Miracle-dz/UniFAR-FTUs huggingface dataset:
Calcium release channel RyR 2 regulates insulin release and glucose homeostasis

The type 2 ryanodine receptor (RyR2) is a Ca2+ release channel on the endoplasmic reticulum (ER) of several types of cells, including cardiomyocytes and pancreatic b cells. In cardiomyocytes, RyR2-dependent Ca2+ release is critical for excitation-contraction coupling; however, a functional role for RyR2 in b cell insulin secretion and diabetes mellitus remains controversial. Here, we took advantage of rare RyR2 mutations that were identified in patients with a genetic form of exercise-induced sudden death (catecholaminergic polymorphic ventricular tachycardia [CPVT]). As these mutations result in a “leaky” RyR2 channel, we exploited them to assess RyR2 channel function in b cell dynamics. We discovered that CPVT patients with mutant leaky RyR2 present with glucose intolerance, which was heretofore unappreciated. In mice, transgenic expression of CPVTassociated RyR2 resulted in impaired glucose homeostasis, and an in-depth evaluation of pancreatic islets and b cells from these animals revealed intracellular Ca2+ leak via oxidized and nitrosylated RyR2 channels, activated ER stress response, mitochondrial dysfunction, and decreased fuel-stimulated insulin release. Additionally, we verified the effects of the pharmacological inhibition of intracellular Ca2+ leak in CPVT-associated RyR2-expressing mice, in human islets from diabetic patients, and in an established [. ] Research Article Cardiology Metabolism
Optic Nerve Head Drusen: An Update

ABSTRACT Optic nerve head drusen are benign acellular calcium concretions that usually form early in life, just anterior to the lamina cribrosa. Improving imaging using optical coherence tomography suggests they are common and may be present in many clinically normal discs. These drusen may change in appearance in early life, but are generally stable in adulthood, and may be associated with visual field defects, anterior ischaemic optic neuropathy, or rarer complications. Based on long-term clinical data and optical coherence tomography, we propose a refined hypothesis as to the cause of optic disc drusen. Here we summarise recent findings and suggest future studies to better understand the forces involved.
Identification of a polyI:C-inducible membrane protein that participates in dendritic cell–mediated natural killer cell activation

In myeloid dendritic cells (mDCs), TLR3 is expressed in the endosomal membrane and interacts with the adaptor toll/interleukin 1 receptor homology domain–containing adaptor molecule 1 (TICAM-1; TRIF). TICAM-1 signals culminate in interferon (IFN) regulatory factor (IRF) 3 activation. Co-culture of mDC pretreated with the TLR3 ligand polyI:C and natural killer (NK) cells resulted in NK cell activation. This activation was triggered by cell-to-cell contact but not cytokines. Using expression profiling and gain/loss-of-function analyses of mDC genes, we tried to identify a TICAM-1–inducing membrane protein that participates in mDC-mediated NK activation. Of the nine candidates screened, one contained a tetraspanin-like sequence and satisfied the screening criteria. The protein, referred to as IRF-3–dependent NK-activating molecule (INAM), functioned in both the mDC and NK cell to facilitate NK activation. In the mDC, TICAM-1, IFN promoter stimulator 1, and IRF-3, but not IRF-7, were required for mDC-mediated NK activation. INAM was minimally expressed on NK cells, was up-regulated in response to polyI:C, and contributed to mDC–NK reciprocal activation via its cytoplasmic tail, which was crucial for the activation signal in NK cells. Adoptive transfer of INAM-expressing mDCs into mice implanted with NK-sensitive tumors caused NK-mediated tumor regression. We identify a new pathway for mDC–NK contact-mediated NK activation that is governed by a TLR signal-derived membrane molecule.
Salivaomics in oral cancer.

