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Machine learning techniques have been previously applied for classification of tumors based largely on morphological features of tumor cells recognized in H&E images. Here, we tested the possibility of using numeric data acquired from software-based quantification of certain marker proteins, i.e. key autophagy proteins (ATGs), obtained from immunohistochemical (IHC) images of renal cell carcinomas (RCC). Using IHC staining and automated image quantification with a tissue microarray (TMA) of RCC, we found ATG1, ATG5 and microtubule-associated proteins 1A/1B light chain 3B (LC3B) were significantly reduced, suggesting a reduction in the basal level of autophagy with RCC. Notably, the levels of the ATG proteins expressed did not correspond to the mRNA levels expressed in these tissues. Applying a supervised machine learning algorithm, the K-Nearest Neighbor (KNN), to our quantified numeric data revealed that LC3B provided a strong measure for discriminating clear cell RCC (ccRCC). ATG5 and sequestosome-1 (SQSTM1/p62) could be used for classification of chromophobe RCC (crRCC). The quantitation of particular combinations of ATG1, ATG16L1, ATG5, LC3B and p62, all of which measure the basal level of autophagy, were able to discriminate among normal tissue, crRCC and ccRCC, suggesting that the basal level of autophagy would be a potentially useful parameter for RCC discrimination. In addition to our observation that the basal level of autophagy is reduced in RCC, our workflow from quantitative IHC analysis to machine learning could be considered as a potential complementary tool for the classification of RCC subtypes and also for other types of tumors for which precision medicine requires a characterization.
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BACKGROUND HIV-positive gay and bisexual men (GBM) in Australia are well engaged in clinical care. We hypothesized that the World Health Organization's hepatitis C virus (HCV) elimination target of an 80% reduction in incidence by 2030 may be reachable ahead of time in this population. METHODS We predicted the effect of treatment and behavioral changes on HCV incidence among HIV-positive GBM up to 2025 using a HCV transmission model parameterized with Australian data. We assessed the impact of changes in behavior that may facilitate HCV transmission in the context of different rates of direct-acting antiviral (DAA) use. RESULTS HCV incidence in our model increased from 0.7 per 100 person years in 2000 to 2.5 per 100 person years in 2016, and had the same trajectory as previously reported clinical data. If the proportion of eligible (HCV RNA positive) patients using DAAs stays at 65%/year between 2016-2025, with high-risk sexual behavior and injecting drug use remaining at current levels, HCV incidence would drop to 0.4 per 100 person years (85% decline from 2016). In the same treatment scenario but with substantial increases in risk behavior, HCV incidence would drop to 0.6 per 100 person years (76% decline from 2016). If the proportion of eligible patients using DAAs dropped from 65%/year in 2016 to 20%/year in 2025 and risk behavior did not change, HCV incidence would drop to 0.7 per 100 person years (70% reduction from 2016). CONCLUSIONS Reaching the World Health Organization HCV elimination target by 2025 among HIV-positive GBM in Australia is achievable.
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l-lactate plays an important role as metabolite and signaling molecule in eukaryotes and bacteria. Monocarboxylate transporters (MCTs) of the SLC16 solute carrier family are responsible for the transport of l-lactate across eukaryotic and bacterial cell membranes. Here we report an efficient protocol for the expression and purification of an SLC16 family homologue in milligram amounts. The purified protein is stable and can thus be used for biochemical and structural studies as shown by successful crystallization.
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OBJECTIVES Chemsex refers to the use of sex-enhancing drugs among men who have sex with men (MSM) in combination with specific sexual and social behaviours. Longitudinal data on this development and the associated health risks are scarce. METHODS Data on all recreational drugs reported in the Swiss HIV Cohort Study (SHCS) from 2007 to 2017 were collected. Drug use was analysed longitudinally for all drug classes. In addition, potential associations between patient characteristics and the consumption of methamphetamine, γ-hydroxybutric acid/γ-butyrolactone (GHB/GBL), 3,4-methylenedioxymethamphetamine (MDMA/XTC), cocaine and amphetamine were analysed. RESULTS We analysed 166 167 follow-up entries for 12 527 SHCS participants, including 7101 free text field entries containing information about recreational drugs other than cannabis, cocaine and heroin. Overall, we observed a stable percentage (9.0%) of recreational drug use (excluding cannabis, amyl nitrite and prescription drugs). For MSM, however, there was an increase in overall drug use from 8.8% in 2007 to 13.8% in 2017, with particularly large increases for methamphetamine (from 0.2 to 2.4%; P
