Miracle-dz/UniFAR-FTUs huggingface dataset:
Klotho alleviates chronic intermittent hypoxia-induced genioglossus myocyte apoptosis by inhibiting endoplasmic reticulum stress

Chronic intermittent hypoxia (CIH) has been shown to induce cell apoptosis in multiple organs of the human body. The present study aimed to assess the effects of exogenous klotho on CIH-induced genioglossus muscle injury, as well as the involvement of endoplasmic reticulum stress (ERS) in this process. A total of 36 adult C57BL/6 male mice were assigned to normoxia control (NC), CIH and CIH + klotho groups (n=12 mice/group). ELISA was performed to detect the level of klotho protein in the serum and in the genioglossus muscle tissue samples. Apoptosis was evaluated using the TUNEL assay. Reactive oxygen species (ROS) levels were quantified using a dihydroethidium assay kit, and the protein and mRNA levels of ERS-associated proteins (namely, glucoseregulated protein 78, C/EBP homologous protein, cleaved caspase-12 and cleaved caspase-3) in genioglossus samples were assessed using immunoblot assay and reverse transcription-quantitative PCR, respectively. Compared with the NC group, the quantities of klotho protein in the serum and genioglossus muscle tissue samples in the CIH group were significantly decreased, whereas the apoptotic rate, ROS levels and protein and mRNA levels of the ERS-associated proteins in the genioglossus muscle were significantly increased. Following supplementation with exogenous klotho protein, the klotho protein levels in the serum and genioglossus muscle tissue of mice were found to be markedly increased, and the apoptotic rate, ROS levels and protein and mRNA levels of the ERS-associated proteins in the genioglossus muscle were decreased compared with those in the CIH group. Taken together, the results of the present study have demonstrated that exogenous klotho may inhibit apoptosis of genioglossus myocytes in mice by inhibiting ROS-associated ERS.
Barriers and Facilitators of Community-Based Health Insurance Policy Renewal in Low- and Middle-Income Countries: A Systematic Review

Purpose A growing number of low- and middle-income countries are implementing small-scale community-based health insurance schemes to tackle the burdens posed by direct out-of-pocket payments. Apart from a few successful experiences, such schemes suffer from the problem of persistent low membership which could be attributed to either initial low enrollment or low renewal rate. However, there is a lack of comprehensive information on the factors that influence subscribers’ policy renewal decisions. Hence, we systematically synthesize information to answer the review question ”what are the barriers and facilitators of community-based health insurance policy renewal in low and middle-income countries? ”. Methods We searched PubMed, Scopus, and Hinari electronic databases in line with the PRISMA guidelines. Our search was limited to studies published from January 2005 to February 2020 in the English language. Additional studies and grey literature were searched using Google Scholar. We included quantitative, qualitative, and mixed-method studies in the review. We assessed the methodological quality of the studies using standardized appraisal tools. The findings were synthesized inductively using a thematic analysis approach. Results Our searches retrieved 2386 records among which 27 were included in the review. The thematic synthesis identified six major themes that influence the decision to renew scheme policy: socio-demographic factors; scheme-related awareness and understanding; participation in scheme and other voluntary groupings, need and benefit factors; health-care quality; and scheme operation and policy. Conclusion Lower socioeconomic status, poor quality of health care, lack of benefit from the scheme, lack of trust in scheme management, and dissatisfaction with scheme services are important barriers for community-based health insurance policy renewal. Better education, understanding the principles of the scheme, active participation in the scheme, and long-term illness experience of member households facilitate renewal decisions. These are important areas of intervention for governments and other relevant stakeholders to retain members and maintain the sustainability of the schemes. Registration The review protocol was registered in PROSPERO international prospective register of systematic reviews (ID = CRD42020168971).
Gene Polymorphism of MUC15, MMP14, BRAF, and COL1A1 Is Associated with Capsule Formation in Hepatocellular Carcinoma

