Miracle-dz/UniFAR-FTUs huggingface dataset:
A Novel HGF/SF Receptor (MET) Agonist Transiently Delays the Disease Progression in an Amyotrophic Lateral Sclerosis Mouse Model by Promoting Neuronal Survival and Dampening the Immune Dysregulation

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease with no effective treatment. The Hepatocyte Growth Factor/Scatter Factor (HGF/SF), through its receptor MET, is one of the most potent survival-promoting factors for motor neurons (MN) and is known as a modulator of immune cell function. We recently developed a novel recombinant MET agonist optimized for therapy, designated K1K1. K1K1 was ten times more potent than HGF/SF in preventing MN loss in an in vitro model of ALS. Treatments with K1K1 delayed the onset of muscular impairment and reduced MN loss and skeletal muscle denervation of superoxide dismutase 1 G93A (SOD1G93A) mice. This effect was associated with increased levels of phospho-extracellular signal-related kinase (pERK) in the spinal cord and sciatic nerves and the activation of non-myelinating Schwann cells. Moreover, reduced activated microglia and astroglia, lower T cells infiltration and increased interleukin 4 (IL4) levels were found in the lumbar spinal cord of K1K1 treated mice. K1K1 treatment also prevented the infiltration of T cells in skeletal muscle of SOD1G93A mice. All these protective effects were lost on long-term treatment suggesting a mechanism of drug tolerance. These data provide a rational justification for further exploring the long-term loss of K1K1 efficacy in the perspective of providing a potential treatment for ALS.
AlgPred 2.0: an improved method for predicting allergenic proteins and mapping of IgE epitopes

AlgPred 2.0 is a web server developed for predicting allergenic proteins and allergenic regions in a protein. It is an updated version of AlgPred developed in 2006. The dataset used for training, testing and validation consists of 10 075 allergens and 10 075 non-allergens. In addition, 10 451 experimentally validated immunoglobulin E (IgE) epitopes were used to identify antigenic regions in a protein. All models were trained on 80% of data called training dataset, and the performance of models was evaluated using 5-fold cross-validation technique. The performance of the final model trained on the training dataset was evaluated on 20% of data called validation dataset; no two proteins in any two sets have more than 40% similarity. First, a Basic Local Alignment Search Tool (BLAST) search has been performed against the dataset, and allergens were predicted based on the level of similarity with known allergens. Second, IgE epitopes obtained from the IEDB database were searched in the dataset to predict allergens based on their presence in a protein. Third, motif-based approaches like multiple EM for motif elicitation/motif alignment and search tool have been used to predict allergens. Fourth, allergen prediction models have been developed using a wide range of machine learning techniques. Finally, the ensemble approach has been used for predicting allergenic protein by combining prediction scores of different approaches. Our best model achieved maximum performance in terms of area under receiver operating characteristic curve 0.98 with Matthew's correlation coefficient 0.85 on the validation dataset. A web server AlgPred 2.0 has been developed that allows the prediction of allergens, mapping of IgE epitope, motif search and BLAST search (https://webs.iiitd.edu.in/raghava/algpred2/).
MicroRNA-21-5p protects melanocytes via targeting STAT3 and modulating Treg/Teff balance to alleviate vitiligo

Vitiligo (VIT) is caused by loss and degradation of functional epidermal melanocytes. Studies have indicated that melanocyte destruction may be associated with an imbalance between regulatory T cells (Treg cells) and effector T cells (Teff cells). The current study aimed to investigate the molecular mechanism through which Treg/Teff balance affects VIT pathogenesis. To explore this, peripheral blood mononuclear cells were isolated from patients with VIT and healthy individuals. The present study revealed that the proportions of CD4+ T cells, Treg cells and T helper 1 (Th1) cells were decreased in patients with VIT, but those of Teff cells (Th17 and Th22 cells) were increased; additionally, Foxp3 expression was decreased, but the expression levels of interferon-γ, interleukin (IL)-17A and IL-22 were increased. Furthermore, in patients with VIT, microRNA (miR)-21-5p expression was decreased, while that of STAT3 was increased. Further in vitro experiments in CD4+ T cells revealed that STAT3 was targeted by miR-21-5p. Functional analysis further indicated that miR-21-5p overexpression in Th17-polarized CD4+ T cells decreased the proportion of Teff cells and associated cytokines, such as IL-17A and IL-22, but increased the proportion of Treg cells and Foxp3. However, the effects of miR-21-5p overexpression were partly reversed by STAT3 overexpression. Increased apoptosis of melanocytes was detected after co-culture with Th17-polarized CD4+ T cells in the presence of a miR-21-5p mimic. However, this indirect effect of the miR-21-5p mimic on melanocytes was decreased via STAT3 overexpression. Therefore, miR-21-5p may protect melanocytes via targeting STAT3 and regulating Treg/Teff balance. The current findings may provide a possible treatment method for managing VIT.
A Low-Cost Calibration Method for Low-Cost MEMS Accelerometers Based on 3D Printing