PURPOSE OF REVIEW The goal of cancer screening is to detect tumor at an early stage, and early cancer detection is the hallmark of successful treatment. In addition to traditional tissue biopsy-based diagnostics, more reliable, inexpensive, and noninvasive methods are required for early diagnosis of cancer. In this review, we highlight some of the recent advancements in the field of salivary diagnostics in oral cancer. RECENT FINDINGS 'Salivaomics' is a broad collection of technologies used to explore different types of molecules contained in saliva. Although many protein and mRNA salivary biomarkers have been identified that can detect oral squamous cell carcinoma (OSCC), none have so far been validated for current clinical use. As the heterogeneity in carcinogenesis and multifactorial cause for OSCC, the most reliable results are gathered with the use of multiple biomarker candidates to improve accuracy and sensitivity of the test used. This further requires sensitive technology to detect salivary biomarkers in low quantities. SUMMARY Large scale studies that incorporate proteomic, transcriptomic, and additional 'omics,' need to be initiated to bring technology to clinical point-of-care applications.
Leverage Data Mining Techniques in Intrusion detection

—Data mining techniques have been successfully applied in many fields including marketing, manufacturing, process control, fraud detection and network management. In recent years, data mining-based Intrusion Detection Systems (IDS) have demonstrated high accuracy, good generalization to novel types of intrusion, and robust behavior in a changing environment. In data mining based intrusion detection system one should have knowledge about the particular domain in relation to intrusion detection so as to efficiently extract relative rule from huge amounts of records. This paper presents a review of the literature in connection with different data mining techniques for intrusion detection.
Two- and three-dimensional coordination polymers based on zinc(II) and furan-2,5-dicarboxylic acid: structure variation due to metal-to-linker ratio.

Two ZnII-based coordination polymers (CPs) were synthesized by the hydrothermal method, using Zn(NO3)2·6H2O and furan-2,5-dicarboxylic acid (FDCA) in dimethylformamide (DMF) solvent, at 95 °C. Poly[tetrakis(dimethylazanium) [tetrakis(μ2-furan-2,5-dicarboxylato-κ2O2:O5)dizinc(II)]], {(C2H8N)4[Zn2(C6H2O5)4]}n or {[DMA]4[ZnII2(FDC)4]}n (DMA = dimethylazanium and FDC = furan-2,5-dicarboxylate), (1), was obtained with a 1:1 molar ratio of ZnII and FDCA. It crystallized in the monoclinic space group C2/c. Coordinated by ZnII ions, FDC2- ligands form 21 double-stranded helices propagating along the b axis. The helices are interconnected and extend laterally in the a direction, forming a two-dimensional (2D) sheet-like network. The 2D sheets are stacked along the c direction without interconnections. DMA cations are cocrystallized in (1) and are hydrogen bonded with carboxylate O atoms of the FDC2- ligands. The hydrogen-bonding pattern consists of R22(4) and R22(10) motifs alternating in a chain. Poly[bis(dimethylazanium) [bis(μ4-furan-2,5-dicarboxylato-κO2:κO2':κO5:κO5)bis(μ3-furan-2,5-dicarboxylato-κO2:κO2':κO5)dizinc(II)] dimethylformamide 3.08-solvate], {(C2H8N)2[Zn2(C6H2O5)4]·3.08C3H7NO}n or {[DMA]2[ZnII3(FDC)4]·3.08DMF}n, (2), was obtained with a 1:2 molar ratio of ZnII and FDCA. It crystallized in the monoclinic space group P21/c, forming a three-dimensional network. The pores are filled with DMA cations and DMF solvent molecules.
Velocity dispersion and backscatter in marrow-filled and water-filled trabecular bone samples in vitro.

The phase velocity and the backscatter coefficient were measured in 28 bovine femoral trabecular bone samples filled with marrow and water in vitro from 0.2 to 0.6 MHz. The phase velocities decreased approximately linearly with increasing frequency and the average dispersion rate of -34 ms-1 MHz-1 in the marrow-filled samples was higher than that of -42 ms-1 MHz-1 in the water-filled samples. The backscatter coefficients exhibited nonlinear, monotonically increasing dependences on the frequency and the average value of the exponent n = 2.92 (frequency dependence) in the marrow-filled samples was higher than the value of n = 2.79 in the water-filled samples.
Finding a very rare mutation in non‐Caucasian LCAT patients from Southwest Asia for the first time

Lecithin cholesterol acyltransferase (LCAT) deficiency is an autosomal recessive disorder occurred by different mutations in the LCAT gene that cause two extremely rare syndromes including familial LCAT deficiency (FLD) and fish‐eye disease (FED). Unlike FED in FLD renal failure is the most important defect due to deposition of abnormal lipoproteins in the renal stroma. In this study, FLD patients from the North of Iran were investigated for mutations in the LCAT gene.
Risk factors related to the recurrence of endometrioma in patients with long-term postoperative medical therapy.

