Miracle-dz/UniFAR-FTUs huggingface dataset:
Current Progress in Natural Deep Eutectic Solvents for the Extraction of Active Components from Plants

Abstract In the last decade, natural deep eutectic solvents (NADESs) have gained more and more attention due to their green, convenient preparation, low toxicity and biodegradability. It is widely used in various fields, especially in the extraction of active components from plants, formed by the combination of hydrogen bond donors (HBDs) and hydrogen bond acceptors (HBAs) at a certain condition. In this article, six preparation methods of NADESs were summarized and the interactions that occur in the eutectic behavior of NADES including hydrogen bonding, electrostatic interaction and van der Waals force were also reviewed. What is more, its significant extraction capacity on flavonoids, phenols, alkaloids and plant pigments endows its extensive applications in the extraction of active components from medicinal plants. Extraction factors including solvents properties (viscosity, carbon chain length, number of hydroxyl groups), extraction condition (water content, extraction temperature, extraction time, solid–liquid ratio), extraction method and recycling method were discussed. In addition, NADESs can also be combined with other technologies, like molecular imprinting, monolithic column, to achieve efficient and specific extraction of active ingredients. Further systematic studies on the biodegradability and biotoxicity are put forward to be urgent.
Clinical phenotype in infants with negative Zika virus immunoglobulin M testing born to mothers with confirmed Zika virus infection during pregnancy

Recommended testing for both infants with Zika‐associated birth defects (i.e., microcephaly and selected brain or eye anomalies) and infants without birth defects whose mothers had laboratory evidence of possible Zika virus (ZIKV) infection during pregnancy includes nucleic acid amplification testing (NAAT) and immunoglobulin M (IgM) testing within days after birth. Brain and eye defects highly specific for congenital ZIKV infection have been described; sporadic reports have documented negative ZIKV testing in such infants.
Reduction/elimination of blood eosinophils in severe asthma: should there be a safety consideration?

ABSTRACT Introduction Eosinophils play a central role in the inflammation of asthma and are the target of new biologic treatments for patients with severe asthma. Biologics targeting the IL-5 pathway have been shown to reduce asthma exacerbations, improve lung function, reduce oral corticosteroid use, and improve quality of life, accompanied by reduced or even eliminated blood eosinophils. Eosinophils have been associated with host protection and tumor growth, raising potential concerns about the consequences of these long-term therapies that reduce or eliminate them. Areas covered In this review, we explore the current safety profile of biologics regarding the impact they may have on blood eosinophils, trying to answer the question about any safety consideration. Expert opinion Eosinophils have been associated with host protection and tumor growth, raising potential concerns about the consequences of long-term therapies that reduce or eliminate these blood cells.
Inhibition of the unfolded protein response reduces arrhythmic risk after myocardial infarction.

Ischemic cardiomyopathy is associated with an increased risk of sudden death, activation of the unfolded protein response (UPR), and reductions in multiple cardiac ion channels. When activated, the protein kinase-like ER kinase (PERK) branch of the UPR reduces protein translation and abundance. We hypothesized that PERK inhibition could prevent ion channel downregulation and reduce arrhythmic risk after myocardial infarct (MI). MI induced by coronary artery ligation resulted in mice exhibited reduced ion channel levels, ventricular tachycardia (VT), and prolonged corrected intervals between the Q and T waves of the ECGs (QTc). Protein levels of major cardiac ion channels were decreased. MI cardiomyocytes showed significantly prolonged action potential duration and decreased maximum upstroke velocity. Cardiac-specific PERK knockout (PERKKO) reduced electrical remodeling in response to MI with shortened QTc intervals, less VT episodes, and higher survival rates (P<0.05 vs. MI). Pharmacological PERK inhibition had similar effects. In conclusion, activated PERK during MI contributed to arrhythmic risk by downregulation of select cardiac ion channels. PERK inhibition prevented these changes and reduced arrhythmic risk. These results suggest that ion channel downregulation during MI is a fundamental arrhythmic mechanism and maintaining ion channel levels is antiarrhythmic.
Non-Markovian modeling of protein folding

