Miracle-dz/UniFAR-FTUs huggingface dataset:
New advances in the treatment of generalized anxiety disorder: the multimodal antidepressant vortioxetine

ABSTRACT Generalized Anxiety Disorder (GAD) is a persistent condition characterized by chronic anxiety, exaggerated worry and tension, mainly comorbid with Major Depressive Disorder (MDD). Currently, selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are recommended as first-line treatment of GAD. However, some patients may not respond to the treatment or discontinue due to adverse effects. Vortioxetine (VRX) is a multimodal antidepressant with a unique mechanism of action, by acting as 5-HT3A, 5-HT1D and 5-HT7 receptor antagonist, partial agonist at the 5-HT1A and 5-HT1B receptors and inhibitor at the 5-HT transporter. Preliminary clinical trials showed contrasting findings in terms of improvement of the anxiety symptomatology and/or cognitive impairment. Here, we aim to systematically review the evidence currently available on the efficacy, safety and tolerability of VRX in the treatment of GAD. The generalizability of results on the efficacy of VRX in patients with anxiety symptomatology and GAD is limited due to few and contrasting RCTs so far available. Only two studies, of which one prevention relapse trial, reported a significant improvement in anxiety symptomatology compared to three with negative findings.
The TMEM127 human tumor suppressor is a component of the mTORC1 lysosomal nutrient-sensing complex

The TMEM127 tumor suppressor gene encodes a transmembrane protein of unknown function mutated in pheochromocytomas and, rarely, in renal cancers. Tumors with inactivating TMEM127 mutations have increased mTORC1 signaling by undefined mechanisms. Here we report that TMEM127 interacts with the lysosome-anchored complex comprised of Rag GTPases, the LAMTOR pentamer (or 'ragulator') and vATPase, which controls amino acid-mediated mTORC1 activation. We found that under nutrient-rich conditions TMEM127 expression reduces mTORC1 recruitment to Rags. In addition, TMEM127 interacts with LAMTOR in an amino acid-dependent manner and decreases the LAMTOR1-vATPase association, while TMEM127-vATPase binding requires intact lysosomal acidification but is amino acid independent. Conversely, both murine and human cells lacking TMEM127 accumulate LAMTOR proteins in the lysosome. Consistent with these findings, pheochromocytomas with TMEM127 mutations have increased levels of LAMTOR proteins. These results suggest that TMEM127 interactions with ragulator and vATPase at the lysosome contribute to restrain mTORC1 signaling in response to amino acids, thus explaining the increased mTORC1 activation seen in TMEM127-deficient tumors.
Large interactive visualization of density functions on big data infrastructure

Point set visualization is required in lots of visualization techniques. Scatter plots as well as geographic heat-maps are straightforward examples. Data analysts are now well trained to use such visualization techniques. The availability of larger and larger datasets raises the need to make these techniques scale as fast as the data grows. The Big Data Infrastructure offers the possibility to scale horizontally. Designing point set visualization methods that fit into that new paradigm is thus a crucial challenge. In this paper, we present a complete architecture which fully fits into the Big Data paradigm and so enables interactive visualization of heatmaps at ultra-scale. A new distributed algorithm for multi-scale aggregation of point set is given and an adaptive GPU based method for kernel density estimation is proposed. A complete prototype working with Hadoop, HBase, Spark and WebGL has been implemented. We give a benchmark of our solution on a dataset having more than 2 billion points.
Evaluating the Nasal Cytology in Acute Rhinosinusitis

