bluuebunny/crossref_metadata_2025_split huggingface dataset:
Galcanezumab in migraine prevention: a systematic review and meta-analysis of randomized controlled trials
Authors: Gklinos Panagiotis , Mitsikostas Dimos D. 
Published: April 2020

Background: Galcanezumab, along with three other monoclonal antibodies targeting the calcitonin gene-related peptide (CGRP) pathway, represents the latest disease-specific and mechanism-based treatment for the prophylaxis of migraine. Galcanezumab shares data also for the prophylaxis of cluster headache. Objective: To provide a pooled safety and efficacy analysis of all phase III randomized controlled trials of galcanezumab in the preventive therapy of migraine. Methods: A computer-based literature search was conducted on MEDLINE and the US National Institutes of Health Clinical Trials Registry for phase III randomized controlled trials of galcanezumab in migraine prevention. The primary outcome was the mean change in monthly migraine days (MMDs). The proportions of patients who reported at least one adverse event (AE), at least one serious adverse event (SAE) or withdrew from the study were used as safety outcomes. Results: Two trials were included in the efficacy meta-analysis and three in the safety meta-analysis. Migraine preventive treatment with subcutaneous galcanezumab, at both 120 mg and 240 mg dosages, was associated with a significantly greater reduction in the mean number of MMDs versus placebo (120 mg, MD = –1.98, 95% CI = –2.33 to –1.63; p < 0.0001) or (240 mg, MD = –1.86, 95% CI = –2.20 to –1.53; p < 0.0001). Galcanezumab was found to be more efficacious in all key secondary outcomes as well. Regarding safety, most of the adverse events were mild to moderate, while drop-out rates and serious adverse events were low. Conclusions: Galcanezumab is an efficacious and well-tolerated preventive treatment for migraine. Larger clinical trials with longer follow-up periods need to be conducted in order to provide more safety data of the above-mentioned drug.
Social capital, gender, and health: an ethnographic analysis of women in a Mumbai slum
Authors: Gundewar Anisha , Chin Nancy P. 
Published: April 2020

Objective: Quantitative studies have demonstrated that social capital can positively impact community health, but qualitative explorations of the factors mediating this relationship are lacking. Furthermore, while the world’s poor are becoming increasingly concentrated in the cities of lower-middle income countries, most of the existing literature on social capital and health explores these variables in Western or rural contexts. Even fewer studies consider the impact of social constructs like race, gender, or class on the creation of social capital and its operationalization in health promotion. Our study aimed to address these gaps in the literature through an ethnographic exploration of social capital among women living in Kaula Bandar (KB) – a marginalized slum on the eastern waterfront of Mumbai, India. We then sought to identify how these women leveraged their social capital to promote health within their households. Methods: This was a mixed-method, qualitative study involving participant observation and 20 in-depth, semi-structured, individual interviews over a nine-month period. Field notes and interview transcripts were manually analyzed for recurring content and themes. Results: We found that women in KB relied heavily on bonding social capital for both daily survival and survival during a health crisis, but that the local contexts of gender and poverty actively impeded the ability of women in this community to build forms of social capital – namely bridging or linking social capital – that could be leveraged for health promotion beyond immediate survival. Conclusions: These findings illustrate the context-specific challenges that women living in urban poverty face in their efforts to build social capital and promote health within their households and communities. Community-based qualitative studies are needed to identify the macro- and micro-level forces, like gender and class oppression, in which these challenges are rooted. Directly addressing these structural inequalities significantly increases the potential for health promotion through social capital formation.
Impact of smoking on cardiovascular outcomes in patients with stable coronary artery disease
Authors: Bouabdallaoui Nadia , Messas Nathan , Greenlaw Nicola , Ferrari Roberto , Ford Ian , Fox Kim M , Tendera Michal , P Naidoo Datshana , Hassager Christian , Gabriel Steg P , Tardif Jean-Claude ,   for the CLARIFY Investigators
Published: April 2020

Abstract

Aims
Smoking is a major preventable risk factor for cardiovascular disease and mortality. However, the ‘smoker’s paradox’ suggests that it is associated with better survival after acute myocardial infarction. We aimed to investigate the impact of smoking on mortality and cardiovascular outcomes in patients with stable coronary artery disease.

