Miracle-dz/UniFAR-FTUs huggingface dataset:
Expert opinion on the use of biological therapy in non-infectious uveitis

ABSTRACT Introduction: Conventional immunosuppressive drugs, anti-TNF alpha treatments and biotherapies are increasingly being used in non-infectious uveitis. Areas covered: The present work was led by a multidisciplinary panel of experts, including internal medicine specialists, rheumatologists and ophthalmologists, and proposes an extensive review on the use of biological agents in non-infectious uveitis. Expert opinion: In case of dependency to steroids or sight-threatening disease, conventional immunosuppressive drugs (methotrexate, azathioprine and mycophenolate mofetil) and/or biological therapies such as anti-TNF alpha treatments (adalimumab, infliximab) can be used to achieve and maintain disease quiescence. Interferon is an efficient immunomodulatory drug that can be proposed as second-line therapy in specific indications (eg. refractory macular edema, sight-threatening Behçet’s uveitis). Other biologics, especially tocilizumab, are showing promising results. Local treatments (steroids, sirolimus etc.) can be used as adjuvant therapies in case of unilateral relapse. Therapeutic response must always be evaluated by clinical examination and appropriate ancillary investigations.
Prelimbic neuronal nitric oxide synthase inhibition exerts antidepressant-like effects independently of BDNF signalling cascades

Abstract Objectives NMDA antagonists and nitric oxide synthase (NOS) inhibitors induce antidepressant-like effects and may represent treatment options for depression. The behavioural effects of NMDA antagonists seem to depend on Tyrosine kinase B receptor (TrkB) activation by BDNF and on mechanistic target of rapamycin (mTOR), in the medial prefrontal cortex (mPFC). However, it is unknown whether similar mechanisms are involved in the behavioural effects of NOS inhibitors. Therefore, this work aimed at determining the role of TrkB and mTOR signalling in the prelimbic area of the ventral mPFC (vmPFC-PL) in the antidepressant-like effect of NOS inhibitors. Methods Pharmacological treatment with LY235959 or ketamine (NMDA antagonists), NPA or 7-NI (NOS inhibitors), BDNF, K252a (Trk antagonist) and rapamycin (mTOR inhibitor) injected systemically or into vmPFC-PL followed by behavioural assessment. Results We found that bilateral injection of BDNF into the vmPFC-PL induced an antidepressant-like effect, which was blocked by pretreatment with K252a and rapamycin. Microinjection of LY 235959 into the vmPFC-PL induced antidepressant-like effect that was suppressed by local rapamycin but not by K252a pretreatment. Microinjection of NPA induced an antidepressant-like effect insensitive to both K252a and rapamycin. Similarly, the antidepressant-like effects of a systemic injection of ketamine or 7-NI were not affected by blockade of mTOR or Trk receptors in the vmPFC-PL. Conclusion Our data support the hypothesis that NMDA blockade induces an antidepressant-like effect that requires mTOR but not Trk signalling into the vmPFC-PL. The antidepressant-like effect induced by local NOS inhibition is independent on both Trk and mTOR signalling in the vmPFC-PL.
The effect of harmaline on seizures induced by amygdala kindling in rats

ABSTRACT Objective: Harmaline and other beta-carbolines act as an inverse agonist for GABA-A receptors and cause central nervous system stimulation and anxiety; thus, it may act hypothetically as a potential seizure augmenter. To examine the hypothesis, the effect of harmaline during the seizures induced by amygdala kindling is investigated here. Methods: Seven groups of male rats were kindled by daily electrical stimulation of the amygdala. After being kindled, Groups I–III, respectively, received 5, 15 and 50 mg/kg harmaline through intraperitoneal injection. The rats in Groups IV and V received vehicle daily (1 ml/kg) and harmaline (5 mg/kg) daily through intraperitoneal injection. Groups VI and VII received artificial cerebrospinal fluid and harmaline (50 mM) through intraventricular injection, respectively. Results: In addition to significant increase of some seizure parameters in the fully kindled groups, harmaline significantly increased cumulative afterdischarge duration (P < 0.05) and decreased stage 1 latency (P < 0.01) in the acquisition groups (Groups V and VII). In Group VII, seizure duration showed a significant increase (P < 0.01) while stage 1 latency and stage 4 latency decreased significantly (P < 0.01). Discussion: According to the results, it is suggested that harmaline may increase neuronal activity and the production of high-frequency action potentials by stimulating NMDA receptors and inhibiting GABA receptors. Overall, drugs and plants containing harmaline may be harmful to epileptic-susceptible people during some traditionally and costume treatments, so these should be avoided.
A high-content imaging approach to profile C. elegans embryonic development