Rhinitis has been found to have profound direct and indirect negative effects on business including costs attributed to loss of productivity and the amount of over the counter medications consumed. Several other studies have examined the immune system’s response in immunocompromised patients by using nasal cytology. This study focused on nasal cytology for a common illness such as acute rhinosinusitis (ARS), in otherwise healthy individuals. Most studies have used nasal cytology to analyze immunocompromised patients, however, this study considers otherwise healthy patients in order to better understand the basic immune response. This study aimed to examine the relationship between neutrophil frequencies found over the course of ARS and symptom severity experienced by subjects. Nasal smears were obtained from subjects at days five, nine, and fourteen of their ARS symptoms. A published symptom survey for ARS was given to participants to provide a qualifying score, signifying a high enough level of symptoms for this study. This survey monitored both emotional and physical symptoms throughout the fourteen-day illness period. Nasal smears were obtained on each visit and stained to observe the different cells present. Wilcoxon Sum Rank Tests were found to be significant between all symptom score visits 1,2, and 3 (p 0.05). Less than ten percent of eosinophils were present in 88.89 percent of subjects. 55.5 percent of subjects did follow an increased amount of neutrophils over the course of their illness. This study reinforces the use of nasal cytology by obtaining nasal smears to demonstrate how neutrophil frequencies change with symptom severity.
GeTe Encapsulated within Single-Walled Carbon Nanotubes

Due to an impressive portfolio of unusual properties arising as a result of their reduced dimensionality, carbon nanotubes are expected to provide a viable solution to down scaling challenges triggered by the aggressive miniaturisation of conventional electronic components. Carbon nanotube–based devices make use of their semiconductor behaviour whereas their metallic behaviour is needed to serve as interconnects. Due to their unique dimensions and geometry, nanometer diameter-sized carbon nanotubes also provide an exceptional opportunity of engineering novel one-dimensional structures within their hollow inner cores. Filling the inner cores of carbon nanotubes with foreign materials opens new possibilities of obtaining one-dimensional structures with sometimes novel structures and modified crystal chemistries compared to their bulk counterparts. One can envisage the use of phase change materials to be encapsulated within carbon nanotubes, as these materials are currently some of the most promising materials for data-storage applications and offer great potential as an emerging non-volatile electronic memory. As well as creating one-dimensional structures in architectures not known before, the encapsulation method offers the opportunity to study the properties and phase change behaviour of these materials at their smallest conceivable scale. We show that the binary chalcogenide compound GeTe, one of the most studied phase change materials, can be effectively encapsulated within single-walled carbon nanotubes and report on a scanning tunnelling microscopy study, coupled with structural investigations by aberration corrected high resolution transmission electron microscopy. As well as resolving the structure of encapsulates at the atomic level, we determine that the filling species arrange themselves into continuous nanowires with lengths of up to a few hundred nm. Based on scanning tunnelling spectroscopy data, information on the electronic structure of encapsulated nanowires has been extracted with the aid of the predicted density of states for the particular nanotubes. Aspects related to charge transfer between the host nanotube and the encased material, as well as information on the occupied band structure of these systems have been examined using ultraviolet photoelectron spectroscopy experiments and the work function of the hybrid systems determined.
Maternal Hypertension, Medication Use, and Hypospadias in the National Birth Defects Prevention Study

OBJECTIVE: To investigate whether antihypertensive classes and specific medications in early pregnancy increase the risk of severe hypospadias and to assess prior associations detected for late-treated and untreated hypertension in the National Birth Defects Prevention Study. METHODS: Using telephone interviews from mothers of 2,131 children with severe hypospadias and 5,129 nonmalformed male control children for 1997–2009 births in a population-based case–control study, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs) with multivariable logistic regression. We adjusted P values to account for multiple testing. RESULTS: Forty-eight (2.3%) case and 70 (1.4%) control mothers reported early pregnancy antihypertensive treatment, 45 (2.1%) case and 31 (0.6%) control mothers reported late treatment, and 315 (14.8%) case and 394 (7.7%) control mothers reported untreated hypertension. Selective &bgr;-blockers, centrally acting agents, renin–angiotensin system-acting agents, diuretics, and specific medications, methyldopa and atenolol, were not associated with hypospadias. Nonselective &bgr;-blockers (adjusted OR 3.22, 95% CI 1.47–7.05) were associated with hypospadias; however, P values adjusted for multiple testing were not statistically significant. We confirmed prior findings for associations between hypospadias and untreated hypertension (adjusted OR 2.09, 95% CI 1.76–2.48) and late initiation of treatment (adjusted OR 3.98, 95% CI 2.41–6.55). The increased risks would translate to severe hypospadias prevalences of 11.5, 17.7, and 21.9 per 10,000 births for women with untreated hypertension, nonselective &bgr;-blocker use, and late initiation of treatment, respectively. CONCLUSION: Our study suggests a relationship between hypospadias and the severity of hypertension. LEVEL OF EVIDENCE: II
Critical Roles of Glutaredoxin in Brain Cells-Implications for Parkinson's Disease.

