Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction of metastatic prostate cancer by prostate-specific antigen in combination with T stage and Gleason Grade: Nationwide, population-based register study

The objective was to investigate the proportion of men with metastatic prostate cancer in groups defined by T stage, Gleason Grade Group (GGG) and serum levels of prostate-specific antigen (PSA) and if PSA can be used to rule in metastatic prostate cancer when combined with T stage and GGG. We identified 102,076 men in Prostate Cancer data Base Sweden 4.0 who were diagnosed with prostate cancer in 2006–2016. Risk of metastases was assessed for PSA stratified on T stage and five-tiered GGG. For men who had not undergone bone imaging, we used multiple imputation to classify metastatic prostate cancer. Advanced T stage, high GGG and high PSA were related to bone metastases. For example: only 79/38 190 (0.2%) of men with T1-2 and GGG 1 had PSA above 500 ng/mL, and 29/79 (44%) of these men had metastases; whereas 1 154/7 018 (16%) of men with T3-4 and GGG 5 had PSA above 500 ng/ml and 1 088/1 154 (94%) of these men had metastases. However, no PSA cut-off could accurately identify the majority of men with metastatic prostate cancer (i.e. high sensitivity) while also correctly classifying most men without metastasis (i.e. high specificity). In conclusion, these results support the use of imaging to confirm bone metastases in men with advanced prostate cancer as no PSA level in combination with T stage and GGG could accurately rule in metastatic prostate cancer and thereby safely omit bone imaging.
Sodium‐Glucose Cotransporter 2 Inhibition for the Prevention of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Meta‐Analysis

Background Several trials have demonstrated protective effects from inhibition of sodium‐glucose cotransporter 2 among patients with type 2 diabetes mellitus. There is uncertainty about the consistency of the cardiovascular benefits achieved across patient subsets. Methods and Results We included 4 large‐scale trials of sodium‐glucose cotransporter 2 inhibition compared with placebo in patients with diabetes mellitus that reported effects on cardiovascular outcomes overall and for participant subgroups defined at baseline by cardiovascular disease, reduced kidney function, and heart failure. Fixed effects models with inverse variance weighting were used to estimate summary hazard ratios and 95% CIs. There were 38 723 patients from 4 trials, with a mean 2.9 years of follow‐up. Of the patients, 22 870 (59%) had cardiovascular disease, 7754 (20%) had reduced kidney function, and 4543 (12%) had heart failure. There were 3828 major adverse cardiac events. There was overall benefit for major adverse cardiac events (0.88; 95% CI, 0.82–0.94; P<0.001) and no evidence that the effects of sodium‐glucose cotransporter 2 inhibition varied across patient subgroups, defined by the presence of cardiovascular disease or heart failure at baseline (all P interaction >0.252; I2<25%). All patient subgroups benefited with respect to hospitalization for heart failure (all P interaction>0.302; I2<10%), cardiovascular death (all P interaction>0.167; I2<50%), and death from any cause (all P interaction>0.354; I2=0%). The only difference in effects across subgroups was for stroke, with protection observed among those with reduced kidney function but not those with preserved kidney function (P interaction=0.020; I2=81%). Conclusions Sodium‐glucose cotransporter 2 inhibitors protect against cardiovascular disease and death in diverse subsets of patients with type 2 diabetes mellitus regardless of cardiovascular disease history.
Hand Gesture Recognition Using Compact CNN via Surface Electromyography Signals

By training the deep neural network model, the hidden features in Surface Electromyography(sEMG) signals can be extracted. The motion intention of the human can be predicted by analysis of sEMG. However, the models recently proposed by researchers often have a large number of parameters. Therefore, we designed a compact Convolution Neural Network (CNN) model, which not only improves the classification accuracy but also reduces the number of parameters in the model. Our proposed model was validated on the Ninapro DB5 Dataset and the Myo Dataset. The classification accuracy of gesture recognition achieved good results.
Routine disaccharidase testing: are we there yet?

