Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification and Characterization of Nep1-Like Proteins From the Grapevine Downy Mildew Pathogen Plasmopara viticola

The obligate biotrophic oomycete Plasmopara viticola causes tremendous problems in viticulture by evoking grapevine downy mildew. P. viticola, like other plant pathogens, achieves infection by suppression of plant innate immunity by secretion of effector molecules into its host plant. An ever-expanding family of proteins with effector-like characteristics is formed by the “Necrosis and Ethylene inducing peptide 1 (Nep1)-like proteins” (NLPs). NLPs can be divided into two groups by their ability to induce necrosis. While cytotoxic NLPs may act as virulence factors for a necrotrophic or hemibiotrophic plant pathogen, the role of non-cytotoxic NLPs is so far unknown. In this study, we identified eight independent NLPs in P. viticola and selected three for functional analysis. While one was identified as a putative pseudo gene, two contain all so far described critical key elements for necrosis formation except for an N-terminal signal peptide. Further characterization revealed that none of the putative necrosis elicitors was able to actually induce necrosis, neither in several susceptible or resistant Vitis species nor in the dicot model plant Nicotiana benthamiana. This inability exists independently of the presence or absence of a signal peptide. However, any possible mechanism for the suppression of the ability to induce necrosis in planta was not detected. Interestingly, expression analysis of the presumed pseudo gene revealed remarkable differences between pure sporangia solution and sporangia in the presence of leaf material. To our knowledge, this is the first report of this kind of regulation that suggests an important function of so far nonfunctional “pseudo” NLP genes during the first hours of infection.
Development of Supervised Learning Predictive Models for Highly Non-linear Biological, Biomedical, and General Datasets

In highly non-linear datasets, attributes or features do not allow readily finding visual patterns for identifying common underlying behaviors. Therefore, it is not possible to achieve classification or regression using linear or mildly non-linear hyperspace partition functions. Hence, supervised learning models based on the application of most existing algorithms are limited, and their performance metrics are low. Linear transformations of variables, such as principal components analysis, cannot avoid the problem, and even models based on artificial neural networks and deep learning are unable to improve the metrics. Sometimes, even when features allow classification or regression in reported cases, performance metrics of supervised learning algorithms remain unsatisfyingly low. This problem is recurrent in many areas of study as, per example, the clinical, biotechnological, and protein engineering areas, where many of the attributes are correlated in an unknown and very non-linear fashion or are categorical and difficult to relate to a target response variable. In such areas, being able to create predictive models would dramatically impact the quality of their outcomes, generating an immediate added value for both the scientific and general public. In this manuscript, we present RV-Clustering, a library of unsupervised learning algorithms, and a new methodology designed to find optimum partitions within highly non-linear datasets that allow deconvoluting variables and notoriously improving performance metrics in supervised learning classification or regression models. The partitions obtained are statistically cross-validated, ensuring correct representativity and no over-fitting. We have successfully tested RV-Clustering in several highly non-linear datasets with different origins. The approach herein proposed has generated classification and regression models with high-performance metrics, which further supports its ability to generate predictive models for highly non-linear datasets. Advantageously, the method does not require significant human input, which guarantees a higher usability in the biological, biomedical, and protein engineering community with no specific knowledge in the machine learning area.
Comparing ABA, AAB, and ABC Renewal of Appetitive Pavlovian Conditioned Responding in Alcohol- and Sucrose-Trained Male Rats

