Miracle-dz/UniFAR-FTUs huggingface dataset:
The iminosugars celgosivir, castanospermine and UV-4 inhibit SARS-CoV-2 replication

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses an unprecedented challenge for healthcare and the global economy. Repurposing drugs that have shown promise in inhibiting other viral infections could allow for more rapid dispensation of urgently needed therapeutics. The Spike protein of SARS-CoV-2 is extensively glycosylated with 22 occupied N glycan sites and is required for viral entry. In other glycosylated viral proteins, glycosylation is required for interaction with calnexin and chaperone-mediated folding in the endoplasmic reticulum, and prevention of this interaction leads to unfolded viral proteins and thus inhibits viral replication. As such, we investigated two iminosugars, celgosivir, a pro-drug of castanospermine, and UV-4, or N-(9-methoxynonyl)-1-deoxynojirimycin, a deoxynojirimycin derivative. Iminosugars are known inhibitors of the α-glucosidase I and II enzymes and were effective at inhibiting authentic SARS-CoV-2 viral replication in a cell culture system. Celgosivir prevented SARS-CoV-2-induced cell death and reduced viral replication and Spike protein levels in a dose-dependent manner in culture with Vero E6 cells. Castanospermine, the active form of celgosivir, was also able to inhibit SARS-CoV-2, confirming the canonical castanospermine mechanism of action of celgosivir. The monocyclic UV-4 also prevented SARS-CoV-2-induced death and reduced viral replication after 24 hours of treatment, although the reduction in viral copies was lost after 48 hours. Our findings suggest that iminosugars should be urgently investigated as potential SARS-CoV-2 inhibitors.
Short-time Effects of Malathion Pesticide on Functional and Histological Changes of Liver and Kidney in Female Mice.

BACKGROUND AND OBJECTIVE The malathion is one of the most important organophosphorus pesticides used in Iraq. The present study was designed to investigate the short-time effects of the malathion on the biochemical parameters of AST, ALT, ALP, urea, creatinine, total cholesterol, triglycerides and total protein as well as histological changes of the liver and kidneys of female laboratory mice for an interval of 6 days. MATERIALS AND METHODS The animals were divided into 3 groups, each group included 8 mice. They were injected with the pesticide in the intraperitoneal region. The 1st group (the control group) was injected with 0.1 mL of distilled water, the 2nd group (the low dose group) was injected with 0.1 mL of the pesticide solution at 3 mg/body weight while the 3rd group (the high dose group) was injected with 0.1 mL of the pesticide solution at a concentration of 6 mg/body weight. RESULTS The biochemical tests of the liver and kidney showed significant elevation in serum AST, urea, creatinine and cholesterol concentrations in mice compared to control group (p<0.05). In addition, the results showed a significant decrease in the ALP, triglycerides and the total protein in serum of the treated mice. Also, the results of histological sections of the liver and kidneys included congestion, necrosis, degeneration of cytoplasm, blood congestion, apoptosis, bleeding and sloughing of epithelial cells to the renal tubular lumen. CONCLUSION Finally, the results indicated that malathion pesticide has the ability to induce hepatic and renal toxicity in mice within 6 days.
Factors inducing transdifferentiation of myoblasts into adipocytes

Fat infiltration in skeletal muscle is observed in several myopathies, is associated with muscular dysfunction, and is strongly correlated with insulin resistance, diabetes, obesity, and aging. In animal production, skeletal muscle fat (also known as intermuscular and intramuscular fat) is positively related to meat quality including tenderness, flavor, and juiciness. Thus, understanding the cell origin and regulation mechanism of skeletal muscle fat infiltration is important for developing therapies against human myopathies as well as for improving meat quality. Notably, age, sarcopenia, oxidative stress, injury, and regeneration can activate adipogenic differentiation potential in myoblasts and affect fat accumulation in skeletal muscle. In addition, several transcriptional and nutritional factors can directly induce transdifferentiation of myoblasts into adipocytes. In this review, we focused on the recent progress in understanding the muscle‐to‐adipocyte differentiation and summarized and discussed the genetic, nutritional, and physiological factors that can induce transdifferentiation of myoblasts into adipocytes. Moreover, the regulatory roles and mechanisms of these factors during the transdifferentiation process were also discussed.
Salivary Cortisol Levels Are Associated with Craving and Cognitive Performance in Cocaine-Abstinent Subjects: A Pilot Study