Significance Protein-folding kinetics is often described as Markovian (i.e., memoryless) diffusion in a one-dimensional free energy landscape, governed by an instantaneous friction coefficient that is fitted to reproduce experimental or simulated folding times. For the α-helix forming polypeptide alanine9 and a specific reaction coordinate that consists of the summed native hydrogen-bond lengths, we demonstrate that the friction extracted from molecular dynamics simulations exhibits significant memory with a decay time that is in the nanosecond range and thus, of the same order as the folding and unfolding times. Our non-Markovian modeling not only reproduces the molecular dynamics simulations accurately but also demonstrates that memory friction effects lead to anomalous and drastically accelerated protein kinetics. We extract the folding free energy landscape and the time-dependent friction function, the two ingredients of the generalized Langevin equation (GLE), from explicit-water molecular dynamics (MD) simulations of the α-helix forming polypeptide alanine9 for a one-dimensional reaction coordinate based on the sum of the native H-bond distances. Folding and unfolding times from numerical integration of the GLE agree accurately with MD results, which demonstrate the robustness of our GLE-based non-Markovian model. In contrast, Markovian models do not accurately describe the peptide kinetics and in particular, cannot reproduce the folding and unfolding kinetics simultaneously, even if a spatially dependent friction profile is used. Analysis of the GLE demonstrates that memory effects in the friction significantly speed up peptide folding and unfolding kinetics, as predicted by the Grote–Hynes theory, and are the cause of anomalous diffusion in configuration space. Our methods are applicable to any reaction coordinate and in principle, also to experimental trajectories from single-molecule experiments. Our results demonstrate that a consistent description of protein-folding dynamics must account for memory friction effects.
Neglected but not negligible aspects of antidepressants and their availability in bipolar depression

Although many antidepressants are available, they are not always used appropriately. For appropriate use of antidepressants, the old concept of a linear dose–response relationship, in which the dose is linearly increased to achieve a sufficient antidepressant effect, should be reconsidered. Furthermore, there is ongoing debate on the safe and appropriate use of antidepressants in patients with bipolar depression. Antidepressants may be used under certain conditions in patients with bipolar depression. These neglected—but not negligible—aspects of antidepressants have been discussed herein.
Evaluating safety in hyaluronic acid lip injections

ABSTRACT Introduction Soft tissue filler augmentation has become increasingly popular due to its perceived ease and impressive results. Unfortunately, although the results are impressive, so are the reported complications. This article describes complications specific to peri-oral soft tissue filler injection and then discusses evidence-based, anatomic prevention and treatment guidelines. Areas Covered The authors aimed at providing an overview of the complications associated with peri-oral soft tissue filler. Hyaluronic Acid (H.A) fillers may have devastating complications which are oft undisclosed or published. This narrative review aims to describe the various complications and provide preventative strategies. Expert opinion Given the paucity of prospective, randomized clinical trials on the subject and in light of complication underreporting, the authors believe that efficacy and safety literature on the subject is lacking. Injectors must rely on the one strength which exists in the lip literature to date, that is anatomy. The basis of all successful injections is a mandatory understanding of normal as well as variations of vital structures in an area, combined with meticulous injection techniques, deposition of small aliquots of product and the ability to recognize unwanted adverse events early enough to act on them.
Detection of Intraorbital Foreign Bodies Using Magnetic Resonance Imaging and Computed Tomography

