Miracle-dz/UniFAR-FTUs huggingface dataset:
Off-Policy Reinforcement Learning for Synchronization in Multiagent Graphical Games

This paper develops an off-policy reinforcement learning (RL) algorithm to solve optimal synchronization of multiagent systems. This is accomplished by using the framework of graphical games. In contrast to traditional control protocols, which require complete knowledge of agent dynamics, the proposed off-policy RL algorithm is a model-free approach, in that it solves the optimal synchronization problem without knowing any knowledge of the agent dynamics. A prescribed control policy, called behavior policy, is applied to each agent to generate and collect data for learning. An off-policy Bellman equation is derived for each agent to learn the value function for the policy under evaluation, called target policy, and find an improved policy, simultaneously. Actor and critic neural networks along with least-square approach are employed to approximate target control policies and value functions using the data generated by applying prescribed behavior policies. Finally, an off-policy RL algorithm is presented that is implemented in real time and gives the approximate optimal control policy for each agent using only measured data. It is shown that the optimal distributed policies found by the proposed algorithm satisfy the global Nash equilibrium and synchronize all agents to the leader. Simulation results illustrate the effectiveness of the proposed method.
Modern management of lymphocyte predominant Hodgkin lymphoma

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) represents 5% of all Hodgkin lymphoma and has distinct clinico‐pathological features. It is typified by the presence of lymphocyte predominant cells, which are CD20+, CD15− and CD30− and are found scattered amongst small B‐lymphocytes arranged in a nodular pattern. Patients typically are males presenting with localized, peripheral lymphadenopathy. Despite frequent and often late or multiple relapses the prognosis is favourable. Deaths due to NLPHL are uncommon, but secondary malignancies and other treatment toxicities contribute appreciably to overall mortality. Secondary aggressive non‐Hodgkin lymphoma can occur in approximately 7–14% of cases of NLPHL. Given this diseases' rarity, the optimal management is unclear and opinions differ as to whether treatment paradigms should be similar to or differ from those for classical Hodgkin lymphoma. This review provides an overview of the existing literature describing of the outcome and treatment approaches for limited and advanced stage NLPHL.
Advances in the Management of Treatment-Resistant Depression.

Treatment-resistant depression (TRD) is a prevalent, disabling, and costly condition affecting 1%-4% of the U.S. POPULATION Current approaches to managing TRD include medication augmentation (with lithium, thyroid hormone, buspirone, atypical antipsychotics, or various antidepressant medications), psychotherapy, and ECT. Advances in understanding the neurobiology of mood regulation and depression have led to a number of new potential approaches to managing TRD, including medications with novel mechanisms of action and focal brain stimulation techniques. This review will define and discuss the epidemiology of TRD, review the current approaches to its management, and then provide an overview of several developing interventions.
Genotyping of Burkholderia mallei from an Outbreak of Glanders in Bahrain Suggests Multiple Introduction Events

Background Glanders, caused by the gram-negative bacterium Burkholderia mallei, is a highly infectious zoonotic disease of solipeds causing severe disease in animals and men. Although eradicated from many Western countries, it recently emerged in Asia, the Middle-East, Africa, and South America. Due to its rareness, little is known about outbreak dynamics of the disease and its epidemiology. Methodology/Principal Findings We investigated a recent outbreak of glanders in Bahrain by applying high resolution genotyping (multiple locus variable number of tandem repeats, MLVA) and comparative whole genome sequencing to B. mallei isolated from infected horses and a camel. These results were compared to samples obtained from an outbreak in the United Arab Emirates in 2004, and further placed into a broader phylogeographic context based on previously published B. mallei data. The samples from the outbreak in Bahrain separated into two distinct clusters, suggesting a complex epidemiological background and evidence for the involvement of multiple B. mallei strains. Additionally, the samples from Bahrain were more closely related to B. mallei isolated from horses in the United Arab Emirates in 2004 than other B. mallei which is suggestive of repeated importation to the region from similar geographic sources. Conclusion/Significance High-resolution genotyping and comparative whole genome analysis revealed the same phylogenetic patterns among our samples. The close relationship of the Dubai/UAE B. mallei populations to each other may be indicative of a similar geographic origin that has yet to be identified for the infecting strains. The recent emergence of glanders in combination with worldwide horse trading might pose a new risk for human infections.
GDF-15 as a Target and Biomarker for Diabetes and Cardiovascular Diseases: A Translational Prospective

