Miracle-dz/UniFAR-FTUs huggingface dataset:
ExIt-OOS: Towards Learning from Planning in Imperfect Information Games

The current state of the art in playing many important perfect information games, including Chess and Go, combines planning and deep reinforcement learning with self-play. We extend this approach to imperfect information games and present ExIt-OOS, a novel approach to playing imperfect information games within the Expert Iteration framework and inspired by AlphaZero. We use Online Outcome Sampling, an online search algorithm for imperfect information games in place of MCTS. While training online, our neural strategy is used to improve the accuracy of playouts in OOS, allowing a learning and planning feedback loop for imperfect information games.
Prevalence of thermotolerant Campylobacter species in dogs and cats in Iran

Abstract Campylobacter is considered the most common bacterial cause of human gastroenteritis in the world with C. jejuni being regarded as the primary cause of bacterial gastroenteritis. A broad range of other Campylobacter species, including C. coli have also been implicated in human gastroenteritis. This study sought to isolate, characterize and assess the antibiogram of Campylobacter jejuni and C. coli from faecal samples obtained from cats and dogs in Isfahan and Shahrekord cities in Iran. Faecal samples were collected from 100 pets comprising of 50 dogs and 50 cats from March 2015 to March 2016; incorporating the four seasons (spring, summer, autumn and winter). Campylobacter spp. was isolated by culture, characterized by biochemical tests and confirmed by PCR‐based assays. Antimicrobial susceptibility test was performed by the Kirby–Bauer disk diffusion method, using Mueller Hinton agar. A total of 19 Campylobacter isolates among them two C. jejuni and one C. coli were recovered from dogs and cats’ faecal samples. The prevalence rates of Campylobacter spp. were 16.0% (8 out of 50) in dogs and 22.0% (11 out of 50) in cats. The highest (4 out of 16, 25%) Campylobacter spp. prevalence among dogs was reported in autumn and the lowest (1 out of 11, 9.1%) in spring, while among the cats, the highest (4 out of 12, 33.3%) Campylobacter spp. prevalence was reported in summer and lowest (1 out of 11, 9.09%) in spring. Campylobacter spp. isolated from faecal samples obtained from cats and dogs exhibited the most frequent antimicrobial resistance against tetracycline at 81.8% and 87.5%, respectively, compared to all other antimicrobial agents. These results show a low prevalence of Campylobacter spp. in faecal samples obtained from pet dogs and cats in Shahrekord and Isfahan cities in Iran. Given the relatively low prevalence of the C. jejuni and C. coli in pet dogs and cats in Isfahan and Shahrekord cities, it can be assumed that their importance as reservoirs for infection in humans is likely to be limited to the studied cities, but should not be neglected.
Integrative Brain Transcriptome Analysis Reveals Region-Specific and Broad Molecular Changes in Shank3-Overexpressing Mice

Variants of the SH3 and multiple ankyrin repeat domain 3 (SHANK3) gene, encoding excitatory postsynaptic core scaffolding proteins, are causally associated with numerous neurodevelopmental and neuropsychiatric disorders, including autism spectrum disorder (ASD), bipolar disorder, intellectual disability, and schizophrenia (SCZ). Although detailed synaptic changes of various Shank3 mutant mice have been well characterized, broader downstream molecular changes, including direct and indirect changes, remain largely unknown. To address this issue, we performed a transcriptome analysis of the medial prefrontal cortex (mPFC) of adult Shank3-overexpressing transgenic (TG) mice, using an RNA-sequencing approach. We also re-analyzed previously reported RNA-sequencing results of the striatum of adult Shank3 TG mice and of the prefrontal cortex of juvenile Shank3+/ΔC mice with a 50–70% reduction of Shank3 proteins. We found that several myelin-related genes were significantly downregulated specifically in the mPFC, but not in the striatum or hippocampus, of adult Shank3 TG mice by comparing the differentially expressed genes (DEGs) of the analyses side by side. Moreover, we also found nine common DEGs between the mPFC and striatum of Shank3 TG mice, among which we further characterized ASD- and SCZ-associated G protein-coupled receptor 85 (Gpr85), encoding an orphan Gpr interacting with PSD-95. Unlike the mPFC-specific decrease of myelin-related genes, we found that the mRNA levels of Gpr85 increased in multiple brain regions of adult Shank3 TG mice, whereas the mRNA levels of its family members, Gpr27 and Gpr173, decreased in the cortex and striatum. Intriguingly, in cultured neurons, the mRNA levels of Gpr27, Gpr85, and Gpr173 were modulated by the neuronal activity. Furthermore, exogenously expressed GPR85 was co-localized with PSD-95 and Shank3 in cultured neurons and negatively regulated the number of excitatory synapses, suggesting its potential role in homeostatic regulation of excitatory synapses in Shank3 TG neurons. Finally, we performed a gene set enrichment analysis of the RNA-sequencing results, which suggested that Shank3 could affect the directional expression pattern of numerous ribosome-related genes in a dosage-dependent manner. To sum up, these results reveal previously unidentified brain region-specific and broad molecular changes in Shank3-overexpressing mice, further elucidating the complexity of the molecular pathophysiology of SHANK3-associated brain disorders.
Foundation species enhance food web complexity through non-trophic facilitation