OBJECTIVES The purpose of this study was to identify clinical risk factors for the recurrence of ovarian endometrioma after ovarian cystectomy in Korean women with long-term postoperative medical therapy. MATERIAL AND METHODS A total of 134 patients who were surgically treated for endometriotic cysts at Pusan National University Hospital were included in this retrospective study. All patients received long-term postoperative medical treatment for at least 12 months after the first-line conservative surgery. Several epidemiologic variables were analyzed as possible risk factors for recurrence. Endometrioma recurrence was considered when a cystic mass was observed on transvaginal or transrectal sonography. Statistical analysis was performed using independent t-tests for parametric continuous variables. RESULTS The mean follow-up period for the 134 patients was 56.5 ± 14.3 months (range, 36-120 months) and the mean duration of the medical therapy was 17.9 ± 17.3 months (range, 12-120 months). The overall recurrence rate was 35/134 (26.12%). Our univariate analysis showed statistically significant differences between the recurrent and non-recurrent groups in terms of weight (P = 0.013), body mass index (P = 0.007), age at the time of surgery (P = 0.013), the diameter of the largest cyst (P = 0.001), the presence of dysmenorrhea (P < 0.0001), and postoperative pregnancy (P = 0.016). Multivariate analysis showed that body mass index (OR 1.153, 95% CI 1.003-1.326, P = 0.046), age at the time of surgery (OR 0.924, 95% CI 0.860-0.992, P = 0.029), and presence of dysmenorrhea (OR 12.226, 95% CI 3.543-42.188, P < 0.0001) were significantly correlated with the recurrence of endometrioma. CONCLUSIONS We found that patients with dysmenorrhea after surgery, and a younger age of the patient at the time of surgery were the highest risk factors associated with the recurrence of endometrioma, despite long-term postoperative medication.
‘Kültürel Kimlik’ ve ‘Kültürel Adaptasyon’ Kavramları Çerçevesinde Malatya Romanlarının Müzik Pratikleri

Bu arastirma, kulturel kimlik ve kulturel adaptasyon kavramlari cercevesinde, Malatya Romanlarinin muzik pratiklerini analiz etmek amaciyla olusturulmustur. Roman diasporasi, dunyanin bircok yerinde bulunmakla birlikte, bu halkin ana vatani, Hindistan’in Kuzey Batisidir. Dolayisiyla calismanin ilk safhasinda Roman halklarinin kokeni, genel ozellikleri ve Turkiye’deki durumlari uzerinde durulduktan sonra, ikinci safhasinda Malatya Romanlari’na gecilmistir. Calismada Malatya bolgesi ile sinirli kalinmasinin nedeni, bolge bazinda daha detayli olarak veri toplanmasi saglamaktir. Batida genelde Roman havalarini, Sanat Muzigini ve yer yer Bati ve Cigan muzigi turlerini icra etmekte olan Romanlar, Malatya’da bu muzige bir de Turk halk muzigini, Malatya’yi temsil eden Arguvan ve Puturge Havalarini ve arabeski eklemislerdir. Ancak Dogu’da tam ve gercek olarak koklesemedikleri icin, Dogu kulturune adapte olma konusunda, ozellikle halk calgilarindan baglamanin performansi icin Malatya’nin yerel muzisyenlerinden yardim almaktadirlar. Malatya’da Romanlar tarafindan icra edilen muzik turleri, calismada ‘elit’ ve ‘avam’ olarak iki ana kisma ayrilan muzik mekânlarina gore de isabetli bir dagilim gostermektedir. Restoran ve otel gibi elit mekânlarda Turk sanat muzigini ve populer muzigi daha fazla icra eden Romanlarin, avam mekânlar olan birahane ve pavyonlarda genelde halk muzigini ve arabeski, pavyon uslubuyla seslendirdikleri saptanmistir.
Urine Spot Samples Can Be Used to Estimate 24-Hour Urinary Sodium Excretion in Children.

