Miracle-dz/UniFAR-FTUs huggingface dataset:
COVID19 Drug Repository: text-mining the literature in search of putative COVID19 therapeutics

Abstract The recent outbreak of COVID-19 has generated an enormous amount of Big Data. To date, the COVID-19 Open Research Dataset (CORD-19), lists ∼130,000 articles from the WHO COVID-19 database, PubMed Central, medRxiv, and bioRxiv, as collected by Semantic Scholar. According to LitCovid (11 August 2020), ∼40,300 COVID19-related articles are currently listed in PubMed. It has been shown in clinical settings that the analysis of past research results and the mining of available data can provide novel opportunities for the successful application of currently approved therapeutics and their combinations for the treatment of conditions caused by a novel SARS-CoV-2 infection. As such, effective responses to the pandemic require the development of efficient applications, methods and algorithms for data navigation, text-mining, clustering, classification, analysis, and reasoning. Thus, our COVID19 Drug Repository represents a modular platform for drug data navigation and analysis, with an emphasis on COVID-19-related information currently being reported. The COVID19 Drug Repository enables users to focus on different levels of complexity, starting from general information about (FDA-) approved drugs, PubMed references, clinical trials, recipes as well as the descriptions of molecular mechanisms of drugs’ action. Our COVID19 drug repository provide a most updated world-wide collection of drugs that has been repurposed for COVID19 treatments around the world.
Underlying mechanisms of oxygen uptake kinetics in chronic post-stroke individuals: A correlational, cross-sectional pilot study

Post-stroke individuals presented deleterious changes in skeletal muscle and in the cardiovascular system, which are related to reduced oxygen uptake (V˙O2) and take longer to produce energy from oxygen-dependent sources at the onset of exercise (mean response time, MTRON) and during post-exercise recovery (MRTOFF). However, to the best of our knowledge, no previous study has investigated the potential mechanisms related to V˙O2 kinetics response (MRTON and MRTOFF) in post-stroke populations. The main objective of this study was to determine whether the MTRON and MRTOFF are related to: 1) body composition; 2) arterial compliance; 3) endothelial function; and 4) hematological and inflammatory profiles in chronic post-stroke individuals. Data on oxygen uptake (V˙O2) were collected using a portable metabolic system (Oxycon Mobile®) during the six-minute walk test (6MWT). The time to achieve 63% of V˙O2 during a steady state (MTRON) and recovery (MRTOFF) were analyzed by the monoexponential model and corrected by a work rate (wMRTON and wMRTOFF) during 6MWT. Correlation analyses were made using Spearman’s rank correlation coefficient (rs) and the bias-corrected and accelerated bootstrap method was used to estimate the 95% confidence intervals. Twenty-four post-stroke participants who were physically inactive took part in the study. The wMRTOFF was correlated with the following: skeletal muscle mass (rs = -0.46), skeletal muscle mass index (rs = -0.45), augmentation index (rs = 0.44), augmentation index normalized to a heart rate of 75 bpm (rs = 0.64), reflection magnitude (rs = 0.43), erythrocyte (rs = -0.61), hemoglobin (rs = -0.54), hematocrit (rs = -0.52) and high-sensitivity C-reactive protein (rs = 0.58), all p < 0.05. A greater amount of oxygen uptake during post-walking recovery is partially related to lower skeletal muscle mass, greater arterial stiffness, reduced number of erythrocytes and higher systemic inflammation in post-stroke individuals.
Time-Restricted Eating Alters Food Intake Patterns, as Prospectively Documented by a Smartphone Application

