Miracle-dz/UniFAR-FTUs huggingface dataset:
New-onset atrial fibrillation in bacteremia is not associated wtih C-reactive protein, but is predictive of increased mortality

Background: Several studies have associated elevated C-reactive protein (CRP) levels to the occurrence of atrial fibrillation (AF). We sought to estimate the frequency and prognostic impact of AF in patients with bacteremia, and to study the possible association between AF and C-reactive protein (CRP) in this population. Materials and Methods: We retrospectively evaluated patient-charts of patients with bacteremia with E.coli or S.pneumoniae admitted to Aker Universitiy Hospital in Oslo throughout the period 1994 to 2004. Variables on known cardiac risk factors for AF, signs of AF, mode of conversion of AF, and, if applicable, date of death, were registered. Initial CRP values were categorized into 4 strata. Odds ratios (ORs) of the 3 highest CRP-categories compared with the lowest ones were obtained from logistic models adjusting for known cardiac risk factors for AF. Cox regression analysis was used to compare new-onset AF and death during the first two weeks after hospitalization. Results: 677 patient charts were studied. 104 patients (15.4%) had new-onset AF. Peak incidence of new-onset AF occurred on the day of admission. Peak CRP values were reached during the two next days. High CRP level at admission did not predict the occurrence of AF. The observed mortality was higher among patients with new-onset AF (p=0.04) during the first two weeks after hospitalization. Conclusions: The frequency of new-onset AF in bacteremia is substantial. Initial CRP levels do not predict new-onset AF. In patients with bacteremia, new-onset AF is associated with increased mortality.
A Facile One-Pot Synthesis of Versatile PEGylated Platinum Nanoflowers and Their Application in Radiation Therapy

Nanomedicine has stepped into the spotlight of radiation therapy over the last two decades. Nanoparticles (NPs), especially metallic NPs, can potentiate radiotherapy by specific accumulation into tumors, thus enhancing the efficacy while alleviating the toxicity of radiotherapy. Water radiolysis is a simple, fast and environmentally-friendly method to prepare highly controllable metallic nanoparticles in large scale. In this study, we used this method to prepare biocompatible PEGylated (with Poly(Ethylene Glycol) diamine) platinum nanoflowers (Pt NFs). These nanoagents provide unique surface chemistry, which allows functionalization with various molecules such as fluorescent markers, drugs or radionuclides. The Pt NFs were produced with a controlled aggregation of small Pt subunits through a combination of grafted polymers and radiation-induced polymer cross-linking. Confocal microscopy and fluorescence lifetime imaging microscopy revealed that Pt NFs were localized in the cytoplasm of cervical cancer cells (HeLa) but not in the nucleus. Clonogenic assays revealed that Pt NFs amplify the gamma rays induced killing of HeLa cells with a sensitizing enhancement ratio (SER) of 23%, thus making them promising candidates for future cancer radiation therapy. Furthermore, the efficiency of Pt NFs to induce nanoscopic biomolecular damage by interacting with gamma rays, was evaluated using plasmids as molecular probe. These findings show that the Pt NFs are efficient nano-radio-enhancers. Finally, these NFs could be used to improve not only the performances of radiation therapy treatments but also drug delivery and/or diagnosis when functionalized with various molecules.
A hepatocyte differentiation model reveals two subtypes of liver cancer with different oncofetal properties and therapeutic targets