Growth differentiation factor-15 (GDF-15) is a stress responsive cytokine. It is highly expressed in cardiomyocytes, adipocytes, macrophages, endothelial cells, and vascular smooth muscle cells in normal and pathological condition. GDF-15 increases during tissue injury and inflammatory states and is associated with cardiometabolic risk. Increased GDF-15 levels are associated with cardiovascular diseases such as hypertrophy, heart failure, atherosclerosis, endothelial dysfunction, obesity, insulin resistance, diabetes, and chronic kidney diseases in diabetes. Increased GDF-15 level is linked with the progression and prognosis of the disease condition. Age, smoking, and environmental factors are other risk factors that may increase GDF-15 level. Most of the scientific studies reported that GDF-15 plays a protective role in different tissues. However, few reports show that the deficiency of GDF-15 is beneficial against vascular injury and inflammation. GDF-15 protects heart, adipose tissue, and endothelial cells by inhibiting JNK (c-Jun N-terminal kinase), Bad (Bcl-2-associated death promoter), and EGFR (epidermal growth factor receptor) and activating Smad, eNOS, PI3K, and AKT signaling pathways. The present review describes the different animal and clinical studies and patent updates of GDF-15 in diabetes and cardiovascular diseases. It is a challenge for the scientific community to use GDF-15 information for patient monitoring, clinical decision-making, and replacement of current treatment strategies for diabetic and cardiovascular diseases.
Pharmacogenetic Study of Deferasirox, an Iron Chelating Agent

Transfusion-associated iron overload induces systemic toxicity. Deferasirox, a convenient long acting oral agent, has recently been introduced in clinical practice with a promising efficacy. But there are some patients who experience drug-related toxicities and cannot tolerate it. To investigate effect of genetic variations on the toxicities and find optimal target population, we analyzed the genetic polymorphisms of UDP-glucuronosyltransferase 1A (UGT1A) subfamily, multi-drug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). A total of 20 functional genetic polymorphisms were analyzed in 98 patients who received deferasirox to reduce transfusion-induced iron overload. We retrospectively reviewed the medical records to find out the drug-related toxicities. Fifteen (15.3%) patients developed hepatotoxicity. Patients without wild-type allele carrying two MRP2 haplotypes containing −1774 del and/or −24T were at increased risk of developing hepatotoxicity compared to patients with the wild-type allele on multivariate analysis (OR = 7.17, 95% CI = 1.79–28.67, P = 0.005). Creatinine elevation was observed in 9 patients (9.2%). Body weight ≥40 kg and homozygosity for UGT1A1*6 were risk factors of creatinine elevation (OR = 8.48, 95% CI = 1.7–43.57, P = 0.010 and OR = 14.17, 95% CI = 1.34–150.35, P = 0.028). Our results indicate that functional genetic variants of enzymes to metabolize and transport deferasirox are associated with drug-related toxicities. Further studies are warranted to confirm the results as the pharmacogenetic biomarkers of deferasirox.
Hypothalamic growth hormone secretagogue receptor regulates growth hormone secretion, feeding, and adiposity

Growth hormone secretagogues (GHSs) stimulate GH secretion and food intake. GHS receptor (GHS-R) mRNA has been identified mainly in the arcuate nucleus (Arc) and ventromedial nucleus of the hypothalamus and in the pituitary. Ghrelin, an endogenous ligand for GHS-R, has recently been purified from rat stomach. Although ghrelin is also expressed in the hypothalamus, the physiological significance of the ghrelin/GHS-R system is still unknown. We have created transgenic (Tg) rats expressing an antisense GHS-R mRNA under the control of the promoter for tyrosine hydroxylase (TH), thus selectively attenuating GHS-R protein expression in the Arc. Tg rats had lower body weight and less adipose tissue than did control rats. Daily food intake was reduced, and the stimulatory effect of GHS treatment on feeding was abolished in Tg rats. GH secretion and plasma insulin-like growth factor-I levels were reduced in female Tg rats. These results suggest that GHS-R in the Arc is involved in the regulation of GH secretion, food intake, and adiposity.
Wearable Biomedical Measurement Systems for Assessment of Mental Stress of Combatants in Real Time

