Miracle-dz/UniFAR-FTUs huggingface dataset:
Development and Psychometric Evaluation of an Instrument Assessing Barriers to Growth Hormone Treatment (BAR-GHT)

Purpose: This paper presents development and validation of a new patient reported outcome measure (PRO), the Barriers to Growth Hormone Therapy (BAR-GHT) in a patient (child/adolescent) and a parent version. The BAR-GHT was developed to measure problems and potential barriers to GHT. Methods: The development and validation of the BAR-GHT was conducted according to the Food and Drug Administration (FDA) Guidance on the development of PROs. Concept elicitation included a literature review and open-ended interviews with young patients, parents, and clinical experts. Qualitative data were analyzed based on grounded theory principles and draft items were rated in terms of their importance and clarity. The instruments underwent psychometric validation in a German clinic-based patient population of children and adolescents who inject themselves and in a parent sample who inject their child. The statistical analysis plan included exploratory factor analysis, reliability, and validity. Results: 29 patients, 22 parents, and 4 clinical experts participated in the concept elicitation, 156 children and adolescents aged 8–18 years and 146 parents completed the validation study. Exploratory factor analysis resulted in six domains: Fear, Public Embarrassment, Annoyance, Daily Routine, Supplies, and Travel. Internal consistencies and test-retest reliabilities of the total score of both the patient version and the parent version were >0.8. Convergent and discriminant validity was demonstrated. Conclusions: The final 19-item BAR-GHT for patients aged 8–18 years and the 16-item version for parents can be considered reliable and valid PROs of barriers to GHT. Clinical Trial Registration: www.ClinicalTrials. gov, identifier: NCT03672617. Universal Trial Number (UTN) of the International Clinical Trials Registry Platform (ICTRP, www.who.int): U1111-1210-1036.
Consequences of Domestication on Gut Microbiome: A Comparative Study Between Wild Gaur and Domestic Mithun

Although the gut microbiome benefits the host in several ways, how anthropogenic forces impact the gut microbiome of mammals is not yet completely known. Recent studies have noted reduced gut microbiome diversity in captive mammals due to changes in diet and living environment. However, no studies have been carried out to understand how the gut microbiome of wild mammals responds to domestication. We analyzed the gut microbiome of wild and captive gaur and domestic mithun (domestic form of gaur) to understand whether the gut microbiome exhibits sequential changes from wild to captivity and after domestication. Both captive and domestic populations were characterized by reduced microbial diversity and abundance as compared to their wild counterparts. Notably, two beneficial bacterial families, Ruminococcaceae and Lachnospiraceae, which are known to play vital roles in herbivores’ digestion, exhibited lower abundance in captive and domestic populations. Consequently, the predicted bacterial functional pathways especially related to metabolism and immune system showed lower abundance in captive and domestic populations compared to wild population. Therefore, we suggest that domestication can impact the gut microbiome more severely than captivity, which might lead to adverse effects on host health and fitness. However, further investigations are required across a wide range of domesticates in order to understand the general trend of microbiome shifts in domestic animals.
A Novel DNA Methyltransferase Dnmt3a3 Splice Variant Represses Preadipocyte Proliferation and Differentiation

Proliferation and differentiation of preadipocyte are essential for the formation of fat tissues. However, the genes that regulate the early stage of preadipocyte differentiation in chicken have remained elusive. Here we identify a novel spliced variant of the DNA methyltransferase Dnmt3a gene, named Dnmt3a3, that controls early preadipocyte differentiation. Dnmt3a3 expression is increased at the onset of preadipocyte differentiation and remains elevated during differentiation. Overexpression of Dnmt3a3 in preadipocytes markedly inhibits proliferation and cell-cycle progression, and this is accompanied by inhibition of the mRNA and protein level of cell-cycle control genes, such as p21 and p27. In addition, forced expression of Dnmt3a3 in differentiating preadipocytes represses early preadipocyte differentiation, and this was found to be accompanied by inhibition of the mRNA expression levels of early preadipocyte differentiation markers, such as GATA2, GATA3, C/EBPα, C/EBPβ, AP2, and PPARγ, or the protein levels of GATA3, C/EBPβ, and PPARγ. Taken together, these data demonstrate the participation of Dnmt3a3 in the proliferation and differentiation process of chicken primary preadipocyte cells.
Manganese-Enhanced Magnetic Resonance Imaging: Application in Central Nervous System Diseases