Cortisol is a glucocorticoid hormone secreted by the adrenal cortex upon the activation of the hypothalamic-pituitary-adrenal (HPA) axis. Assessment of cortisol in saliva has emerged as a reliable way of evaluating HPA function. We examined the relationships between salivary cortisol levels with both craving and cognitive performance, as a possible biomarker of cocaine addiction. Cognitive performance (attention, declarative and working memory, executive functions and recognition of emotions) was assessed in 14 abstinent cocaine-dependent subjects in outpatient treatment and 13 control participants. Three salivary samples were collected at home by all the participants in the morning, afternoon and at bedtime. Patients showed higher levels of cortisol in the morning, as well as higher area under the curve with respect to the ground (AUCg). Regarding cognitive performance, cocaine-abstinent subjects showed worse performance in attention (d2 test), verbal memory (Spanish Complementary Verbal Learning Test, TAVEC) and executive tests (Tower of Hanoi and phonological fluency test) with respect to the control group. Morning cortisol levels and the AUCg index were negatively associated with the age of onset of drug consumption and the AUCg index was also positively associated with craving in our patients’ group. Moreover, morning cortisol levels, as well as the AUCg index, were negatively associated with verbal memory performance. Therefore, our pilot study suggests that salivary cortisol measurements could be a good avenue to predict craving level, as well as cognitive status, especially the declarative memory domain.
Cellular Prion Protein (PrPc): Putative Interacting Partners and Consequences of the Interaction

Cellular prion protein (PrPc) is a small glycosylphosphatidylinositol (GPI) anchored protein most abundantly found in the outer leaflet of the plasma membrane (PM) in the central nervous system (CNS). PrPc misfolding causes neurodegenerative prion diseases in the CNS. PrPc interacts with a wide range of protein partners because of the intrinsically disordered nature of the protein’s N-terminus. Numerous studies have attempted to decipher the physiological role of the prion protein by searching for proteins which interact with PrPc. Biochemical characteristics and biological functions both appear to be affected by interacting protein partners. The key challenge in identifying a potential interacting partner is to demonstrate that binding to a specific ligand is necessary for cellular physiological function or malfunction. In this review, we have summarized the intracellular and extracellular interacting partners of PrPc and potential consequences of their binding. We also briefly describe prion disease-related mutations at the end of this review.
Long-term occurrence of Fasciola hepatica in an alpine ecosystem, Pyrenees, Northeastern Spain.

Fasciola hepatica is a liver parasite of ruminants whose distribution is determined by its intermediate host, the freshwater snail Galba truncatula. In Europe, F. hepatica is mostly associated with lowlands. Infection from sympatric domestic reservoirs is rarely reported in wild mountain ungulates. This study explores F. hepatica in a multi-host system in a European alpine area. Serum samples (n=1209) from Pyrenean chamois (Rupicapra p. pyrenaica), European mouflon (Ovis aries musimon), domestic sheep (Ovis aries) and domestic cattle (Bos taurus) were collected in the National Game Reserve of Freser-Setcases (NGRFS) in Catalonia, Northeastern Spain, from 2008 to 2019, and tested for antibodies against F. hepatica. During the same period, the livers of 214 chamois hunted in the NGRFS were inspected for F. hepatica and associated pathological changes. Finally, 907 freshwater snails were collected in summer 2016 between 1559 and 2224 meters above sea level (asl) in the NGRFS, and F. hepatica DNA sought by PCR. Antibodies against F. hepatica were detected in all four species, with a higher prevalence in cattle and sheep than in chamois. Fasciola hepatica and hepatic lesions were concurrently observed in 13/214 of the chamois livers inspected (6.1%, CI95 2.9-9.3%). Fasciola hepatica DNA was detected in one out of the 907 snails (0.1%, Cl95 0.1 - 0.3%; Ct value 33.3), collected at 2054 m asl. Fasciola hepatica was consistently detected in a high mountain multi-host system, suggesting that its life cycle is completed and that it occurs endemically at the highest elevation reported in Europe. Transhumant livestock are the likely source in this alpine ecosystem, which according to rare occurrence of F. hepatica DNA in G. truncatula is still a suboptimal habitat for F. hepatica life cycle. Studying parasites at their highest distribution range can be useful to monitor climate change in seasonal mountain environments.
One model to rule them all in network science?

