bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of life outcomes with BG-12 (dimethyl fumarate) in patients with relapsing–remitting multiple sclerosis: The DEFINE study
Authors: Kappos Ludwig , Gold Ralf , Arnold Douglas L , Bar-Or Amit , Giovannoni Gavin , Selmaj Krzysztof , Sarda Sujata P , Agarwal Sonalee , Zhang Annie , Sheikh Sarah I , Seidman Emily , Dawson Katherine T 
Published: October 2013

Background: Oral BG-12 (dimethyl fumarate), approved for the treatment of the relapsing forms of MS, has demonstrated clinical efficacy with an acceptable safety profile in the Phase III “Determination of the Efficacy and Safety of Oral Fumarate in Relapsing–Remitting Multiple Sclerosis (RRMS)” (DEFINE) and “Comparator and an Oral Fumarate in RRMS” (CONFIRM) studies. Objectives: To evaluate the health-related quality of life (HRQoL) impairment that is associated with RRMS and to assess the effects of BG-12 on HRQoL in the DEFINE study. Methods: Patients with RRMS were randomized to BG-12 240 mg twice (BID) or three times (TID) daily, or placebo, for 2 years. HRQoL was assessed by the Short Form-36 (SF-36), global assessment of well-being visual analog scale and the EuroQol-5D. Results: In the 1237 patients from DEFINE, HRQoL impairment was greatest in patients who had higher disability scores and in those who had experienced relapse. Change in SF-36 physical component summary scores during 2 years’ treatment significantly favored BG-12 over placebo (both doses: p < 0.001). We saw similar benefits in other measures of functioning and general well-being as early as Week 24. These benefits were maintained during the study. Conclusions: Our results add to evidence for a negative impact of RRMS on HRQoL and they demonstrate the benefits of BG-12 on HRQoL measures, which coupled with significant clinical efficacy, further support its use as a new treatment for RRMS.
Ayahuasca and cancer treatment
Authors: Schenberg Eduardo E 
Published: October 2013

Objectives: Comprehensively review the evidence regarding the use of ayahuasca, an Amerindian medicine traditionally used to treat many different illnesses and diseases, to treat some types of cancer. Methods: An in-depth review of the literature was conducted using PubMed, books, institutional magazines, conferences and online texts in nonprofessional sources regarding the biomedical knowledge about ayahuasca in general with a specific focus in its possible relations to the treatment of cancer. Results: At least nine case reports regarding the use of ayahuasca in the treatment of prostate, brain, ovarian, uterine, stomach, breast, and colon cancers were found. Several of these were considered improvements, one case was considered worse, and one case was rated as difficult to evaluate. A theoretical model is presented which explains these effects at the cellular, molecular, and psychosocial levels. Particular attention is given to ayahuasca’s pharmacological effects through the activity of N,N-dimethyltryptamine at intracellular sigma-1 receptors. The effects of other components of ayahuasca, such as harmine, tetrahydroharmine, and harmaline, are also considered. Conclusion: The proposed model, based on the molecular and cellular biology of ayahuasca’s known active components and the available clinical reports, suggests that these accounts may have consistent biological underpinnings. Further study of ayahuasca’s possible antitumor effects is important because cancer patients continue to seek out this traditional medicine. Consequently, based on the social and anthropological observations of the use of this brew, suggestions are provided for further research into the safety and efficacy of ayahuasca as a possible medicinal aid in the treatment of cancer.
The effects of vitamin D2 or D3supplementation on glycaemic control and related metabolic parameters in people at risk of type 2 diabetes: protocol of a randomised double-blind placebo-controlled trial
Authors: Menon Ravi K , Rickard Anna P , Mannan Nasima , Timms Peter M , Sharp Stephen J , Martineau Adrian , Boucher Barbara J , Chowdhury Tahseen A , Griffiths Christopher J , Griffin Simon J , Hitman Graham A , Forouhi Nita G 
Published: October 2013

Abstract

Background
The global prevalence of type 2 diabetes is increasing. Effective strategies to address this public health challenge are currently lacking. A number of epidemiological studies have reported associations between low concentrations of 25-hydroxy vitamin D and the incidence of diabetes, but a causal link has not been established. We investigate the effect of vitamin D supplementation on the metabolic status of individuals at increased risk of developing type 2 diabetes.