Manganese-enhanced magnetic resonance imaging (MEMRI) relies on the strong paramagnetism of Mn2+. Mn2+ is a calcium ion analog and can enter excitable cells through voltage-gated calcium channels. Mn2+ can be transported along the axons of neurons via microtubule-based fast axonal transport. Based on these properties, MEMRI is used to describe neuroanatomical structures, monitor neural activity, and evaluate axonal transport rates. The application of MEMRI in preclinical animal models of central nervous system (CNS) diseases can provide more information for the study of disease mechanisms. In this article, we provide a brief review of MEMRI use in CNS diseases ranging from neurodegenerative diseases to brain injury and spinal cord injury.
Validation and Application of the Positive Play Scale Adapted for Chinese Gamblers: Its Relation to Disordered Gambling and Gambling Attitudes

The Positive Play Scale (PPS) was designed to track the effectiveness of responsible gambling (RG) policy, with a focus on positive changes in beliefs and behaviors instead of the absence of problem gambling symptoms. The current study aimed to (1) validate the Positive Play Scale Adapted for Chinese gamblers (PPS-AC) using a probability Chinese community sample in Macao, (2) explore the relationships between the PPS-AC and symptoms of gambling disorder (GD), and (3) evaluate the associations of gambling attitudes with the PPS-AC. Through a two-step random sampling procedure, we interviewed 1,002 locally dwelling Macao Chinese adults (44.3% males; Mage = 44.28 years, SDage = 17.35 years) by phone, in which 237 were past-year gamblers (49.8% males; Mage = 40.76 years, SDage = 15.78 years). Results showed that a two-dimension structure fitted the data well for both the positive play behaviors scale and the positive play beliefs scale of the PPS-AC among past-year gamblers. In addition to findings of satisfactory internal consistency, the convergent validity of the PPS-AC was supported by its significant association with RG self-efficacy. All four PPS-AC constructs were negatively correlated with GD symptoms, whereas two behavior constructs of the PPS-AC significantly explained the variance of GD symptoms with negative valences. All gambling attitude dimensions were associated with at least one PPS-AC construct. The current study was the first to adapt the PPS on a probability Chinese community sample and extended its applicability. The findings support the PPS-AC as a reliable and valid tool for assessing positive play, which was negatively associated with symptoms of disordered gambling. Further, the significant associations between gambling attitudes and the PPS-AC provide insights for RG policies.
Developmental Analysis of Mimulus Seed Transcriptomes Reveals Functional Gene Expression Clusters and Four Imprinted, Endosperm-Expressed Genes

The double fertilization of the female gametophyte initiates embryogenesis and endosperm development in seeds via the activation of genes involved in cell differentiation, organ patterning, and growth. A subset of genes expressed in endosperm exhibit imprinted expression, and the correct balance of gene expression between parental alleles is critical for proper endosperm and seed development. We use a transcriptional time series analysis to identify genes that are associated with key shifts in seed development, including genes associated with secondary cell wall synthesis, mitotic cell cycle, chromatin organization, auxin synthesis, fatty acid metabolism, and seed maturation. We relate these genes to morphological changes in Mimulus seeds. We also identify four endosperm-expressed transcripts that display imprinted (paternal) expression bias. The imprinted status of these four genes is conserved in other flowering plants, suggesting that they are functionally important in endosperm development. Our study explores gene regulatory dynamics in a species with ab initio cellular endosperm development, broadening the taxonomic focus of the literature on gene expression in seeds. Moreover, it is the first to validate genes with imprinted endosperm expression in Mimulus guttatus, and will inform future studies on the genetic causes of seed failure in this model system.
Role of Transient Receptor Potential Canonical Channels in Heart Physiology and Pathophysiology

