Miracle-dz/UniFAR-FTUs huggingface dataset:
Inhibition of SARS-CoV-2 main protease: a repurposing study that targets the dimer interface of the protein

Abstract Coronavirus disease-2019 (COVID-19) was firstly reported in Wuhan, China, towards the end of 2019, and emerged as a pandemic. The spread and lethality rates of the COVID-19 have ignited studies that focus on the development of therapeutics for either treatment or prophylaxis purposes. In parallel, drug repurposing studies have also come into prominence. Herein, we aimed at having a holistic understanding of conformational and dynamical changes induced by an experimentally characterized inhibitor on main protease (Mpro) which would enable the discovery of novel inhibitors. To this end, we performed molecular dynamics simulations using crystal structures of apo and α-ketoamide 13b-bound Mpro homodimer. Analysis of trajectories pertaining to apo Mpro revealed a new target site, which is located at the homodimer interface, next to the catalytic dyad. Thereafter, we performed ensemble-based virtual screening by exploiting the ZINC and DrugBank databases and identified three candidate molecules, namely eluxadoline, diosmin, and ZINC02948810 that could invoke local and global conformational rearrangements which were also elicited by α-ketoamide 13b on the catalytic dyad of Mpro. Furthermore, ZINC23881687 stably interacted with catalytically important residues Glu166 and Ser1 and the target site throughout the simulation. However, it gave positive binding energy, presumably, due to displaying higher flexibility that might dominate the entropic term, which is not included in the MM-PBSA method. Finally, ZINC20425029, whose mode of action was different, modulated dynamical properties of catalytically important residue, Ala285. As such, this study presents valuable findings that might be used in the development of novel therapeutics against Mpro. Communicated by Ramaswamy H. Sarma
Role of pH in the synthesis and growth of gold nanoparticles using L-asparagine: a combined experimental and simulation study

The use of biomolecules as capping and reducing agents in the synthesis of metallic nanoparticles constitutes a promising framework to achieve desired functional properties with minimal toxicity. The system’s complexity and the large number of variables involved represent a challenge for theoretical and experimental investigations aiming at devising precise synthesis protocols. In this work, we use L-asparagine (Asn), an amino acid building block of large biomolecular systems, to synthesise gold nanoparticles (AuNPs) in aqueous solution at controlled pH. The use of Asn offers a primary system that allows us to understand the role of biomolecules in synthesising metallic nanoparticles. Our results indicate that AuNPs synthesised in acidic (pH 6) and basic (pH 9) environments exhibit somewhat different morphologies. We investigate these AuNPs via Raman scattering experiments and classical molecular dynamics simulations of zwitterionic and anionic Asn states adsorbing on (111)-, (100)-, (110)-, and (311)-oriented gold surfaces. A combined analysis suggests that the underlying mechanism controlling AuNPs geometry correlates with amine’s preferential adsorption over ammonium groups, enhanced upon increasing pH. Our simulations reveal that Asn (both zwitterionic and anionic) adsorption on gold (111) is essentially different from adsorption on more open surfaces. Water molecules strongly interact with the gold face-centred-cubic lattice and create traps, on the more open surfaces, that prevent the Asn from diffusing. These results indicate that pH is a relevant parameter in green-synthesis protocols with the capability to control the nanoparticle’s geometry, and pave the way to computational studies exploring the effect of water monolayers on the adsorption of small molecules on wet gold surfaces.
In Vitro and In Vivo Antifungal Activity of AmBisome Compared to Conventional Amphotericin B and Fluconazole against Candida auris

Antifungal activity of AmBisome against Candida auris was determined in vitro and in vivo. AmBisome showed MIC50 and MIC90 values of 1 and 2 μg/ml, respectively. ABSTRACT Antifungal activity of AmBisome against Candida auris was determined in vitro and in vivo. AmBisome showed MIC50 and MIC90 values of 1 and 2 μg/ml, respectively. Unlike conventional amphotericin B, significant in vivo efficacy was observed in the AmBisome 7.5 mg/kg treatment group in survival and reduction of kidney tissue fungal burden compared to the untreated group. Our data show that AmBisome has significant antifungal activity against C. auris infection in vitro and in vivo.
Measurement of compensatory wrist joint rotation using three-dimensional motion analysis in patients with unilateral proximal congenital radioulnar synostosis.

