Miracle-dz/UniFAR-FTUs huggingface dataset:
Association between the α1a calcium channel gene CACNA1A and idiopathic generalized epilepsy

Idiopathic generalized epilepsy (IGE) is a common disorder with a strong genetic component. For common forms of IGE, the pattern of inheritance is complex, probably resulting from the action of a few or many genes of small to moderate effect. In this study we used an association strategy to investigate whether genetic variation of the α1A subunit of the voltage-gated calcium channel gene ( CACNA1A ) influences risk for IGE. The α1A subunit is the pore-forming channel in P/Q-type channels that plays an important role in neurotransmitter release.1 Mutations in the mouse homologue cause seizures and ataxia in tottering and leaner mice.2 In humans, mutations in CACNA1A result in episodic ataxia type 2, spinocerebellar ataxia type 6, and familial hemiplegic migraine.3 In an earlier study of only 55 probands, no association was reported between a CAG repeat polymorphism in exon 47 and the common subtypes of IGE.4 Although IGE includes many syndromes, their phenotypes overlap and more than one subtype is often observed within …
Vacuolar membrane transporters OsVIT1 and OsVIT2 modulate iron translocation between flag leaves and seeds in rice.

The plant vacuole is an important organelle for storing excess iron (Fe), though its contribution to increasing the Fe content in staple foods remains largely unexplored. In this study we report the isolation and functional characterization of two rice genes OsVIT1 and OsVIT2, orthologs of the Arabidopsis VIT1. Transient expression of OsVIT1:EGFP and OsVIT2:EGFP protein fusions revealed that OsVIT1 and OsVIT2 are localized to the vacuolar membrane. Ectopic expression of OsVIT1 and OsVIT2 partially rescued the Fe(2+) - and Zn(2+) -sensitive phenotypes in yeast mutant Δccc1 and Δzrc1, and further increased vacuolar Fe(2+) , Zn(2+) and Mn(2+) accumulation. These data together suggest that OsVIT1 and OsVIT2 function to transport Fe(2+) , Zn(2+) and Mn(2+) across the tonoplast into vacuoles in yeast. In rice, OsVIT1 and OsVIT2 are highly expressed in flag leaf blade and sheath, respectively, and in contrast to OsVIT1, OsVIT2 is highly responsive to Fe treatments. Interestingly, functional disruption of OsVIT1 and OsVIT2 leads to increased Fe/Zn accumulation in rice seeds and a corresponding decrease in the source organ flag leaves, indicating an enhanced Fe/Zn translocation between source and sink organs, which might represent a novel strategy to biofortify Fe/Zn in staple foods.
Glycoprotein Disease Markers and Single Protein-omics*

Glycoproteins are well represented among biomarkers for inflammatory and cancer diseases. Secreted and membrane-associated glycoproteins make excellent targets for noninvasive detection. In this review, we discuss clinically applicable markers of cancer diseases and methods for their analysis. High throughput discovery continues to supply marker candidates with unusual glycan structures, altered glycoprotein abundance, or distribution of site-specific glycoforms. Improved analytical methods are needed to unlock the potential of these discoveries in validated clinical assays. A new generation of targeted quantitative assays is expected to advance the use of glycoproteins in early detection of diseases, molecular disease classification, and monitoring of therapeutic interventions.
Quantitative Profiling of N-linked Glycosylation Machinery in Yeast Saccharomyces cerevisiae*

Asparagine-linked glycosylation is a common posttranslational protein modification regulating the structure, stability and function of many proteins. The N-linked glycosylation machinery involves enzymes responsible for the assembly of the lipid-linked oligosaccharide (LLO), which is then transferred to the asparagine residues on the polypeptides by the enzyme oligosaccharyltransferase (OST). A major goal in the study of protein glycosylation is to establish quantitative methods for the analysis of site-specific extent of glycosylation. We developed a sensitive approach to examine glycosylation site occupancy in Saccharomyces cerevisiae by coupling stable isotope labeling (SILAC) approach to parallel reaction monitoring (PRM) mass spectrometry (MS). We combined the method with genetic tools and validated the approach with the identification of novel glycosylation sites dependent on the Ost3p and Ost6p regulatory subunits of OST. Based on the observations that alternations in LLO substrate structure and OST subunits activity differentially alter the systemic output of OST, we conclude that sequon recognition is a direct property of the catalytic subunit Stt3p, auxiliary subunits such as Ost3p and Ost6p extend the OST substrate range by modulating interfering pathways such as protein folding. In addition, our proteomics approach revealed a novel regulatory network that connects isoprenoid lipid biosynthesis and LLO substrate assembly.
Use Patterns and Unlabeled Uses of Target-Specific Oral Anticoagulants