Food webs are an integral part of every ecosystem on the planet, yet understanding the mechanisms shaping these complex networks remains a major challenge. Recently, several studies suggested that non-trophic species interactions such as habitat modification and mutualisms can be important determinants of food web structure. However, it remains unclear whether these findings generalize across ecosystems, and whether non-trophic interactions affect food webs randomly, or affect specific trophic levels or functional groups. Here, we combine analyses of 58 food webs from seven terrestrial, freshwater and coastal systems to test (1) the general hypothesis that non-trophic facilitation by habitat-forming foundation species enhances food web complexity, and (2) whether these enhancements have either random or targeted effects on particular trophic levels, functional groups, and linkages throughout the food web. Our empirical results demonstrate that foundation species consistently enhance food web complexity in all seven ecosystems. Further analyses reveal that 15 out of 19 food web properties can be well-approximated by assuming that foundation species randomly facilitate species throughout the trophic network. However, basal species are less strongly, and carnivores are more strongly facilitated in foundation species' food webs than predicted based on random facilitation, resulting in a higher mean trophic level and a longer average chain length. Overall, we conclude that foundation species strongly enhance food web complexity through non-trophic facilitation of species across the entire trophic network. We therefore suggest that the structure and stability of food webs often depends critically on non-trophic facilitation by foundation species.
Predicting ICU mortality by supervised bidirectional LSTM networks

Mortality prediction in the Intensive Care Unit (ICU) is considered as one of critical steps for the treatment of patients in serious condition. It is a big challenge to model time-series variables for mortality prediction in ICU, because physiological variables such as heart rate and blood pressure are sampled with inconsistent time frequencies. In addition, it is difficult to capture the timing changes of clinical data and to interpret the prediction result of ICU mortality. To deal with these challenges, in this paper, we propose a novel ICU mortality prediction algorithm combining bidirectional LSTM (Long Short-Term Memory) model with supervised learning. First, we preprocess 37 time-series variables related to patients’ signs. Second, we construct the Bidirectional LSTM model with supervision technique to accurately reflect significant changes in patients’ signs. Finally, we train and evaluate our model using a real-world dataset containing 4,000 ICU patients. Experimental results show that our proposed method can significantly outperform many baseline methods.
Weight loss increases all-cause mortality in overweight or obese patients with diabetes

Background: Overweight and obese patients with diabetes are advised to lose weight to improve their health; however, recent studies have demonstrated that weight loss may be associated with worse long-term survival in patients with diabetes. This meta-analysis aimed to examine the relationships between weight loss and all-cause mortality in overweight or obese individuals with diabetes. Methods: We searched the PubMed and EMBASE databases from inception to February 2017. We included prospective studies that reported sufficient information to extract mortality-specific relative risks (RRs) with corresponding 95% confidence intervals (CIs). RRs with 95% CIs were pooled using a random-effects model. A subgroup analysis was also performed to explore sources of heterogeneity. Results: Of the 1652 studies identified, 8 met the inclusion criteria. A total of 18,887 patients were included in this analysis. We found that compared with a stable weight, weight loss was associated with an increased risk of all-cause mortality (RR, 1.15; 95% CI, 1.04 to 1.28) and cardiovascular disease (CVD) mortality (RR, 1.15; 95% CI, 1.02 to 1.29) in overweight or obese adults with diabetes, whereas intentional weight loss was not associated with changes in all-cause mortality (RR, 0.90; 95% CI, 0.67 to 1.22). Weight gain was not associated with changes in all-cause mortality (RR, 1.17; 95% CI, 0.87 to 1.58) or CVD mortality (RR, 0.97; 95% CI, 0.93 to 1.01). Compared with an initial body mass index (BMI) of 25 to 30 kg/m2, an initial BMI of >35 kg/m2 was associated with increased all-cause mortality (RR, 1.23; 95% CI, 1.01 to 1.50), which was further increased with an initial BMI of >40 kg/m2 (RR, 1.50; 95% CI, 1.16 to 1.94). Conclusion: Our results indicate that weight loss but not weight gain increased all-cause mortality and CVD mortality in overweight or obese adults with diabetes.
Plasma brain natriuretic peptide is a biomarker for screening ischemic cerebral small vessel disease in patients with hypertension