The Spanish Ministry of Defense, through its Future Combatant program, has sought to develop technology aids with the aim of extending combatants' operational capabilities. Within this framework the ATREC project funded by the “Coincidente” program aims at analyzing diverse biometrics to assess by real time monitoring the stress levels of combatants. This project combines multidisciplinary disciplines and fields, including wearable instrumentation, textile technology, signal processing, pattern recognition and psychological analysis of the obtained information. In this work the ATREC project is described, including the different execution phases, the wearable biomedical measurement systems, the experimental setup, the biomedical signal analysis and speech processing performed. The preliminary results obtained from the data analysis collected during the first phase of the project are presented, indicating the good classification performance exhibited when using features obtained from electrocardiographic recordings and electrical bioimpedance measurements from the thorax. These results suggest that cardiac and respiration activity offer better biomarkers for assessment of stress than speech, galvanic skin response or skin temperature when recorded with wearable biomedical measurement systems.
Financial Valuation and Risk Management Working Paper No . 361 Risk Minimization in Stochastic Volatility Models : Model Risk and Empirical Performance

In this paper the performance of locally risk-minimizing hedge strategies for European options in stochastic volatility models is studied from an experimental as well as from an empirical perspective. These hedge strategies are derived for a large class of diffusion-type stochastic volatility models, and they are as easy to implement as usual delta hedges. Our simulation results on model risk show that the locally risk-minimizing hedges are robust with respect to uncertainty and even misconceptions about the underlying data generating process. The empirical study indicates that locally risk-minimizing hedge strategies consistently produce lower standard deviations of profit-and-loss-ratios than delta hedges (over different time periods as well as in different markets). The more skewed the market and the more out-of-the-money the option, the higher the benefit.
Apolipoprotein E polymorphisms are associated with ischemic stroke susceptibility in a Northwest China Han population

Ischemic stroke (IS), the leading neurology cause of death and disability worldwide, is influenced by gene polymorphisms. To explore the association between IS and Apolipoprotein E (APOE) gene polymorphisms, a case–control study containing 513 IS patients and 514 controls without IS was conducted in a Northwest China Han population. MassARRAY iPLEX system was applied to determine the APOE polymorphisms according to the alleles of two single nucleotide polymorphisms (SNPs) of APOE, rs429358, and rs7412. The results showed that rs429358 and rs7412 were in Hardy–Weinberg equilibrium (HWE) in both cases and controls groups. APOE ε4 allele, ε4/ε4 genotype, and ε4-containing genotypes were associated with IS. According to the results of Trial of ORG 10172 in Acute Stroke Treatment (TOAST) classification system, APOE ε2 allele, ε4 allele, and ε4/ε4 genotype were associated with large artery atherosclerosis IS subtypes. In addition, the results also indicated that the ε4 allele related to undetermined IS and ε4/ε4 genotype was related to small vessel disease IS. Compared with subjects with non-ε4-containing genotypes, the total cholesterol (TC) and low-density lipoprotein (LDL) level in blood and the proportion of cardiopath history were higher in all subjects with ε4-containing genotypes. Besides, the triacylglycerides (TG) level in blood was higher in controls with ε4-containing genotypes. In conclusion, in a Northwest China Han population, APOE ε4 allele was associated with blood lipid level. The TC and LDL levels were the independent risk factors for IS. APOE was a risk gene for IS, but not independent, especially for large artery atherosclerosis IS.
Efficacy of Distortion Correction on Diffusion Imaging: Comparison of FSL Eddy and Eddy_Correct Using 30 and 60 Directions Diffusion Encoding