Conditioned responding can be renewed by re-exposure to the conditioning context following extinction in a different context (ABA renewal) or by removal from the extinction context (AAB or ABC renewal). ABA renewal is robust in Pavlovian and operant conditioning paradigms. However, fewer studies have investigated AAB and ABC renewal of appetitive conditioning, and those that did predominantly used operant conditioning tasks. Renewal has theoretical relevance for extinction and for exposure-based treatments for substance use disorders that aim to extinguish reactivity to drug-predictive cues. We therefore investigated ABA, AAB, and ABC renewal of Pavlovian conditioned responding to cues that predicted either alcohol or sucrose. Male, Long-Evans rats (Charles River) were exposed to either 15% ethanol (Study 1: “alcohol”) or 10% sucrose (Study 2: “sucrose”) in their home cages. Next, they were trained to discriminate between two auditory stimuli (white noise and clicker; 10 s) in conditioning chambers equipped with distinct olfactory, visual, and tactile contextual stimuli (context A). One conditioned stimulus (CS+) was paired with fluid delivery (0.2 ml/CS+; 3.2 ml/session; alcohol or sucrose in separate experiments), and the second CS (CS−) was not. In all sessions (conditioning, extinction, and test), each CS was presented 16 times/session on a variable-time 67-s schedule, and entries into the fluid port were recorded. CS+ port entries were then extinguished by withholding fluid delivery either in context A or in a second, different context (context B). Next, we assessed ABA, AAB, and ABC renewal in the absence of fluid delivery. During extinction, CS+ port entries were initially elevated in context A relative to context B. ABA renewal of CS+ port entries occurred in both alcohol- and sucrose-trained rats. ABC renewal approached statistical significance when data from both experiments were combined. No AAB renewal was observed, and, in fact, alcohol-trained rats showed AAB suppression. These results corroborate the reliability of ABA renewal and suggest that ABC renewal is a modest effect that may require greater statistical power to detect. From a treatment perspective, the lack of AAB renewal suggests that exposure-based treatments for substance use disorders might benefit from implementation in real-world, drug-use contexts.
Counting Enhances Kindergarteners’ Mappings of Number Words Onto Numerosities

We can make sense of how many a number represents by mapping the symbolic number word system onto the non-symbolic, approximate number system. This study adopted an intervention design to examine whether counting is essential in driving the formation of such symbolic-non-symbolic mappings. We compared kindergarteners’ mapping ability after reading stories (1) without cardinal labels, or (2) with cardinal labels, or (3) with cardinal labels and verbal counting. Results showed that children who had counted when reading the stories showed better mapping between number words and their approximate representations than their peers in the other two conditions – suggesting that counting plays a role in developing early symbolic-non-symbolic mappings. Such findings provides empirical support for parents and early educators to enhance young children’s mappings between numbers words and approximate representations through counting activities – such as counting the items in the story books while reading to children.
Heart Plasticity in Response to Pressure- and Volume-Overload: A Review of Findings in Compensated and Decompensated Phenotypes

The adult human heart has an exceptional ability to alter its phenotype to adapt to changes in environmental demand. This response involves metabolic, mechanical, electrical, and structural alterations, and is known as cardiac plasticity. Understanding the drivers of cardiac plasticity is essential for development of therapeutic agents. This is particularly important in contemporary cardiology, which uses treatments with peripheral effects (e.g., on kidneys, adrenal glands). This review focuses on the effects of different hemodynamic loads on myocardial phenotype. We examine mechanical scenarios of pressure- and volume overload, from the initial insult, to compensated, and ultimately decompensated stage. We discuss how different hemodynamic conditions occur and are underlined by distinct phenotypic and molecular changes. We complete the review by exploring how current basic cardiac research should leverage available cardiac models to study mechanical load in its different presentations.
A Theoretical Model for Urban Walking Among People With Disabilities

This paper is an attempt to advance research on walking at a neighborhood level of analysis for people with disabilities by proposing a theoretical model that combines the knowledge of two disciplines: traffic planning and environmental psychology. The aim is to provide guidance for a discussion and a plan for future interdisciplinary investigations by proposing a model that accounts for the dynamic interaction between environmental characteristics, human processes, and walking experience among individuals with a disability. For this purpose, traffic planners, and environmental psychologists came together to discuss theories, concepts, and thematic relevance in a series of focus group meetings. These meetings led to the selection of the Human Environment Interaction (HEI) model, originally developed from the field of environmental psychology and operationalized to describe how walking experiences result from the interplay between individual abilities, emotional processes, and the physical and social characteristics of the environment (Küller, 1991). The proposed model aims to sustain interdisciplinary discussion and research planning around the topic of neighborhood walking for people with disabilities. By operationalizing each dimension in the model, a good fit between groups with disabilities and individual differences associated with walking experiences is assumed, which, in turn, will have the potential to provide a more conscious analysis of wellbeing-related outcomes, such as usability of the environment, frequency of mobility, and quality of life. However, to improve understanding of urban walking at a neighborhood level for people with disabilities, empirical studies must be carried out to test the proposed model.
NK Cell-Based Immune Checkpoint Inhibition