OBJECTIVE This study aims to investigate compensatory rotational movements of the wrist joint in patients with proximal congenital radioulnar synostosis (CRUS), using a valid and reliable three-dimensional (3D) motion analysis technique. METHODS A total of 26 patients (6 females, 14 males; mean age=15.3 years; and age range=6-32 years) who were diagnosed with unilateral proximal CRUS but were not operated were enrolled in this study. Patients were then categorized into 2 groups: Group I included 5 patients younger than 10 years, and Group II included 15 patients older than 10 years. Eighteen light-reflective skin markers were placed on the bony landmarks of both upper limbs, and both distal forearms were fixed using a U-shaped device to minimize forearm rotation. Each patient grasped the handle of an instrument that used a goniometer to measure wrist rotation; maximal passive pronation and supination angles of the wrist were measured in this manner and also using 3D motion analysis. RESULTS There was a significant correlation between measurements by the goniometer and 3D motion analysis (r=0.985, p<0.001). The test-retest reliability of the 3D motion analysis was acceptable for both the affected side (ICC=0.992) and the contralateral normal side (ICC=0.997) with low standard measurement errors (1.3° and 0.8°, respectively). Although no significant difference was observed in the range of the wrist rotation between the affected and contralateral sides in Group I (p=0.686), there was a significant difference in the wrist rotation between the affected and contralateral sides in Group II (p=0.001). Further, the pronation angle of the wrist joint was significantly larger in the affected side than that in the contralateral normal side in Group II (p=0.001). CONCLUSION The 3D motion analysis technique seems to be a valid and reliable method to measure the rotation of the wrist joint. Unilateral proximal CRUS patients older than 10 years of age may develop rotational hypermobility of the wrist joint compared to the contralateral normal side as a compensatory phenomenon. LEVEL OF EVIDENCE Level III, Diagnostic Study.
Correction for Ozkan-Aydin et al., Collective dynamics in entangled worm and robot blobs

ENGINEERING, PHYSIOLOGY Correction for “Collective dynamics in entangled worm and robot blobs,” by Yasemin Ozkan-Aydin, Daniel I. Goldman, and M. Saad Bhamla, which was first published February 5, 2021; 10.1073/pnas.2010542118 (Proc. Natl. Acad. Sci. U.S.A. 118, e2010542118). The authors note that the following statement should be added to the Acknowledgments: “Funding to D.I. G. and Y.O. -A. was provided by NSF Division of Materials Research Grant 1933283, Army Research Office Multidisciplinary University Research Initiative Grant W911NF1910233, and the Dunn Family Professorship. ” Published under the PNAS license. Published April 12, 2021. www.pnas. org/cgi/doi/10.1073/pnas.2103670118
Assessment of medical morbidities in a rhesus monkey model of naturally occurring low sociality

People with autism spectrum disorder (ASD) exhibit a variety of medical morbidities at significantly higher rates than the general population. Using an established monkey model of naturally occurring low sociality, we investigated whether low‐social monkeys show an increased burden of medical morbidities compared to their high‐social counterparts. We systematically reviewed the medical records of N = 152 (n = 73 low‐social; n = 79 high‐social) rhesus macaques (Macaca mulatta) to assess the number of traumatic injury, gastrointestinal, and inflammatory events, as well as the presence of rare medical conditions. Subjects' nonsocial scores, determined by the frequency they were observed in a nonsocial state (i.e., alone), and macaque Social Responsiveness Scale‐Revised (mSRS‐R) scores were also used to test whether individual differences in social functioning were related to medical morbidity burden. Medical morbidity type significantly differed by group, such that low‐social monkeys incurred higher rates of traumatic injury compared to high‐social monkeys. Nonsocial scores and mSRS‐R scores also significantly and positively predicted traumatic injury rates, indicating that monkeys with the greatest social impairment were most impacted on this health measure. These findings from low‐social monkeys are consistent with well‐documented evidence that people with ASD incur a greater number of traumatic injuries and receive more peer bullying than their neurotypical peers, and add to growing evidence for the face validity of this primate model.
Classification of motor imagery using a time-localised approach