Methods/design
In a randomised double-blind placebo-controlled trial individuals identified as having a high risk of type 2 diabetes (non-diabetic hyperglycaemia or positive diabetes risk score) are randomised into one of three groups and given 4 doses of either placebo, or 100,000 IU Vitamin D2 (ergocalciferol) or 100,000 IU Vitamin D3 (cholecalciferol) at monthly intervals. The primary outcome measure is the change in glycated haemoglobin level between baseline and 4 months. Secondary outcome measures include blood pressure, lipid levels, apolipoproteins, highly sensitive C-reactive protein, parathyroid hormone (PTH) and safety of supplementation. and C-reactive protein. The trial is being conducted at two sites (London and Cambridge, U.K.) and a total of 342 participants are being recruited.

Discussion
Trial data examining whether supplementation of vitamin D improves glycaemic status and other metabolic parameters in people at risk of developing type 2 diabetes are sparse. This trial will evaluate the causal role of vitamin D in hyperglycaemia and risk of type 2 diabetes. Specific features of this trial include recruitment of participants from different ethnic groups, investigation of the relative effectiveness and safety of vitamin D2 and D3 and an evidence based approach to determination of the dose of supplementation.

Trial registration
EudraCT2009-011264-11; ISRCTN86515510
R-RAS2 overexpression in tumors of the human central nervous system
Authors: Gutierrez-Erlandsson Sylvia , Herrero-Vidal Pedro , Fernandez-Alfara Marcos , Hernandez-Garcia Susana , Gonzalo-Flores Sandra , Mudarra-Rubio Alberto , Fresno Manuel , Cubelos Beatriz 
Published: October 2013

AbstractMalignant tumors of the central nervous system (CNS) are the 10thmost frequent cause of cancer mortality. Despite the strong malignancy of some such tumors, oncogenic mutations are rarely found in classic members of theRASfamily of small GTPases. This raises the question as to whether otherRASfamily members may be affected in CNS tumors, excessively activatingRASpathways. TheRAS-related subfamily of GTPases is that which is most closely related to classical Ras and it currently contains 3 members:RRAS,RRAS2andRRAS3. While R-RAS and R-RAS2 are expressed ubiquitously, R-RAS3 expression is restricted to the CNS. Significantly, both wild type and mutatedRRAS2(also known as TC21) are overexpressed in human carcinomas of the oral cavity, esophagus, stomach, skin and breast, as well as in lymphomas. Hence, we analyzed the expression of R-RAS2 mRNA and protein in a wide variety of human CNS tumors and we found the R-RAS2 protein to be overexpressed in all of the 90 CNS cancer samples studied, including glioblastomas, astrocytomas and oligodendrogliomas. However, R-Ras2 was more strongly expressed in low grade (World Health Organization grades I-II) rather than high grade (grades III-IV) tumors, suggesting that R-RAS2 is overexpressed in the early stages of malignancy. Indeed, R-RAS2 overexpression was evident in pre-malignant hyperplasias, both at the mRNA and protein levels. Nevertheless, such dramatic changes in expression were not evident for the other two subfamily members, which implies that RRAS2 is the main factor triggering neural transformation.
Chemically linked phage idiotype vaccination in the murine B cell lymphoma 1 model
Authors: Roehnisch Tim , Then Cornelia , Nagel Wolfgang , Blumenthal Christina , Braciak Todd , Donzeau Mariel , Böhm Thomas , Bourquin Carole , Oduncu Fuat 
Published: October 2013