Background: Target-specific oral anticoagulants (TSOAs) have advantages and disadvantages over warfarin, and they differ by indication, dosage adjustment, and drug interactions. Objective: The purpose of this retrospective cohort study is to determine use patterns and unlabeled uses of TSOAs. Methods: From July 1, 2012, to April 30, 2014, orders for warfarin, dabigatran, rivaroxaban, or apixaban in a tertiary medical center were included. Electronic medical records were reviewed to collect information regarding characteristics of the patients receiving these medications. Unlabeled use was defined as an indication or dose not approved by the US Food and Drug Administration. The percentage of orders for each study drug per month and the percentage of orders for each TSOA that contained an unlabeled use were calculated. Results: Of a total of 869 orders, 140 (16.1%) were for TSOAs (13 dabigatran, 97 rivaroxaban, and 30 apixaban orders). Compared with the first 4 months of the study period, the monthly percentage of orders for a TSOA increased by 2.5-fold in the last 4 months. Of the 3 TSOAs, only orders for dabigatran decreased (5.6% in July 2012 vs 0% in April 2014). Of the 140 TSOA orders, 28 (20.0 %) were unlabeled uses (3 unlabeled indications and 25 unlabeled dose), which included 16 unlabeled renally adjusted doses. The percentage of unlabeled uses did not significantly differ by TSOA. Conclusion: The use of TSOAs has increased and unlabeled uses are common. These data provide opportunities for quality improvement in the use of TSOA in clinical practice.
Characterization of the Molecular Mechanisms Underlying Glucose Stimulated Insulin Secretion from Isolated Pancreatic β-cells Using Post-translational Modification Specific Proteomics (PTMomics)*

Normal pancreatic islet β-cells (PBCs) abundantly secrete insulin in response to elevated blood glucose levels, in order to maintain an adequate control of energy balance and glucose homeostasis. However, the molecular mechanisms underlying the insulin secretion are unclear. Improving our understanding of glucose-stimulated insulin secretion (GSIS) mechanisms under normal conditions is a prerequisite for developing better interventions against diabetes. Here, we aimed at identifying novel signaling pathways involved in the initial release of insulin from PBCs after glucose stimulation using quantitative strategies for the assessment of phosphorylated proteins and sialylated N-linked (SA) glycoproteins. Islets of Langerhans derived from newborn rats with a subsequent 9–10 days of maturation in vitro were stimulated with 20 mm glucose for 0 min (control), 5 min, 10 min, and 15 min. The isolated islets were subjected to time-resolved quantitative phosphoproteomics and sialiomics using iTRAQ-labeling combined with enrichment of phosphorylated peptides and formerly SA glycopeptides and high-accuracy LC-MS/MS. Using bioinformatics we analyzed the functional signaling pathways during GSIS, including well-known insulin secretion pathways. Furthermore, we identified six novel activated signaling pathways (e.g. agrin interactions and prolactin signaling) at 15 min GSIS, which may increase our understanding of the molecular mechanism underlying GSIS. Moreover, we validated some of the regulated phosphosites by parallel reaction monitoring, which resulted in the validation of eleven new phosphosites significantly regulated on GSIS. Besides protein phosphorylation, alteration in SA glycosylation was observed on several surface proteins on brief GSIS. Interestingly, proteins important for cell-cell interaction, cell movement, cell-ECM interaction and Focal Adhesion (e.g. integrins, semaphorins, and plexins) were found regulated at the level of sialylation, but not in protein expression. Collectively, we believe that this comprehensive Proteomics and PTMomics survey of signaling pathways taking place during brief GSIS of primary PBCs is contributing to understanding the complex signaling underlying GSIS.
Advances in Understanding and Treating Childhood Sexual Abuse: Implications for Research and Policy