Significance Developmental signaling pathways play important roles in cancer initiation and therapeutic resistance. Poorly differentiated hepatocellular carcinomas (HCCs) usually show phenotypic resemblance to their ancestral precursor cells and are associated with poor clinical outcome. In a recent study, a dynamic oncofetal-like gene expression signature during liver development was identified from an in vitro hepatocyte differentiation model. Two subtypes of liver cancer with different oncofetal properties and upstream oncogenic drivers were found in clinical patients with poor prognosis. Clinically available small-molecule inhibitors HLM6474 and SIS3 specifically targeting the oncofetal drivers extensively down-regulated subtype-specific developmental signaling and significantly inhibited tumorigenicity. Further treatment of HCC patients with specified small-molecular inhibitors according to subtype-specific biomarkers might accurately block the tumor-initiating steps and eliminate tumor progression. Clinical observation of the association between cancer aggressiveness and embryonic development stage implies the importance of developmental signals in cancer initiation and therapeutic resistance. However, the dynamic gene expression during organogenesis and the master oncofetal drivers are still unclear, which impeded the efficient elimination of poor prognostic tumors, including human hepatocellular carcinoma (HCC). In this study, human embryonic stem cells were induced to differentiate into adult hepatocytes along hepatic lineages to mimic liver development in vitro. Combining transcriptomic data from liver cancer patients with the hepatocyte differentiation model, the active genes derived from different hepatic developmental stages and the tumor tissues were selected. Bioinformatic analysis followed by experimental assays was used to validate the tumor subtype-specific oncofetal signatures and potential therapeutic values. Hierarchical clustering analysis revealed the existence of two subtypes of liver cancer with different oncofetal properties. The gene signatures and their clinical significance were further validated in an independent clinical cohort and The Cancer Genome Atlas database. Upstream activator analysis and functional screening further identified E2F1 and SMAD3 as master transcriptional regulators. Small-molecule inhibitors specifically targeting the oncofetal drivers extensively down-regulated subtype-specific developmental signaling and inhibited tumorigenicity. Liver cancer cells and primary HCC tumors with different oncofetal properties also showed selective vulnerability to their specific inhibitors. Further precise targeting of the tumor initiating steps and driving events according to subtype-specific biomarkers might eliminate tumor progression and provide novel therapeutic strategy.
The In Vivo Antioxidant and Hepatoprotective Actions of Selected Chinese Teas

Tea is a popular beverage and shows very strong in vitro antioxidant activity. However, the relationship among in vitro and in vivo antioxidant activities in teas is seldom reported. In this study, in vivo antioxidant and hepatoprotective activities of 32 selected Chinese teas were evaluated on a mouse model with acute alcohol-induced liver injury. The results showed that most teas significantly reduced the levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, triacylglycerol, and total bilirubin in the sera of mice at a dose of 400 mg/kg. In addition, most teas greatly decreased the malondialdehyde level and increased the levels of superoxide dismutase, glutathione peroxidase, and glutathione in the liver of mice, indicating the antioxidant and hepatoprotective activities of teas. Furthermore, the in vivo antioxidant activity of dark tea was stronger than that of green tea, opposite to the results of the in vitro study. Among these 32 teas, Black Fu Brick Tea, Pu-erh Tea, and Qing Brick Tea showed the strongest antioxidant and hepatoprotective activities. Moreover, total phenolic content as well as the contents of epicatechin, gallocatechin gallate, and chlorogenic acid were found to contribute, at least partially, to the antioxidant and hepatoprotective actions of these teas. Overall, teas are good dietary components with antioxidant and hepatoprotective actions.
PIK3Cδ expression by fibroblasts promotes triple-negative breast cancer progression.

As there is growing evidence for the tumor microenvironment's (TME) role in tumorigenesis, we investigated the role of fibroblast-expressed kinases in triple negative breast cancer (TNBC). Using a high-throughput kinome screen combined with 3D invasion assays, we identified fibroblast-expressed PIK3Cδ (f-PIK3Cδ) as a key regulator of progression. Although PIK3Cδ was expressed in primary fibroblasts derived from TNBC patients, it was undetectable in breast cancer cell lines. Genetic and pharmacologic gain- and loss-of functions experiments verified the contribution of f-PIK3Cδ in TNBC cell invasion. Integrated secretomics and transcriptomics analyses revealed a paracrine mechanism via which f-PIK3Cδ confers its pro-tumorigenic effects. Inhibition of f-PIK3Cδ promoted the secretion of factors, including PLGF and BDNF, which led to upregulation of NR4A1 in TNBC cells where it acts as a tumor suppressor. Inhibition of PIK3Cδ in an orthotopic BC mouse model reduced tumor growth only after inoculation with fibroblasts, indicating a role of f-PIK3Cδ in cancer progression. Similar results were observed in the MMTV-PyMT transgenic BC mouse model, along with a decrease on tumor metastasis emphasizing the potential immune-independent effects of PIK3Cδ inhibition. Finally, analysis of BC patient cohorts and TCGA datasets identified f-PIK3Cδ (protein and mRNA levels) as an independent prognostic factor for overall and disease free survival, highlighting it as a therapeutic target for TNBC.
Use of a Pleurotus ostreatus Complex Cell Wall Extract as Elicitor of Plant Defenses: From Greenhouse to Field Trial