SIGNIFICANCE Glutaredoxin (Grx)1, an evolutionarily conserved and ubiquitous enzyme, regulates redox signal transduction and protein redox homeostasis by catalyzing reversible S-glutathionylation. Grx1 plays different roles in different cell types. In Parkinson's disease (PD), Grx1 regulates apoptosis signaling in dopaminergic neurons, so that loss of Grx1 leads to increased cell death; in microglial cells, Grx1 regulates proinflammatory signaling, so that upregulation of Grx1 promotes cytokine production. Here we examine the regulatory roles of Grx1 in PD with a view toward therapeutic innovation. Recent Advances: In postmortem midbrain PD samples, Grx1 was decreased relative to controls, specifically within dopaminergic neurons. In Caenorhabditis elegans models of PD, loss of the Grx1 homologue led to exacerbation of the neurodegenerative phenotype. This effect was partially relieved by overexpression of neuroprotective DJ-1, consistent with regulation of DJ-1 content by Grx1. Increased GLRX copy number in PD patients was associated with earlier PD onset; and Grx1 levels correlated with levels of proinflammatory tumor necrosis factor-α in mouse and human brain samples. In vitro studies showed Grx1 to be upregulated on proinflammatory activation of microglia. Direct overexpression of Grx1 increased microglial activation; silencing Grx1 diminished activation. Grx1 upregulation in microglia corresponded to increased neuronal cell death in coculture. Overall, these studies identify competing roles of Grx1 in PD etiology. CRITICAL ISSUES The dilemma regarding Grx1 as a PD therapeutic target is whether to stimulate its upregulation for neuroprotection or inhibit its proinflammatory activity. FUTURE DIRECTIONS Further investigation is needed to understand the preponderant role of Grx1 regarding dopaminergic neuronal survival.
Preparation of fully hydrolyzed polyvinyl alcohol electrospun nanofibers with diameters of sub-200 nm by viscosity control

Fully hydrolyzed polyvinyl alcohol (FH-PVA) electrospun fibers with uniform diameters of less than 200 nm were fabricated by reducing the viscosity of FH-PVA aqueous solutions. A novel viscosity-modifier (hydrazine monochloride [HMC]) gradually reduced the viscosity of FH-PVA aqueous solution over a period of several days. This phenomenon is counter to the effect of the usual salt addition. After being stored for several days, the viscosity decreased by up to 60% compared with that of an equivalent pure FH-PVA solution. From small angle X-ray scattering (SAXS) and proton nuclear magnetic resonance (1H NMR) spectra observations it is evident that this effect results from the reconfiguration of hydrogen bonding. The viscosity control of FH-PVA solutions with HMC were used to electrospin highly uniform ultrafine fibers (diameter <200 nm).
A Comprehensive Review on Metabolic Syndrome