A ubiquitous sensor in embedded systems is the accelerometer, as it enables a range of applications. However, accelerometers experience nonlinearities in their outputs caused by error terms and axes misalignment. These errors are a major concern because, in applications such as navigations systems, they accumulate over time, degrading the position accuracy. Through a calibration procedure, the errors can be modeled and compensated. Many methods have been proposed; however, they require sophisticated equipment available only in laboratories, which makes them complex and expensive. In this article, a simple, practical, and low-cost calibration method is proposed. It uses a 3D printed polyhedron, benefiting from the popularisation and low-cost of 3D printing in the present day. Additionally, each polyhedron could hold as much as 14 sensors, which can be calibrated simultaneously. The method was performed with a low-cost sensor and it significantly reduced the root-mean-square error (RMSE) of the sensor output. The RMSE was compared with the reported in similar proposals, and our method resulted in higher performance. The proposal enables accelerometer calibration at low-cost, and anywhere and anytime, not only by experts in laboratories. Compensating the sensor’s inherent errors thus increases the accuracy of its output.
Associations Between Self- and Informant-Reported Abilities of Instrumental Activities of Daily Living and Cognitive Functions in Older Adults With Mild Cognitive Impairment

Abstract Objective Older adults (OAs) with mild cognitive impairment (MCI) show disabilities in instrumental activities of daily living (IADLs), which have been linked to compromised cognitive functioning. However, it is unclear which cognitive functions are primarily involved. The present study sought to identify the cognitive function(s) most strongly associated with the IADL limitations in MCI. Method OAs with MCI (N = 120) completed cognitive tasks measuring general cognitive processing speed, working memory (WM) maintenance and updating, inhibition, and shifting ability. IADL abilities were assessed through both self- and informant reports. Results Self-reported IADL abilities were positively associated with both cognitive processing speed and WM updating capacity. Informant-reported IADL abilities were also positively associated with processing speed and WM updating, in addition to cognitive shifting ability. Conclusion Both general processing speed and WM updating capacity were consistently predictive of IADL abilities. These results might inform the design of training programs aimed at maintaining or improving functional independence in individuals with MCI to focus more on these cognitive functions. However, the strength of the association between specific cognitive functions and IADL abilities in OAs with MCI depends on the source of the information about the IADL abilities, which highlights the need for gathering data from both the examinee and informants.
SARS-CoV-2 Proteins Induce IFNG in Th1 Lymphocytes Generated from CD4+ Cells from Healthy, Unexposed Polish Donors

The outbreak of the SARS-CoV-2 virus in December 2019 has caused the deaths of several hundred thousand people worldwide. Currently, the pathogenesis of COVID-19 is poorly understood. During the course of COVID-19 infection, many patients experience deterioration, which might be associated with systemic inflammation and cytokine storm syndrome; however, other patients have mild symptoms or are asymptomatic. There are some suggestions that impaired cellular immunity through a reduction in Th1 response and IFNG (interferon gamma) expression, as well as cross-reactivity with common cold coronaviruses, might be involved in the differential COVID-19 course. Here, we show that CD4+ cells isolated from unexposed healthy donors that were differentiated towards the Th1 lineage in the presence of SARS-CoV-2 proteins exhibited induction of IFNG. Interestingly, the same cells induced to differentiate towards a Th17 lineage did not exhibit changes in IFNG expression or Th17-related cytokines. This suggests the cellular response to SARS-CoV-2 viral proteins is primarily associated with Th1 lymphocytes and may be dependent on past infections with common cold coronaviruses or vaccinations that induce unspecific cellular responses, e.g., BCG (Bacillus Calmette-Guérin). Thus, our results might explain the high variability in the course of COVID-19 among populations of different countries.
Evolution de l'arôme au cours de la conservation du vin : formation de 4-(1-éthoxyéthyl)-phénol et 4-(1-éthoxyéthyl)-gaïacol