Fungi constitute an abundant source of natural polysaccharides, some of them harboring original structures which can induce responses in mammalian or plant cells. An alkaline extract from the edible mushroom Pleurotus ostreatus has been obtained and called Pleuran complex cell wall extract (CCWE). It consists of a glucan-peptide complex whose components fall in a quite broad range of molecular weights, from 30 to 80 kDa. Pleuran extract has been tested on cultivated plants in laboratory conditions and also during field trial for its capacity to stimulate plant defenses in response to pathogen attack. Following Pleuran CCWE treatment, enhanced levels of various biochemical markers associated with plant responses have been observed, including enzymatic activities (e.g., peroxidase) or expression of some pathogenesis-related genes. In addition, during field experiments, we have noticed significant reductions in disease symptom levels in relation to different plant/pathogen systems (wheat/septoria, vine/mildew). These results confirmed that Pleuran CCWE could be used as an elicitor of plant defenses and could help in reducing pesticide applications against plant pathogens.
Interaction between Vegetarian Versus Omnivorous Diet and Unhealthy Eating Patterns (Orthorexia Nervosa, Cognitive Restraint) and Body Mass Index in Adults

The objective of the present study was two-fold: Firstly, to investigate unhealthy eating patterns and body mass index among individuals following a vegetarian diet and those following an omnivorous diet. Secondly, to examine interaction between vegetarian versus omnivorous diet and unhealthy eating patterns (orthorexia nervosa, cognitive restraint) and body mass index using a structural equation modeling approach (SEM). The study included 370 participants: 188 participants following a vegetarian diet and 182 following an omnivorous diet. Unhealthy eating patterns and body mass index were measured. Our results showed that individuals following a vegetarian diet were more likely to engage in orthorexic eating behavior compared to individuals following an omnivorous diet. In addition, they had a significantly lower levels of cognitive restraint and lower body mass index than individuals following an omnivorous diet. Use of SEM method showed that: (1) following a vegetarian diet and orthorexia nervosa were directly associated, (2) following an omnivorous diet and cognitive restraint were directly related and (3) following an omnivorous diet had a greater tendency to cognitive restraint and an elevated body mass index. More research is necessary to further understand the complexity of the relationship between type of diet and unhealthy eating patterns in adults.
Canine Dilated Cardiomyopathy: Diffuse Remodeling, Focal Lesions, and the Involvement of Macrophages and New Vessel Formation