ABSTRACT Purpose We analyze the detectability of intraorbital foreign bodies (OrbFBs) of various types and sizes using computed tomography (CT) and magnetic resonance imaging using a three-Tesla machine (MRI 3 T). Methods An ex vivo model of sheep eyes with preserved extraocular muscles and orbital fat tissue placed in the orbital cavity of the human skull was created for this study. Foreign bodies made of four different materials – plastic, bottle glass, stone and wood – each in three different sizes (large, intermediate and small) were inserted into the soft tissue of the orbit in the extraocular space. Each orbit was scanned by CT and MRI. Images were analyzed by a senior radiologist and underwent masked review by three oculoplastic surgeons. Results Analysis of MRI and CT scans identified distinguishing characteristics for each of the four materials. This information was further integrated into a clinical algorithm. CT allowed easier identification of most of the embedded materials compared to MRI. Smaller OrbFB size was associated with lower detectability. Review of CT yielded 94.4% agreement between oculoplastic specialists in detecting OrbFbs using CT scans and allowed detection of most OrbFBs. In contrast, the overall agreement with MRI was lower: 66.7% with T1 MPRAGE, 50% with T1TSE, 88.9% with T2 TSE and 72.2% with T2 TSE FS. Plastic was the most difficult material to detect in all size categories. Conclusions CT offers a clear advantage over MRI for detecting and localizing nonmetallic OrbFBs of all sizes, except for plastic. Plastic OrbFBs can be detected with CT depending on size but are more visible in MRI scans.
A rapid liquid chromatography-tandem mass spectrometry method for the analysis of urinary 5-hydroxyindoleacetic acid (5-HIAA) that incorporates a 13C-labelled internal standard

Background Urinary 5-hydroxyindoleacetic acid (5-HIAA) is a first-line investigation for gastrointestinal neuroendocrine tumours that secrete serotonin. It also has clinical utility for monitoring disease progression and therapeutic response. Aim To develop and validate a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for urinary 5-hydroxyindoleacetic acid that incorporates a supported liquid extraction and 13C-labelled internal standard. Methods Samples were diluted in ammonium acetate containing a 13C-labelled internal standard (5-hydroxyindole-3a,4,5,6,7,7a-13C6-3-acetic acid). Supported liquid extraction was performed followed by chromatographic separation using the 2.1 × 30 mm CORTECS® UPLC® T3 column. Mass spectrometry detection (Waters Xevo TQ-XS) was performed in electrospray positive mode using the transitions 192.3 > 146.4 m/z (quantifier) and 192.3 > 118.4 m/z (qualifier) for 5-hydroxyindoleacetic acid and 198.2 > 152.4 m/z for 13C-5-HIAA. Results A well-defined 5-hydroxyindoleacetic acid peak was observed at 0.8 min with a run time of 2.4 min. The assay was linear (r2 > 0.99) to 382 µmol/L, with a lower limit of quantification of 5.3 µmol/L (CV <15%). Analysis of 29 external quality assurance samples showed good agreement between our method and the UKNEQAS method mean (4.7% positive bias). The intra- and inter-assay precision was within acceptable limits, and the assay was stable up to 96 h postextraction with minimal carryover. Conclusion We have developed a robust LC-MS/MS method with semi-automated extraction that offers an improved run time and performance over the existing, labour-intensive, HPLC method. The method was quick, precise, showed good agreement with UKNEQAS external quality assurance material and is in routine service for clinical samples.
A large-scale study of stress, emotions, and blood pressure in daily life using a digital platform

