Miracle-dz/UniFAR-FTUs huggingface dataset:
A nomogram combining long non-coding RNA expression profiles and clinical factors predicts survival in patients with bladder cancer

Bladder cancer (BCa) is a heterogeneous disease with various tumorigenic mechanisms and clinical behaviors. The current tumor-node-metastasis (TNM) staging system is inadequate to predict overall survival (OS) in BCa patients. We developed a BCa-specific, long-non-coding-RNA (lncRNA)-based nomogram to improve survival prediction in BCa. We obtained the large-scale gene expression profiles of samples from 414 BCa patients in The Cancer Genome Atlas database. Using an lncRNA-mining computational framework, we identified three OS-related lncRNAs among 826 lncRNAs that were differentially expressed between BCa and normal samples. We then constructed a three-lncRNA signature, which efficiently distinguished high-risk from low-risk patients and was even viable in the TNM stage-II, TNM stage-III and ≥65-year-old subgroups (all P<0.05). Using clinical risk factors, we developed a signature-based nomogram, which performed better than the molecular signature or clinical factors alone for prognostic prediction. A bioinformatical analysis revealed that the three OS-related lncRNAs were co-expressed with genes involved in extracellular matrix organization. Functional assays demonstrated that RNF144A-AS1, one of the three OS-related lncRNAs, promoted BCa cell migration and invasion in vitro. Our three-lncRNA signature-based nomogram effectively predicts the prognosis of BCa patients, and could potentially be used for individualized management of such patients.
High Intensity Interval Training Does Not Have Compensatory Effects on Physical Activity Levels in Older Adults

Background: Exercise has beneficial effects on older adults, but controversy surrounds the purported “compensatory effects” that training may have on total daily physical activity and energy expenditure in the elderly. We wanted to determine whether 8 weeks of high-intensity interval training (HIIT) induced such effects on physical activity and energy expenditure in healthy, active older adult men. Methods: Twenty-four healthy elderly male volunteers were randomized to two groups. The experimental group performed HIIT (7 × 2 min cycling repetitions, 3 d/w); the control group performed continuous moderate-intensity training (20–30 min cycling, 3 d/w). Physical activity and energy expenditure were measured with a multisensor activity monitor SenseWear Armband Mini. Results: During HIIT, significant changes were observed in moderate and vigorous physical activity, average daily metabolic equivalents (METs), physical activity level, and activity energy expenditure (p < 0.05) but not in total energy expenditure. Sleep and sedentary time, and levels of light physical activity remained constant during the training period. Conclusions: The findings suggest that HIIT induced no compensatory effect: HIIT does not adversely affect lifestyle, as it does not reduce daily energy expenditure and/or increase sedentary time.
A Virtual Multidisciplinary Care Program for Management of Advanced Chronic Kidney Disease: Matched Cohort Study

Background It is not well established whether a virtual multidisciplinary care program for persons with advanced chronic kidney disease (CKD) can improve their knowledge about their disease, increase their interest in home dialysis therapies, and result in more planned outpatient (versus inpatient) dialysis starts. Objective We aimed to evaluate the feasibility and preliminary associations of program participation with disease knowledge, home dialysis modality preference, and outpatient dialysis initiation among persons with advanced CKD in a community-based nephrology practice. Methods In a matched prospective cohort, we enrolled adults aged 18 to 85 years with at least two estimated glomerular filtration rates (eGFRs) of less than 30 mL/min/1.73 m2 into the Cricket Health program and compared them with controls receiving care at the same clinic, matched on age, gender, eGFR, and presence of heart failure and diabetes. The intervention included online education materials, a virtual multidisciplinary team (nurse, pharmacist, social worker, dietician), and patient mentors. Prespecified follow-up time was nine months with extended follow-up to allow adequate time to determine the dialysis start setting. CKD knowledge and dialysis modality choice were evaluated in a pre-post survey among intervention participants. Results Thirty-seven participants were matched to 61 controls by age (mean 67.2, SD 10.4 versus mean 68.8, SD 9.5), prevalence of diabetes (54%, 20/37 versus 57%, 35/61), congestive heart failure (22%, 8/37 versus 25%, 15/61), and baseline eGFR (mean 19, SD 6 versus mean 21, SD 5 mL/min/1.73 m2), respectively. At nine-month follow-up, five patients in each group started dialysis (P=.62). Among program participants, 80% (4/5) started dialysis as an outpatient compared with 20% (1/5) of controls (OR 6.28, 95% CI 0.69-57.22). In extended follow-up (median 15.7, range 11.7 to 18.1 months), 19 of 98 patients started dialysis; 80% (8/10) of the intervention group patients started dialysis in the outpatient setting versus 22% (2/9) of control patients (hazard ratio 6.89, 95% CI 1.46-32.66). Compared to before participation, patients who completed the program had higher disease knowledge levels (mean 52%, SD 29% versus mean 94%, SD 14% of questions correct on knowledge-based survey, P<.001) and were more likely to choose a home modality as their first dialysis choice (36%, 7/22 versus 68%, 15/22, P=.047) after program completion. Conclusions The Cricket Health program can improve patient knowledge about CKD and increase interest in home dialysis modalities, and may increase the proportion of dialysis starts in the outpatient setting.
Molecular characterization of pre-extensive drug resistant Mycobacterium tuberculosis in Northeast Brazil