Abstract Brain–computer interface (BCI) is getting increasing attention where classification of motor imagery (MI) using electroencephalography (EEG) signal plays a vital role. In traditional EEG-based BCI setup, after applying pre-processing like band-pass filtering and spatial filtering, features are extracted and are fed to the classifier. However, most of the traditional features are extracted from a single time window, which is usually the full-time frame of a cue-based MI signal. Such features are usually statistical characteristics like log-variance of the whole-time signal. Thus, the information, which is localised in time and crucial for subject-specific MI classification, is not best captured. In this work, a new time-localised approach is proposed where multiple time windows are used for feature extraction. We have developed a number of feature representations using those time windows. Our experimental results corroborate that the proposed approach can achieve higher accuracy of classification when compared to methods using conventional features using the same platform.
TRB sequences targeting ORF1a/b are associated with disease severity in hospitalized COVID‐19 patients

The potential protective or pathogenic role of the adaptive immune response to SARS‐CoV‐2 infection has been vigorously debated. While COVID‐19 patients consistently generate a T lymphocyte response to SARS‐CoV‐2 antigens, evidence of significant immune dysregulation in these patients continues to accumulate. In this study, next generation sequencing of the T cell receptor beta chain (TRB) repertoire was conducted in hospitalized COVID‐19 patients to determine if immunogenetic differences of the TRB repertoire contribute to disease course severity. Clustering of highly similar TRB CDR3 amino acid sequences across COVID‐19 patients yielded 781 shared TRB sequences. The TRB sequences were then filtered for known associations with common diseases such as EBV and CMV. The remaining sequences were cross‐referenced to a publicly accessible dataset that mapped COVID‐19 specific TCRs to the SARS‐CoV‐2 genome. We identified 158 SARS‐CoV‐2 specific TRB sequences belonging to 134 clusters in our COVID‐19 patients. Next, we investigated 113 SARS‐CoV‐2 specific clusters binding only one peptide target in relation to disease course. Distinct skewing of SARS‐CoV‐2 specific TRB sequences toward the nonstructural proteins (NSPs) encoded within ORF1a/b of the SARS‐CoV‐2 genome was observed in clusters associated with critical disease course when compared to COVID‐19 clusters associated with a severe disease course. These data imply that T‐lymphocyte reactivity towards peptides from NSPs of SARS‐CoV‐2 may not constitute an effective adaptive immune response and thus may negatively affect disease severity.
Differences Between Pediatric Acute Myocarditis Related and Unrelated to SARS-CoV-2