AbstractBackgroundB cell malignancies are characterized by clonal expansion of B cells expressing tumor-specific idiotypes on their surface. These idiotypes are ideal target antigens for an individualized immunotherapy. However, previous idiotype vaccines mostly lacked efficiency due to a low immunogenicity of the idiotype. The objective of the present study was the determination of the feasibility, safety and immunogenicity of a novel chemically linked phage idiotype vaccine.MethodsIn the murine B cell lymphoma 1 model, tumor idiotypes were chemically linked to phage particles used as immunological carriers. For comparison, the idiotype was genetically expressed on the major phage coat protein g8 or linked to keyhole limpet hemocynanin. After intradermal immunizations with idiotype vaccines, tolerability and humoral immune responses were assessed.ResultsFeasibility and tolerability of the chemically linked phage idiotype vaccine was demonstrated. Vaccination with B cell lymphoma 1 idiotype expressing phage resulted in a significant survival benefit in the murine B cell lymphoma 1 protection model (60.2 ± 23.8 days vs. 41.8 ± 1.6 days and 39.8 ± 3.8 days after vaccination with wild type phage or phosphate buffered saline, respectively). Superior immunogenicity of the chemically linked phage idiotype vaccine compared to the genetically engineered phage idiotype and keyhole limpet hemocynanin-coupled idiotype vaccine was demonstrated by significantly higher B cell lymphoma 1 idiotype-specific IgG levels after vaccination with chemically linked phage idiotype.ConclusionWe present a novel, simple, time- and cost-efficient phage idiotype vaccination strategy, which represents a safe and feasible therapy and may produce a superior immune response compared to previously employed idiotype vaccination strategies.
What Went Wrong with the Veil? A Comparative Analysis of the Discourse of the Veil in France, Iran, and Indonesia
Authors: Safitri Dian Maya 
Published: October 2013

This paper attempts to discuss several current issues about the veil. Three countries are selected, namely France, Iran, and Indonesia, due to their different policies and perspectives concerning the veil. Using discourse analysis, this paper examines the violation of human rights, particularly those of Muslim women, by the ban of the veil in France and the obligation to wear it in Iran. Finally, inspired by the theoretical work of Gramsci, this paper analyzes how the terms “secular” and “religious“ are used by the state to justify their hegemony over certain minority groups. Moreover, this paper offers the “correct concept of secularism” as that entails civic reason, constitutionalism, and human-rights based citizenship, and proposed by An-Na’im as the best avenue to safeguard the problem of human rights in France and Iran. The remainder of this paper discusses Indonesia, the largest Moslem country in the world, that is, in fact, “a secular country” based on Pancasila, which respects religious freedom, including for women to wear the veil or not. It also opens full, equal, and fair access for all Indonesian women, regardless of their ethnicity and religious affiliation, to compete in the workforce and to pursue education. The author’s intention is to clarify false stereotypes about the veil, to enlighten readers about abuse of power by both French and Iranian governments in violating the rights of women on the issue of veil, and to inform readers --using the case of Indonesia as an example-- about the importance of state neutrality in supporting the rights of freedom of and from religion.
Maqasid and the Challenges of Modernity
Authors: Hallaq Wael B. 
Published: October 2013

A central feature of public Muslim discourse over the past three decades has been the call to restore the Shari‘a in one form or another. Some reformers have proposed a new theoretical underpinning for this restoration, arguing for the adoption of foundational concepts that bear little, if any, resemblance to their pre-modern counterparts. A central question that ineluctably emerges in this aporia is: What narrative must be adopted as the representation of the historical Shari‘a, the Shari‘a that prevailed until the early portion of the nineteenth century? If the colonial narrative is ipso facto programmatic and teleological, and if it served and still serves the purposes of all but those of the subaltern majority, then what other narrative must be adopted in the project of creating the new symbiosis? And if the jural voices of the subaltern are to come in for serious consideration, then how are we to represent them, if we can at all? And if we cannot, then into what espistemic predicament, if not a perennial aporia, does this throw both the privileged scholar and the reformer/intellectual? This article does not provide answers to these questions but rather addresses the problematics that these and related questions raise in dealing with the challenge of introducing into the modern Muslim condition one form of Islamic law or another.
Activity limitation and participation restriction to among the elderly in North India: determinants and related management practices
Authors: Malhotra Geetu , Sharma Manoj Kumar , Singh Amarjeet , Dudeja Puja 
Published: October 2013

Abstract

Background: Eight percent of India’s population is aged over 60 years. This study was done among the elderly in a city in North India to (i) ascertain the level of Activity Limitation (AL) and Participation Restriction (PR), (ii) determine the factors affecting AL and PR, and (iii) ascertain their management practices.