ABSTRACT The Caenorhabditis elegans embryo is an important model for analyzing mechanisms of cell fate specification and tissue morphogenesis. Sophisticated lineage-tracing approaches for analyzing embryogenesis have been developed but are labor intensive and do not naturally integrate morphogenetic readouts. To enable the rapid classification of developmental phenotypes, we developed a high-content method that employs two custom strains: a Germ Layer strain that expresses nuclear markers in the ectoderm, mesoderm and endoderm/pharynx; and a Morphogenesis strain that expresses markers labeling epidermal cell junctions and the neuronal cell surface. We describe a procedure that allows simultaneous live imaging of development in 80-100 embryos and provide a custom program that generates cropped, oriented image stacks of individual embryos to facilitate analysis. We demonstrate the utility of our method by perturbing 40 previously characterized developmental genes in variants of the two strains containing RNAi-sensitizing mutations. The resulting datasets yielded distinct, reproducible signature phenotypes for a broad spectrum of genes that are involved in cell fate specification and morphogenesis. In addition, our analysis provides new in vivo evidence for MBK-2 function in mesoderm fate specification and LET-381 function in elongation. Summary: A high-content imaging-based method for phenotypically profiling genes that are required for cell fate specification and tissue morphogenesis in the C. elegans embryo uncovers previously unreported in vivo functions for MBK-2 and LET-381.
A Novel and Practical Scheme for Resolving the Quality of Samples in Background Modeling

In view of its important application value, background modeling is studied so widely that many techniques have emerged, which mainly concentrate on the selections of the basic model, the granularity of processing, the components in a framework, etc. However, the quality of samples (QoS) for training has long been ignored. There are two aspects regarding this issue, which are how many samples are suitable and which samples are reliable. To tackle the “how many” problem, in this paper, we propose a convergent method, coined Bi-Variance (BV), to decide an appropriate endpoint in the training sequence. In this way, samples in the range from the first frame to the endpoint can be used for model establishment, rather than using all the samples. With respect to the “which” problem, we construct a pixel histogram for each pixel and subtract one from each bin (called number of intensity values (NoIV-1)), which can efficiently get rid of outliers. Furthermore, our work is plug-and-play in nature, so that it could be applied to diverse sample-based background subtraction methods. In experiments, we integrate our scheme into several state-of-the-art methods, and the results show that the performance of these methods in three indicators, recall, precision, and F-measure, improved from 4.95% to 16.47%, from 5.39% to 26.54%, and from 12.46% to 20.46%, respectively.
The T‐type calcium channel blocker Z944 reduces conditioned fear in Genetic Absence Epilepsy Rats from Strasbourg and the non‐epileptic control strain

Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are a rodent model of childhood absence epilepsy (CAE) that display a gain‐of‐function mutation in the gene encoding the Cav3.2 T‐type calcium channel. GAERS demonstrate heightened learning and delayed extinction of fear conditioning. Our objective in the present study was to examine the effects of the pan‐T‐type calcium channel blocker Z944 on the acquisition, consolidation and extinction of conditioned fear in GAERS and the non‐epileptic control (NEC) strain. Z944 (10 mg/kg; ip) was administered 15 min prior to either acquisition, extinction day 1 (24 hr later), acquisition and extinction day 1, or during the consolidation (post‐acquisition) of tone‐cued fear conditioning. Extinction was examined 24 and 48 hr after conditioning. In drug naïve GAERS, increased freezing during the acquisition and extinction phases of fear conditioning was found. Short‐term effects of Z944 on performance were observed as Z944 increased freezing during testing on the day it was administered. Z944 administered prior to the acquisition phase had a long‐term effect on extinction. Specifically, both GAERS and NECs showed a decrease in freezing during extinction relative to drug naïve GAERS and NEC rats respectively. Regardless of strain or treatment, female rats showed reduced extinction of fear relative to male rats. These results demonstrate that T‐type calcium channels contribute to the neural systems that mediate the learning and memory of conditioned fear. Overall, these findings suggest that T‐type calcium channel blockers show promise in the treatment of learning impairments observed in disorders such as CAE.
Open-Source License Violations of Binary Software at Large Scale