If you have ever used a social network platform, you know that you are regularly prompted about people you may know in the network. Sometimes these recommendations are striking—we get a suggestion for a person we have met only once, or an old acquaintance that we have not seen in years. How could anyone (let alone a computer) possibly guess? Predicting acquaintances in a social network is just one example of the general problem of link prediction (1⇓⇓⇓–5), which consists of predicting connections (links) in a network (6) from the observation of other connections (Fig. 1). Besides social networking, the problem of link prediction occurs in many contexts, from recommender systems, where customers are recommended (linked to) items based on their previous ratings or purchases (7), to the prediction of unknown harmful (or perhaps synergistic) interactions between drugs (8). Fig. 1. In the problem of link prediction, we are asked to identify which unobserved links in a network are more likely to exist. Nodes could represent individuals or drugs, and links could represent, respectively, friendship relationships in a social network or harmful drug–drug interactions. In this example, links A B and C D exist but have not been observed, so we aim to predict them. Model 1 pays attention only to the connectivity of nodes, and it captures that many nodes are connected to A, so it correctly predicts the A B link. However, since there is nothing especial about the connectivity of C and D, it misses the C D link. Conversely, model 2 pays attention only to group structure, so it realizes that all nodes in the group at Right are connected to each other, and it predicts the C D link. However, since in the group at Left many pairs of nodes are … [↵][1]1Email: roger.guimera{at}urv.cat. [1]: #xref-corresp-1-1
Studies on the southern elephant seal, Mirounga leonina (L.). III. The annual cycle in relation to age and sex

The annual cycle of the southern elephant seal, Mirounga leonina (L.), at Macquarie and Heard Islands, where there are large undisturbed populations, is described from records of branded seals up to 9 years old, and from classifmd counts. Each age and sex has its own regular sequence of seasonal activities, and the onset of breeding largely replaces the autumn-winter haul-out of immature individuals. The moult is described, and the possible significance of the autumn-winter haulout is discussed. The pupping period in spring is constant and well synchronized annually and regionally. Weaning anticipates the summer rise of zooplankton in surface waters. There is no difference in parturition date between primiparous and multiparous cows of all ages, no matter when the moult was completed. An environmental timer of implantation is postulated as the means of ensuring seasonal constancy of breeding. Food does not appear to be limiting at any season, and population movements are confined to partial dispersal of immatures. Few cows are recorded breeding more than a short distance from their birthplace, but local changes of location are common. Ten marked individuals are known to have moved from one subantarctic island to another, and two from Heard Island to the Antarctic continent. The seasonal cycle is compared with other Pinnipedia; solitary and gregarious breeding, harem formation and polygyny, and aquatic and terrestrial mating are discussed. As efficiency on land deteriorated owing to aquatic adaptation, it is suggested that social grouping by cows in exposed breeding habitats, probably for protection of pups, and early terrestrial mating provided the opportunity for harem formation, the hierarchy of dominance among bulls, and polygyny.
Structural and Functional Aspects of Targeting the Secreted Human Group IIA Phospholipase A2