Transient receptor potential canonical (TRPC) channels are involved in the regulation of cardiac function under (patho)physiological conditions and are closely associated with the pathogenesis of cardiac hypertrophy, arrhythmias, and myocardial infarction. Understanding the molecular mechanisms and the regulatory pathway/locus of TRPC channels in related heart diseases will provide potential new concepts for designing novel drugs targeting TRPC channels. We will present the properties and regulation of TRPC channels and their roles in the development of various forms of heart disease. This article provides a brief review on the role of TRPC channels in the regulation of myocardial function as well as how TRPC channels may serve as a therapeutic target in heart failure and cardiac arrhythmias including atrial fibrillation.
Trimetazidine-Induced Parkinsonism: A Systematic Review

Importance: Trimetazidine (TMZ) is a medication given to patients with stable coronary artery disease. While it is reportedly well-tolerated, there are increasing numbers of reports of adverse events such as parkinsonism. Objectives: The purpose of this study was to systematically review the currently available literature on TMZ-induced parkinsonism. Evidence Review: A search of Scopus, MEDLINE, EMBASE, the Cochrane Library, the Health Technology Assessment Database, PubMed, Science Direct, and Google Scholar was conducted on or before November 7, 2019. The literature search included cohort studies, prospective and/or retrospective studies, meta-analysis, and other systematic reviews published as an original article, including abstracts and full texts. We included patients taking TMZ who developed one or more of the parkinsonian symptoms of bradykinesia, tremors, rigidity, and postural instability, where these symptoms improved after withdrawal of the said medication. Findings: There are currently five studies on TMZ use and associated parkinsonism. The literature included two case reports, one case series, and one retrospective and one prospective study. We found no results from randomized clinical trials. Overall, 88 patients developed TMZ-induced parkinsonism. Regression of parkinsonism was reported in all of the participants after withdrawal of TMZ. A total of 49 patients (55.7%) had complete regression of symptoms, while 39 patients (44.3%) had significant reduction of symptoms. The duration between TMZ (dose, 60–80 mg/day) intake and onset of symptoms ranged from 4 months to 20 years. The most commonly reported extrapyramidal symptoms were akinesia, rigidity, postural disturbances, and gait disorders, which were usually mild and symmetric. Conclusions and Relevance: The current literature suggests that TMZ can induce parkinsonism that is reversible with drug withdrawal. It is warranted to examine patients, especially the elderly, on TMZ for parkinsonian symptoms and those with pre-existing neurodegenerative diseases. Further studies are needed to assess the risk-benefit ratio of this drug, especially in the elderly age group.
Dysfunction of Inferior Parietal Lobule During Sensory Gating in Patients With Amnestic Mild Cognitive Impairment

Patients with amnestic mild cognitive impairment (aMCI) demonstrate significant cognitive deficits, especially in the memory aspect. The memory deficiency might be attributed to the difficulties in the inhibitory function to suppress redundant stimuli. Sensory gating (SG) refers to the attenuation of neural responses to the second identical stimulus in a paired-click paradigm, in which auditory stimuli are delivered in pairs with inter-stimulus intervals (ISI) of 500 ms and inter-pair intervals of 6–8 s. It is considered as an electrophysiological signal to reflect the brain’s automatic response to gate out repetitive sensory inputs. However, there has been no study systematically investigating SG function in aMCI patients. Thus, the present study used magnetoencephalography (MEG) to record neuromagnetic responses to a paired-click paradigm in 23 healthy controls (HC) and 26 aMCI patients. The Stimulus 2/Stimulus 1 (S2/S1) amplitude ratio was used to represent the SG function. Compared to HC, aMCI patients showed M50 SG deficits in the left inferior frontal gyrus (IFG) and right inferior parietal lobule (IPL). M100 SG defects were also observed in the right IPL. Based on the ROIs showing significant between-group SG differences, we found that a more deficient M50 SG function in the right IPL was associated with poorer performance in the immediate recall of Logic Memory (LM), Chinese Version Verbal Learning Test (CVVLT) and Digit Span Backward (DSB) Test. Furthermore, the M50 SG ratios of the right IPL together with the neuropsychological performance of LM and CVVLT demonstrated very good accuracy in the discrimination of aMCI from HC. In conclusion, compared to HC, aMCI patients showed a significant SG deficit in the right IPL, which was correlated with the auditory short-term memory function. We suggest the combination of SG in the right IPL, LM and CVVLT to be sensitive indicators to differentiate aMCI patients from HC.
Glioma Migration Through the Corpus Callosum and the Brainstem Detected by Diffusion and Magnetic Resonance Imaging: Initial Findings

