūm, UroLift, and PAE had a minimal impact on patients’ sexual function with respect to baseline, especially regarding preservation of ejaculation. Patient summary: We reviewed outcomes for recently introduced ultra-minimally invasive surgical treatments for patients with lower urinary tract symptoms caused by benign prostate enlargement or obstruction. The evidence suggests that these novel techniques are beneficial in terms of controlling symptoms while preserving sexual function. Take Home Message: Novel ultra-minimally invasive treatments can yield fast and effective relief of lower urinary tract symptoms without affecting a patient's quality of life

    AKT overactivation can suppress DNA repair via p70S6 kinase-dependent downregulation of MRE11

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    Deregulated AKT kinase activity due to PTEN deficiency in cancer cells contributes to oncogenesis by incompletely understood mechanisms. Here, we show that PTEN deletion in HCT116 and DLD1 colon carcinoma cells leads to suppression of CHK1 and CHK2 activation in response to irradiation, impaired G2 checkpoint proficiency and radiosensitization. These defects are associated with reduced expression of MRE11, RAD50 and NBS1, components of the apical MRE11/RAD50/NBS1 (MRN) DNA damage response complex. Consistent with reduced MRN complex function, PTEN-deficient cells fail to resect DNA double-strand breaks efficiently after irradiation and show greatly diminished proficiency for DNA repair via the error-free homologous recombination (HR) repair pathway. MRE11 is highly unstable in PTEN-deficient cells but stability can be significantly restored by inhibiting mTORC1 or p70S6 kinase (p70S6K), downstream kinases whose activities are stimulated by AKT, or by mutating a residue in MRE11 that we show is phosphorylated by p70S6K in vitro. In primary human fibroblasts, activated AKT suppresses MRN complex expression to escalate RAS-induced DNA damage and thereby reinforce oncogene-induced senescence. Taken together, our data demonstrate that deregulation of the PI3K-AKT/ mTORC1/ p70S6K pathways, an event frequently observed in cancer, exert profound effects on genome stability via MRE11 with potential implications for tumour initiation and therapy

    Mapping H4K20me3 onto the chromatin landscape of senescent cells indicates a function in control of cell senescence and tumor suppression through preservation of genetic and epigenetic stability

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    Background: Histone modification H4K20me3 and its methyltransferase SUV420H2 have been implicated in suppression of tumorigenesis. The underlying mechanism is unclear, although H4K20me3 abundance increases during cellular senescence, a stable proliferation arrest and tumor suppressor process, triggered by diverse molecular cues, including activated oncogenes. Here, we investigate the function of H4K20me3 in senescence and tumor suppression. Results: Using immunofluorescence and ChIP-seq we determine the distribution of H4K20me3 in proliferating and senescent human cells. Altered H4K20me3 in senescence is coupled to H4K16ac and DNA methylation changes in senescence. In senescent cells, H4K20me3 is especially enriched at DNA sequences contained within specialized domains of senescence-associated heterochromatin foci (SAHF), as well as specific families of non-genic and genic repeats. Altered H4K20me3 does not correlate strongly with changes in gene expression between proliferating and senescent cells; however, in senescent cells, but not proliferating cells, H4K20me3 enrichment at gene bodies correlates inversely with gene expression, reflecting de novo accumulation of H4K20me3 at repressed genes in senescent cells, including at genes also repressed in proliferating cells. Although elevated SUV420H2 upregulates H4K20me3, this does not accelerate senescence of primary human cells. However, elevated SUV420H2/H4K20me3 reinforces oncogene-induced senescence-associated proliferation arrest and slows tumorigenesis in vivo. Conclusions: These results corroborate a role for chromatin in underpinning the senescence phenotype but do not support a major role for H4K20me3 in initiation of senescence. Rather, we speculate that H4K20me3 plays a role in heterochromatinization and stabilization of the epigenome and genome of pre-malignant, oncogene-expressing senescent cells, thereby suppressing epigenetic and genetic instability and contributing to long-term senescence-mediated tumor suppression
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