Miracle-dz/UniFAR-FTUs huggingface dataset:
Tracing-corrected estimates of disengagement from HIV care and mortality among patients enrolling in HIV care without overt immunosuppression in Tanzania

ABSTRACT In the era of “test and treat”, it is important to understand HIV care outcomes and their determinants in patients presenting to care with early-stage disease. We surveyed 924 adults newly enrolling in HIV care at four clinics in Tanzania before the adoption of universal treatment eligibility, and collected longitudinal clinical data. Participants who defaulted from care were tracked in the community. Cumulative incidence of disengagement from care and death was estimated using competing risk methods. By 12 months after enrollment, 18.2% of patients had disengaged from care and 6.9% had died. Factors associated with disengagement included male sex (adjusted subhazard ratio [aSHR] versus female = 1.75, 95% confidence interval [CI]: 1.06–2.89), provider-initiated HIV diagnosis (aSHR versus self-referred = 1.71, 95% CI: 1.03–2.86), ineligibility for antiretroviral treatment (ART) at enrollment (aSHR versus eligibility = 2.82, 95% CI: 1.84–4.32) and increased anticipated stigma score (aSHR = 1.04 per 5-point increase, 95% CI: 1.02–1.05). Higher life satisfaction score (aSHR = 0.97 per 5-point increase, 95% CI: 0.95–0.99) and having 1–2 close friends (aSHR versus none = 0.58, 95% CI: 0.47–0.71) were protective. The findings highlight the continued importance of social environment for HIV care outcomes and the potential of universal ART eligibility to reduce HIV care attrition.
Societal costs of informal care of community-dwelling frail elderly people

Aims: The aims of this study are to describe informal care activities and to estimate the societal cost of informal care of community-dwelling frail elderly people in Sweden. Methods: This study was performed within the frame of the TREEE project that included 408 frail elderly patients. At index hospitalisation (baseline), primary informal caregivers of the patients were provided with a questionnaire on informal care during a period of three months. Questions concerning other (secondary) informal caregivers were also included. A rough estimate of the total cost of informal care of frail elderly people in Sweden was obtained by combining data from this study with published data and official statistics. Results: In total, 176 informal caregivers responded, and 89% had provided informal care. The informal caregivers (primary and secondary) provided care for an average of 245 hours over three months. Taking care of the home was the dominating activity. In total, the mean cost of informal care was estimated to approximately 18,000 SEK (€1878) over three months, corresponding to an annual cost of approximately 72,000 SEK (€7477) per frail elderly person. The total annual societal costs of informal care of community dwelling frail elderly people aged 75 years and older in Sweden was estimated to be approximately 11,000 million SEK (€1150 million). Conclusions: The care of frail elderly people provided by informal caregivers is extensive and represents a great economic value. Although our calculations are associated with uncertainty, the size indicates that supporting informal caregivers should be a priority for society.
Identification of Novel Loci and New Risk Variant in Known Loci for Colorectal Cancer Risk in East Asians

Background: Risk variants identified so far for colorectal cancer explain only a small proportion of familial risk of this cancer, particularly in Asians. Methods: We performed a genome-wide association study (GWAS) of colorectal cancer in East Asians, including 23,572 colorectal cancer cases and 48,700 controls. To identify novel risk loci, we selected 60 promising risk variants for replication using data from 58,131 colorectal cancer cases and 67,347 controls of European descent. To identify additional risk variants in known colorectal cancer loci, we performed conditional analyses in East Asians. Results: An indel variant, rs67052019 at 1p13.3, was found to be associated with colorectal cancer risk at P = 3.9 × 10–8 in Asians (OR per allele deletion = 1.13, 95% confidence interval = 1.08–1.18). This association was replicated in European descendants using a variant (rs2938616) in complete linkage disequilibrium with rs67052019 (P = 7.7 × 10–3). Of the remaining 59 variants, 12 showed an association at P < 0.05 in the European-ancestry study, including rs11108175 and rs9634162 at P < 5 × 10−8 and two variants with an association near the genome-wide significance level (rs60911071, P = 5.8 × 10−8; rs62558833, P = 7.5 × 10−8) in the combined analyses of Asian- and European-ancestry data. In addition, using data from East Asians, we identified 13 new risk variants at 11 loci reported from previous GWAS. Conclusions: In this large GWAS, we identified three novel risk loci and two highly suggestive loci for colorectal cancer risk and provided evidence for potential roles of multiple genes and pathways in the etiology of colorectal cancer. In addition, we showed that additional risk variants exist in many colorectal cancer risk loci identified previously. Impact: Our study provides novel data to improve the understanding of the genetic basis for colorectal cancer risk.
Conditional Generative Denoising Autoencoder