Background: Acute myocarditis (AM) is defined as inflammation of the myocardium. The aim of our study is a comparative analysis of the differences between AM related and unrelated to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: The retrospective study included children with AM treated from January 2018 to November 2020. Results: The study included 24 patients; 7 of 24 had AM related to SARS-CoV-2 and they were older than 7. They were more likely to have abdominal pain (P = 0.014), headache (P = 0.003), cutaneous rash (P = 0.003), and conjunctivitis (P = 0.003), while fulminant myocarditis was commonly registered in AM unrelated to SARS-CoV-2 (P = 0.04). A multisystem inflammatory syndrome in children associated with COVID-19 was diagnosed in six adolescents. Patients with AM related SARS-CoV-2 had lower serum cardiac troponin I (cTnI) (P = 0.012), and platelets (P < 0.001), but had a higher C-reactive protein (CRP) value (P = 0.04), and N-terminal-pro hormone BNP in comparison to patients with AM unrelated to SARS-CoV-2. The patients with AM related to SARS-CoV-2 had significant reduction of CRP (P = 0.007). Inotropic drug support was used for shorter durations in patients with AM related to SARS-CoV-2, than in others (P = 0.02). Children with AM related to SARS-CoV-2 had significant improvement of left ventricle systolic function on the third day in hospital (P = 0.001). Patients with AM unrelated to SARS-CoV-2 AM had more frequent adverse outcomes (P = 0.04; three died and four dilated cardiomyopathy). Conclusions: In contrast to patients with AM unrelated to SARS-CoV-2, patients with AM related to SARS-CoV-2 had a higher CRP value, polymorphic clinical presentation, shorter durations of inotropic drugs use as well as prompt recovery of left ventricle systolic function.
DNA methylation status of SERPINA3 gene involved in mRNA expression in three cattle breeds

Abstract DNA methylation could take part in the gene expression and acts an important role in muscle development. In this study, DNA methylation and expression in adipose and muscle tissues were examined at the same time to evaluate the extent of epigenetic modifications and gene expression on the differentially methylated region (DMR) in SERPINA3. Chain reaction of bisulfite sequencing polymerase (BSP) was used to compared difference among DNA methylation patterns. The result of quantitative real-time PCR (qPCR) analysis showed that there was an extensive expression of SERPINA3 gene in tissue and there was a significant difference existing in muscle and adipose between Jiaxian cattle and individual of other breeds with increasing hybridization (p < 0.05). The statistic analyses indicated that DNA methylation patterns had a significant influence to the level of mRNA in tissue of fat and muscle. This study may be an important reference for investigating development of muscle tissue in cattle, and may promote the process of cattle molecular breeding.
Research on the economic loss of hospital-acquired pneumonia caused by Klebsiella pneumonia base on propensity score matching

Abstract Background: Hospital-acquired pneumonia (HAP) caused by Klebsiella pneumonia (KP) is a common nosocomial infection (NI). However, the reports on the economic burden of hospital-acquired pneumonia caused by Klebsiella pneumonia (KP-HAP) were scarce. The study aims to study the direct economic loss caused by KP-HAP with the method of propensity score matching (PSM) to provide a basis for the cost accounting of NI and provide references for the formulation of infection control measures. Methods: A retrospective investigation was conducted on the hospitalization information of all patients discharged from a tertiary group hospital in Shenzhen, Guangdong province, China, from June 2016 to August 2019. According to the inclusion and exclusion criteria, patients were divided into the HAP group and noninfection group, the extended-spectrum beta-lactamases (ESBLs) positive KP infection group, and the ESBLs-negative KP infection group. After the baselines of each group were balanced with the PSM, length of stay (LOS) and hospital cost of each group were compared. Results: After the PSM, there were no differences in the baselines of each group. Compared with the noninfection group, the median LOS in the KP-HAP group increased by 15 days (2.14 times), and the median hospital costs increased by 7329 yuan (0.89 times). Compared with the ESBLs-negative KP-HAP group, the median LOS in the ESBLs-positive KP-HAP group increased by 7.5 days (0.39 times), and the median hospital costs increased by 22,424 yuan (1.90 times). Conclusion: KP-HAP prolonged LOS and increased hospital costs, and HAP caused by ESBLs-positive KP had more economic losses than ESBLs-negative, which deserves our attention and should be controlled by practical measures.
Power Systems of Plasma Reactors for Non-Thermal Plasma Generation