Le defaut d'arome, du a des teneurs excessives en vinylphenols dans deux vins blancs issus de varietes Muscat de Frontignan et Riesling, decroit au cours de la conservation. L'analyse de ces vins a montre que cette evolution est due a la diminution des teneurs en 4-vinylphenol et en 4-vinylgaiacol. Ces vinylphenols subissent en effet une addition acidocatalysee lente d'ethanol conduisant a deux composes nouveaux, le 4-(1-ethoxyethyl)-phenol et le 4-(1-ethoxyethyl)-gaiacol, identifies positivement par comparaison analytique avec les composes de reference qui ont ete synthetises. Ces composes subissent une elimination thermique d'ethanol conduisant aux vinylphenols de depart, ce qui rend delicate leur analyse par chromatographie en phase gazeuse. La determination de leur seuil de detection (respectivement 2,5 et 12,8 mg.kg -1 ) a montre que ces composes n'interviennent probablement pas directement sur l'arome des vins aux concentrations detectees.
Crystal structures of γ-glutamylmethylamide synthetase provide insight into bacterial metabolism of oceanic monomethylamine

Monomethylamine (MMA) is an important climate-active oceanic trace gas and ubiquitous in the oceans. γ-Glutamylmethylamide synthetase (GmaS) catalyzes the conversion of MMA to γ-glutamylmethylamide, the first step in MMA metabolism in many marine bacteria. The gmaS gene occurs in ∼23% of microbial genomes in the surface ocean and is a validated biomarker to detect MMA-utilizing bacteria. However, the catalytic mechanism of GmaS has not been studied because of the lack of structural information. Here, the GmaS from Rhodovulum sp. 12E13 (RhGmaS) was characterized, and the crystal structures of apo-RhGmaS and RhGmaS with different ligands in five states were solved. Based on structural and biochemical analyses, the catalytic mechanism of RhGmaS was explained. ATP is first bound in RhGmaS, leading to a conformational change of a flexible loop (Lys287-Ile305), which is essential for the subsequent binding of glutamate. During the catalysis of RhGmaS, the residue Arg312 participates in polarizing the γ-phosphate of ATP and in stabilizing the γ-glutamyl phosphate intermediate; Asp177 is responsible for the deprotonation of MMA, assisting the attack of MMA on γ-glutamyl phosphate to produce a tetrahedral intermediate; and Glu186 acts as a catalytic base to abstract a proton from the tetrahedral intermediate to finally generate glutamylmethylamide. Sequence analysis suggested that the catalytic mechanism of RhGmaS proposed in this study has universal significance in bacteria containing GmaS. Our results provide novel insights into MMA metabolism, contributing to a better understanding of MMA catabolism in global carbon and nitrogen cycles.
Measuring Health Care Interprofessionals' Moral Resilience: Validation of the Rushton Moral Resilience Scale.

Background: Health care interprofessionals face competing obligations to their patients, employers, and themselves. When ethical conflicts ensue and competing obligations cannot be resolved, health care interprofessionals have reported experiencing symptoms of burnout, moral distress, and other types of moral suffering. Recently, moral resilience or "the capacity of an individual to sustain or restore their integrity in response to moral adversity," has been proposed as a resource to address moral suffering while contributing to well-being. Objectives: Develop and validate an instrument to measure moral resilience. Design: Phase one: item development and expert review. Phase two: focus groups with health care interprofessionals to refine items. Phase three: psychometric testing. Setting/Subjects: Seven hundred twenty-three health care interprofessionals participated; inclusion criteria included being a chaplain, nurse, physician, or social worker, and having practiced at least 1 year. Participants were recruited from seven academic and community hospitals in the Eastern United States. Results: One hundred items were created for expert review. Following focus groups to refine items, 35 items remained for psychometric testing. Eighteen items were removed following item analysis. Exploratory factor analysis (EFA) of the remaining items suggested a four-factor solution, titled Responses to Moral Adversity, Personal Integrity, Moral Efficacy, and Relational Integrity, respectively. Overall reliability was α = 0.84. The Rushton Moral Resilience Scale (RMRS) demonstrated convergent validity with the Connor Davidson Resilience Scale-10 and criterion validity with the Maslach Burnout Inventory-Human Services Survey. Conclusion: The RMRS demonstrated acceptable validity and reliability. Examining the factor structure of moral resilience contributes to burgeoning moral resilience science and enables future research. Moral Resilience offers a promising pathway to support interprofessionals' integrity even when faced with ethical challenges.
Strictly Lobar Microbleeds Reflect Amyloid Angiopathy Regardless of Cerebral and Cerebellar Compartments