Diffusion imaging is a unique noninvasive tool to detect brain white matter trajectory and integrity in vivo. However, this technique suffers from spatial distortion and signal pileup or dropout originating from local susceptibility gradients and eddy currents. Although there are several methods to mitigate these problems, most techniques can be applicable either to susceptibility or eddy-current induced distortion alone with a few exceptions. The present study compared the correction efficiency of FSL tools, “eddy_correct” and the combination of “eddy” and “topup” in terms of diffusion-derived fractional anisotropy (FA). The brain diffusion images were acquired from 10 healthy subjects using 30 and 60 directions encoding schemes based on the electrostatic repulsive forces. For the 30 directions encoding, 2 sets of diffusion images were acquired with the same parameters, except for the phase-encode blips which had opposing polarities along the anteroposterior direction. For the 60 directions encoding, non–diffusion-weighted and diffusion-weighted images were obtained with forward phase-encoding blips and non–diffusion-weighted images with the same parameter, except for the phase-encode blips, which had opposing polarities. FA images without and with distortion correction were compared in a voxel-wise manner with tract-based spatial statistics. We showed that images corrected with eddy and topup possessed higher FA values than images uncorrected and corrected with eddy_correct with trilinear (FSL default setting) or spline interpolation in most white matter skeletons, using both encoding schemes. Furthermore, the 60 directions encoding scheme was superior as measured by increased FA values to the 30 directions encoding scheme, despite comparable acquisition time. This study supports the combination of eddy and topup as a superior correction tool in diffusion imaging rather than the eddy_correct tool, especially with trilinear interpolation, using 60 directions encoding scheme.
Regression of cardiac hypertrophy in the SHR by combined renin-angiotensin system blockade and dietary sodium restriction

Altered operation of the renin-angiotensin-aldosterone system (RAAS) and dietary sodium intake have been identified as independent risk factors for cardiac hypertrophy. The way in which sodium intake and the operation of the renin-angiotensin-aldosterone system interact in the pathogenesis of cardiac hypertrophy is poorly understood. The aims of this study were to investigate the cardiac effects of the renin-angiotensin system (RAS) blockade in the spontaneously hypertensive rat (SHR), using co-treatment with an angiotensin II receptor blocker (ARB) and an angiotensin-converting enzyme (ACE) inhibitor with different sodium intakes. Our experiments with SHR show that, at high levels of sodium intake (4.0%), aggressive RAS blockade treatment with candesartan (3 mg/kg) and perindopril (6 mg/kg) does not result in regression of cardiac hypertrophy. In contrast, RAS blockade coupled with reduced sodium diet (0.2%) significantly regresses cardiac hypertrophy, impairs animal growth and is associated with elevated plasma renin and dramatically suppressed plasma angiotensinogen levels. Histological analyses indicate that the differential effect of reduced sodium on heart growth during RAS blockade is not associated with any change in myocardial interstitial collagen, but reflects modification of cellular geometry. Dimensional measurements of enzymatically-isolated ventricular myocytes show that, in the RAS blocked, reduced sodium group, myocyte length and width were decreased by about 16—19% compared with myocytes from the high sodium treatment group. Our findings highlight the importance of `titrating' sodium intake with combined RAS blockade in the clinical setting to optimise therapeutic benefit.
In Vitro investigating the antidiabetic activity of Rumex abyssinica, Hibiscus sabdariffa, and Cinnamomum zeylanicum

Background: Diabetes is a metabolic disorder symptomized by high blood glucose level.The treatment is associated with adverse side-effects regarding health and economic burdens of the diseased. The difficulty in insulin injection, the non-compliance, prolonged treatment, makes to the diabetic patients to have a poor controlled blood glucose level particularly in resource limited settings. As alternative, people are using medicinal plants as they are cheap, readily available, and lesser side effects. Even though the need for herbal medicine are culturally and socially accepted but the toxicity ,active principles, and mechanism of action are generally not known well so this study aims to investigate in vitro potential effects of Rumex abyssinica, Hibiscus sabdariffa, and Cinnamomum zeylanicum in glucose regulation. Methodology: Different parts from the 3 plants were subjected to hot Soxhlet extraction using solvents with different polarity. The in vitro anti-diabetic activity of the extracts was investigated by measuring their effect on assays of α-amylase inhibition and glucose transport across yeast cells. Result: The result of α-amylase inhibition reveled highest, significant (p0.001) from aqueous extracts (0.5 mg/ml) of Hibiscus sabdariffa and Rumex abyssinica by 85.11%, and 77.91% respectively.Though chloroform extract of Cinnamomum zeylanicum was not significant exhibited 92.49% α-amylase inhibition at 0.5 mg/ml. In the glucose transport assay, the aqueous extract (0.5 mg/ml) of Cinnamomum zeylanicum, Hibiscus sabdariffa, and Rumex abyssinica increased glucose transport across yeast cells by 52.44%, 52.16%, and 50.57% respectively, at 25mM glucose concentration. Conclusion: All the three selected medicinal plants were found to have an effective inhibition of α-amylase and glucose absorption by the aqueous extract. This shows that the plants extract contains an active water-soluble ingredients which may have anti-diabetic activity in vivo when taken in the form of tea. Therfore, we kindly recommend that , a further invivo, toxicological, phytochemical, and molecular analysis of these plants to be conducted in case control stdudies as it has been used as tea in the community.
In Silico Analysis of the Metabolic Potential and Niche Specialization of Candidate Phylum "Latescibacteria" (WS3)