Abstract Recently, many different plasma sources are being investigated for exhaust gases treatment, odor abatement, VOC removal, soil conditioning, surface decontamination or tissue disinfection and sterilization. Among many different plasma reactors investigated in laboratories, gliding arc discharges (GAD), dielectric barrier discharges (DBD), pulsed discharges (PD), atmospheric pressure glow discharges (APGD) and atmospheric pressure plasma jets (APPJ) seem to be the most promising for high pressure low temperature applications. They can be designed as multi-electrodes’ high power system that can be used in environment protection processes, like decontamination of large surfaces and treatment of large volume of polluted gases, as well as small size and low power devices for biomedical applications, like plasma healing, disinfection and sterilization. Paper presents review of power supply systems for cold plasma reactors. Dielectric Barrier Discharge (DBD), Gliding Arc Discharge (GAD) and atmospheric pressure plasma jet (APPJ) reactors with their supply systems have been discussed from the point view of their characteristics, possibility to control power to the discharge and efficiency. Taking into account the plasma reactor characteristics and nature (nonlinear resistive and/or capacitive) different solutions of power suppliers have been presented: transformer type, AC/DC/AC inverter, RF-frequency system and frequency resonant inverter.
Modulating Brain Rhythms of Pain using Transcranial Alternating Current Stimulation (tACS)? A Sham-controlled Study in Healthy Human Participants

Pain protects the body. However, pain can also occur for longer periods without serving protective functions. Such chronic pain conditions are difficult to treat. Thus, a better understanding of the underlying neural mechanisms and new approaches for the treatment of pain are urgently needed. Here, we investigated a causal role of oscillatory brain activity for pain and explored the potential of transcranial alternating current stimulation (tACS) as a new treatment approach for pain. To this end, we investigated whether tACS can modulate pain and pain-related autonomic activity in 29 healthy human participants using a tonic heat pain paradigm as an experimental model of chronic pain. In 6 recording sessions, participants received tACS over prefrontal or somatosensory cortices at alpha or gamma frequencies or sham tACS. During tACS, pain ratings and autonomic responses were collected. TACS did not modulate pain intensity, the stability of pain ratings or the translation of the noxious stimulus into pain. Likewise, tACS did not change autonomic responses. Bayesian statistics further indicated a lack of tACS effects in most conditions. The only exception was alpha tACS over somatosensory cortex where evidence for tACS effects was inconclusive. Taken together, the present study did not find significant tACS effects on tonic experimental pain in healthy human participants. However, considering the conceptual plausibility of using tACS to modulate pain and the urgent need for novel pain treatments, further tACS studies are warranted. Based on the present findings, such studies might apply refined stimulation protocols targeting alpha oscillations in somatosensory cortices.
Climate change and health in urban informal settlements in low- and middle-income countries – a scoping review of health impacts and adaptation strategies

ABSTRACT Background: Climate change affects human health with those with the least resources being most vulnerable. However, little is known about the impact of climate change on human health and effective adaptation methods in informal settlements in low- and middle-income countries. Objective: The objective of this scoping review was to identify, characterize, and summarize research evidence on the impact of climate change on human health in informal settlements and the available adaptation methods and interventions. Method: A scoping review was conducted using the Arksey and O’Malley framework. The four bibliographic databases PubMed, Web of Science, Embase, and the Cochrane library were searched. Eligibility criteria were all types of peer-reviewed publications reporting on climate change or related extreme weather events (as defined by the United Nations Framework Convention on Climate Change), informal settlements (as defined by UN-Habitat), low- and middle-income countries (as defined by the World Bank) and immediate human health impacts. Review selection and characterization were performed by two independent reviewers using a predefined form. Results: Out of 1197 studies initially identified, 15 articles were retained. We found nine original research articles, and six reviews, commentaries, and editorials. The articles were reporting on the exposures flooding, temperature changes and perceptions of climate change with health outcomes broadly categorized as mental health, communicable diseases, and non-communicable diseases. Six studies had a geographical focus on Asia, four on Africa, and one on South America, the remaining four articles had no geographical focus. One article investigated an adaptation method for heat exposure. Serval other adaptation methods were proposed, though they were not investigated by the articles in this review. Conclusion: There is a paucity of original research and solid study designs. Further studies are needed to improve the understanding of the impact, the most effective adaptation methods and to inform policy making.