Time-restricted eating (TRE) can facilitate weight loss, yet its effect on eating patterns remains unknown. Twenty adults with BMI ≥ 25 kg/m2 underwent a 12-week randomized trial, examining the effect of an 8-h, time-restricted eating intervention on dietary patterns. Oral intake was documented using a smartphone. Dietary patterns, assessed as frequency of eating occasions (EOs) and types of meals/snacks and beverages, were compared between baseline (T0), early-intervention (T1), and end-intervention (T2). At T1 and T2, both groups had less EOs compared to T0, with greater reduction seen in the TRE group (−28%) than the non-TRE group (−12%) at T2 (p = 0.01 vs. non-TRE). Comparing T1 to T0, the TRE group documented less incomplete meals (−32.5%: p = 0.02), high quality snacks (−23.6%: p = 0.03), and low quality snacks (−36.6%: p = 0.004). Comparing T2 to T0, the TRE group documented less incomplete meals (−33.9%: p = 0.03), high quality snacks (−28.1%: p < 0.001) and low quality snacks (−51.2%: p < 0.001). Caffeinated beverage intake was reduced in the TRE group at T1 (−20.2%) and T2 (−28.8%) vs. T0, but remained unaltered in the non-TRE group. By using a smartphone application to document dietary intake, TRE significantly reduced the number of EOs, snacks, and caffeinated beverages, relative to baseline and relative to the non-TRE.
Secondary structure determination of conserved SARS-CoV-2 RNA elements by NMR spectroscopy

Abstract The current pandemic situation caused by the Betacoronavirus SARS-CoV-2 (SCoV2) highlights the need for coordinated research to combat COVID-19. A particularly important aspect is the development of medication. In addition to viral proteins, structured RNA elements represent a potent alternative as drug targets. The search for drugs that target RNA requires their high-resolution structural characterization. Using nuclear magnetic resonance (NMR) spectroscopy, a worldwide consortium of NMR researchers aims to characterize potential RNA drug targets of SCoV2. Here, we report the characterization of 15 conserved RNA elements located at the 5′ end, the ribosomal frameshift segment and the 3′-untranslated region (3′-UTR) of the SCoV2 genome, their large-scale production and NMR-based secondary structure determination. The NMR data are corroborated with secondary structure probing by DMS footprinting experiments. The close agreement of NMR secondary structure determination of isolated RNA elements with DMS footprinting and NMR performed on larger RNA regions shows that the secondary structure elements fold independently. The NMR data reported here provide the basis for NMR investigations of RNA function, RNA interactions with viral and host proteins and screening campaigns to identify potential RNA binders for pharmaceutical intervention.
The Pyocin Regulator PrtR Regulates Virulence Expression of Pseudomonas aeruginosa by Modulation of Gac/Rsm System and c-di-GMP Signaling Pathway

In Pseudomonas aeruginosa, the second messenger cyclic-di-GMP and Gac/Rsm signaling pathways are associated with the transition from acute to chronic infection. Therefore, identification of the molecular mechanisms that govern lifestyle choice in bacteria is very important. ABSTRACT In Pseudomonas aeruginosa, the second messenger cyclic-di-GMP and Gac/Rsm signaling pathways are associated with the transition from acute to chronic infection. Therefore, identification of the molecular mechanisms that govern lifestyle choice in bacteria is very important. Here, we identified a novel cyclic-di-GMP modulator, PrtR, which was shown to repress pyocin production by inhibition of PrtN and activate the type III secretion system (T3SS) through PtrB. Compared to a wild-type strain or a prtN mutant, the prtR prtN double mutant exhibited a wrinkly colony and hyperbiofilm phenotype, as well as an increase in intracellular c-di-GMP levels. Interestingly, a diguanylate cyclase (DGC) gene, siaD, was repressed by PrtR. Further experiments revealed that PrtR directly interacts with SiaD and facilitates the accumulation of c-di-GMP in cells. We also demonstrated that PrtR regulates the activity of the Gac/Rsm system, thus affecting expression of the T3SS and type VI secretion system (T6SS) and the formation of biofilm. Taken together, the present findings indicate that PrtR, as a c-di-GMP modulator, plays key roles in the adaptation to opportunistic infection of P. aeruginosa. Additionally, this study revealed a novel mechanism for PrtR-mediated regulation of the lifestyle transition via the Gac/Rsm and c-di-GMP signaling networks.
Surface receptor‐mediated targeted drug delivery systems for enhanced cancer treatment: A state‐of‐the‐art review