Open-source licenses are widely used in open-source projects. However, developers using or modifying the source code of open-source projects do not always strictly follow the licenses. GPL and AGPL, two of the most popular copyleft licenses, are most likely to be violated, because they require developers to open-source the entire project if any code under GPL/AGPL protection is included whether modified or not. There are few license violation detectors focusing on binary software, owning to the challenge of mapping binary code to source code efficiently and accurately at large scale. In this paper, we propose a scalable and fully-automated system to check open-source license violation of binary software at large scale. We match source code to binary code by analyzing file attributes of executable files and code features that are not affected by compilation and could vary between projects. Moreover, to break the barrier of large-scale analysis, we introduce an automatic extractor to parse executable files from installation packages that are broadly available in software download sites. In empirical experiments of binary-to-source mapping, we have got a remarkable high accuracy of 99.5% and recall of 95.6% without significant loss of precision. Besides, 2270 pairs of binary-to-source mapping relationships are discovered, with 110 license violations of GPL and AGPL licenses related to 7.2% of the 1000 real-world binary software projects.
Is Waist-to-Height Ratio Superior to Body Mass Index and Waist Circumference in Predicting the Incidence of Hypertension?

Background: It is still controversial which anthropometric indicator could be the best predictor of the incident hypertension. Objectives: To examine the relative power of body mass index (BMI), waist circumference (WC), skinfold thickness, waist-to-hip ratio (WHR), and waist-to-height ratio (WHTR) in predicting the incidence of hypertension in Chinese adults. Method: Data were obtained from the China Health and Nutrition Survey. Overweight was defined as BMI ≥23 kg/m2 and general obesity as BMI ≥27.5 kg/m2. Abdominal obesity was defined by WC values ≥90 cm for males and ≥80 cm for females. Skinfold thickness, WHR, and WHTR were divided into low and high groups according to receiver operating characteristics. Cox regressions and nomograms were employed to compare the relative power of 5 indicators in predicting incident hypertension. Results: When all indicators were analyzed simultaneously, the best predictor of incident hypertension was general obesity (p < 0.001, adjusted hazard ratio [HR] 1.9, 95% CI 1.6–2.2). The results stratified by sex showed that BMI and WC were the more powerful predictors of hypertension in males (adjusted HR 1.8 and 1.3, 95% CI 1.4–2.3 and 1.1–1.5, respectively) as well as in females (adjusted HR 2.0 and 1.4, 95% CI 1.6–2.4 and 1.2–1.6, respectively). Conclusions: BMI and WC may predict incident hypertension better than skinfold thickness, WHR, and WHTR in the Chinese population.
Prognostic Value of Glial Fibrillary Acidic Protein in Patients With Moderate and Severe Traumatic Brain Injury: A Systematic Review and Meta-Analysis