Childhood sexual abuse is a major public health problem affecting thousands of children and adolescents in the United States each year. For more than 20 years, researchers, healthcare professionals, and policymakers have had considerable disagreements about various aspects of child sexual abuse. Although everyone agrees that sexual abuse is a harmful thing for children to experience, there is a lack of consensus on a definition of sexual abuse, investigation of allegations, long-term consequences, what constitutes appropriate psychotherapy, and what public health policies should be developed to prevent sexual abuse. The purpose of this article is to explore advances that have been made in understanding and treating child sexual abuse, to look at the implications for further research, and to address the public health policies that exist for preventing child sexual abuse.
The value of death scene examination in the recognition of unsafe sleeping conditions in the young

Although protocols for death scene examination in cases of unexpected infant and early childhood death have been widely available for over a decade, approaches lack standardisation. In addition, scene examinations are not mandatory in all countries and there has not been uniform support for their implementation. It is, however, well recognised that certain causes of death will not be identified if only pathological findings at autopsy are relied upon. These cases particularly involve accidental asphyxia in the young. Unless full death scene examinations are conducted by trained personnel as soon as possible after death vital information may be lost. Careful re-enactment of the scene with a doll surrogate and photographic and video recordings will enable clear and permanent documentation of findings. Obtaining full death scene information will greatly help in identifying potentially dangerous sleeping situations and/or devices that will assist in preventing future deaths through community awareness campaigns. It will also facilitate subsequent peer review of cases if required. Although more information on a case may increase the complexity of subsequent analyses this should not be a disincentive to conducting full inquiries.
Implementing the Comprehensive, Continuous, Integrated System of Care Model for Individuals with Co-Occurring Disorders: Preliminary Findings from a Residential Facility Serving Homeless Individuals

ABSTRACT This study assessed the effectiveness of an evidence-based treatment model for homeless individuals with co-occurring diagnosed mental health and substance use disorders. The model, Comprehensive, Continuous, Integrated System of Care (CCISC), has been recognized by the Substance Abuse and Mental Health Services Administration as one of the best treatment protocols in the United States (Minkoff & Cline, 2004). During residential treatment, clients received medical care, counseling, psychiatric/psychological evaluation, recreational and vocational services, as well as comprehensive discharge planning. All 76 participants were administered measures assessing housing and employment status, as well as mental health symptomatology and levels of substance use at both baseline and six-month follow-up. Analyses revealed significant improvement in all assessment categories at six-month follow-up as well as client satisfaction with the program. The Comorbidity Program Audit and Self-Survey for Behavioral Health Services (COMPASS), a standardized measure to assess fidelity to the CCISC model, was utilized annually and indicated that the CCISC principles of care were being implemented as intended. These results underscore the effectiveness of an evidence-based model for treating clients with co-occurring mental health and substance use disorders.
Fatal immune haemolysis due to antibodies to individual metabolites of 5‐fluorouracil

Confusion still exists in the diagnosis of drug‐induced immune haemolysis (DIH). The aim of this study was to demonstrate antibodies specific to 5‐fluorouracil (5‐FU) in a patient with fatal immune haemolysis (IH). The case of a patient who died due to protracted IH is described. A 57‐year‐old female underwent treatment with oxaliplatin, 5‐FU and folinic acid due to cholangiocarcinoma. Following drug administration, she was transfused because of a mild non‐haemolytic anaemia and died following haemolysis. Serological testing including antibody screening, direct antiglobulin test and detection of drug‐dependent antibodies was performed using standard techniques. The patient's serum was observed to be red in colour due to the presence of free haemoglobin prior to and following blood transfusion, and contained antibodies reactive with RBCs only in the presence of urine from several patients treated with 5‐FU (ex vivo antigens). Drug‐induced immune haemolysis (DIH) and metabolite‐dependent antibodies should always be taken into consideration when a patient being administered any type of drug develops haemolysis.
Effects of Isosaline Extracts of Tetrapleura Tetrapetra and Olax Subscorpioides on Certain Biochemical Parameters of Albino Rats