Enhanced cancer treatment remains as one of the focused areas for researchers around the world. Hence, the progress in this direction will be a challenge and an opportunity in, inter‐disciplinary field to mitigate the suffering of millions in the upcoming decades. As we see, cancer death rate has also progressively increased despite the current impressive treatment regimens but also due to the non‐availability of vaccines and the re‐occurring of cancer in substantially recovered patients. Currently, numerous treatment strategies like surgical removal of solid tumors followed by radiation with a combination of immunotherapy/chemotherapy by the researchers and clinicians are routinely being followed. However, recurrence and distant metastasis often occur following radiation therapy, commonly due to the generation of radio‐resistance through deregulation of the cell cycle, cell death, and inhibition of DNA damage repair mechanisms. Thus, chemotherapeutic/immunotherapeutic treatment systems have progressed remarkably in the latest years owing to destroying tumors, noninvasive, and affordable charge of therapy. But, traditional chemotherapeutic approaches target the DNA of mutated and normal healthy cells, resulting in a significantly increased risk of toxicity and drug resistance. Thus, many receptors targeted therapies are in the developmental phase of discovery. Cancer cells have a specialized set of surface receptors that provide potential targets for cancer therapeutics. Cell surface receptor‐dependent endocytosis is well a known major mechanism for the internalization of macromolecular drugs. This review emphasizes the recent development of several surface receptors mediated cancer‐targeting approaches for the effective delivery of various therapeutic formulations.
Exertional Heat Stroke, Modality Cooling Rate, and Survival Outcomes: A Systematic Review

Background and Objectives: The purpose of this systematic review is to synthesize the influence cooling modality has on survival with and without medical complications from exertional heat stroke (EHS) in sport and military populations. Methods and Materials: All peer-reviewed case reports or series involving EHS patients were searched in the following online databases: PubMed, Scopus, SPORTDiscus, Medline, CINAHL, Academic Search Premier, and the Cochrane Library: Central Registry of Clinical Trials. Cooling methods were subdivided into “adequate” (>0.15 °C/min) versus “insufficient” (<0.15 °C/min) based on previously published literature on EHS cooling rates. Results: 613 articles were assessed for quality and inclusion in the review. Thirty-two case reports representing 521 EHS patients met the inclusion criteria. Four hundred ninety-eight (498) patients survived EHS (95.58%) and 23 (4.41%) patients succumbed to complications. Fischer’s Exact test on 2 × 2 contingency tables and relative risk ratios were calculated to determine if modality cooling rate was associated with patient outcomes. EHS patients that survived who were cooled with an insufficient cooling rate had a 4.57 times risk of medical complications compared to patients who were treated by adequate cooling methods, regardless of setting (RR = 4.57 (95%CI: 3.42, 6.28)). Conclusions: This is the largest EHS dataset yet compiled that analyzes the influence of cooling rate on patient outcomes. Zero patients died (0/521, 0.00%) when treatment included a modality with an adequate cooling rate. Conversely, 23 patients died (23/521, 4.41%) with insufficient cooling. One hundred seventeen patients (117/521, 22.46%) survived with medical complications when treatment involved an insufficient cooling rate, whereas, only four patients had complications (4/521, 0.77%) despite adequate cooling. Cooling rates >0.15 °C/min for EHS patients were significantly associated with surviving EHS without medical complications. In order to provide the best standard of care for EHS patients, an aggressive cooling rate >0.15 °C/min can maximize survival without medical complications after exercise-induced hyperthermia.
Multiomic analysis elucidates Complex I deficiency caused by a deep intronic variant in NDUFB10

The diagnosis of Mendelian disorders following uninformative exome and genome sequencing remains a challenging and often unmet need. Following uninformative exome and genome sequencing of a family quartet including two siblings with suspected mitochondrial disorder, RNA sequencing (RNAseq) was pursued in one sibling. Long‐read amplicon sequencing was used to determine and quantify transcript structure. Immunoblotting studies and quantitative proteomics were performed to demonstrate functional impact. Differential expression analysis of RNAseq data identified significantly decreased expression of the mitochondrial OXPHOS Complex I subunit NDUFB10 associated with a cryptic exon in intron 1 of NDUFB10, that included an in‐frame stop codon. The cryptic exon contained a rare intronic variant that was homozygous in both affected siblings. Immunoblot and quantitative proteomic analysis of fibroblasts revealed decreased abundance of Complex I subunits, providing evidence of isolated Complex I deficiency. Through multiomic analysis we present data implicating a deep intronic variant in NDUFB10 as the cause of mitochondrial disease in two individuals, providing further support of the gene‐disease association. This study highlights the importance of transcriptomic and proteomic analyses as complementary diagnostic tools in patients undergoing genome‐wide diagnostic evaluation.
An impedimetric assay for the identification of abnormal mitochondrial dynamics in living cells