Significance Exaggerated blood pressure (BP) reactivity is associated with the development of hypertension and cardiovascular disease. Stress, and, to a lesser extent, emotions are suggested to be linked to BP reactivity, but this theorizing lacks robust evidence beyond small laboratory or field studies with narrow participant demographics. Using an app-based research study and analyzing more than 330,000 daily responses from over 20,000 people, we show that momentary stress, conceptualized as the perception of demands relative to resources, is associated with greater BP and heart rate reactivity. High-arousal negative emotions are associated with increased physiologic reactivity whereas low-arousal positive emotions are associated with decreased reactivity. These data point to daily stress experiences as likely candidates for improving physical health. Stress is often associated with pathophysiologic responses, like blood pressure (BP) reactivity, which when experienced repeatedly may be one pathway through which stress leads to poor physical health. Previous laboratory and field studies linking stress to physiological measures are limited by small samples, narrow demographics, and artificial stress manipulations, whereas large-scale studies often do not capture measures like BP reactivity in daily life. We examined perceived stress, emotions, heart rate, and BP during daily life using a 3-wk app-based study. We confirmed the validity of a smartphone-based optic sensor to measure BP and then analyzed data from more than 330,000 daily responses from over 20,000 people. Stress was conceptualized as the ratio of situational demands relative to individual resources to cope. We found that greater demands were associated with higher BP reactivity, but critically, the ratio of demands relative to resources improved prediction of BP changes. When demands were higher and resources were lower, there was higher BP reactivity. Additionally, older adults showed greater concordance between self-reported stress and physiologic responses than younger adults. We also observed that physiologic reactivity was associated with current emotional state, and both valence and arousal mattered. For example, BP increased with high-arousal negative emotions (e.g., anger) and decreased with low-arousal positive emotions (e.g., contentment). Taken together, this work underscores the potential for expanding stress science and public health data using handheld phones to reliably and validly measure physiologic responses linked to stress, emotion, and physical health.
Sri Lanka’s early success in the containment of COVID-19 through its rapid response: Clinical & epidemiological evidence from the initial case series

Background Despite the rising global burden, Sri Lanka reported a relatively low caseload and mortality (13 deaths as of 20 October 2020) for COVID-19. This warrants exploration of the clinical and epidemiological characteristics of the case series during the initial passive case detection phase in Sri Lanka, in order to understand the success in containment of the disease for more than nine months in the country through its initial early and rapid pandemic response. Methods A retrospective study was conducted using secondary data (hospital records and investigation reports) extracted from all laboratory-confirmed patients admitted to the three main state-sector hospitals in Sri Lanka from 11 March to 7 April 2020. Clinical outcomes were categorized as mild, severe and critical, as per the international classification. Kruskal-Wallis H, Mann Whitney U and Fisher’s exact tests compared differences between the variables. Results The case series comprised 146 live discharges and six deaths. Majority were males (63.2%); mean age of 40.9 (SD = 17.9); and symptomatic (72.4%). Sixty-one (40.1%) had co-morbidities, the commonest being diabetes (20.4%) and hypertension (17.8%). Mild (93.4%), severe (2.6%) and critical (4.0%) disease outcomes were noted. Disease severity was significantly higher with older age (p = 0.037), co-morbidities (p = 0.026); and higher white-cell (p = 0.045) and lymphocyte (p = 0.043) counts; but not with being symptomatic (p = 0.683). The commonest symptoms were fever (62.5%), dry cough (48.0%) and sore throat (26.9%). The median duration (IQR) was 3.0 (1.0–5.0) and 18.0 (15.0–29.5) days, respectively before and during hospitalization. Conclusions In contrast to high-risk countries, the younger age, milder disease and low mortality observed in local patients during the initial phase of the pandemic, reflect the early success in containment of the pandemic in Sri Lanka. However, once the disease becomes severe, the factors determining disease fatality remain the same as in other countries. This highlights the value of establishing strong public health systems and disease surveillance in a country, which could provide long-term effects on disease control.
A matrix of structure-based designs yields improved VRC01-class antibodies for HIV-1 therapy and prevention

ABSTRACT Passive transfer of broadly neutralizing antibodies is showing promise in the treatment and prevention of HIV-1. One class of antibodies, the VRC01 class, appears especially promising. To improve VRC01-class antibodies, we combined structure-based design with a matrix-based approach to generate VRC01-class variants that filled an interfacial cavity, used diverse third-complementarity-determining regions, reduced potential steric clashes, or exploited extended contacts to a neighboring protomer within the envelope trimer. On a 208-strain panel, variant VRC01.23LS neutralized 90% of the panel at a geometric mean IC80 less than 1 μg/ml, and in transgenic mice with human neonatal-Fc receptor, the serum half-life of VRC01.23LS was indistinguishable from that of the parent VRC01LS, which has a half-life of 71 d in humans. A cryo-electron microscopy structure of VRC01.23 Fab in complex with BG505 DS-SOSIP.664 Env trimer determined at 3.4-Å resolution confirmed the structural basis for its ~10-fold improved potency relative to VRC01. Another variant, VRC07-523-F54-LS.v3, neutralized 95% of the 208-isolated panel at a geometric mean IC80 of less than 1 μg/ml, with a half-life comparable to that of the parental VRC07-523LS. Our matrix-based structural approach thus enables the engineering of VRC01 variants for HIV-1 therapy and prevention with improved potency, breadth, and pharmacokinetics.
Emotional Intelligence and Pro-Social Behavior as Predictors of Academic Achievement Among University Students