Methods
The international CLARIFY registry included 32,703 patients with stable coronary artery disease between 2009 and 2010. Among the 32,378 patients included in the present analysis, Cox proportional hazards models (adjusted for age, sex, geographic region, prior myocardial infarction, and revascularization status) were used to estimate associations between smoking status and outcomes. Patients were stratified as follows: 41.3% of patients never smoked, 12.5% were current smokers and 46.2% were former smokers.

Results
Current smokers were younger than never-smokers and former smokers (59 vs. 66 and 64 years old, respectively, p &lt; 0.0001). There were more men among current or former smokers compared with never-smokers. Compared with never-smokers, both current and former smokers were at higher risk of all-cause death (hazard ratio = 1.96 and 1.37) and cardiovascular death (hazard ratio = 1.92 and 1.38) within five years (all p &lt; 0.05). Similarly graded and increased risks were present for myocardial infarction and the composite of cardiovascular death, myocardial infarction and stroke (all p &lt; 0.05).

Conclusion
In contrast to the ‘smoker’s paradox’, current smokers with stable coronary artery disease have a greatly increased risk of future cardiovascular events, including mortality, compared with never-smokers. In former smokers, cardiovascular risk remains elevated albeit at an intermediate level between that of current and never-smokers, reinforcing the importance of smoking cessation. (ISRCTN43070564).
A comparative study on efficacy of fixed combination timolol/brinzolamide versus travoprost monotherapy in drug-naïve open-angle glaucoma patients
Authors: Dixit Alok , Ashish Atul , Sharma Reena 
Published: April 2020

Background: Glaucoma is most common irreversible cause of blindness in India. First line management of open-angle glaucoma is either beta blockers or prostaglandin analogs monotherapy. Monotherapy rarely achieves target intraocular pressure within 2 years and patients are shifted to combination medications, usually fixed-dose combination. Objective: To compare travoprost monotherapy and timolol/brinzolamide fixed-dose combination for their intraocular pressure lowering efficacy, their effects on hemodynamic parameters and cup disc ratio reversibility in newly diagnosed drug-naïve open-angle glaucoma patients. Material and methods: In a 12-week, prospective, randomised, single-blind study, patients were randomised to receive twice daily 0.5% timolol and 0.2% brinzolamide fixed-dose combination (n = 52) or once daily travoprost 0.004% (n = 52). Intraocular pressure, blood pressure, pulse rate and cup disc ratio were compared across treatment groups over 3 months. Results: Significant reduction ( p < 0.001) in intraocular pressure by 27.99% and 30.49% at 12th-week visit as compared with baseline was observed in monotherapy and fixed-dose combination group, respectively. Significant changes in pulse rate (9 beats/min) and systolic blood pressure (2.35 mmHg) was observed in fixed-dose combination group. No cup disc ratio reversibility was observed at the end of study. Conjunctival hyperaemia ( n = 14) and transient blurring of vision ( n = 16) were most commonly reported adverse drug reaction in monotherapy and fixed-dose combination, respectively. Conclusion: The 0.5% timolol and 0.2% brinzolamide fixed-dose combination produced greater reduction in intraocular pressure than those produced by 0.004% travoprost alone in drug-naïve open-angle glaucoma patients.
Refinement of waste phosphogypsum from Prahovo, Serbia: characterization and assessment of application in civil engineering
Authors: Išek Josip I. , Kaluđerović Lazar M. , Vuković Nikola S. , Milošević Maja , Vukašinović Ivana , Tomić Zorica P. 
Published: April 2020