Background The presence of a capsule is an important prognostic factor in hepatocellular carcinoma (HCC). Capsule formation is affected by tumor-host interaction, which may include collagen deposition and extracellular matrix (ECM) degradation. Purpose This study aimed to examine whether single-nucleotide polymorphisms (SNPs) in the genes for COL1A1 MUC15, MMP14, CD97, SMYD3, BRAF, and transforming growth factor beta 1 (TGF-β) are related to capsule formation. Methods We prospectively recruited and analyzed 185 patients with HCC with or without a capsule between 2019 and 2020. The SNPs involved were analyzed by polymerase chain reaction. Differences in the allele and genotype frequency between the cases and controls were evaluated using the chi-square test. Odds ratios and 95% confidence intervals were calculated by logistic regression analysis with adjustment for age and sex. Stratification analyses were also performed with preselected variables. Results The single-locus analysis showed that the presence of a capsule was significantly associated with five SNPs : MUC15 rs17309195 (P=0.01), rs12271124 (P= 0.02), rs10430847 (P=0.04), MMP14 rs17884816 (P=0.01), and BRAF rs74512895 (P=0.03). Adjusted logistic regression revealed that the decreased capsule formation was statistically significantly associated with BRAF rs76603725, COL1A1 rs2269336, and MUC15 rs17309195, while MMP14 rs17884816 and MUC15 rs10430847, rs2063278, and rs967490 were associated with increased capsule formation. The MUC15 block 2 haplotype was associated with increased capsule formation. Conclusions MUC15, MMP14, BRAF, and COL1A1 gene polymorphisms are associated with capsule formation in HCC. Studies involving larger samples are needed to confirm our results.
Acute Promyelocytic Leukemia: A Long-Term Retrospective Study in Mexico

Background The present retrospective study reviewed acute promyelocytic leukemia (APL) cases recorded in Mexico between January 2007 and January 2017. The primary objective of the study was to evaluate overall survival (OS) in Mexican patients with APL. Secondary objective was to evaluate the impact of induction treatment with different anthracyclines on OS, event-free survival (EFS) and complications in this patient population. Methods The medical charts of patients referred to medical institutions in Mexico from January 2007 through January 2017 for the treatment of suspected APL were reviewed retrospectively. Patients aged 15 - 75 years, in whom the diagnosis of APL was confirmed, who had an Eastern Cooperative Group performance status of 0 - 2, and who were eligible for combined treatment with intensive chemotherapy and all-trans retinoic acid (ATRA), were included in the study. Study participants received induction and consolidation treatment with ATRA plus either daunorubicin or idarubicin, followed by 2 years of single-agent ATRA as maintenance therapy. Patients who were unable to pay for ATRA treatment received anthracycline-based induction and consolidation, with methotrexate plus mercaptopurine as maintenance therapy. Results A total of 360 patients from 21 public and private hospitals were included in the study. The median age of the population was 37 years, and 51% were male. Of the 360 patients, 205 (57%) vs. 155 (43%) received daunorubicin vs. idarubicin as induction treatment for APL. ATRA was administered to 201 (98%) patients in the daunorubicin group vs. 138 (89%) in the idarubicin group (P = 0.001), and was initiated at diagnosis in 92% vs. 73% of recipients, respectively (P = 0.0001). At 150 months, OS and EFS for the entire population were 84% and 79%, respectively. Both OS (90% vs. 76%, P = 0.003) and EFS (85% vs. 72%, P = 0.001) were significantly prolonged in daunorubicin vs. idarubicin recipients. Rates of complications were similar in the two groups. Conclusions As arsenic trioxide (ATO) is not currently available in Mexico, anthracycline plus ATRA is the mainstay of treatment for APL here. Our results confirm the efficacy of this strategy, with high OS and EFS rates being observed 12.5 years after diagnosis.
Role of FoxO1 in regulating autophagy in type 2 diabetes mellitus (Review)

Type 2 diabetes mellitus (T2DM) is a major chronic disease that is characterized by pancreatic β-cell dysfunction and insulin resistance. Autophagy is a highly conserved intracellular recycling pathway and is involved in regulating intracellular homeostasis. Transcription factor Forkhead box O1 (FoxO1) also regulates fundamental cellular processes, including cell differentiation, metabolism and apoptosis, and proliferation to cellular stress. Increasing evidence suggest that autophagy and FoxO1 are involved in the pathogenesis of T2DM, including β-cell viability, apoptosis, insulin secretion and peripheral insulin resistance. Recent studies have demonstrated that FoxO1 improves insulin resistance by regulating target tissue autophagy. The present review summarizes current literature on the role of autophagy and FoxO1 in T2DM. The participation of FoxO1 in the development and occurrence of T2DM via autophagy is also discussed.
Do Certain Biomarkers Predict Adverse Outcomes in Coronavirus Disease 2019?