This journal article was primarily carried out to pinpoint whether emotional intelligence and pro-social behavior predicts academic achievement of University students. To achieve this, data was gathered from 111 (m = 50, F = 53) students by using stratified simple random sampling technique. As the results of Pearson correlation coefficient showed that, there was statistically significant positive association between emotional intelligence and pro-social behavior. However, it was found that there was no relationship between emotional intelligence and academic achievement. On the other hand, there was a statistically significant negative correlation between pro-social behavior and academic achievement of students. Findings from multiple regression indicated that, emotional intelligence predicted pro-social behavior of students, whereas, emotional intelligence didn’t predict academic achievement of students. On the other hand, pro-social behavior negatively and significantly predicted academic achievement of students. Besides, there was no significant gender difference in emotional intelligence and pro-social behavior. However, there was statistically significant disparity amidst male and female students in academic achievement and male students exceed female counterparts in general level of academic performance. As one sample t-test result depicted, Majority of students have high level of emotional intelligence, pro-social behavior and academic performance. The researcher forwarded the following recommendations for instructors, the university management and Medias. Socio-emotional training’s should be provided to students, intensive studies should be conducted on this topic, teachers of the university should advocate the importance of emotional intelligence and pro-social behavior in the class room, the university and broadcasting Medias should give attention for the topic.
To comply or not comply? A latent profile analysis of behaviours and attitudes during the COVID-19 pandemic

How and why do people comply with protective behaviours during COVID-19? The emerging literature employs a variable-centered approach, typically using a narrow selection of constructs within a study. This study is the first to adopt a person-centred approach to identify complex patterns of compliance, and holistically examine underlying psychological differences, integrating multiple psychology paradigms and epidemiology. 1575 participants from Australia, US, UK, and Canada indicated their behaviours, attitudes, personality, cognitive/decision-making ability, resilience, adaptability, coping, political and cultural factors, and information consumption during the pandemic’s first wave. Using Latent Profile Analysis, two broad groups were identified. The compliant group (90%) reported greater worries, and perceived protective measures as effective, whilst the non-compliant group (about 10%) perceived them as problematic. The non-compliant group were lower on agreeableness and cultural tightness-looseness, but more extraverted, and reactant. They utilised more maladaptive coping strategies, checked/trusted the news less, and used official sources less. Females showed greater compliance than males. By promoting greater appreciation of the complexity of behaviour during COVID-19, this research provides a critical platform to inform future studies, public health policy, and targeted behaviour change interventions during pandemics. The results also challenge age-related stereotypes and assumptions.
Detection of Strongly Bound Thioflavin T Species in Amyloid Fibrils by Ligand-Detected 1H NMR

Thioflavin T (ThT) is used widely for the detection of amyloid fibrils. Detection is based on the dramatic enhancement of its fluorescence following binding to amyloid fibrils. The biophysical basis for this effect remains poorly understood but may lie in the elucidation of ThT binding modes at the atomic level. Here, we use ThT-detected 1H NMR to identify strongly bound ThT in fibrils formed by the islet amyloid polypeptide. Our results together with the molecular rotor model of ThT proposed by others provide the basis for the characteristic amyloid-induced increase in ThT fluorescence. In the strongly bound ThT species, the rotation of the aromatic rings of ThT relative to each other is sterically hindered, and thus the transition to the nonfluorescent state of ThT is blocked. Knowledge of the interaction of ligands with amyloid assemblies may lead to the development of small molecules for the detection and inhibition of amyloid formation.