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PURPOSE To conduct a meta-analysis to determine specific computed tomography (CT) patterns and clinical features that discriminate between nonspecific interstitial pneumonia (NSIP) and usual interstitial pneumonia (UIP). MATERIALS AND METHODS The PubMed/Medline and Embase databases were searched for studies describing the radiological patterns of UIP and NSIP in chest CT images. Only studies involving histologically confirmed diagnoses and a consensus diagnosis by an interstitial lung disease (ILD) board were included in this analysis. The radiological patterns and patient demographics were extracted from suitable articles. We used random-effects meta-analysis by DerSimonian & Laird and calculated pooled odds ratios for binary data and pooled mean differences for continuous data. RESULTS Of the 794 search results, 33 articles describing 2,318 patients met the inclusion criteria. Twelve of these studies included both NSIP (338 patients) and UIP (447 patients). NSIP-patients were significantly younger (NSIP: median age 54.8 years, UIP: 59.7 years; mean difference (MD) -4.4; p = 0.001; 95% CI: -6.97 to -1.77), less often male (NSIP: median 52.8%, UIP: 73.6%; pooled odds ratio (OR) 0.32; p<0.001; 95% CI: 0.17 to 0.60), and less often smokers (NSIP: median 55.1%, UIP: 73.9%; OR 0.42; p = 0.005; 95% CI: 0.23 to 0.77) than patients with UIP. The CT findings from patients with NSIP revealed significantly lower levels of the honeycombing pattern (NSIP: median 28.9%, UIP: 73.4%; OR 0.07; p<0.001; 95% CI: 0.02 to 0.30) with less peripheral predominance (NSIP: median 41.8%, UIP: 83.3%; OR 0.21; p<0.001; 95% CI: 0.11 to 0.38) and more subpleural sparing (NSIP: median 40.7%, UIP: 4.3%; OR 16.3; p = 0.005; 95% CI: 2.28 to 117). CONCLUSION Honeycombing with a peripheral predominance was significantly associated with a diagnosis of UIP. The NSIP pattern showed more subpleural sparing. The UIP pattern was predominantly observed in elderly males with a history of smoking, whereas NSIP occurred in a younger patient population.
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INTRODUCTION The objective of this systematic review was to assess the available evidence in the literature for the effects of fixed orthodontic retainers on periodontal health. METHODS The following databases were searched up to August 31, 2019: Medline, EMBASE, the Cochrane Oral Health Group's Trials Register, CENTRAL, ClinicalTrials.gov, the National Research Register, and Pro-Quest Dissertation Abstracts and Thesis database. Randomized controlled trials (RCTs), controlled clinical trials, cohort studies of prospective and retrospective design, and cross-sectional studies reporting on periodontal measurements of patients who received fixed retention after orthodontic treatment were eligible for inclusion. The quality of the included RCTs was assessed per the revised Cochrane risk of bias tool for randomized trials (RoB 2.0), whereas the risk of bias of the included cohort studies was assessed using the Risk Of Bias In Nonrandomized Studies of Interventions tool. A modified version of the Newcastle-Ottawa scale was used for cross-sectional studies. RESULTS Eleven RCTs, 4 prospective cohort studies, 1 retrospective cohort study, and 13 cross-sectional studies fulfilled the inclusion criteria. The quality of evidence was low for most of the included studies. In contrast to the general consensus, 2 RCTs, 1 prospective cohort study, and 2 cross-sectional studies reported poorer periodontal conditions in the presence of a fixed retainer. The results of the included studies comparing different types of fixed retainers were heterogeneous. CONCLUSIONS According to the currently available literature, orthodontic fixed retainers seem to be a retention strategy rather compatible with periodontal health, or at least not related to severe detrimental effects on the periodontium.
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Congenital extrahepatic portosystemic shunt (CEPS) or Abernethy malformation is a rare condition in which splanchnic venous blood bypasses the liver draining directly into systemic circulation through a congenital shunt. Patients may develop hepatic encephalopathy (HE), pulmonary hypertension (PaHT), or liver tumors, among other complications. However, the actual incidence of such complications is unknown, mainly because of the lack of a protocolized approach to these patients. This study characterizes the clinical manifestations and outcome of a large cohort of CEPS patients with the aim of proposing a guide for their management. This is an observational, multicenter, international study. Sixty-six patients were included; median age at the end of follow-up was 30 years. Nineteen patients (28%) presented HE. Ten-, 20-, and 30-year HE incidence rates were 13%, 24%, and 28%, respectively. No clinical factors predicted HE. Twenty-five patients had benign nodular lesions. Ten patients developed adenomas (median age, 18 years), and another 8 developed HCC (median age, 39 years). Of 10 patients with dyspnea, PaHT was diagnosed in 8 and hepatopulmonary syndrome in 2. Pulmonary complications were only screened for in 19 asymptomatic patients, and PaHT was identified in 2. Six patients underwent liver transplantation for hepatocellular carcinoma or adenoma. Shunt closure was performed in 15 patients with improvement/stability/cure of CEPS manifestations. Conclusion: CEPS patients may develop severe complications. Screening for asymptomatic complications and close surveillance is needed. Shunt closure should be considered both as a therapeutic and prophylactic approach.
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Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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