PURPOSE OF REVIEW Disaccharidase testing, as applied to the evaluation of gastrointestinal disturbances is available but it is not routinely considered in the diagnostic work-up. The purpose of this review was to determine if disaccharidase testing is clinically useful and to consider how the results could alter patient management. RECENT FINDINGS Indicate that carbohydrate maldigestion could contribute functional bowel disorders and negatively impact the fecal microbiome. Diagnostic techniques include enzyme activity assays performed on random endoscopically obtained small intestinal biopsies, immunohistochemistry, stable isotope tracer and nonenriched substrate load breath testing, and genetic testing for mutations. More than 40 sucrase--isomaltase gene variants coding for defective or reduced enzymatic activity have been reported and deficiency conditions are more common than previously thought. SUMMARY The rationale for disaccharidase activity testing relates to a need to fully assess unexplained recurrent abdominal discomfort and associated symptoms. All disaccharidases share the same basic mechanism of mucosal expression and deficiency has far reaching consequences. Testing for disaccharidase expression appears to have an important role in symptom evaluation, but there are accuracy and logistical issues that should be considered. It is likely that specific recommendations for patient management, dietary modification, and enzyme supplementation would come from better testing methods.
Interval exercise induces milder respiratory responses compared to continuous exercise

ABSTRACT The purpose of this study was to explore the respiratory response of acute interval and continuous exercise (CE) of low and high intensity. Fourteen recreational athletes (7 men and 7 women; VO2max = 35.7 ± 6.1 mlkg–1min–1) performed a bout of continuous and a bout of interval exercise (IE) both consisted of 5-min cycling at low intensity [80% of the power output (W) of the predetermined gas exchange threshold (GET) (80%WGET)] and 5-min cycling at high intensity {WGET plus the work rate corresponding to 50% of the difference between peak power output (PPO) at oxygen uptake (VO2max) test and the WGET [WGET + 0.50 Δ(PPO – WGET)]}. CE compared to IE induced significant higher heart rate and ventilation as well as significant higher levels of mouth occlusion pressure for 0.1 s (P0.1) (P < 0.05) during low and high intensities. Our results indicate that CE stimulates respiration more than IE when the exercise is performed at the same relative intensity.
Adaptive and Innate Immune Cells in Fetal Human Cytomegalovirus-Infected Brains

Background: The understanding of the pathogenesis of cytomegalovirus (CMV)-induced fetal brain lesions is limited. We aimed to quantify adaptive and innate immune cells and CMV-infected cells in fetal brains with various degrees of brain damage. Methods: In total, 26 archived embedded fetal brains were studied, of which 21 were CMV-infected and classified in severely affected (n = 13) and moderately affected (n = 8), and 5 were uninfected controls. The respective magnitude of infected cells, immune cells (CD8+, B cells, plasma cells, NK cells, and macrophages), and expression of immune checkpoint receptors (PD-1/PD-L1 and LAG-3) were measured by immunochemistry and quantified by quantitative imaging analysis. Results: Quantities of CD8+, plasma cells, NK cells, macrophages, and HCMV+ cells and expression of PD-1/PD-L1 and LAG-3 were significantly higher in severely affected than in moderately affected brains (all p values < 0.05). A strong link between higher number of stained cells for HCMV/CD8 and PD-1 and severity of brain lesions was found by component analysis. Conclusions: The higher expression of CD8, PD-1, and LAG-3 in severely affected brains could reflect immune exhaustion of cerebral T cells. These exhausted T cells could be ineffective in controlling viral multiplication itself, leading to more severe brain lesions. The study of the functionality of brain leucocytes ex vivo is needed to confirm this hypothesis.
Highlights in heart failure