ABSTRACT In Fortaleza, the capital of Ceara State, Brazil, the detection rate of tuberculosis (TB) in 2018 was 65.5/100,000 inhabitants with a cure rate of 59.1%, which is higher than the country average. This study investigated the risk factors associated with drug-resistant tuberculosis (DR-TB) and identified the drug-resistance phenotype and resistance-conferring mutations. The geographic distribution of DR-TB in Fortaleza, Brazil, was also determined. From March 2017 to February 2018, 41 DR-TB isolates and 69 drug-susceptible pulmonary TB isolates were obtained from patients seen at a referral hospital in Fortaleza, Brazil. Samples were subjected to phenotypic and genetic analysis of resistance; the spatial distribution of the participants was also analyzed. Primary resistance was high (50.9%) among participants. The following risk factors for DR were identified: being female ( p = 0.03), having diabetes ( p < 0.01), history of previous TB disease ( p < 0.01), and the number of intra-domiciliary contacts ( p < 0.01). Analysis by multiplex allele-specific polymerase chain reaction detected mutations in the genes katG (65.8%) , rpoB (43.9%), inhA promoter (14.6%), and gyrA (9.8%). Sequencing identified mutations in the the genes katG (75.6%), inhA promoter (19.5%), rpoB (85.4%), and gyrA (100%). There was no mutation in the rrs gene. Spatial analysis showed DR-TB isolates distributed in areas of low socioeconomic status in the city of Fortaleza. Our results emphasized the importance of detecting resistance to TB drugs. The resistance found in the gene gyrA is of concern due to the high number of pre-extensive DR-TB cases in Fortaleza.
Comparison between CT and MRI in detection of metastasis of the retroperitoneum in testicular germ cell tumors: a prospective trial

Abstract Introduction: To minimize the radiation exposure of mostly young testicular cancer patients, it is essential to find out whether CT could be replaced by magnetic resonance imaging (MRI) in the staging and follow-up of the patients. In this trial, we examined whether abdominal MRI is as effective as computed tomography (CT) in the detection of retroperitoneal metastases of testicular cancer. Material and methods: This prospective study included 50 patients, 46 cases of retroperitoneal metastases and 4 controls without abdominal metastases (mean age 33, 5 years, range 20–65 years). Imaging of the retroperitoneum was performed using CT and 1.5 T MRI with diffusion weighted imaging (DWI). One experienced radiologist re-analyzed all of the examinations without knowledge of clinical information. All metastatic or suspicious lymph nodes were noted and measured two-dimensionally from axial images. Nodal detection and the size of detected nodes on CT and MRI were compared. Results: There was no significant difference in the detection of retroperitoneal metastasis between CT and MRI. The sensitivity of MRI was 0.98. There was no statistically significant difference in the sizes of lymph nodes found in CT and MRI, and even very small lymph nodes could be detected in MRI as well as in CT. Conclusion: MRI with DWI is as good as CT in detection of retroperitoneal lymph node metastases regardless of lymph node size, and it can be used as part of follow-up of testicular cancer patients instead of ionizing radiation producing imaging methods.
Accuracy of Vital Signs Measurements by a Smartwatch and a Portable Health Device: Validation Study