Objectives: Biomarkers have been suggested as potential prognostic predictors following a moderate or severe traumatic brain injury but their prognostic accuracy is still uncertain. The objective of this systematic review is to assess the ability of the glial fibrillary acidic protein to predict prognosis in patients with moderate or severe traumatic brain injury. Data Sources: MEDLINE, Embase, CENTRAL, and BIOSIS electronic databases and conference abstracts, bibliographies of selected studies, and narrative reviews were searched. Study Selection: Pairs of reviewers identified eligible studies. Cohort studies including greater than or equal to four patients with moderate or severe traumatic brain injury and reporting glial fibrillary acidic protein levels according to the outcomes of interest, namely Glasgow Outcome Scale or Extended Glasgow Outcome Scale, and mortality, were eligible. Data Extraction: Pairs of reviewers independently extracted data from the selected studies using a standardized case report form. Mean levels were log-transformed, and their differences were pooled with random effect models. Results are presented as geometric mean ratios. Methodologic quality, risk of bias, and applicability concerns of the included studies were assessed. Data Synthesis: Seven-thousand seven-hundred sixty-five citations were retrieved of which 15 studies were included in the systematic review (n = 1,070), and nine were included in the meta-analysis (n = 701). We found significant associations between glial fibrillary acidic protein serum levels and Glasgow Outcome Scale score less than or equal to 3 or Extended Glasgow Outcome Scale score less than or equal to 4 (six studies: geometric mean ratio 4.98 [95% CI, 2.19–11.13]; I2 = 94%) and between mortality (seven studies: geometric mean ratio 8.13 [95% CI, 3.89–17.00]; I2 = 99%). Conclusions: Serum glial fibrillary acidic protein levels were significantly higher in patients with an unfavorable prognosis. Glial fibrillary acidic protein has a potential for clinical bedside use in helping for prognostic assessment. Further research should focus on multimodal approaches including tissue biomarkers for prognostic evaluation in critically ill patients with traumatic brain injury.
Endophytic Fungal Volatile Compounds as Solution for Sustainable Agriculture

Endophytic fungi produce various mixtures of carbon-based compounds, which are known as volatile organic compounds (VOCs). Research regarding the use of VOCs as pesticide substitutes has garnered much attention. This review summarizes the recent knowledge about VOCs regarding their origin and chemical properties and emphasizes their antimicrobial potential against a wide variety of agricultural pathogens. Several studies have highlighted the importance of VOCs as antimicrobial agents. Nevertheless, the application of VOCs in biofumigation methods still requires the advanced evaluation of their phytotoxicity.
The Role of Tocotrienol in Preventing Male Osteoporosis—A Review of Current Evidence

Male osteoporosis is a significant but undetermined healthcare problem. Men suffer from a higher mortality rate post-fracture than women and they are marginalized in osteoporosis treatment. The current prophylactic agents for osteoporosis are limited. Functional food components such as tocotrienol may be an alternative option for osteoporosis prevention in men. This paper aims to review the current evidence regarding the skeletal effects of tocotrienol in animal models of male osteoporosis and its potential antiosteoporotic mechanism. The efficacy of tocotrienol of various sources (single isoform, palm and annatto vitamin E mixture) had been tested in animal models of bone loss induced by testosterone deficiency (orchidectomy and buserelin), metabolic syndrome, nicotine, alcoholism, and glucocorticoid. The treated animals showed improvements ranging from bone microstructural indices, histomorphometric indices, calcium content, and mechanical strength. The bone-sparing effects of tocotrienol may be exerted through its antioxidant, anti-inflammatory, and mevalonate-suppressive pathways. However, information pertaining to its mechanism of actions is superficial and warrants further studies. As a conclusion, tocotrienol could serve as a functional food component to prevent male osteoporosis, but its application requires validation from a clinical trial in men.
Neurorehabilitation of Traumatic Brain Injury (TBI): A Clinical Review

Traumatic brain injury (TBI) and its potential long-term consequences are of major concern for public health. Neurorehabilitation of affected individuals has some specific characteristics in contrast to neurorehabilitation of patients with acquired brain lesions of other aetiology. This review will deal with the clinical consequences of the distinct lesions of TBI. In severe TBI, clinical course often follows a typical initial sequence of coma; followed by disturbed consciousness; later, post-traumatic agitation and amnesia; and finally, recovery of function occurs. In the different phases of neurorehabilitation, physicians should be aware of typical medical complications such as paroxysmal sympathetic hyperactivity, posttraumatic hydrocephalus, and posttraumatic neuroendocrine dysfunctions. Furthermore, we address questions on timing and on existing evidence for different rehabilitation programmes and for holistic neuropsychological rehabilitation approaches.
Barriers and Enablers to Implementing a High-Dependency Care Model in Pediatric Care