Heart failure (HF) remains a major cause of mortality, morbidity, and poor quality of life. It is an area of active research. This article is aimed to give an update on recent advances in all aspects of this syndrome. Major changes occurred in drug treatment of HF with reduced ejection fraction (HFrEF). Sacubitril/valsartan is indicated as a substitute to ACEi/ARBs after PARADIGM‐HF (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.73 to 0.87 for sacubitril/valsartan vs. enalapril for the primary endpoint and Wei, Lin and Weissfeld HR 0.79, 95% CI 0.71–0.89 for recurrent events). Its initiation was then shown as safe and potentially useful in recent studies in patients hospitalized for acute HF. More recently, dapagliflozin and prevention of adverse‐outcomes in DAPA‐HF trial showed the beneficial effects of the sodium–glucose transporter type 2 inhibitor dapaglifozin vs. placebo, added to optimal standard therapy [HR, 0.74; 95% CI, 0.65 to 0.85;0.74; 95% CI, 0.65 to 0.85 for the primary endpoint]. Trials with other SGLT 2 inhibitors and in other patients, such as those with HF with preserved ejection fraction (HFpEF) or with recent decompensation, are ongoing. Multiple studies showed the unfavourable prognostic significance of abnormalities in serum potassium levels. Potassium lowering agents may allow initiation and titration of mineralocorticoid antagonists in a larger proportion of patients. Meta‐analyses suggest better outcomes with ferric carboxymaltose in patients with iron deficiency. Drugs effective in HFrEF may be useful also in HF with mid‐range ejection fraction. Better diagnosis and phenotype characterization seem warranted in HF with preserved ejection fraction. These and other burning aspects of HF research are summarized and reviewed in this article.
NN Reinforcement Learning Adaptive Control for a Class of Nonstrict-Feedback Discrete-Time Systems

This article investigates an adaptive reinforcement learning (RL) optimal control design problem for a class of nonstrict-feedback discrete-time systems. Based on the neural network (NN) approximating ability and RL control design technique, an adaptive backstepping RL optimal controller and a minimal learning parameter (MLP) adaptive RL optimal controller are developed by establishing a novel strategic utility function and introducing external function terms. It is proved that the proposed adaptive RL optimal controllers can guarantee that all signals in the closed-loop systems are semiglobal uniformly ultimately bounded (SGUUB). The main feature is that the proposed schemes can solve the optimal control problem that the previous literature cannot deal with. Furthermore, the proposed MPL adaptive optimal control scheme can reduce the number of adaptive laws, and thus the computational complexity is decreased. Finally, the simulation results illustrate the validity of the proposed optimal control schemes.
Predicted Prognosis of Patients with Pancreatic Cancer by Machine Learning

Purpose: Pancreatic cancer remains a disease of high mortality despite advanced diagnostic techniques. Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic cancers. MUC1 and MUC4 expression are related to the aggressive behavior of human neoplasms and a poor patient outcome. In contrast, MUC2 is a tumor suppressor, and we have previously reported that MUC2 is a favorable prognostic factor in pancreatic neoplasia. This study investigates whether the methylation status of three mucin genes from postoperative tissue specimens from patients with pancreatic neoplasms could serve as a predictive biomarker for outcome after surgery. Experimental Design: We evaluated the methylation status of MUC1, MUC2, and MUC4 promoter regions in pancreatic tissue samples from 191 patients with various pancreatic lesions using methylation-specific electrophoresis. Then, integrating these results and clinicopathologic features, we used support vector machine-, neural network-, and multinomial-based methods to develop a prognostic classifier. Results: Significant differences were identified between the positive- and negative-prediction classifiers of patients in 5-year overall survival (OS) in the cross-validation test. Multivariate analysis revealed that these prognostic classifiers were independent prognostic factors analyzed by not only neoplastic tissues but also nonneoplastic tissues. These classifiers had higher predictive accuracy for OS than tumor size, lymph node metastasis, distant metastasis, and age and can complement the prognostic value of the TNM staging system. Conclusions: Analysis of epigenetic changes in mucin genes may be of diagnostic utility and one of the prognostic predictors for patients with pancreatic ductal adenocarcinoma.
Mothers’ and fathers’ lived experiences of postpartum depression and parental stress after childbirth: a qualitative study