Background The gold standard to assess salt intake is 24-h urine collections. Use of a urine spot sample can be a simpler alternative, especially when the goal is to assess sodium intake at the population level. Several equations to estimate 24-h urinary sodium excretion from urine spot samples have been tested in adults, but not in children. Objective The objective of this study was to assess the ability of several equations and urine spot samples to estimate 24-h urinary sodium excretion in children. Methods A cross-sectional study of children between 6 and 16 y of age was conducted. Each child collected one 24-h urine sample and 3 timed urine spot samples, i.e., evening (last void before going to bed), overnight (first void in the morning), and morning (second void in the morning). Eight equations (i.e., Kawasaki, Tanaka, Remer, Mage, Brown with and without potassium, Toft, and Meng) were used to estimate 24-h urinary sodium excretion. The estimates from the different spot samples and equations were compared with the measured excretion through the use of several statistics. Results Among the 101 children recruited, 86 had a complete 24-h urine collection and were included in the analysis (mean age: 10.5 y). The mean measured 24-h urinary sodium excretion was 2.5 g (range: 0.8-6.4 g). The different spot samples and equations provided highly heterogeneous estimates of the 24-h urinary sodium excretion. The overnight spot samples with the Tanaka and Brown equations provided the most accurate estimates (mean bias: -0.20 to -0.12 g; correlation: 0.48-0.53; precision: 69.7-76.5%; sensitivity: 76.9-81.6%; specificity: 66.7%; and misclassification: 23.0-27.7%). The other equations, irrespective of the timing of the spot, provided less accurate estimates. Conclusions Urine spot samples, with selected equations, might provide accurate estimates of the 24-h sodium excretion in children at a population level. At an individual level, they could be used to identify children with high sodium excretion. This study was registered at clinicaltrials.gov as NCT02900261.
Intelligence-based Cybersecurity Awareness Training- an Exploratory Project

Cybersecurity training should be adaptable to evolving the cyber threat landscape, cost effective and integrated well with other enterprise management components. Unfortunately, very few cybersecurity training platforms can satisfy such requirements. This paper proposes a new and novel model for conducting cybersecurity training with three main objectives: (i) training should be initiated by emerging relevant threats and delivered first to the most vulnerable members (ii) the process has to be agile (iii) training results must be able to provide actionable intelligence. For the first time, this paper establishes a type system (ontology and associated relationships) that links the domain of cybersecurity awareness training with that of cyber threat intelligence. Powered by IBM Watson Knowledge Studio platform, the proposed method was found to be practical and scalable. Main contributions such as exports of the type system, the manually annotated corpus of 100 threat reports and 127 cybersecurity assessment results, the dictionaries for pre-annotation, etc were made publicly available.
Doubly Bayesian Optimization

Probabilistic programming systems enable users to encode model structure and naturally reason about uncertainties, which can be leveraged towards improved Bayesian optimization (BO) methods. Here we present a probabilistic program embedding of BO that is capable of addressing main issues such as problematic domains (noisy, non-smooth, high-dimensional) and the neglected inner-optimization. Not only can we utilize programmable structure to incorporate domain knowledge to aid optimization, but dealing with uncertainties and implementing advanced BO techniques become trivial, crucial for use in practice (particularly for non-experts). We demonstrate the efficacy of the approach on optimization benchmarks and a real-world drug development scenario.
An Evaluation

Considerable time and energy goes into the organisation of careers expos held each year in many parts of Australia. While in some centres these have been replaced by alternative forms of information-sharing on careers, in other places they have persisted either as the regular careers event of the year or run to complement a range of careers activities. In Darwin, alternatives have been considered yet there has been some reluctance to forego the annual event. To analyse the success of the 1996 Darwin Careers Expo, a survey of exhibitors, teachers and students was undertaken on behalf of the Careers Expo Planning Committee. Students completed the survey in a very positive way, and their cooperation warrants acknowledgment. Overall, the results affirm the benefits of the organisers’ and exhibiters’ efforts and provide some insights into ways of improving the next Expo.
Systematic review of systematic reviews of non-pharmacological interventions to treat behavioural disturbances in older patients with dementia. The SENATOR-OnTop series