We present a generative denoising autoencoder model that has an embedded data classifier in its architecture in order to take advantage of class-based discriminating features and produce better data samples. The proposed model is a conditional generative model and is sampled with a Markov chain Monte Carlo (MCMC) process according to a label that denotes the desired (or undesired) class or classes. In this sense, any chosen predefined class or characteristic may have a positive or negative effect on the image generation process, meaning that it can be instructed to be present or absent from the generated sample. We argue that allowing discriminative information in the form of feature detectors to be present in the latent representation of the autoencoder can be generally beneficial. This technique is an alternative approach to variational autoencoders (VAEs) that enforce a prior on the latent distribution. We further claim that supervised learning may be generally able to serve unsupervised learning through an interaction between the two paradigms. However, the extreme majority of research done on the interaction of the two learning regimes has the goal of using unsupervised learning to improve supervised learning. In this article, we explore the two learning paradigms’ interaction in the opposite direction.
The socio-economic status gradient in median lifespan by birth cohorts: Evidence from Dutch Olympic athletes born between 1852 and 1947

This paper quantifies the socio-economic status (SES) gradient in median lifespan for three birth cohort groups. For this, mortality models were estimated using unique data on the SES of Dutch Olympic athletes born between 1852 and 1947, and who were followed until their death (or December 2018). The empirical findings show that for the older birth cohorts (1852–1899) there were no significant differences in median lifespan between SES groups. For the middle cohorts (1900–1919), the low SES athletes had a significantly lower median lifespan of five years less compared to medium SES athletes and the median lifespans of high and medium SES athletes did not differ significantly. For the younger cohorts (1920–1947), large and statistically significant differences were found between the three SES groups: low SES athletes had a median lifespan of about six years lower than medium SES athletes, while high SES athletes had an almost five years higher median lifespan compared to medium SES athletes. These new findings, which can be reconciled with the existing literature, suggest a strong steepening of the population SES-lifespan gradient over time in the Netherlands.
The extent of Ssa1/Ssa2 Hsp70 chaperone involvement in nuclear protein quality control degradation varies with the substrate

Protein misfolding is a recurring phenomenon that cells must manage; otherwise misfolded proteins can aggregate and become toxic should they persist. To counter this burden, cells have evolved protein quality control (PQC) mechanisms that manage misfolded proteins. Two classes of systems that function in PQC are chaperones that aid in protein folding and ubiquitin–protein ligases that ubiquitinate misfolded proteins for proteasomal degradation. How folding and degradative PQC systems interact and coordinate their respective functions is not yet fully understood. Previous studies of PQC degradation pathways in the endoplasmic reticulum and cytosol have led to the prevailing idea that these pathways require the activity of Hsp70 chaperones. Here, we find that involvement of the budding yeast Hsp70 chaperones Ssa1 and Ssa2 in nuclear PQC degradation varies with the substrate. In particular, nuclear PQC degradation mediated by the yeast ubiquitin–protein ligase San1 often involves Ssa1/Ssa2, but San1 substrate recognition and ubiquitination can proceed without these Hsp70 chaperone functions in vivo and in vitro. Our studies provide new insights into the variability of Hsp70 chaperone involvement with a nuclear PQC degradation pathway.
Validation of Peptest™ in Patients with Gastro-Esophageal Reflux Disease and Laryngopharyngeal Reflux Undergoing Impedance Testing.