Supplemental Digital Content is available in the text. Background and Purpose: We aimed to determine whether lobar cerebellar microbleeds or concomitant lobar cerebellar and deep microbleeds, in the presence of lobar cerebral microbleeds, attribute to underlying advanced cerebral amyloid angiopathy pathology or hypertensive arteriopathy. Methods: We categorized 71 patients with suspected cerebral amyloid angiopathy markers (regardless of the presence of deep and cerebellar microbleeds) into 4 groups according to microbleed distribution: L (strictly lobar cerebral, n=33), L/LCbll (strictly lobar cerebral and strictly lobar cerebellar microbleeds, n=13), L/Cbll/D (lobar, cerebellar, and deep microbleeds, n=17), and L/D (lobar and deep, n=8). We additionally categorized patients with cerebellar microbleeds into 2 groups according to dentate nucleus involvement: strictly lobar cerebellar (n=16) and dentate (n=14). We then compared clinical characteristics, Aβ (amyloid-β) positivity on PET (positron emission tomography), magnetic resonance imaging cerebral amyloid angiopathy markers, and cerebral small vessel disease burden among groups. Results: The frequency of Aβ positivity was higher in the L and L/LCbll groups (81.8% and 84.6%) than in the L/Cbll/D and L/D groups (37.5% and 29.4%; P<0.001), while lacune numbers were lower in the L and L/LCbll groups (1.7±3.3 and 1.7±2.6) than in the L/Cbll/D and L/D groups (8.0±10.3 and 13.4±17.7, P=0.001). The L/LCbll group had more lobar cerebral microbleeds than the L group (93.2±121.8 versus 38.0±40.8, P=0.047). The lobar cerebellar group had a higher Aβ positivity (75% versus 28.6%, P=0.011) and lower lacune number (2.3±3.7 versus 8.6±1.2, P=0.041) than the dentate group. Conclusions: Strictly lobar cerebral and cerebellar microbleeds are related to cerebral amyloid angiopathy, whereas any combination of concurrent lobar and deep microbleeds suggest hypertensive angiopathy regardless of cerebral or cerebellar compartments.
Nitric Oxide Signaling in Plants

Nitric oxide (NO) is an integral part of cell signaling mechanisms in animals and plants. In plants, its enzymatic generation is still controversial. Evidence points to nitrate reductase being important, but the presence of a nitric oxide synthase-like enzyme is still contested. Regardless, NO has been shown to mediate many developmental stages in plants, and to be involved in a range of physiological responses, from stress management to stomatal aperture closure. Downstream from its generation are alterations of the actions of many cell signaling components, with post-translational modifications of proteins often being key. Here, a collection of papers embraces the differing aspects of NO metabolism in plants.
Recovery, restoration, and risk: a cross-sectional survey of the impact of COVID-19 on GPs in the first UK city to lock down