Immunotherapy, with an increasing number of therapeutic dimensions, is becoming an important mode of treatment for cancer patients. The inhibition of immune checkpoints, which are the source of immune escape for various cancers, is one such immunotherapeutic dimension. It has mainly been aimed at T cells in the past, but NK cells are a newly emerging target. Simultaneously, the number of checkpoints identified has been increasing in recent times. In addition to the classical NK cell receptors KIRs, LIRs, and NKG2A, several other immune checkpoints have also been shown to cause dysfunction of NK cells in various cancers and chronic infections. These checkpoints include the revolutionized CTLA-4, PD-1, and recently identified B7-H3, as well as LAG-3, TIGIT & CD96, TIM-3, and the most recently acknowledged checkpoint-members of the Siglecs family (Siglec-7/9), CD200 and CD47. An interesting dimension of immune checkpoints is their candidacy for dual-checkpoint inhibition, resulting in therapeutic synergism. Furthermore, the combination of immune checkpoint inhibition with other NK cell cytotoxicity restoration strategies could also strengthen its efficacy as an antitumor therapy. Here, we have undertaken a comprehensive review of the literature to date regarding NK cell-based immune checkpoints.
Downregulation of miR-3568 Protects Against Ischemia/Reperfusion-Induced Cardiac Dysfunction in Rats and Apoptosis in H9C2 Cardiomyocytes Through Targeting TRIM62

microRNA-3568 (miR-3568) has been reported to be associated with atherosclerosis. Only few data describe the expression and underlying mechanism of miR-3568 in regulating cardiac ischemia–reperfusion (I/R) injury such as apoptosis. In this study, we therefore sought to investigate the potential function of miR-3568 in simulated I/R-induced apoptosis in H9C2 cardiomyocytes and related signaling pathways involved. Flow cytometry was performed to examine the cell apoptosis. The expression of miR-3568, Survivin, Bcl-2, ERK, JNK, p38, AKT, and STAT3 was measured by western blot and quantitative real-time PCR. The correlation between TRIM62 and p-STAT3 was measured by co-immunoprecipitation and ubiquitination. We found that miR-3568 expression in simulated I/R-induced H9C2 cardiomyocytes was increased in a time-dependent manner. miR-3568 mimic transfection in H9C2 cardiomyocytes significantly enhanced cell apoptosis, decreased the expression of Bcl-2 and Survivin, and activated STAT3 signaling, which were reversed by miR-3568 inhibitor. The direct interaction between miR-3568 and the 3′-untranslated region (UTR) of TRIM62 mRNA was confirmed by dual-luciferase reporter assay. TRIM62 overexpression or AG490, a selective inhibitor of JAK2/STAT3 significantly, significantly inhibited I/R and miR-3568 mimic induced cell apoptosis and STAT3 activation. TRIM62 was found to interact with and induce ubiquitination of p-STAT3. The facilitating role of miR-3568 in I/R injury was also observed in our in vivo rat models. In conclusion, our study suggests that miR-3568 promotes simulated I/R-induced apoptosis in H9C2 cardiomyocytes through targeting TRIM62.
Optimization of Extraction Conditions of Phytochemical Compounds and Anti-Gout Activity of Euphorbia hirta L. (Ara Tanah) Using Response Surface Methodology and Liquid Chromatography-Mass Spectrometry (LC-MS) Analysis