ABSTRACT Purpose: The study aims are to explore the lived experiences of mothers and fathers of postpartum depression and parental stress after childbirth. Methods: Qualitative interviews conducted, and analysed from an interpretative phenomenological analysis (IPA) perspective. Results: Both mothers and fathers described experiences of inadequacy, although fathers described external requirements, and mothers described internal requirements as the most stressful. Experiences of problems during pregnancy or a traumatic delivery contributed to postpartum depression and anxiety in mothers and affected fathers’ well-being. Thus, identifying postpartum depression with the Edinburgh Postnatal Depression Scale, mothers described varying experiences of child health care support. Postpartum depression seemed to affect the spouses’ relationships, and both mothers and fathers experienced loneliness and spouse relationship problems. Experiences of emotional problems and troubled upbringing in the parents’ family of origin may contribute to vulnerability from previous trauma and to long-term depressive symptoms for mothers. Conclusions: The findings of this study demonstrate the significant impact of postpartum depression and parental stress has in parents’ everyday lives and on the spouse relationship. These results support a change from an individual parental focus to couples’ transition to parenthood in child health care.
Arrhythmogenic risks of stem cell replacement therapy for cardiovascular diseases

Ischemic heart disease and congestive heart failure are major contributors to high morbidity and mortality. Approximately 1.5 million cases of myocardial infarction occur annually in the United States; the yearly incidence rate is approximately 600 cases per 100,000 people. Although significant progress to improve the survival rate has been made by medications and implantable medical devices, damaged cardiomyocytes are unable to be recovered by current treatment strategies. After almost two decades of research, stem cell therapy has become a very promising approach to generate new cardiomyocytes and enhance the function of the heart. Along with clinical trials with stem cells conducted in cardiac regeneration, concerns regarding safety and potential risks have emerged. One of the contentious issues is the electrical dysfunctions of cardiomyocytes and cardiac arrhythmia after stem cell therapy. In this review, we focus on the cell sources currently used for stem cell therapy and discuss related arrhythmogenic risk.
Is Explanation a Marketing Problem? The Quest for Trust in Artificial Intelligence and Two Conflicting Solutions

a Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy; b Applied Research Division for Cognitive and Psychological Science, IEO, European Institute of Oncology IRCCS, Milan, Italy; c Division of Early Drug Development for Innovative Therapy, IEO, European Institute of Oncology IRCCS, Milan, Italy Received: November 27, 2019 Accepted: January 20, 2020 Published online: January 28, 2020
Histological characteristics of early-stage oral tongue cancer in young versus older patients: A multicenter matched-pair analysis.

The mean age of diagnosis of new oral squamous cell carcinoma (OSCC) cases is around 60 years with less than 5% of all patients aged 45 years or younger (Taybos, 2003). Oral tongue squamous cell carcinoma (OTSCC) is the most common, and presents with the worst prognosis (Ng et al., 2017). Several risk factors have been associated with OTSCC, many of which appear to be more related to older age (Farquhar et al., 2018). Young OTSCC patients lack these risk factors or when present, they have much shorter exposure time to the risk factors, suggesting different genomic and molecular changes than seen in older OTSCC patients (Llewellyn et al., 2004).
The association between fitness and obesity in diverse multi-ethnic college students

Abstract Objective We examined differences and associations between physical fitness and behavioral factors with obesity in a multi-ethnic student population. Participants: Study population included non-Hispanic whites (NHW, n = 1,454); Hispanics (n = 1,436) and Asians (n = 1,016) at a metropolitan university from Fall 2006 to Fall 2013. Methods: Analyses of Variance and regression analyses, utilizing cross-sectional data, measured the association between fitness, and behavior with obesity. Results: BMI differences (p < .05) were observed between NHW (23.17 ± 3.67), Hispanics (24.32 ± 3.67), and Asians (22.92 ± 4.12). Fitness parameters, relative VO2 max, % body fat, and total fitness score were significantly (p < .0001) associated with obesity. Stress was strongly significantly associated with obesity in Hispanics (p < .001) and somewhat in NHW. Conclusions: Obesity disparities persist in college. Physical fitness and stress management interventions should be targeted towards Hispanic and NHW college students, which may curb current and/or adult-onset obesity.
Pearls & Oy-sters: Chemotherapy-associated hyperammonemic encephalopathy