Mitochondrial dynamics (fission and fusion) plays an important role in cell functions. Disruption in mitochondrial dynamics has been associated with diseases such as neurobiological disorders and cardiovascular diseases. Analysis of mitochondrial fission/fusion has been mostly achieved through direct visualization of the fission/fusion events in live‐cell imaging of fluorescently labeled mitochondria. In this study, we demonstrated a label‐free, non‐invasive Electrical Impedance Spectroscopy (EIS) approach to analyze mitochondrial dynamics in a genetically modified human neuroblastoma SH‐SY5Y cell line with no huntingtin protein expression. Huntingtin protein has been shown to regulate mitochondria dynamics. We performed EIS studies on normal SH‐SY5Y cells and two independent clones of huntingtin‐null cells. The impedance data was used to determine the suspension conductivity and further cytoplasmic conductivity and relate to the abnormal mitochondrial dynamics. For instance, the cytoplasm conductivity value was increased by 11% from huntingtin‐null cells to normal cells. Results of this study demonstrated that EIS is sensitive to characterize the abnormal mitochondrial dynamics that can be difficult to quantify by the conventional microscopic method.
Objective Blends of Multiple Ensemble-Mean NLDAS Drought Indices

Correspondence to: Youlong Xia, Environmental Modeling Center, NCEP/NOAA, College Park, Maryland; E-mail: youlong.xia@noaa.gov. Objective Blends of Multiple Ensemble-Mean NLDAS Drought Indices Youlong Xia, Michael Ek, Christa Peters-Lidard, David Mocko, Justin Sheffield, and Eric F. Wood Environmental Modeling Center (EMC), NCEP/NOAA/NWS, College Park, MD IMSG at NOAA/NCEP/EMC, College Park, MD Hydrological Sciences Laboratory, NASA/GSFC, Greenbelt, MD Department of Environmental and Civil Engineering, Princeton University, Princeton, NJ
Moderating Role of Dispositional Traits on Work-family Interface (WFI) and Marital Adjustment among Pakistani Employees

Personality has an important function in shaping responses towards marital life while managing work and family issues simultaneously. This research explores two personality dimensions: neuroticism and agreeableness as moderators in relation to both positive and negative aspects of the work-family interface and marital adjustment amongst industrial sector employees in Pakistan. Quantitative data were obtained from 345 (172 women and 173 men) dual-income, married employees, who were living with their dependent children and working in different manufacturing firms of Karachi city (Pakistan). This research put forward that agreeableness buffered and neuroticism exacerbated the impact of work-family interface on marital adjustment. Findings revealed that inter-role conflict negatively and inter-role integration positively envisaged marital adjustment of employees. Moreover, the employees who possess high degree of agreeableness were better in making adjustments in their marital life by integrating their work and family life together. The current study contributes towards the understanding of personal attributes as moderators between both aspects of work-family interface and marital adjustment among industrial employees in Pakistan.Gender-role identity denotes a major limitation for this research.
Detecting and Explaining Self-Admitted Technical Debts with Attention-based Neural Networks

Self-Admitted Technical Debt (SATD) is a sub-type of technical debt. It is introduced to represent such technical debts that are intentionally introduced by developers in the process of software development. While being able to gain short-term benefits, the introduction of SATDs often requires to be paid back later with a higher cost, e.g., introducing bugs to the software or increasing the complexity of the software. To cope with these issues, our community has proposed various machine learning-based approaches to detect SATDs. These approaches, however, are either not generic that usually require manual feature engineering efforts or do not provide promising means to explain the predicted outcomes. To that end, we propose to the community a novel approach, namely HATD (Hybrid Attention-based method for self-admitted Technical Debt detection), to detect and explain SATDs using attention-based neural networks. Through extensive experiments on 445,365 comments in 20 projects, we show that HATD is effective in detecting SATDs on both in-the-lab and in-the-wild datasets under both within-project and cross-project settings. HATD also outperforms the state-of-the-art approaches in detecting and explaining SATDs.
Mixtures of Probabilistic Principal Component Analysers