Gout is a common disease affected most of the people due to the elevation of uric acid in the blood. Flavonoid and phenolic compounds are reported to exert the anti-gout activity of medicinal plants. Hence, this study aimed at optimizing the extraction conditions of phenolic and flavonoid compounds as well as the anti-gout (xanthine oxidase inhibitory activity) in vitro of Euphorbia hirta using response surface methodology (RSM). The plant part used was the whole plant excluding roots. The effects of three independent variables (extraction time, X1; extraction temperature, X2; and solid-to-liquid ratio, X3) on three response variables (total flavonoid content, Y1; total phenolic content, Y2; and xanthine oxidase inhibitory activity, Y3) were determined using central composite design (CCD) while phytochemical profiling of the extracts was determined by liquid chromatography-mass spectrometry (LC-MS). Quadratic models produced a satisfactory fitting of the experimental data with regard to total flavonoid content (r2 = 0.9407, p < 0.0001), total phenolic content (r2 = 0.9383, p < 0.0001), and xanthine oxidase inhibitory activity (r2 = 0.9794, p < 0.0001). The best extraction conditions observed for total flavonoid content, total phenolic content, and xanthine oxidase inhibitory activity were at a temperature of 79.07°C for 17.42 min with solid-to-liquid ratio of 1 : 20 g/ml. The optimum values for total flavonoid, total phenolic, and xanthine oxidase inhibitory activity were 67.56 mg RE/g, 155.21 mg GAE/g, and 91.42%, respectively. The main phytochemical compounds in the optimized E. hirta extract are neochlorogenic acid, quercetin-3β-D-glucoside, syringic acid, caffeic acid, ellagic acid, astragalin, afzelin, and quercetin. As conclusion, this study clearly demonstrated the best conditions to obtain higher xanthine oxidase inhibitory activity and phytochemical compounds which can be further used for the development of anti-gout agents.
An uncommon presentation of a sinister entity

Abstract A case of a female patient presenting with clinical findings ominous for a neoplastic bowel obstruction is reported. Abdominal computed tomography demonstrated a bowel obstruction with evidence of intussusception. Laparotomy revealed an irreducible ileoileal intussusception and segments of the jejunum infiltrated with pigmented deposits. There was no perforation and no evidence of an ulcerating or fungating mass. Intestinal melanoma is not an uncommon sequela of cutaneous melanoma, yet the disease can occur as a primary intestinal process, albeit this is a rarity. Surgical resection is the primary treatment modality and may offer the hope of increased symptom-free survival and overall survival for those patients suffering from metastatic or primary melanoma of the small intestine.
Functional characterization of full-length BARD1 strengthens its role as a tumor suppressor in neuroblastoma

BARD1 is associated with the development of high-risk neuroblastoma patients. Particularly, the expression of full length (FL) isoform, FL BARD1, correlates to high-risk neuroblastoma development and its inhibition is sufficient to induce neuroblastoma cells towards a worst phenotype. Here we have investigated the mechanisms of FL BARD1 in neuroblastoma cell lines depleted for FL BARD1 expression. We have shown that FL BARD1 expression protects the cells from spontaneous DNA damage and from damage accumulated after irradiation. We demonstrated a role for FL BARD1 as tumor suppressor to prevent unscheduled mitotic entry of DNA damaged cells and to lead to death cells that have bypassed cell cycle checkpoints. FL BARD1-depleted cells that have survived to checkpoints acquire features of aggressiveness. Overall, our results show that FL BARD1 may defend cells against cancer and prevent malignant transformation of cells.
Comprehensive Curriculum for Internal Medicine Residents on Primary Care of Patients Identifying as Lesbian, Gay, Bisexual, or Transgender

Introduction Significant gaps remain in the training of health professionals regarding the care of individuals who identify as lesbian, gay, bisexual, and transgender (LGBT). Although curricula have been developed at the undergraduate medical education level, few materials address the education of graduate medical trainees. The purpose of this curriculum was to develop case-based modules targeting internal medicine residents to address LGBT primary health care. Methods We designed and implemented a four-module, case-based, interactive curriculum at one university's internal medicine residency program. The modules contained facilitator and learner guides and addressed four main content areas: understanding gender and sexuality; performing a sensitive history and physical examination; health promotion and disease prevention; and mental health, violence, and reproductive health. Knowledge, perceived importance, and confidence were assessed before and after each module to assess curricular effectiveness and acceptability. General medicine faculty delivered these modules. Results Perceived importance of LGBT topics was high at baseline and remained high after the curricular intervention. Confidence significantly increased in many areas, including being able to provide resources to patients and to institute gender-affirming practices (p < .05). Knowledge improved significantly on almost all topics (p < .0001). Faculty felt the materials gave enough preparation to teach, and residents perceived that the faculty were knowledgeable. Discussion This resource provides an effective curriculum for training internal medicine residents to better understand and feel confident addressing LGBT primary health care needs. Despite limitations, this is an easily transferable curriculum that can be adapted in a variety of curricular settings.
Comparison of Serum Inhibin B and Follicle-Stimulating Hormone (FSH) Level between Normal and Infertile Men in Yaoundé