BACKGROUND AND AIMS Pepsin in the gastric refluxate is a marker for a prior reflux event and rapid detection might be achieved using the Peptest™, an in vitro diagnostic medical device. The aim of this study was to validate the use of Peptest™ to reliably diagnose reflux in patients with gastro-esophageal reflux disease (GERD) and laryngopharyngeal reflux (LPR) disease diagnosed with multichannel intraluminal impedance/ pHmetry (MII-pH). METHODS 20 reflux patients were recruited of whom 10 had classical GERD and 10 had LPR. All patients underwent MII-pH and provided expectorated saliva samples when a MII-pH reflux event was observed, or reflux symptoms were experienced, and all were tested for the presence of pepsin using the Peptest™. RESULTS Pepsin was detected in 31 out of 45 samples (68.9%). At least 1 positive pepsin result was seen in 16 patients (80%) and this was the same, irrespective of the GERD or LPR diagnosis. Peptest™ had a positive predictive value of 69% to detect MII-pH reflux events. CONCLUSIONS Peptest™ is a good first-line diagnostic procedure to use in reflux sufferers to confirm the presence of reflux.
Inflammatory Serine Proteases Play a Critical Role in the Early Pathogenesis of Diabetic Cardiomyopathy

Background/Aims: Diabetic cardiomyopathy (DCM) is characterized by structural and functional alterations that can lead to heart failure. Several mechanisms are known to be involved in the pathogenesis of DCM, however, the molecular mechanism that links inflammation to DCM is incompletely understood. To learn about this mechanism, we investigated the role of inflammatory serine proteases (ISPs) during the development of DCM. Methods: Eight weeks old mice with deletion of dipeptidyl peptidase I (DPPI), an enzyme involved in the maturation of major ISPs, and wild type (WT) mice controls were injected with streptozotocin (50 mg/kg for 5 days intraperitoneally) and studied after 4, 8, 16, and 20 week after induction of type 1 diabetes mellitus (T1DM). Induction of diabetes was followed by echocardiographic measurements, glycemic and hemoglobulin A1c profiling, immunoblot, qPCR, enzyme activity assays, and immunohistochemistry (IHC) analysis of DPPI, ISPs, and inflammatory markers. Fibrosis was determined from left ventricular heart by Serius Red staining and qPCR. Apoptosis was determined by TUNEL assay and immunoblot analysis. Results: In the diabetic WT mice, DPPI expression increased along with ISP activation, and DPPI accumulated abundantly in the left ventricle mainly from infiltrating neutrophils. In diabetic DPPI-knockout (DPPI-KO) mice, significantly decreased activation of ISPs, myocyte apoptosis, fibrosis, and cardiac function was improved compared to diabetic WT mice. In addition, DPPI-KO mice showed a decrease in overall inflammatory status mediated by diabetes induction which was manifested by decreased production of pro-inflammatory cytokines like TNF-α, IL-1β and IL-6. Conclusion: This study elucidates a novel role of ISPs in potentiating the immunological responses that lead to the pathogenesis of DCM in T1DM. To the best of our knowledge, this is the first study to report that DPPI expression and activation promotes the inflammation that enhances myocyte apoptosis and contributes to the adverse cardiac remodeling that subsequently leads to DCM.
Long Noncoding RNA PTTG3P Expression Is an Unfavorable Prognostic Marker for Patients With Hepatocellular Carcinoma

Objective: PTTG3P, which maps to chromosome 8q13.1, is a novel long noncoding RNA with oncogenic properties in cancers. In this study, we aimed to investigate the prognostic value of PTTG3P in terms of overall survival and recurrence-free survival and its potential regulatory network and transcription pattern in patients with hepatocellular carcinoma. Patients and Methods: An in silico analysis was performed using data from the Cancer Genome Atlas-Liver Hepatocellular Carcinoma. Results: Results showed that the high PTTG3P expression group was consistently associated with shorter overall survival and recurrence-free survival, regardless of pathological stages or tumor grade. High PTTG3P expression was an independent indicator of shorter overall survival (hazard ratio: 2.177, 95% confidence interval: 1.519-3.121, P < .001) and recurrence-free survival (hazard ratio: 2.222, 95% confidence interval: 1.503-3.283, P < .001). The genes strongly coexpressed with PTTG3P are enriched in several KEGG pathways that are closely associated with carcinogenesis and malignant transformation of hepatocellular carcinoma. Conclusion: Based on the findings, we infer that PTTG3P expression might serve as an independent prognostic biomarker in primary hepatocellular carcinoma.
The Neuropsychological Profile of Mild Cognitive Impairment in Lewy Body Dementias