Abstract Plasma brain natriuretic peptide (BNP), a diagnostic marker of cardiovascular diseases, has been previously linked to cerebrovascular diseases. Our goal was to determine whether plasma BNP level is helpful for identifying high-risk individuals who are likely to present with the 3 main subtypes of cerebral small vessel diseases (CSVDs), namely, white matter lesions, lacunar infarcts, and cerebral microbleeds, on magnetic resonance imaging (MRI) in patients with hypertension. Three hundred forty-six consecutive hypertensive patients presenting at our cardiology or neurology clinic were investigated. Plasma BNP level was measured by chemiluminescent microparticle immunoassay. The presence of CSVD was assessed by 1.5-T brain MRI. Multivariate linear regression was used to determine whether individual or combined MRI-defined CSVD subtypes were associated with BNP level, after adjustment for several covariates. The mean age of patients was 69.1 ± 9.8 years, and 44.2% were female. The highest quartile BNP group was positively associated with advanced age, female sex, clinically manifesting cardiac diseases, and ischemic CSVD (white matter lesions and lacunar infarcts) and no association with cerebral microbleeds. According to multivariate linear regression, white matter lesions [&bgr; = 0.722; 95% confidence interval (95% CI), 0.624–0.819] and lacunar infarcts (&bgr; = 0.635; 95% CI, 0.508–0.762) were independently associated with BNP level, even after controlling for vascular risk factors and clinically manifesting cardiac diseases. Combined white matter lesions and lacunar infarcts were more strongly associated with BNP level than each subtype alone. With the cutoff value of 106.4 pg/mL, BNP level had a sensitivity, a specificity, and an area under the curve of 95.2%, 64.9%, and 0.799, respectively, for white matter lesions, whereas the values were 143.0 pg/mL, 81.6%, 73.5%, and 0.848, respectively, for lacunar infarcts. Plasma BNP level, which is independently correlated with individual or combined white matter lesions and lacunar infarcts, is a useful molecular marker for identifying ischemic CSVD in patients with hypertension.
Liver disease and mortality among patients with hip fracture: a population-based cohort study

Purpose The aim of this study was to examine the prognostic impact of liver disease on mortality following hip fracture (HF). Patients and methods This nationwide cohort study, based on prospectively collected data retrieved from Danish registries, included all patients diagnosed with incident HF in Denmark during 1996–2013. Patients were classified based on the coexisting liver disease at the time of HF, ie, no liver disease, noncirrhotic liver disease, and liver cirrhosis. We computed 30-day and 31–365-day mortality risks. To compare patients with and without liver disease, we computed mortality adjusted hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) using Cox regression controlled for potential confounders. Results Among 152,180 HF patients, 2,552 (1.7%) patients had noncirrhotic liver disease and 1,866 (1.2%) patients had liver cirrhosis. Thirty-day mortality was 9.4% among patients with noncirrhotic liver disease, 12.6% among patients with liver cirrhosis patients, and 9.7% among patients without liver disease. Compared to patients without liver disease, crude and adjusted HRs within 30 days following HF were, respectively, 0.96 (95% CI: 0.85–1.10) and 1.24 (95% CI: 1.09–1.41) for patients with noncirrhotic liver disease and 1.30 (95% CI: 1.14–1.48) and 2.25 (95% CI: 1.96–2.59) for those with liver cirrhosis. Among patients who survived 30 days post-HF, the 31–365-day mortality was 18.5% among patients with noncirrhotic liver disease, 26.4% among patients with liver cirrhosis, and 19.4% among patients without liver disease. Corresponding crude and adjusted HRs were, respectively, 0.95 (95% CI: 0.86–1.04) and 1.08 (95% CI: 0.99–1.20) for patients with noncirrhotic liver disease and 1.40 (95% CI: 1.27–1.54) and 1.91 (95% CI: 1.72–2.12) for those with liver cirrhosis. Conclusion Liver disease patients, especially those with liver cirrhosis, had increased 30-day mortality and 31–365-day mortality following HF, compared to patients without liver disease.
Ultrafast demagnetization in iron: Separating effects by their nonlinearity