The effects of isosaline extracts of Tetrapleura tetrapetra and Olax subscorpioides were investigated in albino rats. The treatment of rats with these extracts resulted in an increase in the activities of serum alanine aminotransferase, liver aspartate aminotransferase, alanine aminotransferase, acid phosphatase and alkaline phosphatase. The extract of Tetrapleura tetrapetra caused a significant increase in blood glucose and liver glycogen levels while the extract of Olax subscorpioides caused a slight reduction but not statistically significant in the levels of blood glucose and liver glycogen. Both extracts exhibited a significant reduction of protein in the livers of treated rats.
Counselling provision in specialist drug treatment services

Background Counselling is one of the most common treatment options in drug services, and recent research has convincingly demonstrated its effectiveness if certain quality parameters regarding intensity and qualifications of those providing it are observed. However, there is a remarkable paucity of literature on the nature of counselling provision in UK drug treatment. Aims To describe the extent and nature of counselling provision in UK drug treatment services. Method A national survey of specialist drug services in England and Wales was carried out, and information was obtained from 326 services. Results Levels of counselling provision were very similar in nonstatutory, community‐based, residential day care and statutory, community‐based services (around 90%), with slightly lower levels in inpatient services (78%, difference not significant). In the majority of services (74%), individual sessions were provided by drug workers without counselling accreditation. In 32% of agencies, counselling was provided only by drug workers, whereas 36% of agencies employed both drug workers and accredited counsellors. In 17% of agencies, sessions were run by accredited counsellors only. Volunteers without formal training provided one‐to‐one sessions in 27% of agencies, mostly in agencies also employing counsellors and drug workers. Most agencies (66%) operated a schedule of weekly sessions; 12% of agencies offered fortnightly or less frequent sessions, whereas 15% of agencies offered several sessions a week. More than three‐quarters of all sessions were scheduled to last between 50 and 60 minutes. Conclusion Typically, counselling is provided on a weekly to fortnightly basis by drug workers without formal counselling qualifications. In‐depth research is needed to examine whether and how sessions provided by drug workers differ from sessions provided by counsellors, as past research has only demonstrated the effectiveness of counselling in studies using highly trained counselling staff.
How Learning Logic Programming Affects Recursion Comprehension

Recursion is a central concept in computer science, yet it is difficult for beginners to comprehend. Israeli high-school students learn recursion in the framework of a special modular program in computer science (Gal-Ezer & Harel, 1999). Some of them are introduced to the concept of recursion in two different paradigms: the procedural programming paradigm and the logic programming (LP) paradigm. Here we discuss the implication of first learning recursion in LP on the students’ understanding of the concept. The declarative approach for teaching recursion in logic programming seems to enhance students’ recursion comprehension. We found that students who learned recursion in LP before learning it in a procedural paradigm differed, in terms of their mental models of recursion, from those who were acquainted with recursion in procedural programming only. More of the LP students possessed an adequate model of recursion as a process than did the non-LP students. Moreover, the LP students also attained a unique conception of recursion as a tool for knowledge representation.
Blood and bombs: the demand and use of blood following the London Bombings of 7 July 2005 – a retrospective review

Mass casualty events (MCE) present health systems with a sudden demand on key services. The overall objective of this study was to describe the experience of the National Blood Service (NBS) following the largest UK MCE in recent times. Data was collated from the NBS database and directly from the hospitals involved. All data was collected immediately following the event and included: all blood components requested, issued and transfused in relation to the bombings, blood stock levels at the time and the injury profiles of the casualties transfused. The total NBS order from hospitals for the event was 1455 units of blood components. All requests were fulfilled, this included: 978 units of red cells (RC), 36 doses of platelets, 141 units of fresh frozen plasma (FFP) and 300 doses of cryoprecipitate. The amount of blood ordered was three times that initially used and the total number of RC transfused in treating all victims from admission to discharge was approximately 440 units. The greatest use of blood components was for those casualties who had sustained traumatic amputations amongst their injury profile. Published data with which to compare these results is lacking, although the RC use was similar to the initial mean individual usage described in previous military and civilian bombings. The overall implication for any blood service remains, there is now likely to be a far greater demand for plasma, platelets and cryoprecipitate in any future incidents involving victims suffering major haemorrhage.
Interpretation of mycobacterial antibodies in the cerebrospinal fluid of adults with tuberculous meningitis