Dilated cardiomyopathy (DCM) is among the most common cardiac diseases in dogs. Its pathogenesis is not fully understood, but myocardial remodeling and inflammation are suspected to be involved. The present study aimed to characterize the pathological processes in canine DCM, investigating morphological changes in association with the expression of relevant cytokines and remodeling markers. The myocardium of 17 dogs with DCM and 6 dogs without cardiac diseases was histologically evaluated, and selected cases were further examined by immunohistochemistry, morphometry, and reverse transcription quantitative PCR. In DCM, the myocardium exhibited subtle but statistically significant diffuse quantitative changes. These comprised increased interstitial collagen deposition and macrophage numbers, as well as an overall reduced proportion of contractile tissue. This was accompanied by a significant increase in myocardial transcription of intracellular adhesion molecule (ICAM) 1, inflammatory cytokines, and remodeling enzymes. Laser microdissection showed that cardiomyocytes transcribed most relevant markers including ICAM-1, tumor necrosis factor α, transforming growth factor β (TGF-β), matrix metalloproteinase 2 (MMP-2), tissue inhibitor of MMP (TIMP) 1 and TIMP-2. In addition, there were multifocal cell-rich lesions characterized by fibrosis, neovascularization, macrophage infiltration, and cardiomyocyte degeneration. In these, macrophages were often found to express ICAM-1, TGF-β, and vascular endothelial growth factor; the former two were also expressed by cardiomyocytes. These results characterize the diffuse myocardial remodeling processes that occur in DCM. The observed multifocal cell-rich lesions might result from reduced tissue perfusion. Macrophages and cardiomyocytes seem to actively contribute to the remodeling processes, which ultimately lead to cardiac dilation and dysfunction. The precise role of the involved cells and the factors initiating the remodeling process still needs to be identified.
Psychological correlates of interest in genetic testing among Korean American adoptees and their parents

Adopted persons increasingly have turned to genetic testing to obtain health information or to search for birth family. The present study investigated psychological factors that may contribute to interest among adoptees and their parents in genetic testing for the adoptee, including adoptees' ethnic identity development, their thoughts or curiosity about birth family (birth family thoughts), and the interaction of these two factors. Data were drawn from the second wave of a longitudinal study, conducted in 2014, on transracially, transnationally adopted Korean American adolescents and their adoptive parents. In a sample of 106 adolescent–parent dyads, 2 adolescents (1.89%) had undergone genetic testing. Among the dyads in which adolescents had not sought genetic testing, 47.12% of adolescents and 43.27% of parents indicated interest in genetic testing for the adolescent adoptee. Adolescents' interest in genetic testing was independent from parents' interest. Neither adolescent psychological adjustment nor physical health was related to interest in genetic testing in either adolescents or parents. Adolescents' birth family thoughts were related to adolescents' interest in genetic testing, but not to parents' interest in genetic testing for their child. This study showed ethnic identity exploration and resolution moderated the relationship between birth family thoughts and adolescents' interest in genetic testing. Results point to the relevance of birth family thoughts and identity development to genetic testing in transnational and transracial adolescent adoptees.
Double‐faced implication of CD4+Foxp3+ regulatory T cells expanded by acute dengue infection via TLR2/MyD88 pathway

Dengue infection causes dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). CD4+Foxp3+ Tregs are expanded in patients during dengue infection, and appear to be associated with clinical severity. However, molecular pathways involved in Treg proliferation and the reason for their insufficient control of severe diseases are poorly understood. Here, dengue infection induced the proliferation of functional CD4+Foxp3+ Tregs via TLR2/MyD88 pathway. Surface TLR2 on Tregs was responsible for their proliferation, and dengue‐expanded Tregs subverted in vivo differentiation of effector CD8+ T cells. An additional interesting finding was that dengue‐infected hosts displayed changed levels of susceptibility to other diseases in TLR2‐dependent manner. This change included enhanced susceptibility to tumors and bacterial infection, but highly enhanced resistance to viral infection. Further, the transfer of dengue‐proliferated Tregs protected the recipients from dengue‐induced DHF/DSS and LPS‐induced sepsis. In contrast, dengue‐infected hosts were more susceptible to sepsis, an effect attributable to early TLR2‐dependent production of proinflammatory cytokines. These facts may explain the reason why in some patients, dengue‐proliferated Tregs is insufficient to control DF and DHF/DSS. Also, our observations lead to new insights into Treg responses activated by dengue infection in a TLR2‐dependent manner, which could differentially act on subsequent exposure to other disease‐producing situations.
Predictive value of prognostic nutritional index in patients with oral squamous cell carcinoma.