The laser-driven ultrafast demagnetization effect is one of the long-standing problems in solid-state physics. The time scale is given not only by the transfer of energy, but also by the transport of angular momentum away from the spin system. Through a double-pulse experiment resembling two-dimensional spectroscopy, we separate the different pathways by their nonlinear properties. We find (a) that the loss of magnetization within 400 fs is not affected by the previous excitations (linear process), and (b) we observe a picosecond demagnetization contribution that is strongly affected by the previous excitations. Our experimental approach is useful not only for studying femtosecond spin dynamics, but can also be adapted to other problems in solid-state dynamics.
Dynamic brain network states in human generalized spike-wave discharges

Generalised spike-wave discharges (GSW) in idiopathic generalised epilepsy (IGE) appear to have abrupt onset on EEG. However, in rodent models, GSW emerge during evolving brain network states. Using EEG-fMRI, Tangwiriyasakul et al. reveal that GSW onset in human IGE, as in rodent models, emerges during evolving brain network states.
MiR-592 suppresses the development of glioma by regulating Rho-associated protein kinase

MicroRNAs are a class of small noncoding RNAs that regulate the translation of target mRNA transcripts. MiR-592 has been considered to play important roles in the initiation and progression of cancer by targeting various molecules in several human cancers, but its role in glioma has not been explored. This study aims to explore the suppressive mechanism of miR-592 in the regulation of glioma development, an effect that is crucial for the further exploration of miR-592 as a novel therapeutic target for glioma. Our results proved that the expression of miR-592 was lower and the expression of Rho-associated protein kinase (ROCK1) was higher in glioma tissue than in adjacent tissue and that lower miR-592 expression was associated negatively with ROCK1 expression. Then, we showed that miR-592 was downregulated in glioma and could suppress the growth of the glioma cell lines U87 and U251. ROCK1, which is a known oncogene, was identified as a direct target of miR-592. A luciferase reporter assay indicated that miR-592 regulates ROCK1 expression through binding to its 3′-UTR. Furthermore, our results showed that miR-592 targets the ROCK1 transcript and suppresses glioma cell growth and invasive growth, thereby providing a potential therapeutic target for glioma treatment.
The Prevalence of Orthostatic Hypotension: A Systematic Review and Meta-Analysis

Abstract Background Orthostatic hypotension (OH) is associated with increased risk of falls, cognitive impairment and death, as well as a reduced quality of life. Although it is presumed to be common in older people, estimates of its prevalence vary widely. This study aims to address this by pooling the results of epidemiological studies. Methods MEDLINE, EMBASE, PubMed, Web of Science, and ProQuest were searched. Studies were included if participants were more than 60 years, were set within the community or within long-term care and diagnosis was based on a postural drop in systolic blood pressure (BP) ≥20 mmHg or diastolic BP ≥10 mmHg. Data were extracted independently by two reviewers. Random and quality effects models were used for pooled analysis. Results Of 23,090 identified records, 20 studies were included for community-dwelling older people (n = 24,967) and six were included for older people in long-term settings (n = 2,694). There was substantial variation in methods used to identify OH with differing supine rest duration, frequency and timing of standing BP, measurement device, use of standing and tilt-tables and interpretation of the diagnostic drop in BP. The pooled prevalence of OH in community-dwelling older people was 22.2% (95% CI = 17, 28) and 23.9% (95% CI = 18.2, 30.1) in long-term settings. There was significant heterogeneity in both pooled results (I2 > 90%). Conclusions OH is very common, affecting one in five community-dwelling older people and almost one in four older people in long-term care. There is great variability in methods used to identify OH.
Comparative analysis of methods for evaluation of protein models against native structures