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Given the rapid spread of the disease, the World Health Organization (WHO) declared the 2019 - 2020 coronavirus outbreak a Public Health Emergency of International Concern (PHEIC) on January 30, 2020, and a pandemic on March 11, 2020. There have been several reports of the limited resources including the lack of intensive care unit (ICU) beds and mechanical ventilators. Thus, biomarkers that predict ICU stay and mortality will be an important tool to appropriately allocate the limited resources. The aim of this review was to identify laboratory markers that can effectively predict the risk of severe infection and increased mortality in COVID-19 cases. We conducted a systematic review of existing literature in six databases to evaluate the predictive value of various biomarkers. We used the keywords “COVID-19”, “SARS-CoV-2”, “Novel corona virus pneumonia”, “Biomarkers”, “Adverse outcomes”, “Mortality”, etc. among many others to refine our search. Several biomarkers were identified to be associated with adverse outcomes in the above studies. These biomarkers can be used as a tool to identify patients at increased risk for adverse outcomes so that the need for aggressive critical care in such patients is met.
The Effect of Tai Chi Chuan on Emotional Health: Potential Mechanisms and Prefrontal Cortex Hypothesis

Deep involvement in the negative mood over long periods of time likely results in emotional disturbances/disorders and poor mental health. Tai Chi Chuan (TCC) is regarded as a typical mind-body practice combining aerobic exercise and meditation to prevent and treat negative mood. Although there are an increasing number of TCC studies examining anxiety, depression, and mental stress, the mechanisms underlying these negative emotions are not fully understood. This review study examined TCC studies related to emotional health from both clinical patients and healthy individuals. Next, several potential mechanisms from physiological, psychological, and neurological perspectives were evaluated based on direct and indirect research evidence. We reviewed recent functional magnetic resonance imaging studies, which demonstrated changes in brain anatomy and function, mainly in the prefrontal cortex, following TCC practice. Finally, the effects of TCC on emotion/mental health is depicted with a prefrontal cortex hypothesis that proposed “an immune system of the mind” indicating the role of the prefrontal cortex as a flexible hub in regulating an individual's mental health. The prefrontal cortex is likely a key biomarker among the multiple complex neural correlates to help an individual manage negative emotions/mental health. Future research is needed to examine TCC effects on mental health by examining the relationship between the executive control system (mainly prefrontal cortex) and limbic network (including amygdala, insula, and hippocampal gyrus).
Cost-Effectiveness of Post-Autotransplant Lenalidomide in Persons with Multiple Myeloma

Considerable data indicate post-transplant lenalidomide prolongs progression-free survival and probably survival after an autotransplant for multiple myeloma (MM). However, optimal therapy duration is unknown, controversial and differs in the EU and US. We compared outcomes and cost-effectiveness of 3 post-transplant lenalidomide strategies in EU and US settings: (1) none; (2) until failure; and (3) 2-year fixed duration. We used a Markov decision model, which included six health states and informed by published data. The model estimated the lenalidomide strategy given to failure achieved 1.06 quality-adjusted life years (QALYs) at costs per QALY gained of €29,232 in the EU and $133,401 in the US settings. Two-year fixed-duration lenalidomide averted €7,286 per QALY gained in the EU setting and saved 0.84 QALYs at $60,835 per QALY gained in the US setting. These highly divergent costs per QALY in the EU and US settings resulted from significant differences in post-transplant lenalidomide costs and 2nd-line therapies driven by whether post-transplant failure was on or off-lenalidomide. In Monte Carlo simulation analyses which allowed us to account for the variability of inputs, 2-year fixedduration lenalidomide remained the preferred strategy for improving healthcare sustainability in the EU and US settings.
Psychological Impact of COVID-19, Isolation, and Quarantine: A Cross-Sectional Study