Let us formalize PCA in the following way. Given observed points {tn}, n ∈ {1 . N}, of dimension d, it aims at finding a number q < d of orthonormal axes (thus forming a linear subspace of dimension q < d) such that the variance of the projection of the observed vectors onto this subspace is maximal. The idea is that the directions along which the variance of the observed data is maximal are those which carry the most information about the individual observations, and should therefore be preserved as such to discriminate the observations. On the other hand, the directions along which the observed variance is minimal give little information about the individual observations: all observed vectors are ”roughly the same” along this direction, hence this axe rather gives information about the structure of the problem; this information can be stored in the form of the lower-dimensional linear subspace, and forgotten at the level of individual observations.
Time Consistent Equilibria in Dynamic Models With Recursive Payoffs and Behavioral Discounting

We prove existence of time consistent equilibria in a wide class of dynamic models with recursive payoffs and generalized discounting involving both behavioral and normative applications. Our generalized Bellman equation method identifies and separates both: recursive and strategic aspects of the equilibrium problem and allows to precisely determine the sufficient assumptions on preferences and stochastic transition to establish existence. In particular we show existence of minimal state space stationary Markov equilibrium (a time-consistent solution) in a deterministic model of consumption-saving with beta-delta discounting and its generalized versions involving magnitude effects, non-additive payoffs, semi-hyperbolic or hyperbolic discounting (over possibly unbounded state and unbounded above reward space). We also provide an equilibrium approximation method for a hyperbolic discounting model.
The state of the Organization of the Islamic Conference (OIC) at the dawn of the new millennium

An ever-increasing number of inter-governmental organizations (IGO) exist to promote political, defense, economic, and scientific cooperation among member states. The Organization of the Islamic Conference (OIC) is a unique IGO with the primary objective of promoting “Islamic solidarity” among the member states. A majority Muslim population qualifies a state for inclusion in this Organization, whose voluntary membership has more than doubled since its inception three decades ago. Yet, the processes related to globalization, the influences of nationalism, and the differences in the relative levels of social and economic development among member states often prevent deepening their cooperation in the 21 century. This study examines the state of the OIC at the end of the millennium. To assess levels of development and policy options for future cooperation, the OIC states were ranked on the basis of their composite development index scores. As expected, many of the states registering a high development index are the oil-exporters located in the Middle East, North Africa, and Southeast Asia. At the lower end of the spectrum are the majority of the least developed Islamic states in sub-Saharan Africa and South Asia. Successes and failures of the Organization and policy options are also discussed.
1 Association between Psychological Factors and 2 Evacuation Status and the Incidence of 3 Cardiovascular Diseases after the Great East Japan 4 Earthquake : A Prospective Study of the Fukushima 5 Health Management Survey 6

Evidence regarding the effect of psychological factors and evacuation on cardiovascular 33 disease occurrence after large-scale disasters is limited. This prospective study followed up a total 34 of 37,810 Japanese men and women aged 30–89 years from the Fukushima Prefecture with no 35 history of stroke or heart disease at baseline (2012), until 2017. This period included 3000 36 cardiovascular events recorded through questionnaires and death certificates. The participants’ 37 psychological distress, trauma reaction, and evacuation status were defined, and divided into four 38 groups based on combinations of psychological factors and evacuation status. We calculated the 39 hazard ratios and 95% confidence intervals for only psychological, only evacuation, or both of them 40 compared with neither using Cox proportional hazard models. Psychological factors along with 41 evacuation resulted in approximately 5% to 25% higher magnitude of stroke and heart disease risk 42 than psychological factors only among men. Compared to neither, the multivariable hazard ratios 43 of those with both psychological distress and evacuation were 1.75 for stroke and 1.49 for heart 44 disease, and those of both trauma reaction and evacuation were 2.01 and 1.57, respectively, among 45 men. Evacuation combined with psychological factors increased the risk of stroke and heart disease 46 risks especially in men after the Great East Japan Earthquake. 47 Preprints (www.preprints.org) | NOT PEER-REVIEWED | Posted: 16 September 2020 doi:10.20944/preprints202009.0339. v1 © 2020 by the author(s). Distributed under a Creative Commons CC BY license.