Objective Hormones play a vital role in initiating and maintaining male reproductive function. The present study explores the influence and predictive ability of two reproductive hormones on semen quality among men who were partners in an infertile couple. Design During our cross sectional study, men were recruited from private and public hospital and laboratories for clinical evaluation of fertility status. Methods Fresh semen samples were assessed for quality (concentration, motility and morphology) according to the 2010 World Health Organization manual and the serum levels of hormones, including follicle-stimulating hormone (FSH), Inhibin B was measured (ELISA). Results We found a significant difference in the two groups regarding sperm concentration (p < 0.0001), total sperm count (p < 0.0001), total sperm count (p < 0.0001), total sperm count (p < 0.0001), total sperm count (p < 0.0001), total sperm count ( Conclusion Consistent with other studies, our results show strong association between semen quality and FSH and Inhibin B.
Vitamin D: Newer Concepts of Its Metabolism and Function at the Basic and Clinical Level

Abstract The interest in vitamin D continues unabated with thousands of publications contributing to a vast and growing literature each year. It is widely recognized that the vitamin D receptor (VDR) and the enzymes that metabolize vitamin D are found in many cells, not just those involved with calcium and phosphate homeostasis. In this mini review I have focused primarily on recent studies that provide new insights into vitamin D metabolism, mechanisms of action, and clinical applications. In particular, I examine how mutations in vitamin D metabolizing enzymes—and new information on their regulation—links vitamin D metabolism into areas such as metabolism and diseases outside that of the musculoskeletal system. New information regarding the mechanisms governing the function of the VDR elucidates how this molecule can be so multifunctional in a cell-specific fashion. Clinically, the difficulty in determining vitamin D sufficiency for all groups is addressed, including a discussion of whether the standard measure of vitamin D sufficiency, total 25OHD (25 hydroxyvitamin) levels, may not be the best measure—at least by itself. Finally, several recent large clinical trials exploring the role of vitamin D supplementation in nonskeletal diseases are briefly reviewed, with an eye toward what questions they answered and what new questions they raised.
Intravitreal Melphalan Chemotherapy for Vitreous Seeds in Retinoblastoma

Objective To evaluate our experience with intravitreal melphalan chemotherapy as a second-line regimen for RB patients with refractory or recurrent vitreous seeds. Methods A retrospective case series of 16 eyes from 16 patients with intraocular RB who received intravitreal melphalan chemotherapy using the antireflux injection technique. Data included demographics, stage at diagnosis, treatment modalities, side effects, eye salvage, and survival. Results The total number of injections was 64 (median, 3 injections per eye; range, 3–8), and the median age at time of injection was 22 months (range, 9–63 months). Nine (56%) patients were males, and 13 (81%) patients had bilateral RB. Complete response was seen in 13 (81%) eyes: in 9 (100%) eyes with focal vitreous seeds and in 4 (57%) eyes with diffuse vitreous seeds (P=0.062). At a median follow-up of 18 months (range, 6–48 months), the eye salvage rate was 81%, local retinal toxicity confined to the site of injection was seen in 2/3 of the eyes, 2 (12%) eyes had cataract, and none of the patients had orbital recurrence and distant metastasis or was dead. Conclusion Intravitreal melphalan is a promising modality for treatment of vitreous seeds, and the dose of 20–30 μg of melphalan sounds to be safe and effective for refractory and recurrent vitreous seeds. μg of melphalan sounds to be safe and effective for refractory and recurrent vitreous seeds.