Purpose The COVID-19 pandemic has resulted in mandatory isolation and quarantine. The objective of this study was to describe and compare the psychological impacts of COVID-19 isolation and quarantine. Methods This was a cross-sectional retrospective study. Participants were Bahrainis aged >18 years who had undergone either isolation or quarantine. Eligible participants were identified from the COVID-19 contacts (quarantine) and cases (isolation) database of Bahrain. Validated questionnaires for self-reported depression (Center for Epidemiological Studies — depression [CES-D]), posttraumatic stress (Impact of Event Scale — revised [IES-R]), and perceived stigma (Stigma Scale [SS]) were administered. Results Mean CES-D, IES-R, and SS scores were 16.76±5.65, 13.50±14.67, and 25.29±7.99, respectively. In sum, 40% (205 of 502) of participants showed clinically significant depression, and <20% (98 of 502) had indications of some posttraumatic distress, with greater depression and distress in those isolated than those quarantined. Perceived stigma was reported by 53.4% (268 of 502) of participants, more prominent among those quarantined. Depression and posttraumatic stress scores were significantly higher in females, college students, those with a history of mental health conditions, knowing a COVID-19 fatality, and experiencing social conflict. Age was a significant variable correlated with all three scales, with younger participants indicating more distress, depression, and stigma. Duration of segregation was significantly correlated with CES-D, score showing more depressive symptoms as the duration of isolation increased. Significant predictors were age, sex, history of mental illness, and COVID-19 status. Conclusion Isolated and quarantined individuals reported depression, perceived stigma, and to a lesser extent distress. Psychological interventions identifying and targeting people with different-severity psychological burdens are in urgent need.
Current Advances in the Use of Nanophytomedicine Therapies for Human Cardiovascular Diseases

Abstract Considering the high prevalence of cardiovascular diseases (CVDs), the primary cause of death during the last several decades, it is necessary to develop proper strategies for the prevention and treatment of CVDs. Given the excessive side effects of current therapies, alternative therapeutic approaches like medicinal plants and natural products are preferred. Lower toxicity, chemical diversity, cost-effectiveness, and proven therapeutic potentials make natural products superior compared to other products. Nanoformulation methods improve the solubility, bioavailability, circulation time, surface area-to-volume ratio, systemic adverse side effects, and drug delivery efficiency of these medications. This study intended to review the functionality of the most recent nanoformulated medicinal plants and/or natural products against various cardiovascular conditions such as hypertension, atherosclerosis, thrombosis, and myocardial infarction. Literature review revealed that curcumin, quercetin, and resveratrol were the most applied natural products, respectively. Combination therapy, conjugation, or fabrication of nanoparticles and nanocarriers improved the applications and therapeutic efficacy of herbal- or natural-based nanoformulations. In the context of CVDs prevention and/or treatment, available data suggest that natural-based nanoformulations are considerably efficient, alone or in blend with other herbal/synthetic medicines. However, clinical trials are mandatory to elucidate the safety, cardioprotective effect, and mechanism of actions of nanophytomedicines.
A series of pyrimidine based blue to green thermally activated delayed fluorescent emitters realizing a high EQE of 25%

Here, we developed a series of pyrimidine-based TADF emitters, 2-functionalized-4,6-bis[4-(9,9-dimethyl-9,10- dihydroacridine)phenyl]pyrimidine called Ac–RPM. We introduced a phenylacridine moiety into the 4,6-position of pyrimidine core to induce a twisted structure leading to a high PLQY of ~80%, and a small singlet and triplet excited energy difference of <0.20 eV. The optimized device realized a power efficiency of 62 lm W−1, a high EQEmax of 25%, light-blue emissions with the Commission Internationale de l’Eclairage chromaticity (CIE) coordinates of (0.19, 0.37) and a low turn-on voltage of <3.0 V. Further, we investigated the strucutre–property relationship to unlock the potential of pyrimidine-based emitter. Consequently, we developed a green emitter realizing a power efficiency of over 110 lm W−1 while maintaining extremely low voltages of 2.2 V at 1 cd m−2 and 3.0 V at 1000 cd m−2 at CIE of (0.36, 0.58). Apparently, these performances exceed those of previous TADF devices and are comparable to those of their state-of-the-art phosphorescent devices.
Quasinormal modes of dS and AdS black holes: Feedforward neural network method