Motivation Measuring discrepancies between protein models and native structures is at the heart of development of protein structure prediction methods and comparison of their performance. A number of different evaluation methods have been developed; however, their comprehensive and unbiased comparison has not been performed. Results We carried out a comparative analysis of several popular model assessment methods (RMSD, TM‐score, GDT, QCS, CAD‐score, LDDT, SphereGrinder and RPF) to reveal their relative strengths and weaknesses. The analysis, performed on a large and diverse model set derived in the course of three latest community‐wide CASP experiments (CASP10‐12), had two major directions. First, we looked at general differences between the scores by analyzing distribution, correspondence and correlation of their values as well as differences in selecting best models. Second, we examined the score differences taking into account various structural properties of models (stereochemistry, hydrogen bonds, packing of domains and chain fragments, missing residues, protein length and secondary structure). Our results provide a solid basis for an informed selection of the most appropriate score or combination of scores depending on the task at hand. Supplementary information Supplementary data are available at Bioinformatics online.
Effect of Hybrid Kernel and Iterative Reconstruction on Objective and Subjective Analysis of Lung Nodule Calcification in Low-Dose Chest CT

Objective To evaluate the differences in subjective calcification detection rates and objective calcium volumes in lung nodules according to different reconstruction methods using hybrid kernel (FC13-H) and iterative reconstruction (IR). Materials and Methods Overall, 35 patients with small (< 4 mm) calcified pulmonary nodules on chest CT were included. Raw data were reconstructed using filtered back projection (FBP) or IR algorithm (AIDR-3D; Canon Medical Systems Corporation), with three types of reconstruction kernel: conventional lung kernel (FC55), FC13-H and conventional soft tissue kernel (FC13). The calcium volumes of pulmonary nodules were quantified using the modified Agatston scoring method. Two radiologists independently interpreted the role of each nodule calcification on the six types of reconstructed images (FC55/FBP, FC55/AIDR-3D, FC13-H/FBP, FC13-H/AIDR-3D, FC13/FBP, and FC13/AIDR-3D). Results Seventy-eight calcified nodules detected on FC55/FBP images were regarded as reference standards. The calcium detection rates of FC55/AIDR-3D, FC13-H/FBP, FC13-H/AIDR-3D, FC13/FBP, and FC13/AIDR-3D protocols were 80.7%, 15.4%, 6.4%, 52.6%, and 28.2%, respectively, and FC13-H/AIDR-3D showed the smallest calcium detection rate. The calcium volume varied significantly with reconstruction protocols and FC13/AIDR-3D showed the smallest calcium volume (0.04 ± 0.22 mm3), followed by FC13-H/AIDR-3D. Conclusion Hybrid kernel and IR influence subjective detection and objective measurement of calcium in lung nodules, particularly when both techniques (FC13-H/AIDR-3D) are combined.
Barrier Properties and Transcriptome Expression in Human iPSC‐Derived Models of the Blood–Brain Barrier

Cell‐based models of the blood–brain barrier (BBB) are important for increasing the knowledge of BBB formation, degradation and brain exposure of drug substances. Human models are preferred over animal models because of interspecies differences in BBB structure and function. However, access to human primary BBB tissue is limited and has shown degeneration of BBB functions in vitro. Human induced pluripotent stem cells (iPSCs) can be used to generate relevant cell types to model the BBB with human tissue. We generated a human iPSC‐derived model of the BBB that includes endothelial cells in coculture with pericytes, astrocytes and neurons. Evaluation of barrier properties showed that the endothelial cells in our coculture model have high transendothelial electrical resistance, functional efflux and ability to discriminate between CNS permeable and non‐permeable substances. Whole genome expression profiling revealed transcriptional changes that occur in coculture, including upregulation of tight junction proteins, such as claudins and neurotransmitter transporters. Pathway analysis implicated changes in the WNT, TNF, and PI3K‐Akt pathways upon coculture. Our data suggest that coculture of iPSC‐derived endothelial cells promotes barrier formation on a functional and transcriptional level. The information about gene expression changes in coculture can be used to further improve iPSC‐derived BBB models through selective pathway manipulation. Stem Cells 2018;36:1816–12