Abstract Objectives: Dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD) have substantial clinical and biological overlap, with cognitive deficits typically observed in the executive and visuospatial domains. However, the neuropsychological profiles of mild cognitive impairment (MCI) associated with these disorders are not well understood. Methods: This systematic review examined existing literature on cognition in MCI due to LB disease (MCI-LB) and PD (PD-MCI) using an electronic search of seven databases (Medline, Embase, Psychinfo, PubMed, ProQuest, Scopus, and ScienceDirect). MCI-LB results were reviewed narratively given the small number of resulting papers (n = 7). Outcome variables from PD-MCI studies (n = 13) were extracted for meta-analysis of standardised mean differences (SMD). Results: In MCI-LB, executive dysfunction and slowed processing speed were the most prominent impairments, while visuospatial and working memory (WM) functions were also poor. MCI-LB scored significantly lower on verbal memory tests relative to controls, but significantly higher than patients with MCI due to Alzheimer’s disease. Quantitative analysis of studies in PD-MCI showed a similar profile of impairment, with the largest deficits in visuospatial function (Benton Judgement of Line Orientation, SMD g = −2.09), executive function (Trail Making Test B, SMD g = −1.65), verbal ability (Naming Tests, SMD g = −0.140), and WM (Trail Making Test A, SMD g = −1.20). In both MCI-LB and PD-MCI, verbal and visuospatial memory retrieval was impaired, while encoding and storage appeared relatively intact. Conclusions: The findings of this systematic review indicate similar neuropsychological profiles in the MCI stages of DLB and PDD. Executive impairment may at least partially explain poor performance in other domains.
Polyphenolic Profiles of Yellow Bean Seed Coats and Their Relationship to Iron Bioavailability.

Previous work with Caco-2 cell cultures has shown that individual polyphenols can either promote or inhibit iron uptake. This investigation was designed to characterize the relationship between iron bioavailability and seed coat polyphenol composition in a panel of fourteen yellow beans representing five market classes with the potential for fast cooking time and high iron content. The study included two white and two red mottled bean lines, which represent high and low iron bioavailability capacity in dry beans, respectively. Polyphenols were measured quantitatively by HPLC-MS/UV and iron bioavailability of seed coat extracts was measured in Caco-2 assays. Thirteen of the yellow bean seed types contained high concentrations (up to 35.3 ± 2.7 µmol/g) of kaempferol 3-glucoside (k 3-g), a known promoter of iron uptake. A general association between the ratio of promoting to inhibiting polyphenols (P/I) and iron uptake was observed. The presence of iron uptake-inhibiting condensed tannins proportionately countered the promotional effects of kaempferol compounds. Unidentified factors present in seed coats other than polyphenols also appeared to affect iron uptake.
A Randomized Clinical Trial Examining the Effects of Instructions for Electronic Cigarette Use on Smoking-Related Behaviors, and Biomarkers of Exposure.