Methods: This cross-sectional study was conducted in Chandigarh, India during January–May 2012 among 100 elderly each from rural (villages), urban (sectors), and slum (colonies) areas. AL and PR were assessed according to the International Classification of Functioning, Disability, and Health (ICF) Questionnaire.

Results: Severe AL was reported by 32%, 2% had no AL, 18% had PR, and 8% had severe PR. AL increased with age (p=0.002); AL was more prevalent in rural areas (p=0.015). PR was higher in the elderly living with their families (p=0.003). Assistive and Enabling Devices (AEDs) included spectacles and hearing aids. A walking stick was the most common AED used.

Conclusions: AL was significantly more prevalent in the elderly aged above 70 years. PR was significantly more prevalent in the elderly staying with families. Spectacle use was very low in slum areas.
Reversal of alcohol induced testicular hyperlipidemia by supplementation of ascorbic acid and its comparison with abstention in male guinea pigs
Authors: Radhakrishnakartha Harikrishnan , Appu Abhilash Puthuvelvippel , Madambath Indira 
Published: October 2013

Abstract

Background: Chronic ethanol exposure causes hyperlipidemia. The present study was designed to investigate the impact of ascorbic acid supplementation on ethanol induced hyperlipidemia in testis and to compare it with that of abstinence from taking alcohol.

Methods: Thirty-six male guinea pigs were divided into two groups and were maintained for 90 days as follows (1) control (C) (2) ethanol treated group (E) (4 g/kg body wt/day). Ethanol was administered for 90 days and on 90th day, alanine amino transaminase (ALT), aspartate amino transaminase (AST) and γ-glutamyltransferase (GGT) in serum was assayed. The animals in the ethanol group were further divided into an ascorbic acid supplemented group (25 mg/100 g body wt/day) (E+AA) and an ethanol abstention group (EAG) and those in the control group were divided into a control group and a control+ascorbic acid group (C+AA).

Results: There was significant increase in levels of testicular cholesterol, free fatty acid, phospholipids and triglycerides in the ethanol group. There was also a significant increase in the activity of HMG CoA reductase and decrease in activity of testicular glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme in ethanol-ingested animals that further led to decreased levels of serum testosterone. Alcohol administration also enhanced the activity of testicular alcohol dehydrogenase (ADH). Ascorbic acid supplementation and abstention altered all these parameters induced by chronic alcohol administration. Histological studies were also in line with the above results.

Conclusions: Ascorbic acid was able to reinstate the cholesterol homeostasis in testis which could have further restored the testicular steroidogenesis. The present study demonstrated that ascorbic acid is effective in reducing the hyperlipidemia induced by chronic alcohol administration and produced a better recovery than abstention.
Can Offering a Signing Bonus Motivate Effort? Experimental Evidence of the Moderating Effects of Labor Market Competition
Authors: Choi Jongwoon (Willie) 
Published: October 2013

ABSTRACT
Employers often rely on informal controls such as trust to motivate organizationally desirable behaviors from their workers by appealing to the latter's reciprocity. Notably, trust and reciprocity can promote a “gift exchange” between employers and workers. Using an experiment, I investigate whether labor market competition moderates the emergence of a gift exchange in labor markets in which signing bonus offers serve as a potential signal of trust and the duration of the employment relationship is endogenously determined. I find that offering a signing bonus more positively affects both workers' beliefs about the employer's trust in them and their effort when there is an excess supply of workers than when there is an excess demand for workers. I also find that the initial effects of signing bonuses may not persist over time. Additional analyses suggest that both employers' and workers' expectations may affect whether and how trust and reciprocity develop over time.
MRI brain in monohalomethane toxic encephalopathy: A case report
Authors: Deshmukh Yogeshwari S , Atre Ashish , Shah Darshan , Kothari Sudhir 
Published: October 2013