Background New consumer health devices are being developed to easily monitor multiple physiological parameters on a regular basis. Many of these vital sign measurement devices have yet to be formally studied in a clinical setting but have already spread widely throughout the consumer market. Objective The aim of this study was to investigate the accuracy and precision of heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and oxygen saturation (SpO2) measurements of 2 novel all-in-one monitoring devices, the BodiMetrics Performance Monitor and the Everlast smartwatch. Methods We enrolled 127 patients (>18 years) from the Thomas Jefferson University Hospital Preadmission Testing Center. SBP and HR were measured by both investigational devices. In addition, the Everlast watch was utilized to measure DBP, and the BodiMetrics Performance Monitor was utilized to measure SpO2. After 5 min of quiet sitting, four hospital-grade standard and three investigational vital sign measurements were taken, with 60 seconds in between each measurement. The reference vital sign measurements were calculated by determining the average of the two standard measurements that bounded each investigational measurement. Using this method, we determined three comparison pairs for each investigational device in each subject. After excluding data from 42 individuals because of excessive variation in sequential standard measurements per prespecified dropping rules, data from 85 subjects were used for final analysis. Results Of 85 participants, 36 (42%) were women, and the mean age was 53 (SD 21) years. The accuracy guidelines were only met for the HR measurements in both devices. SBP measurements deviated 16.9 (SD 13.5) mm Hg and 5.3 (SD 4.7) mm Hg from the reference values for the Everlast and BodiMetrics devices, respectively. The mean absolute difference in DBP measurements for the Everlast smartwatch was 8.3 (SD 6.1) mm Hg. The mean absolute difference between BodiMetrics and reference SpO2 measurements was 3.02%. Conclusions Both devices we investigated met accuracy guidelines for HR measurements, but they failed to meet the predefined accuracy guidelines for other vital sign measurements. Continued sale of consumer physiological monitors without prior validation and approval procedures is a public health concern.
Student Tobacco Use Behaviors on College Campuses by Strength of Tobacco Campus Policies

Purpose: To examine the association between strength of policy and self-reported tobacco use behavior, controlling for demographic characteristics, polytobacco use, knowledge of campus tobacco policy, and perceived policy compliance by others. Design: Cross-sectional, online survey. Setting: Ten participating State University of New York (SUNY) campuses; 5 with designated smoking/tobacco use areas and 5 with 100% tobacco-free policies. Subjects: Convenience sample of students from SUNY campuses: only tobacco users (N = 576 students) included for analysis. Measures: Items assessing tobacco use behaviors on campus, policy knowledge, and observation of others using tobacco on campus. Analysis: T tests and chi-square tests of association used to compare responses between tobacco users across campuses. Generalized estimating equations modeling used to evaluate predictors of tobacco use on campus; model estimated with students nested within campus. Results: Those on campuses without a comprehensive policy were more likely to report (in the past week) having seen others smoke on campus (98% vs 69%, P < .001), having personally smoked on campus (65% vs 36%, P < .001), and seeing others use tobacco products on campus (88% vs 67%, P < .001), compared to those on tobacco-free campuses. Conclusion: Tobacco-free campus policies provide numerous protective factors for tobacco users and nonusers. However, compliance strategies are imperative for intended policy success.
Application of the ASCO Value Framework and ESMO Magnitude of Clinical Benefit Scale to Assess the Value of Abiraterone and Enzalutamide in Advanced Prostate Cancer.