Objective Microbiological identification of Mycobacterium tuberculosis is insensitive and slow, and clinical distinction of tuberculous meningitis (TBM) from other subacute or chronic meningoenchephalitides (SACM) is difficult. Successful use of highly specific M. tuberculosis serological assays on cerebrospinal fluid has been reported, but their performance for diagnosis in a tuberculosis endemic country where they would be of most value is unclear. We sought to determine the biological basis for the uncertainty in interpretation of antibody detection in the CSF of TBM patients.
Infant Feeding in Finnish Children <7 yr of Age With Newly Diagnosed IDDM

Objective We studied associations between the type of feeding in infancy and the incidence of insulin-dependent diabetes mellitus (IDDM). Research Design And Methods We studied 103 newly diagnosed diabetic children <7 yr of age and 103 age- and sex-matched population-based control children in a countrywide study. Results The risk of IDDM was decreased (P < 0.05) among children breast-fed for at least 7 mo (odds ratio [OR] 0.45, 95% confidence interval [CI] 0.24–0.85) or exclusively breast-fed for at least 3 (OR 0.33, 95% CI 0.13–0.84) or 4 (OR 0.43, 95% CI 0.22–0.84) mo. Also, children who were ≥4 mo old at the time of introduction of supplementary milk feeding had a lower risk of diabetes (OR 0.48, 95% CI 0.26–0.91). Conclusions The protective effects of a long duration of breast-feeding and a late introduction of dairy products on the risk of IDDM remained significant after adjusting for the mother's education.
Insecticide‐treated net ownership and usage in Niger after a nationwide integrated campaign

Objectives In December 2005 and March 2006, Niger conducted nationwide integrated campaigns to distribute polio vaccine and long lasting insecticide‐treated nets (LLINs) to children <5 years of age. We evaluated the campaign effectiveness, net retention, insecticide‐treated net (ITN) ownership, and usage.
Emergência médica na prática odontológica no Estado de Santa Catarina: ocorrência, equipamentos e drogas, conhecimento e treinamento dos cirurgiões-dentistas

Esta pesquisa teve por objetivo verificar a ocorrencia de emergencias medicas na pratica odontologica, a adequacao de equipamentos e drogas, e o nivel de conhecimento e treinamento dos profissionais da odontologia no enfrentamento dos eventos emergenciais, tanto no servico publico quanto na clinica privada. Os questionarios foram enviados via postal, aos 6.000 cirurgioes-dentistas (CDs) inscritos ate abril de 2004 no Conselho Regional de Odontologia do Estado de Santa Catarina. Houve um retorno de 506 questionarios (8,43%). A partir da analise dos dados, constatou-se que os CDs respondentes estao conscientes da importância do tema e sentem-se despreparados para solucionar uma emergencia medica. As emergencias relatadas com maior frequencia foram: lipotimia, taquicardia, hipertensao, reacao ao anestesico local e hipoglicemia. O servico publico encontra-se com uma quantidade maior de equipamentos e drogas para emergencia medica. Foi enviado, tambem, oficio as sete instituicoes de ensino superior com cursos de odontologia no Estado, consulta esta que acusou a inexistencia de disciplinas especificas que tratem das emergencias medicas. O tema normalmente e abordado em outras disciplinas com pequena carga horaria, e nos semestres iniciais do curso.
Word Length, Word Frequencies and Zipf’s Law in the Greek Language

The aim of this paper is to report for the first time the 1000 most common words and lemmas of Modern Greek and some of their quantitative characteristics. The frequency word list produced is based on the Hellenic National Corpus (HNC), a corpus of Modern Greek language consisting of about 13 million words of written texts. In particular, we investigate the application of Zipf’s law in both the 1000 most common words and lemmas. In addition we examine the frequency distribution of the grammatical categories in the 1000 most common words and lemmas as well as the average word length in the whole HNC and the growth of the average word length as a function of the number of the most common words.