AbstractMonohalomethanes are alkylating agents that have been used as methylating agents, laboratory reagents, refrigerants, aerosol propellants, pesticides, fumigants, fire-extinguishing agents, anesthetics, degreasers, blowing agents for plastic foams, and chemical intermediates. Compounds in this group are methyl chloride, methyl bromide, methyl iodide (MI), and methyl fluoride. MI is a colorless volatile liquid used as a methylating agent to manufacture a few pharmaceuticals and is also used as a fumigative insecticide. It is a rare intoxicant. Neurotoxicity is known with both acute and chronic exposure to MI. We present the characteristic magnetic resonance imaging (MRI) brain findings in a patient who developed neuropsychiatric symptoms weeks after occupational exposure to excessive doses of MI.
Validation of the global reference for fetal weight and birth weight percentiles
Authors: Badade Anirudh B , Bhide Amar , Satoskar Purnima , Wadekar Darshan 
Published: October 2013

AbstractThe objective of this study was to evaluate whether the global reference curves adapted on the basis of WHO data for India and the Hadlock reference curves fit the population in India and to validate the reference curves. The data were retrieved retrospectively from the records of women registration for antenatal care at a charitable maternity hospital in Mumbai, India. All pregnancies were dated on CRL obtained before 14 weeks. Births before 34 th week were excluded. The expected frequencies of birth weights below the 1 st , 5 th , 10 th , 50 th , 90 th , 95 th and 99 th centiles from three reference ranges were compared with observed frequencies. It was found that the WHO generic reference adapted to India significantly underpredicted the birth weights and that the Hadlock reference ranges significantly overpredicted the birth weights. The use of generic reference adapted to Sri Lanka showed a better fit to the observed data. We concluded that global reference curves adapted on the basis of WHO data for India and the Hadlock reference ranges do not fit all the population in India and the charts need validation. Reference charts modified on the basis of data for Sri Lankan population show a better fit to the observed data, and therefore are more appropriate for use in clinical practice in South India.
Efficacy of Retigabine in Adjunctive Treatment of Partial Onset Seizures in Adults
Authors: Splinter Michele Y. 
Published: October 2013

Objective To evaluate efficacy and tolerability of retigabine (ezogabine, US adopted name) in the adjunctive treatment of partial-onset seizures in adults. Retigabine is the first anticonvulsant in its class, decreasing neuronal excitability by opening voltage-gated potassium channels. Methods MEDLINE and EMBASE were systematically searched using search terms retigabine and ezogabine for randomized controlled trials published from 1980 through August 17, 2013. Additionally, articles relating to pharmacology, pharmacokinetics, tolerability and interactions were examined for inclusion. Published abstracts and websites of the Food and Drug Administration and European Medication Agency were reviewed for additional relevant information. Results One phase IIb and two phase III trials were identified. Retigabine has been reported to have dose dependent efficacy in adjunctive treatment of resistant partial-onset seizures in adults in doses of 600, 900 and 1200 mg/day. Similar to other anticonvulsants, the most common adverse events were central nervous system related. Retigabine has several unique adverse events compared to other anticonvulsants: urinary retention and, with extended use, pigment changes to the skin and retina. Retigabine is metabolized by glucuronidation and acetylation. There are few drug interactions with retigabine. Conclusions Retigabine has been shown to have efficacy when used as adjunctive therapy in partial-onset seizures. It has a novel mechanism of action, activation of voltage-gated potassium channels. It has less drug interactions than many other anticonvulsants because it is not metabolized through the P-450 system. Its place in therapy has yet to be determined, especially with recent reports of pigment discoloration of skin and the retina with extended use.