Background The COVID-19 pandemic has impacted GPs immensely. Work patterns have changed, risk stratification has been proposed, and the mental health of clinicians has been adversely affected. The COVID-19 prevalence among GPs is unknown. This study focuses on assessing the impact of COVID-19 on GPs in Leicestershire, the first UK city to lock down locally. Aim This survey assessed the prevalence of COVID-19 in GPs and explored GP work patterns in comparison with national guidance. It used a validated perceived stress tool to evaluate the impact of COVID-19 on GP stress perception. Design & setting The cross-sectional retrospective survey was sent to all the GPs in Leicestershire. Method A total of 111 GPs in Leicestershire took part voluntarily in an anonymised questionnaire-based study. A 29-item survey using SmartSurvey software was designed with multiple choice and Likert response scale questions. Results COVID-19 prevalence in GPs in Leicestershire was 8.1%; 70.3% of GPs were of Black, Asian, and minority ethnic (BAME) origin; 91.9% of GPs had undergone risk stratification; and 79.3% of GPs felt supported by their practice, but only 59.5% felt supported with mental health. GPs described feeling more stressed during the COVID-19 pandemic than they had been previously. Conclusion This is the first study evaluating COVID-19 prevalence among GPs in Leicestershire. Despite government interventions, GPs felt less supported with their mental health compared with pre-COVID-19 times. Thus, the NHS in England should focus on GP stress and wellbeing as they work towards the restoration and recovery of primary care while battling the second wave.
Circulating plasma factors involved in rejuvenation

Aging is defined as a time-dependent functional decline that occurs in many physiological systems. This decline is the primary risk factor for prominent human pathologies such as cancer, metabolic disorders, cardiovascular disorders, and neurodegenerative diseases. Aging and age-related diseases have multiple causes. Parabiosis experiments, in which the circulatory systems of young and old mice were surgically joined, revealed that young plasma counteracts aging and rejuvenates organs in old mice, suggesting the existence of rejuvenating factors that become less abundant with aging. Diverse approaches have identified a large number of plasma proteins whose levels differ significantly between young and old mice, as well as numerous rejuvenating factors that reverse aged-related impairments in multiple tissues. These observations suggest that increasing the levels of key rejuvenating factors could promote restorative biological processes or inhibit pathological degeneration. Inspired by such findings, several companies have begun selling “young blood transfusions,” and others have tested young plasma as a treatment for Alzheimer’s disease. Here, we summarize the current findings regarding rejuvenating factors.
Measuring COVID-19 Related Anxiety in Parents: Psychometric Comparison of Four Different Inventories

Background The COVID-19 outbreak and the measures to contain the global pandemic can have an impact on the well-being and mental health status of individuals. Parents of young children are particularly at risk for high levels of parental stress due to the current public health crisis, which can impact parenting behaviors and children’s well-being. Although different initial scales have been developed to measure COVID-19–related anxiety, they have not yet been tested sufficiently in parent samples. A brief measure of COVID-19–related anxiety is necessary for both quick assessment in practice and in larger epidemiological studies of parents. Objective The purpose of this study is to compare the distributions, validities, and reliabilities of four different COVID-19 anxiety scales: Fear of COVID-19 Scale, Coronavirus Anxiety Scale, Pandemic Anxiety Scale, and one subscale of the COVID Stress Scales. Based on the psychometric properties of these scales, we aim to provide recommendations for a brief unidimensional inventory to assess COVID-19–related anxiety among parents. Methods A cross-sectional web-based survey of 515 German-speaking parents (465 mothers, 90.3%) with at least one child aged 0-6 years was conducted during a 6-week period (June 29 to August 9, 2020). Half of the parents were recruited via Facebook parenting groups, while the other half were recruited through childcare centers. We psychometrically tested 25 items on COVID-19–related anxiety using the framework of classical test theory, including item analysis, correlational analysis of family variables, and exploratory factor analysis. Moreover, an item response theory approach was applied to estimate item discriminations and item difficulties. Results Based on the psychometric properties, three items of the Pandemic Anxiety Scale were identified as a single unidimensional factor. The adapted scale demonstrated acceptable internal consistency (α=.79), moderate to high item discrimination, strong positive intercorrelation with two other COVID-19 anxiety scales, and a small positive association with parenting stress. Mothers and fathers did not differ in total scores (t513=−0.79, P=.42). Conclusions Factor analysis suggests that existing COVID-19–related anxiety scales measure different latent constructs of anxiety. Furthermore, all scales showed only small to moderate correlations with trait health anxiety, suggesting that COVID-19–related anxiety is distinct from general health anxiety. The adapted “disease anxiety” subscale of the Pandemic Anxiety Scale is an economical measure for assessing COVID-19–related anxiety in parents. Directions for future research are outlined.