Purpose: Glioma cell infiltration, in which the glioma tumor cells spread long distances from the primary location using white matter (WM) or blood vessels, is known as a significant challenge for surgery or localized chemotherapy and radiation therapy. Following the World Health Organization (WHO), the glioma grading system ranges from stages I to IV, in which lower-grade gliomas represent benign tumors, and higher grade gliomas are considered the most malignant. Materials and Methods: We gathered magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) data for seven patients with right precentral gyrus-located tumors and six age- and sex-matched healthy subjects for analysis. Tract-Based Spatial Statistics (TBSS) was utilized to evaluate whole-brain WM implication due to probable tumor infiltration. Also, along-tract statistics were used in order to trace the implicated WM tracts. Finally, for cortical evaluation of probable tumor cell migration, voxel-based morphometry (VBM) was utilized, which allowed us to do whole-brain cortical estimation. Results: The TBSS results revealed significantly higher fractional anisotropy (FA) and lower mean diffusivity (MD) in the left side superior corona radiata. Also, higher FA was observed in the right corticostriatal tract. Along-tract statistics were also compiled on the corpus callosum (CC), which is anatomically known as a hub between hemispheres. The body of the CC, which connected with the superior corona radiata anatomically, showed significantly higher FA values relative to healthy subjects, which are in line with the TBSS results. Consistent with these results, whole-brain gray matter changes were analyzed via VBM, which showed significant hypertrophy of both sides of the brainstem. Conclusion: In future investigations, focusing on the genetic basis of the glioma patients in line with imaging studies on a larger sample size, which is known as genetics imaging, would be a suitable approach for tracing this process.
Simulation in Neonatal Resuscitation

Approximately 1 in 10 newborns will require basic resuscitation interventions at birth. Some infants progress to require more advanced measures including the provision of positive pressure ventilation, chest compressions, intubation and administration of volume/cardiac medications. Although advanced resuscitation is infrequent, it is crucial that personnel adequately trained in these techniques are available to provide such resuscitative measures. In 2000, Louis Halmalek et al. called for a “New Paradigm in Pediatric Medical Education: Teaching Neonatal Resuscitation in a Simulated Delivery Room Environment. ” This was one of the first articles to highlight simulation as a method of teaching newborn resuscitation. The last decades have seen an exponential growth in the area of simulation in newborn care, in particular in newborn resuscitation and stabilization. Simulation is best defined as an instructional strategy “used to replace or amplify real experiences with guided experiences that evoke or replicate substantial aspects of the real world in a fully interactive manner. ” Simulation training has now become an important point of how we structure training and deliver improved healthcare to patients. Some of the key aspects of simulation training include feedback, deliberate practice, outcome measurement, retention of skills and curriculum integration. The term “Train to win” is often used in sporting parlance to define how great teams succeed. The major difference between sports teams is that generally their game day comes once a week, whereas in newborn resuscitation every day is potentially “game day. ” In this review we aim to summarize the current evidence on the use of simulation based education and training in neonatal resuscitation, with particular emphasis on the evidence supporting its effectiveness. We will also highlight recent advances in the development of simulation based medical education in the context of newborn resuscitation to ensure we “train to win. ”
Anti-proliferative and cytotoxic effect of Iranian snake (Vipera raddei kurdistanica) venom on human breast cancer cells via reactive oxygen species-mediated apoptosis