Human group IIA secretory phospholipase A2 (hGIIA) promotes the proliferation of cancer cells, making it a compelling therapeutic target, but it is also significant in other inflammatory conditions. Consequently, suitable inhibitors of hGIIA have always been sought. The activation of phospholipases A2 and the catalysis of glycerophospholipid substrates generally leads to the release of fatty acids such as arachidonic acid (AA) and lysophospholipid, which are then converted to mediator compounds, including prostaglandins, leukotrienes, and the platelet-activating factor. However, this ability of hGIIA to provide AA is not a complete explanation of its biological role in inflammation, as it has now been shown that it also exerts proinflammatory effects by a catalysis-independent mechanism. This mechanism is likely to be highly dependent on key specific molecular interactions, and the full mechanistic descriptions of this remain elusive. The current candidates for the protein partners that may mediate this catalysis-independent mechanism are also introduced in this review. A key discovery has been that selective inhibition of the catalysis-independent activity of hGIIA is achieved with cyclised derivatives of a pentapeptide, FLSYK, derived from the primary sequence of hGIIA. The effects of hGIIA on cell function appear to vary depending on the pathology studied, and so its mechanism of action is complex and context-dependent. This review is comprehensive and covers the most recent developments in the understanding of the many facets of hGIIA function and inhibition and the insight they provide into their clinical application for disease treatment. A cyclic analogue of FLSYK, c2, the most potent analogue known, has now been taken into clinical trials targeting advanced prostate cancer.
The Effects of Respiratory Training in Parkinson’s Disease: A Systematic Review

Background: Signs of respiratory dysfunction can be present already early in the course of Parkinson’s disease (PD). Respiratory training could alleviate this, but its effectiveness is not well understood. Objective: The purpose of this systematic review is to review the efficacy of different respiratory training interventions in PD. Methods: A search strategy was performed in four databases: PubMed, Physiotherapy Evidence Database (PEDro), Cochrane Library, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Methodological quality of original full-text articles was assessed using the Cochrane Risk of Bias tool for randomized controlled trials (RCTs) and the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool for the controlled trials (CTs). Levels of evidence were rated by the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Results: Six papers reporting on four randomized controlled trials and another four controlled trials were included. Positive effects were reported for inspiratory muscle strength training (IMST), expiratory muscle strength training (EMST), air stacking, breath-stacking, incentive spirometry and postural training on respiratory muscle strength, swallowing safety, phonatory aspects and chest wall volumes. Best methodological quality was found for breath-stacking and incentive spirometry. Best levels of evidence were found for EMST, IMST and EMST plus air stacking. Conclusion: Respiratory training shows positive effects and should be considered when people with PD experience respiratory dysfunction. Future studies should focus on standardizing both training devices, instruments to measure outcomes and intervention protocols to further increase the level of evidence.
The effect of oil structure on the diffusion of solutes across synthetic membranes and human epidermis

Dermal and transdermal delivery offers a number of potential advantages for drug delivery. However the skin provides an efficient barrier, preventing both excessive water loss from the body and the ingress of xenobiotics. Nevertheless, the vehicle used in the topical formulation can enhance the diffusion of a drug through membranes and reduce the barrier properties. It is hypothesized that oils and oil blends may interact with membranes to different extents depending on the physicochemical properties of the oil(s) and membrane. The aim of this study was to investigate the interaction of oily vehicles with different synthetic membranes (silicone, polyurethane (PU), high density polyethylene (HDPE) and cellulose acetate nitrate (CAN)) and human epidermis with a view to understanding the effect of the co-administration of oil blends on the permeation of model solutes (methyl parabens (MP), butyl parabens (BP) and caffeine (CF)). A gas chromatographic method was developed and validated to quantify the amounts of oil sorbed by silicone membrane (the principal membrane employed). High pressure liquid chromatography was used to quantify the amount of model solute that permeated the membranes contained within Franz diffusion cells. The uptake of different oils (isopropyl myristate (IPM), oleic acid (OA), hexadecane, isohexadecane (IHD) and light liquid paraffin) by the membranes was studied by monitoring the change in weight and thickness of the membranes after immersion in oil. Multivariate analysis (principal component analysis and quantitative structureproperty relationship) was used with a view to identifying the key molecular properties of vehicle components, permeants and the barrier membrane that influenced the permeation of the compounds through different membranes. These mathematical tools were also employed to understand and predict compound permeation across human epidermis from the oily vehicles. The permeation studies of model permeants through silicone membrane and CAN membrane were performed using systems having the same thermodynamic activity. The flux values achieved from different vehicles were different, which indicated vehicle sorption by the membrane potentially altering membrane properties. In solvent uptake studies the buffer showed a greater affinity for the more hydrophilic
Mindful Mentors: Is a Longitudinal Mind–Body Skills Training Pilot Program Feasible for Pediatric Cardiology Staff?