INTRODUCTION Electronic cigarettes (e-cigarettes) have the potential to significantly reduce exposure to harmful constituents associated with cigarette smoking when smokers completely substitute cigarettes with e-cigarettes. This study examined patterns of e-cigarette and cigarette use, and extent of toxicant exposure, if smokers were instructed and incentivized to completely switch to e-cigarettes compared to instructions to use the product ad libitum. METHODS U.S. adult daily smokers (n =264; 48.3% female; Mage = 47.0), uninterested in quitting smoking immediately, were recruited from Minneapolis, MN, Columbus, OH, and Buffalo, NY. Participants were randomized to eight weeks of instructions for: a) ad libitum use of e-cigarettes (AD-E); 2) complete substitution of cigarettes with e-cigarettes (CS-E); 3) complete substitution of cigarettes with nicotine gum or lozenge (CS-NRT); or 4) continue smoking of usual brand cigarettes (UB). Participants were incentivized for protocol compliance, including complete switching in the CS-E and CS-NRT groups. Outcome variables were cigarette smoking rate and tobacco-related biomarkers of exposure. RESULTS Smokers in the CS-E and CS-NRT groups showed lower rates of smoking, and lower exposure to carbon monoxide, tobacco carcinogens and other toxicants than smokers in the AD-E groups. In general, no significant differences were observed between CS-E vs. CS-NRT or between AD-E vs. UB for most biomarkers. Significantly higher 7-day point prevalence smoke-free rates were observed for CS-E vs. CS-NRT. CONCLUSIONS Smokers instructed and incentivized to completely switch to e-cigarettes resulted in lower smoking rates and greater reductions in exposures to harmful chemicals than smokers instructed to use the product ad libitum.
An investigation of antihypertensive class, dementia, and cognitive decline: A meta-analysis.

OBJECTIVE High blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data. METHODS To identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data. RESULTS Over 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those ≤65 years of age. CONCLUSION Our findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals. CLINICAL TRIALS REGISTRATION The review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454.
Immersion by Rotation-Based Application of the Matrix for Fast and Reproducible Sample Preparations and Robust Results in Mass Spectrometry Imaging.

Automated matrix deposition for matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is crucial for producing reproducible analyte ion signals. Here we report an innovative method employing an automated immersion apparatus, which enables a robust matrix deposition within 5 minutes and with scalable throughput by using MAPS matrix and non-polar solvents. MSI results received from mouse heart and rat brain tissues were qualitatively similar to those from nozzle sprayed samples with respect to peak number and quality of the ion images. Overall, the immersion-method enables a fast and careful matrix deposition and has the future potential for implementation in clinical tissue diagnostics.
Income and Other Contributors to Poor Outcomes in US Sarcoidosis Patients.

RATIONALE Socioeconomic factors are associated with worse disease severity at presentation in sarcoidosis, but the relative importance of socioeconomic variables on morbidity and disease burden has not been fully elucidated. OBJECTIVES To determine the association between income and sarcoidosis outcomes after controlling for socioeconomic and disease-related factors. METHODS Using the Sarcoidosis Advanced Registry for Cures (SARC) database, we analyzed data from 2318 United States sarcoidosis patients to determine the effect of income and other variables on outcomes. We divided comorbidities arising after diagnosis into those likely related to steroid use and those likely related to sarcoidosis. We assessed the development of health-related, functional and socioeconomic outcomes following the diagnosis of sarcoidosis. MEASUREMENTS AND MAIN RESULTS In multivariate analysis, low income patients had significantly higher rates of new sarcoidosis related comorbidities [<$35,000 OR 2.4 (1.7-3.3), $35,000-$85,000 OR 1.4 (1.1-1.9), >$85,000 (REF)], new steroid related comorbidities [<$35,000 OR 1.3 (0.9-2.0), $35,000-$85,000 OR 1.5 (1.1-2.1), >$85,000 (REF)], had lower health-related quality of life as assessed by the Sarcoidosis Health Questionnaire (p<0.001) and experienced more impact on family finances [<$35,000 OR 7.9 (4.9-12.7), $35,000-$85,000 OR 2.7 (1.9-3.9), >$85,000 (REF)]. The use of supplemental oxygen, need for assistive devices, and job loss were more common in lower income patients. Development of comorbidities after diagnosis of sarcoidosis occurred in 63% of patients and were strong independent predictors of poor outcomes. In random forest modeling, income was consistently a leading predictor of outcome. CONCLUSIONS These results suggest the burden from sarcoidosis preferentially impacts the economically disadvantaged.