OBJECTIVES To determine the prognostic significance of preoperative prognostic nutritional index (PNI) in patients with primary oral squamous cell carcinoma (OSCC) after ablative surgery. MATERIALS AND METHODS A total of 333 patients from two tertiary referral centers were enrolled as training and validation cohorts. The PNI was calculated as 10× serum albumin (g/dL) + 0.005× total lymphocyte number (per mm3 ) and its optimal cutoff value for patient stratification was identified by X-tile software. Cox's proportional regression analyses and receiver operating characteristics (ROC) curves were employed to identify prognostic factors and their predictive performance. RESULTS The optimal cut-off value of PNI was 47.4. Patients with low PNI had significantly shorter overall (OS) and disease-free survival than those with high PNI. Moreover, multivariate regression analyses indicated that PNI was an independent prognostic factor for OS in the training (Hazard Ratio [HR], 2.267; 95% confidence interval [CI]:1.335-3.849; P=0.002) and validation (HR, 2.247; 95% CI: 1.352-3.735; P=0.002) cohorts. ROC analyses revealed similar or superior predictive performance of PNI as compared to other prognostic parameters. CONCLUSIONS Our findings reveal that decreased preoperative PNI significantly associates with worse prognosis for patients with OSCC, which serves as a novel prognostic biomarker for OSCC.
Federated Reinforcement Learning for Training Control Policies on Multiple IoT Devices

Reinforcement learning has recently been studied in various fields and also used to optimally control IoT devices supporting the expansion of Internet connection beyond the usual standard devices. In this paper, we try to allow multiple reinforcement learning agents to learn optimal control policy on their own IoT devices of the same type but with slightly different dynamics. For such multiple IoT devices, there is no guarantee that an agent who interacts only with one IoT device and learns the optimal control policy will also control another IoT device well. Therefore, we may need to apply independent reinforcement learning to each IoT device individually, which requires a costly or time-consuming effort. To solve this problem, we propose a new federated reinforcement learning architecture where each agent working on its independent IoT device shares their learning experience (i.e., the gradient of loss function) with each other, and transfers a mature policy model parameters into other agents. They accelerate its learning process by using mature parameters. We incorporate the actor–critic proximal policy optimization (Actor–Critic PPO) algorithm into each agent in the proposed collaborative architecture and propose an efficient procedure for the gradient sharing and the model transfer. Using multiple rotary inverted pendulum devices interconnected via a network switch, we demonstrate that the proposed federated reinforcement learning scheme can effectively facilitate the learning process for multiple IoT devices and that the learning speed can be faster if more agents are involved.
Prevalence of sexual experience among Korean adolescent: age-period-cohort analysis

OBJECTIVES Since exposure to sexual content and early sexual initiation among adolescents have become serious social issues in Korea, an in-depth analysis of trends in the prevalence of sexual experience among Korean adolescents is necessary to project the trends and policies required for the next 10 years. The objective of this study was to identify the contributions of age, period, and birth cohort effects on the prevalence of sexual experience in Korean adolescents. METHODS We analyzed age-specific, period-specific, and birth cohort–specific trends in the prevalence of sexual experience among 911,502 adolescents (469,593 boys, 51.5%; 441,909 girls, 48.5%) aged 12 years to 17 years from the 2006 to 2017 Korean Youth Risk Behavior Web-based Survey. Joinpoint regression analysis was conducted to examine significant changes in the prevalence of sexual experience and to find the optimal number and location of places where trends changed. RESULTS The prevalence of sexual experience generally increased with age in all periods in both boys and girls. In boys, the prevalence of sexual experience increased in recent periods, especially in the age group of 12-13 years, while the prevalence of sexual experience decreased in the age group of 16-17 years. In girls, the age group of 12-13 years showed an increased prevalence of sexual experience in recent periods. However, the prevalence showed a decreasing trend in the age group of 16-17 years. CONCLUSIONS In boys and girls, sexual experience increased with age, although this tendency has slowed in recent cohorts. Therefore, early sex education is needed.