Hyperammonemic encephalopathy (HE) is a metabolic condition precipitated by elevated blood ammonia, which may be idiopathic or secondary to increased production (e.g., infection with urease-positive bacteria) or decreased elimination of ammonia (e.g., liver failure), or drug-induced (e.g., valproic acid).
Priming chromatin for segregation: functional roles of mitotic histone modifications

ABSTRACT Posttranslational modifications (PTMs) of histone proteins are important for various cellular processes including regulation of gene expression and chromatin structure, DNA damage response and chromosome segregation. Here we comprehensively review mitotic histone PTMs, in particular phosphorylations, and discuss their interplay and functions in the control of dynamic protein–protein interactions as well as their contribution to centromere and chromosome structure and function during cell division. Histone phosphorylations can create binding sites for mitotic regulators such as the chromosomal passenger complex, which is required for correction of erroneous spindle attachments and chromosome bi-orientation. Other histone PTMs can alter the structural properties of nucleosomes and the accessibility of chromatin. Epigenetic marks such as lysine methylations are maintained during mitosis and may also be important for mitotic transcription as well as bookmarking of transcriptional states to ensure the transmission of gene expression programs through cell division. Additionally, histone phosphorylation can dissociate readers of methylated histones without losing epigenetic information. Through all of these processes, mitotic histone PTMs play a functional role in priming the chromatin for faithful chromosome segregation and preventing genetic instability, one of the characteristic hallmarks of cancer cells.
The effect of silymarin on liver enzymes in patients taking isotretinoin: A randomized clinical trial

The aim of the present study was to investigate the effect of silymarin (Livergol) on liver enzymes in patients taking isotretinoin (Roaccutane). In this double‐blind clinical trial, 74 patients with acne and taking isotretinoin were randomly assigned into intervention (N = 37) and control (N = 37) groups. The intervention group received a 140 mg Livergol capsule per day for 30 days. The control group received a starch‐containing capsule as a placebo once a day for 30 days. Liver enzyme levels were measured before and after the intervention. The data were analyzed using chi‐square test, Independent t test, paired sample t test and analysis of covariance (ANCOVA). The results showed no statistically significant difference between the intervention and control groups at the beginning of study in levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) (p > .05). At the end of the study, a statistically significant difference was observed between the two groups in levels of AST and ALT (p < .05). Livergol prevented liver enzymes from increasing, so it can be used as an effective, low‐cost, and low‐complication treatment for the problem of increased levels of liver enzymes following the use of isotretinoin.
Genetic and genomic approaches to address rapid rancidity of rice bran

Abstract Rice bran is an invaluable by-product of paddy processing industry. It is rich in minerals, protein, lipids, and crude fiber. In addition, it also possesses compounds with anti-oxidant, anti-allergic, anti-diabetic, and anti-cancer properties. It forms a basis for the extraction of rice bran oil and preparation of various functional foods with health benefits and potential to prevent chronic health issues. Nevertheless, the rapid deterioration of bran upon storage acts as a major limitation in exploiting the full potential of rice bran. In this review, we have discussed three strategies to address rapid rancidity of rice bran and enhance its shelf life and storability vis-a-vis emphasizing the importance of rice bran in terms of its nutritional composition. One strategy is through exploitation of the null mutations in the genes governing lipases and lipoxygenases leading to nonfunctional enzymes (enzyme deficient approach), another strategy is through reducing the PUFA content that is more prone to oxidation (substrate deficient approach) and a third strategy is through enhancing the antioxidant content that effectively terminate the lipid peroxidation by donating the hydrogen atom.