PURPOSE As novel hormonal therapies, such as abiraterone and enzalutamide, move into earlier stages of treatment of advanced prostate cancer, there are significant cost implications. We used the ASCO Value Framework (AVF) and European Society of Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale (MCBS) to quantify and compare the incremental clinical benefit and costs of these agents in the metastatic castration-resistant prostate cancer (mCRPC) and metastatic castration-sensitive prostate cancer (mCSPC) settings. METHODS We searched PubMed for randomized phase III trials of abiraterone and enzalutamide in mCRPC and mCSPC. Incremental clinical benefit was quantified using the AVF and ESMO-MCBS by 2 independent assessors. Incremental drug costs were calculated using average wholesale prices (AWPs) from the RED BOOK Online. RESULTS In mCRPC, 2 abiraterone trials (COU-AA-301 and COU-AA-302) and 2 enzalutamide trials (AFFIRM and PREVAIL) met search criteria. AVF scores ranged from 46.3 to 66.6, suggesting clinical benefit; ESMO-MCBS scores ranged from 3 to 5, with lower clinical benefit in the mCRPC predocetaxel setting. The overall incremental AWP ranged from $83,460.94 to $205,128.85. In mCSPC, 4 trials met criteria (LATITUDE, STAMPEDE, ENZAMET, and ARCHES; AVF scores were 79.8, 33.3, 59, and 17, respectively). All of the studies showed benefit except ARCHES. By ESMO-MCBS, both LATITUDE and STAMPEDE showed benefit (score for 4 for both studies); ENZAMET and ARCHES were not evaluable. The overall cost of treatment was significantly higher in the mCSPC setting. CONCLUSION The AVF and ESMO-MCBS frameworks generated slightly different results but suggested that abiraterone and enzalutamide show clinical benefit in both mCRPC and mCSPC but trended to lower clinical benefit and increased costs in earlier disease stages. Further refinement of the AVF and ESMO-MCBS is needed to facilitate their use and their ability to inform clinical practice in a rapidly changing treatment landscape.
Ecological Risks of Metal and Metalloid Contamination in the Rio Doce Estuary

The rupture of a mining dam in southeastern Brazil in 2015 was the country's greatest environmental tragedy. In order to evaluate the ecological risks of the mine tailings on the Rio Doce estuary, this study assessed trace metal contamination and sediment quality indices up to 2.9 y after the dam rupture. Surface sediments were collected from 17 stations on the Rio Doce estuary and Cd, Pb, Cr, Zn, Cu, and As concentrations were determined by inductively coupled plasma atomic emission spectroscopy (ICP‐OES). Four ecological risk indices (modified contamination degree [mCd], pollution load index [PLI], risk index [RI], and sediment quality guideline quotient [SQG‐Q]) suggest a high risk by metal contamination with possible adverse biological effects, with moderate seasonal variability. Based on a precautionary approach, our results support fisheries closures and the need for public health monitoring in the affected areas, and support other studies that suggest chronic metal contamination of the Rio Doce estuary. Integr Environ Assess Manag 2020;16:655–660. © 2020 SETAC
Soybean Resistance to Soybean Mosaic Virus

Soybean mosaic virus (SMV) occurs in all soybean-growing areas in the world and causes huge losses in soybean yields and seed quality. During early viral infection, molecular interactions between SMV effector proteins and the soybean resistance (R) protein, if present, determine the development of resistance/disease in soybean plants. Depending on the interacting strain and cultivar, R-protein in resistant soybean perceives a specific SMV effector, which triggers either the extreme silent resistance or the typical resistance manifested by hypersensitive responses and induction of salicylic acid and reactive oxygen species. In this review, we consider the major advances that have been made in understanding the soybean–SMV arms race. We also focus on dissecting mechanisms SMV employs to establish infection and how soybean perceives and then responds to SMV attack. In addition, progress on soybean R-genes studies, as well as those addressing independent resistance genes, are also addressed.
TORC1 regulates vacuole membrane composition through ubiquitin- and ESCRT-dependent microautophagy

Cellular adaptation in response to nutrient limitation requires the induction of autophagy and lysosome biogenesis for the efficient recycling of macromolecules. Here, we discovered that starvation and TORC1 inactivation not only lead to the upregulation of autophagy and vacuole proteins involved in recycling, but also result in the downregulation of many vacuole membrane proteins to supply amino acids as part of a vacuole remodeling process. Downregulation of vacuole membrane proteins is initiated by ubiquitination, which is accomplished by the coordination of multiple E3 ubiquitin ligases, including Rsp5, the Dsc complex, and a newly characterized E3 ligase, Pib1. The Dsc complex is negatively regulated by TORC1 through the Rim15-Ume6 signaling cascade. After ubiquitination, vacuole membrane proteins are sorted into the lumen for degradation by ESCRT-dependent microautophagy. Thus, our study uncovered a complex relationship between TORC1 inactivation and vacuole biogenesis.
Percutaneous intrarenal transplantation of differentiated induced pluripotent stem cells into newborn mice