Objective To provide an overview of non-pharmacological interventions for behavioural and psychological symptoms in dementia (BPSD). Design Systematic overview of reviews. Data sources PubMed, EMBASE, Cochrane Database of Systematic Reviews, CINAHL and PsycINFO (2009–March 2015). Eligibility criteria Systematic reviews (SRs) that included at least one comparative study evaluating any non-pharmacological intervention, to treat BPSD. Data extraction Eligible studies were selected and data extracted independently by 2 reviewers. The AMSTAR checklist was used to assess the quality of the SRs. Data analysis Extracted data were synthesised using a narrative approach. Results 38 SRs and 142 primary studies were identified, comprising the following categories of non-pharmacological interventions: (1) sensory stimulation interventions (12 SRs, 27 primary studies) that encompassed: acupressure, aromatherapy, massage/touch therapy, light therapy and sensory garden; (2) cognitive/emotion-oriented interventions (33 SRs; 70 primary studies) that included cognitive stimulation, music/dance therapy, dance therapy, snoezelen, transcutaneous electrical nerve stimulation, reminiscence therapy, validation therapy, simulated presence therapy; (3) behaviour management techniques (6 SRs; 32 primary studies) and (4) other therapies (5 SRs, 12 primary studies) comprising exercise therapy, animal-assisted therapy, special care unit and dining room environment-based interventions. Music therapy was effective in reducing agitation (SMD, −0.49; 95% CI −0.82 to −0.17; p=0.003), and anxiety (SMD, −0.64; 95% CI −1.05 to −0.24; p=0.002). Home-based behavioural management techniques, caregiver-based interventions or staff training in communication skills, person-centred care or dementia care mapping with supervision during implementation were found to be effective for symptomatic and severe agitation. Conclusions A large number of non-pharmacological interventions for BPSD were identified. The majority of the studies had great variation in how the same type of intervention was defined and applied, the follow-up duration, the type of outcome measured, usually with modest sample size. Overall, music therapy and behavioural management techniques were effective for reducing BPSD.
Chemical characterization and biological activity of six different extracts of propolis through conventional methods and supercritical extraction

Propolis is a natural product with many demonstrated biological activities and propolis extract has been used in the food, pharmaceutical and cosmetics industries. Different works have showed the variations in the chemical composition, and consequently, on the biological activity of the propolis that are associated with its type and geographic origin. Due to this study evaluated propolis extracts obtained through supercritical extraction and ethanolic extraction (conventional) in three samples of different types of propolis (red, green and brown), collected from different regions in Brazil (state of Bahia). Analyses were performed to determine the humidity, water activity, the content of total ash, proteins, lipids and fiber in raw propolis samples. The content of phenolic compounds, flavonoids, in vitro antioxidant activity (DPPH), catechin, ferulic acid and luteolin and antimicrobial activity against two bacteria (Staphylococcus aureus and Escherichia coli) were determined for all extracts. For the green and red ethanolic extracts the anti-leishmanicidal potential was also evaluated. The physicochemical profiles showed agreement in relation to the literature. The results identified significant differences among the extracts (p>0.05), which are in conformity with their extraction method, as well as with type and botanical origin of the samples. The extraction with supercritical fluid was not efficient to obtain extracts with the highest contents of antioxidants compounds, when compared with the ethanolic extracts. The best results were shown for the extracts obtained through the conventional extraction method (ethanolic) indicating a higher selectivity for the extraction of antioxidants compounds. The red variety showed the largest biological potential, which included the content of antioxidants compounds. The results found in this study confirm the influence of the type of the raw material on the composition and characteristics of the extracts. The parameters analysis were important to characterize and evaluate the quality of the different Brazilian propolis extracts based on the increased use of propolis by the natural products industry.
Filaggrin null mutations are associated with altered circulating Tregs in atopic dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a complex pathogenesis. Although regulatory T cells (Tregs) have previously been studied in AD, their role remains controversial, likely owing to patient heterogeneity. Thus, we recruited adult AD patients and age‐matched healthy controls, and assessed their filaggrin (FLG) genotype, serum IgE level, and eczema area and severity index (EASI). We found increased proportions of all circulating Treg subpopulations in AD patients. Moreover, we show positive correlations between circulating Tregs and serum IgE FLG null mutations limited the expansion of both memory and effector Tregs and enhanced that of recently thymus‐emigrated Tregs. Furthermore, proportions of circulating Th2‐ or Th17‐Tregs but not Th1‐Tregs were increased in AD patients, and accentuated by FLG null mutations, thereby mimicking the immune deviation observed in Th cell populations. Moreover, ICOS+ Tregs showed reduced production of interleukin‐10, suggesting impaired immunosuppression in AD. The level of demethylation of FOXP3i1, which reflects the stability of FOXP3 expression, was similar in the blood and skin of AD patients and healthy controls. Overall, these results show that Tregs may participate into AD pathogenesis and that FLG null mutations exert further modifications on specific subpopulations of circulating Tregs.