In this paper, we show how the quasinormal modes (QNMs) arise from the perturbations of massive scalar fields propagating in the curved background by using the artificial neural networks. To this end, we architect a special algorithm for the feedforward neural network method (FNNM) to compute the QNMs complying with the certain types of boundary conditions. To test the reliability of the method, we consider two black hole spacetimes whose QNMs are well known: [Formula: see text] pure de Sitter (dS) and five-dimensional Schwarzschild anti-de Sitter (AdS) black holes. Using the FNNM, the QNMs of are computed numerically. It is shown that the obtained QNMs via the FNNM are in good agreement with their former QNM results resulting from the other methods. Therefore, our method of finding the QNMs can be used for other curved spacetimes that obey the same boundary conditions.
Effects of renormalization and non-Hermiticity on nonlinear responses in strongly correlated electron systems

Nonlinear responses in condensed matter are intensively studied because they provide rich information about the materials and hold the possibility of being applied in diodes or high-frequency optical devices. While nonlinear responses in noninteracting models have been explored widely, the eﬀect of strong correlations on the nonlinear response is still poorly understood, even though it has been suggested that correlations can enhance the nonlinear response. In this work, we ﬁrst give an analytical derivation of nonlinear responses using Green’s function methods at ﬁnite temperature. Then, we discuss the diﬃculties of considering dissipation using conventional methods, such as the reduced density matrix method. We reveal that the relaxation time approximation leads to severe limitations when considering optical responses. Finally, we demonstrate that correlation eﬀects, such as the renormalization of the band structure and diﬀerent lifetimes in orbitals or sublattices, can signiﬁcantly enhance nonlinear responses and even change the sign of the nonlinear conductivity.
Approximation and Convergence of Large Atomic Congestion Games

We consider the question of whether and in what sense, Wardrop equilibria provide a good approximation for Nash equilibria in atomic unsplittable congestion games with a large number of small players. We examine two different definitions of small players. In the first setting, we consider games in which each player’s weight is small. We prove that when the number of players goes to infinity and their weights to zero, the random flows in all (mixed) Nash equilibria for the finite games converge in distribution to the set of Wardrop equilibria of the corresponding nonatomic limit game. In the second setting, we consider an increasing number of players with a unit weight that participate in the game with a decreasingly small probability. In this case, the Nash equilibrium flows converge in total variation toward Poisson random variables whose expected values are Wardrop equilibria of a different nonatomic game with suitably defined costs. The latter can be viewed as symmetric equilibria in a Poisson game in the sense of Myerson, establishing a plausible connection between the Wardrop model for routing games and the stochastic fluctuations observed in real traffic. In both settings, we provide explicit approximation bounds, and we study the convergence of the price of anarchy. Beyond the case of congestion games, we prove a general result on the convergence of large games with random players toward Poisson games.
Fusion 360 gallery

Parametric computer-aided design (CAD) is a standard paradigm used to design manufactured objects, where a 3D shape is represented as a program supported by the CAD software. Despite the pervasiveness of parametric CAD and a growing interest from the research community, currently there does not exist a dataset of realistic CAD models in a concise programmatic form. In this paper we present the Fusion 360 Gallery, consisting of a simple language with just the sketch and extrude modeling operations, and a dataset of 8,625 human design sequences expressed in this language. We also present an interactive environment called the Fusion 360 Gym, which exposes the sequential construction of a CAD program as a Markov decision process, making it amendable to machine learning approaches. As a use case for our dataset and environment, we define the CAD reconstruction task of recovering a CAD program from a target geometry. We report results of applying state-of-the-art methods of program synthesis with neurally guided search on this task.