Background Stress and burnout among medical professionals are common and costly, placing professionals, organizations, and patients at risk. Objectives To determine feasibility and acceptability of a longitudinal mind–body skills training initiative to help staff decrease stress and burnout, improve well-being, and empower them to utilize basic mindfulness methods with coworkers, patients, and families. Methods Prospective cohort, mixed methods approach. Nurses, doctors, technicians, social workers, child life specialists were eligible to participate. The 12-month curriculum consisted of 16 hours of intensive education/practice over 2 days, with training in mindfulness skills, self-compassion, nonviolent communication, overcoming barriers to practice, and mindful listening/speaking, followed by monthly 1 hour booster/debriefing sessions. Results A total of 37 staff participated (RN = 18, MD = 5, Technician = 6, Social Worker = 3, Child life = 3, others = 2) in the initial training, and 24 (65%) completed the 3- and 12-month follow-up surveys. Compared with pretraining scores, there were significant improvements 3 to 12 months after the initial training in stress (P < .0001), distress (P ≤ .04), anxiety (P = .01), self-efficacy in providing non-drug therapies (P < .0001), mindfulness (P = .002), burnout (P < .0001), and confidence in providing compassionate care (P < .0001). In addition, 25 (67%) participants initiated projects incorporating what they learned into staff/patient wellness activities. Conclusion This longitudinal pilot program was feasible and was associated with improvements in measures of psychological well-being over the 12-month intervention. The innovative approach of training participants to teach basic techniques to coworkers and other staff can increase the impact of this program beyond any individual participant. Future research will investigate the aspects of implementation and potential effects on patient care and experience.
Role of Yoga and Meditation as Complimentary Therapeutic Regime for Stress-Related Neuropsychiatric Disorders: Utilization of Brain Waves Activity as Novel Tool

During recent decades, stress-related neuropsychiatric disorders such as anxiety, depression, chronic tension headache, and migraine have established their stronghold in the lives of a vast number of people worldwide. In order to address this global phenomenon, intensive studies have been carried out leading to the advancement of drugs like anti-depressants, anxiolytics, and analgesics which although help in combating the symptoms of such disorders but also create long-term side effects. Thus, as an alternative to such clinical practices, various complementary therapies such as yoga and meditation have been proved to be effective in alleviating the causes and symptoms of different neuropsychiatric disorders. The role of altered brain waves in this context has been recognized and needs to be pursued at the highest level. Thus, the current study provides a review focused on describing the effects of yoga and meditation on anxiety and depression as well as exploring brain waves as a tool for assessing the potential of these complementary therapies for such disorders.
Degradation of Aflatoxin B1 in Dried Figs by Sodium Bisulfite With or Without Heat, Ultraviolet Energy or Hydrogen Peroxide.

Dried fig fruits were spiked to contain 250 ppb aflatoxin B1 (AFB1) and treated with sodium bisulfite (1% in the aqueous phase of the mixture). This treatment caused 28.2% of added toxin to degrade in 72 h at 25°C. When hydrogen peroxide (H2O2, 0.2% in the aqueous phase) was added 10 min before the bisulfite treatment, 65.5% of added toxin was degraded in 72 h. In both instances, most of the degradation occurred during the second day of treatment. Heating bisulfite-treated samples at 45 to 65°C for 1 h caused up to 68.4% of added AFB1 to be degraded. Ultraviolet radiation (from a low-energy source) degraded 45.7% of AFB1 in fig samples that were treated for 30 min; the rate of degradation was not enhanced when bisulfite or H2O2 was present during this treatment.