The “Latescibacteria” (formerly WS3), member of the Fibrobacteres–Chlorobi–Bacteroidetes (FCB) superphylum, represents a ubiquitous candidate phylum found in terrestrial, aquatic, and marine ecosystems. Recently, single-cell amplified genomes (SAGs) representing the “Latescibacteria” were obtained from the anoxic monimolimnion layers of Sakinaw Lake (British Columbia, Canada), and anoxic sediments of a coastal lagoon (Etoliko lagoon, Western Greece). Here, we present a detailed in-silico analysis of the four SAGs to gain some insights on their metabolic potential and apparent ecological roles. Metabolic reconstruction suggests an anaerobic fermentative mode of metabolism, as well as the capability to degrade multiple polysaccharides and glycoproteins that represent integral components of green (Charophyta and Chlorophyta) and brown (Phaeophycaea) algae cell walls (pectin, alginate, ulvan, fucan, hydroxyproline-rich glycoproteins), storage molecules (starch and trehalose), and extracellular polymeric substances (EPSs). The analyzed SAGs also encode dedicated transporters for the uptake of produced sugars and amino acids/oligopeptides, as well as an extensive machinery for the catabolism of all transported sugars, including the production of a bacterial microcompartment (BMC) to sequester propionaldehyde, a toxic intermediate produced during fucose and rhamnose metabolism. Finally, genes for the formation of gas vesicles, flagella, type IV pili, and oxidative stress response were found, features that could aid in cellular association with algal detritus. Collectively, these results indicate that the analyzed “Latescibacteria” mediate the turnover of multiple complex organic polymers of algal origin that reach deeper anoxic/microoxic habitats in lakes and lagoons. The implications of such process on our understanding of niche specialization in microbial communities mediating organic carbon turnover in stratified water bodies are discussed.
Evolutionary engineering of a glycerol-3-phosphate dehydrogenase-negative, acetate-reducing Saccharomyces cerevisiae strain enables anaerobic growth at high glucose concentrations

Glycerol production by Saccharomyces cerevisiae, which is required for redox‐cofactor balancing in anaerobic cultures, causes yield reduction in industrial bioethanol production. Recently, glycerol formation in anaerobic S. cerevisiae cultures was eliminated by expressing Escherichia coli (acetylating) acetaldehyde dehydrogenase (encoded by mhpF) and simultaneously deleting the GPD1 and GPD2 genes encoding glycerol‐3‐phosphate dehydrogenase, thus coupling NADH reoxidation to reduction of acetate to ethanol. Gpd– strains are, however, sensitive to high sugar concentrations, which complicates industrial implementation of this metabolic engineering concept. In this study, laboratory evolution was used to improve osmotolerance of a Gpd– mhpF‐expressing S. cerevisiae strain. Serial batch cultivation at increasing osmotic pressure enabled isolation of an evolved strain that grew anaerobically at 1 M glucose, at a specific growth rate of 0.12 h−1. The evolved strain produced glycerol at low concentrations (0.64 ± 0.33 g l−1). However, these glycerol concentrations were below 10% of those observed with a Gpd+ reference strain. Consequently, the ethanol yield on sugar increased from 79% of the theoretical maximum in the reference strain to 92% for the evolved strains. Genetic analysis indicated that osmotolerance under aerobic conditions required a single dominant chromosomal mutation, and one further mutation in the plasmid‐borne mhpF gene for anaerobic growth.