The in vivo engraftment of induced pluripotent stem cell (iPSC)‐derived podocytes following allogeneic transplantation into host kidneys remains a challenge. Here we investigate the survival and engraftment of human dermal fibroblasts‐derived differentiated iPSCs using a newborn mouse model, which represents a receptive immunoprivileged host environment. iPSCs were generated from skin biopsies of patients using Sendai virus reprogramming. Differentiation of nephrin (NPHS1)‐green fluorescent protein (GFP) iPSCs into kidney podocytes (iPSC‐PODs) was performed by the addition of Activin A, bone morphogenetic protein 7 (BMP7), and retinoic acid over 10 days of culture. To assess the in vivo incorporation of cells, undifferentiated iPSCs or day 10 iPSC‐PODs, were labeled with either carboxyfluorescein succinimidyl ester (CFSE) or Qdot nanocrystals (Q705). Thereafter, 1 × 105 differentiated iPSC‐PODs were injected directly into the kidneys of mouse pups at postnatal day one (P1). Using co‐expression analysis of glomerular and podocyte‐specific markers, Day 10 differentiated iPSC‐PODs that were positive for podocin, were detected following direct kidney injection into newborn mice up to 1 week after transplantation. Undifferentiated iPSC‐PODs were not detected at the same timepoint. The transplanted cells were viable and located in the outer nephrogenic zone where they were found to colocalize with, or sit adjacent to, cells positive for glomerular‐specific markers including podocin, synaptopodin, and Wilms' tumor 1 (WT1). This study provides proof‐of‐principle that transplanted iPSC–POD can survive in recipient newborn mouse kidneys due to the immature and immunoprivileged nature of the developing postnatal kidneys.
An Investigation of Psychosis Subgroups With Prognostic Validation and Exploration of Genetic Underpinnings: The PsyCourse Study.

Importance Identifying psychosis subgroups could improve clinical and research precision. Research has focused on symptom subgroups, but there is a need to consider a broader clinical spectrum, disentangle illness trajectories, and investigate genetic associations. Objective To detect psychosis subgroups using data-driven methods and examine their illness courses over 1.5 years and polygenic scores for schizophrenia, bipolar disorder, major depression disorder, and educational achievement. Design, Setting, and Participants This ongoing multisite, naturalistic, longitudinal (6-month intervals) cohort study began in January 2012 across 18 sites. Data from a referred sample of 1223 individuals (765 in the discovery sample and 458 in the validation sample) with DSM-IV diagnoses of schizophrenia, bipolar affective disorder (I/II), schizoaffective disorder, schizophreniform disorder, and brief psychotic disorder were collected from secondary and tertiary care sites. Discovery data were extracted in September 2016 and analyzed from November 2016 to January 2018, and prospective validation data were extracted in October 2018 and analyzed from January to May 2019. Main Outcomes and Measures A clinical battery of 188 variables measuring demographic characteristics, clinical history, symptoms, functioning, and cognition was decomposed using nonnegative matrix factorization clustering. Subtype-specific illness courses were compared with mixed models and polygenic scores with analysis of covariance. Supervised learning was used to replicate results in validation data with the most reliably discriminative 45 variables. Results Of the 765 individuals in the discovery sample, 341 (44.6%) were women, and the mean (SD) age was 42.7 (12.9) years. Five subgroups were found and labeled as affective psychosis (n = 252), suicidal psychosis (n = 44), depressive psychosis (n = 131), high-functioning psychosis (n = 252), and severe psychosis (n = 86). Illness courses with significant quadratic interaction terms were found for psychosis symptoms (R2 = 0.41; 95% CI, 0.38-0.44), depression symptoms (R2 = 0.28; 95% CI, 0.25-0.32), global functioning (R2 = 0.16; 95% CI, 0.14-0.20), and quality of life (R2 = 0.20; 95% CI, 0.17-0.23). The depressive and severe psychosis subgroups exhibited the lowest functioning and quadratic illness courses with partial recovery followed by reoccurrence of severe illness. Differences were found for educational attainment polygenic scores (mean [SD] partial η2 = 0.014 [0.003]) but not for diagnostic polygenic risk. Results were largely replicated in the validation cohort. Conclusions and Relevance Psychosis subgroups were detected with distinctive clinical signatures and illness courses and specificity for a nondiagnostic genetic marker. New data-driven clinical approaches are important for future psychosis taxonomies. The findings suggest a need to consider short-term to medium-term service provision to restore functioning in patients stratified into the depressive and severe psychosis subgroups.