Metabolic syndrome is defined by a constellation of interconnected physiological, biochemical, clinical, and metabolic factors that directly increases the risk of cardiovascular disease, type 2 diabetes mellitus, and all cause mortality. Insulin resistance, visceral adiposity, atherogenic dyslipidemia, endothelial dysfunction, genetic susceptibility, elevated blood pressure, hypercoagulable state, and chronic stress are the several factors which constitute the syndrome. Chronic inflammation is known to be associated with visceral obesity and insulin resistance which is characterized by production of abnormal adipocytokines such as tumor necrosis factor α, interleukin-1 (IL-1), IL-6, leptin, and adiponectin. The interaction between components of the clinical phenotype of the syndrome with its biological phenotype (insulin resistance, dyslipidemia, etc.) contributes to the development of a proinflammatory state and further a chronic, subclinical vascular inflammation which modulates and results in atherosclerotic processes. Lifestyle modification remains the initial intervention of choice for such population. Modern lifestyle modification therapy combines specific recommendations on diet and exercise with behavioural strategies. Pharmacological treatment should be considered for those whose risk factors are not adequately reduced with lifestyle changes. This review provides summary of literature related to the syndrome's definition, epidemiology, underlying pathogenesis, and treatment approaches of each of the risk factors comprising metabolic syndrome.
Application of vacuum sealing drainage to the treatment of seawater‐immersed blast‐injury wounds

The aims of this study were to observe the effects of vacuum sealing drainage (VSD) with three different negative pressures on the wound healing rate, macrophage count and the expression of hyaluronic acid (HA) as well as its receptor CD44 in seawater‐immersed blast‐injury wounds (SIBIW) and to determine the optimal negative pressure value. In a minipig SIBIW model, different suction pressures and routine dressing were applied. Histological and immunohistochemical comparisons as well as molecular biology methods were performed to compare the wound healing conditions, macrophage count and the levels of HA and CD44. The wound healing rate of the VSD group was significantly higher than that of the control group, with the −120 mmHg group exhibiting the best effects. The macrophage count of the VSD group was higher than that of the control group. The HA level fluctuation was higher in the VSD group, with the −120 mmHg and the −180 mmHg groups showing the most significant fluctuation (P < 0·05). CD44 was expressed in the full‐thickness wound‐limbic tissues and was higher in the treatment group than that in the control group, with the −120 mmHg group having the most obvious expression. VSD significantly improved the healing ability and increased the macrophage count and the HA content. It also promoted CD44 expression. −120 mmHg is the optimal negative pressure value.
Design of a Novel Gene Therapy Construct to Achieve Sustained Brain-Derived Neurotrophic Factor Signaling in Neurons

Brain-derived neurotrophic factor (BDNF) acting through the tropomyosin-related receptor-B (TrkB) is an important signaling system for the maintenance and survival of neurons. Gene therapy using either recombinant adeno-associated virus (AAV) or lentiviral vectors can provide sustained delivery of BDNF to tissues where reduced BDNF signaling is hypothesized to contribute to disease pathophysiology. However, elevation in BDNF at target sites has been shown to lead to a downregulation of TrkB receptors, thereby reducing the effect of chronic BDNF delivery over time. A novel gene sequence has been designed coding both the ligand (BDNF) and the TrkB receptor in a single transgene separated by a short viral-2A sequence. The single transgene is efficiently processed intracellularly in vitro and in vivo to yield the two mature proteins, which are then independently transported to their final cellular locations: TrkB receptors to the cell surface, and BDNF contained within secretory vesicles. To accommodate the coding sequences of both BDNF and TrkB receptors within the narrow confines of the AAV vectors (4.7 kb pairs), the coding region for the pro-domain of BDNF was removed and the signal peptide sequence modified to improve production, intracellular transport, and secretion of mature BDNF (mBDNF). Intracellular processing and efficacy was shown in HEK293 cells and SH-SY5Y neuroblastoma cells using plasmid DNA and after incorporating the TrkB-2A-mBDNF into an AAV2 vector. Increased BDNF/TrkB-mediated intracellular signaling pathways were observed after AAV2 vector transfection while increased TrkB phosphorylation could be detected in combination with neuroprotection from hydrogen peroxide–induced oxidative stress. Correct processing was also shown in vivo in mouse retinal ganglion cells after AAV2 vector administration to the eye. This novel construct is currently being investigated for its efficacy in animal models to determine its potential to progress to human clinical studies in the future.
Daytime sleep duration and the development of childhood overweight: the KOALA Birth Cohort Study