Background: As the level of acuity of pediatric hospital admissions continues to increase, additional pressure is being placed on hospital resources and the nursing workforce. Local Problem: Currently, there is no formalized approach to care for high-acuity patients on our pediatric inpatient unit. Methods: We used a qualitative descriptive design, guided by the Theoretical Domains Framework and Capability, Opportunity, Motivation-Behaviour (COM-B) model, to conduct focus groups and interviews with clinicians and administrators to identify potential barriers and enablers to implementing a high-dependency care (HDC) model. An HDC model focuses on the relationship between adequate nursing staff resources and patient acuity to improve patient health outcomes. Results: Participants identified the need for clear guidelines and supportive physical structures to facilitate HDC implementation. Anticipated benefits included enhanced nursing confidence and family-centered care. Conclusions: Study findings highlight multilevel factors to consider prior to implementing an HDC model on a pediatric inpatient unit.
The “New York City Marathon”: participation and performance trends of 1.2M runners during half-century

ABSTRACT The aim of the present study was to examine trends in participation, performance, age and nationality during a ~ 50-years period in the largest dataset ever studied in the “New York City Marathon”. We analysed 1,174,331 finishers (women, n= 349,145, age 39.7 ± 8.7 years; men, n= 825,186, 41.7 ± 9.2 years). The overall participation increased across calendar years for all nationalities, and this increase was more pronounced in women, which resulted in a decreasing men-to-women ratio. Men were faster and older than women. Ethiopians and Kenyans were the fastest and youngest in women and men, respectively. Japanese were the slowest and Germans were the oldest in both sexes. Race time increased across years. Coaches and fitness trainers should be aware of these trends and should emphasize the development of training programs for older and slower runners.
Agro-Food Byproducts as a New Source of Natural Food Additives

Nowadays, the agro-food industry generates high amounts of byproducts that may possess added value compounds with high functionality and/or bioactivity. Additionally, consumers’ demand for healthier foodstuffs has increased over the last years, and thus the food industry has strived to answer this challenge. Byproducts are generally secondary products derived from primary agro-food production processes and represent an interesting and cheaper source of potentially functional ingredients, such as peptides, carotenoids, and phenolic compounds, thus promoting a circular economy concept. The existing body of work has shown that byproducts and their extracts may be successfully incorporated into foodstuffs, for instance, phenolic compounds from eggplant can be potentially used as a mulfitunctional food additive with antimicrobial, antioxidant, and food colorant properties. As such, the aim of this review is to provide insights into byproducts and their potential as new sources of foodstuffs additives.
Durability of dolutegravir plus boosted darunavir as salvage or simplification of salvage regimens in HIV-1 infected, highly treatment-experienced subjects

Background: Dolutegravir (DTG) plus boosted darunavir (bDRV) is a compact, adherence-friendly salvage regimen with the highest genetic barrier to HIV-1 resistance. Objective: Aim of the present study is to assess the long term (96-week) safety and efficacy of DTG + bDRV in a of multidrug-experienced HIV-1 infected patients, simplifying or building rescue regimens. Methods: All HIV-1-infected subjects from eleven Italian centers switched to DTG + bDRV between March 2014 and September 2015 were included and followed for minimum 96 weeks. Results: The cohort comprises 130 subjects, switched from 42 different, complex or at least twice-daily regimens, mainly for simplification (44.6%), viral failure (30.0%) or toxicity (16.6%). At baseline 118 had documented resistance to 1–5 antiretroviral classes and 12 lacked genotypic results either for historical reasons or for problems with primer annealing; 52 (40%) had uncontrolled viral replication, three above 500.000 copies/mL. At week 96 two showed ≥50 HIV-1 RNA copies/mL, 23 had 1–49 copies/mL and 101 had no virus detected. The proportion of subjects presenting abnormal values at baseline significantly decreased for serum glucose, creatinine, AST, total cholesterol and triglycerides. Conclusions: These long-term data confirm the reliability of the two-drug regimen consisting of bDRV plus DTG in salvage settings in HIV-1 infection.