Background and purpose: Breast cancer is the most commonly occurring cancer in women around the world. Despite new advances in cancer therapy, breast cancer remains a disease with high morbidity and mortality. Snake venom is a poisonous mixture of different molecules, such as carbohydrates, nucleosides, amino acids, lipids, proteins, and peptides. Previous studies demonstrated that some snake venoms showed in vitro anti-cancer effects. In this study, the effects of the Iranian snake (Vipera raddei kurdistanica) venom on breast cancer cells were investigated. Experimental approach: The effect of increasing concentrations of snake venom on breast cell viability was assessed by trypan blue, MTT, and lactate dehydrogenase measurements. Apoptosis was detected and quantified by fluorescent staining and DNA fragmentation assay. The expression level of some apoptotic-related genes was investigated using real-time polymerase chain reaction (RT-PCR). The Western blotting method was also used to detect the protein expression profiles in the cells. Findings / Results: After treatment for 24, 48, 72, and 96 h, the cell viability was significantly reduced in a time- and dose-dependent manner (P < 0.05). The venom effect on normal breast cells was significantly smaller than cancer cells (P > 0.05). Apoptosis was significantly increased (P < 0.05). The RT-PCR and western blot data confirmed the increase of apoptosis in cells treated with venom. Conclusion and implications: These data suggested that the vipera raddei kurdistanica venom had a cytotoxic property via activation of apoptosis in breast cancer cells.
Analysis on Risk Factors of Depressive Symptoms in Occupational Noise-induced Hearing Loss Patients: A Cross-sectional Study

Objective: The aim of this study was to evaluate the risk factors of depressive symptoms in occupational noise-induced hearing loss (NIHL) patients. Methods: A total of 106 patients were divided into depressive symptoms (ONHLPD) and without depressive symptoms (non-ONHLPD) according to the Self-rating Depression Scale. Questionnaires and laboratory data were collected and analyzed. Data were analyzed with independent t-test, Wilcoxon test, Pearson correlation analysis and multiple linear regression models. Results: The prevalence of depressive symptoms was 53.8% in occupational NIHL patients. In ONHLPD, duration of the hearing loss, level of serum cortisol, scores of Pittsburgh Sleep Quality Index and Tinnitus Handicap Inventory were all significantly higher than those of non-ONHLPD. Conclusion: The prevalence of depressive symptoms was relatively high in occupational NIHL patients. Duration of the hearing loss, sleep quality and tinnitus severity were the risk factors for occupational NHIL patients with depressive symptoms.
Isolation of a Novel Phage and Targeting Biofilms of Drug-Resistant Oral Enterococci

Introduction: Enterococci are now recognized as the second most cause of nosocomial infections worldwide. The emergence of multidrug-resistant strains in the organism has given rise to alternative strategies such as phage therapy. In this study, an Enterococcus faecalis infecting phage was isolated and its efficiency against biofilms formed by drug-resistant enterococci obtained from chronic periodontitis was evaluated. Materials and Methods: Bacteriophage against E. faecalis was isolated from sewage sample. The phage was propagated and identified using transmission electron microscope (TEM). In vitro biofilm formation was assessed. Results: TEM microscopy showed that the phage belonged to Siphoviridae family. In the presence of the novel phage, the metabolic activity of enterococci biofilm was reduced at 48 h of contact. A difference of at least 5 log CFU/ml was seen in the live cells of the control biofilm, and the phage treated biofilm of enterococci isolates. Conclusion: The study shows that the novel phage inhibits biofilm production in oral enterococci isolates from periodontitis patients but has a narrow host range. The role of bacteriophages as strong biotechnological and natural therapeutic agents for E. faecalis in chronic periodontitis can be considered.
Reinforcement learning: Multi-armed bandits

Reinforcement learning is a branch of machine learning inspired by the way animals (including humans) learn to live and improve themselves by interacting with their environment. Typically, young animals are curious, try a lot of different actions before concentrating on the best ones, following a trial-and-error strategy. It is tempting (but far from easy) to let machines learn this way to improve their intelligence and accomplish some specific tasks. The applications are numerous: robotics, medecine, content recommendation, advertising, marketing, chatbots, games, to quote a few. In this note, we focus on so-called multi-armed bandits, a class of reinforcement learning problems where an agent must take a sequence of actions while observing the corresponding sequence of rewards. A key feature of multi-armed bandits is that the agent does not modify its environment through its actions. Its assigned objective is to discover the best actions, that is, those offering the highest rewards, and to exploit them. In particular, the agent faces the so-called exploration-exploitation dilemna: she must typically try all actions to learn what is the best (exploration) but needs to quickly converge to the (believed) best one to accumulate rewards (exploitation).