Reduced nighttime sleep is a risk factor for childhood overweight, but the association between daytime sleep and overweight is unknown. The aim of this study is to evaluate daytime sleep duration as an independent risk factor for childhood overweight. Data from the KOALA Birth Cohort Study on daytime and nighttime sleep at 2 years (N = 2322), and body mass index (BMI) around 2, 5, 6, 7, 8 and 9 years were used. Multivariable general estimating equation regression analyses were performed to examine the associations of sleep duration with BMI (linear) and overweight (logistic). No associations between daytime sleep and BMI or overweight were found, whereas longer nighttime sleep was associated with lower BMI and lower risk of overweight persisting up to age 9. Daytime sleep duration is probably less relevant for prevention of childhood overweight.
Cultural Adaptation of a Dyadic Intervention for Korean Couples Coping with Alzheimer’s Disease

ABSTRACT Objectives: The Couples Life Story Approach (CLSA) was recently developed in the U.S. for older couples dealing with dementia to improve their quality of life. The purpose of this article is to describe how the CLSA was adapted to be culturally appropriate for older Korean couples and to discuss cultural themes that emerged during the implementation process. Methods: The intervention was adapted using the Cultural Adaptation Process Model. The revised materials were implemented on 56 Korean couples. A multiple case study method was used to analyze the clinical data. Results: Four cultural themes were identified: (1) dealing with negative memories in early years of marriage; (2) communication styles and patterns; (3) ways to incorporate difficult life events into the Life Story Book; and (4) complex dynamics of heirarchy in the relationship between older couples and the interventionist. With each theme, case examples are described that illustrate relevant issues. Conclusions: Cultural adaptation can be conducted systematically to improve the delivery of the CLSA for different populations. Clinical Implications: Cliniocians working with older Korean couples affected by dementia should consider cultural uniqueness in a life-story approach.
Seed-Point Detection of Clumped Convex Objects by Short-Range Attractive Long-Range Repulsive Particle Clustering

Locating the center of convex objects is important in both image processing and unsupervised machine learning/data clustering fields. The automated analysis of biological images uses both of these fields for locating cell nuclei and for discovering new biological effects or cell phenotypes. In this work, we develop a novel clustering method for locating the centers of overlapping convex objects by modeling particles that interact by a short-range attractive and long-range repulsive potential and are confined to a potential well created from the data. We apply this method to locating the centers of clumped nuclei in cultured cells, where we show that it results in a significant improvement over existing methods (8.2% in F$_1$ score); and we apply it to unsupervised learning on a difficult data set that has rare classes without local density maxima, and show it is able to well locate cluster centers when other clustering techniques fail.
Relationship of performance on the sensory organization test to landing characteristics

ABSTRACT Jump landing tasks have been used to assess landing characteristics and require significant sensorimotor feedback to maintain functional joint stability (FJS) throughout the task. Postural stability (PS) also requires significant sensorimotor feedback and control and would seemingly involve similar sensory feedback pathways. However, previous literature clarifying the relationship between these two processes, maintaining FJS and PS, is limited. 80 Special Tactics Operators. PS was assessed using the Sensory Organization Test (SOT). SOT variables included: Composite, Somatosensory, Visual, Vestibular, and Preference scores. Landing characteristics were assessed using motion analysis during a double-legged (DLSJ) and single-legged (SLSJ) stop jump task. Pearson’s correlation coefficients were calculated to assess the relationship between SOT scores and landing characteristics (α < .05). For the DLSJ, significant correlations were found between: Composite and peak posterior ground reaction forces (−.257), Vestibular and peak knee abduction moment (−.237), and Preference and initial contact hip flexion (−.297), peak hip flexion (−.249). For the SLSJ, significant correlations were found between: Somatosensory and peak vertical ground reaction forces (−.246); Preference and initial contact hip flexion (−.295), peak hip flexion (−.262). The results indicate that the SOT may not be a sensitive enough tool to assess sensorimotor control in a healthy, athletic population.