AbstractTwo samples collected from the phosphogypsum deposits of the chemical products industry Elixir Prahovo (Serbia) were subjected to a recrystallization experiment performed over several repeated cycles. In these tests, phosphogypsum was separated into recrystallized (purified) gypsum, insoluble residue and supernatant. Both raw phosphogypsum and recrystallized gypsum were examined using inductively coupled plasma optical emission spectrometry, X-ray diffraction and scanning electron microscopy with energy-dispersive spectrometry. The activity concentrations of 238U, 235U, 226Ra, 210Pb, 232Th and 40K were investigated using γ-ray spectrometry. Based on the activity concentration results, a number of radiometric parameters were calculated for the original and recrystallized phosphogypsum (i.e. radium equivalent activity, γ indices for construction materials, α index and external and internal hazard indices). Raw phosphogypsum samples showed greater mean activity concentration levels of 238U and 226Ra than the international recommended limits, while the recrystallized gypsum demonstrated notably lower activity concentrations for these two isotopes. The activity concentration of 226Ra in recrystallized gypsum is ~6 times lower than in raw phosphogypsum. Therefore, recrystallized gypsum does not present a radiation hazard when used as a building material, while raw phosphogypsum meets the requirements only for road construction materials.
Fedratinib in myelofibrosis
Authors: Mullally Ann , Hood John , Harrison Claire , Mesa Ruben 
Published: April 2020

Abstract
Following the discovery of the JAK2V617F mutation in myeloproliferative neoplasms in 2005, fedratinib was developed as a small molecular inhibitor of JAK2. It was optimized to yield low-nanomolar activity against JAK2 (50% inhibitory concentration = 3 nM) and was identified to be selective for JAK2 relative to other JAK family members (eg, JAK1, JAK3, and TYK2). It quickly moved into clinical development with a phase 1 clinical trial opening in 2008, where a favorable impact on spleen and myelofibrosis (MF) symptom responses was reported. A phase 3 trial in JAK2 inhibitor treatment-naive MF patients followed in 2011 (JAKARTA); a phase 2 trial in MF patients resistant or intolerant to ruxolitinib followed in 2012 (JAKARTA-2). Clinical development suffered a major setback between 2013 and 2017 when the US Food and Drug Administration (FDA) placed fedratinib on clinical hold due to the development of symptoms concerning for Wernicke encephalopathy (WE) in 8 of 608 subjects (1.3%) who had received the drug. It was ultimately concluded that there was no evidence that fedratinib directly induces WE, but clear risk factors (eg, poor nutrition, uncontrolled gastrointestinal toxicity) were identified. In August 2019, the FDA approved fedratinib for the treatment of adults with intermediate-2 or high-risk MF. Notably, approval includes a “black box warning” on the risk of serious and fatal encephalopathy, including WE. FDA approval was granted on the basis of the JAKARTA studies in which the primary end points (ie, spleen and MF symptom responses) were met in ∼35% to 40% of patients (JAKARTA) and 25% to 30% of patients (JAKARTA-2), respectively.
A cross-sectional study of prevalence, distribution, cause, and impact of blood product recalls in the United States
Authors: Alqemlas Ibrahim , Shankar Sneha , Handagama Winode , Felse P. Arthur 
Published: April 2020

AbstractDefective blood products that are recalled because of safety or potency deviations can trigger adverse health events and constrict the nation’s blood supply chain. However, the underlying characteristics and impact of blood product recalls are not fully understood. In this study, we identified 4700 recall events, 7 reasons for recall, and 144 346 units affected by recalls. Using geospatial mapping of the newly defined county-level recall event density, we discovered hot spots with high prevalence and likelihood of blood product recall events. Distribution patterns and distribution distances of recalled blood products vary significantly between product types. Blood plasma is the most recalled product (87 980 units), and leukocyte-reduced products (34 230 units) are recalled in larger numbers than non-leukocyte-reduced products (8076 units). Donor-related reasons (92 382 units) and sterility deviations (22 408 units) are the major cause of blood product recalls. Monetary loss resulting from blood product recalls is estimated to be $17.9 million, and economic sensitivity tests show that donor-related reasons and sterility deviations contribute most to the overall monetary burden. A total of 2.8 million days was required to resolve recall events, and probabilistic survival time analysis shows that sterility deviations and contamination took longer to resolve because of their systemic effect on blood collection and processing. Our studies demonstrate that better donor screening procedures, rigorous sterility requirements, improved containment methods, and mitigation of recall events in high-prevalence regions will enable a more robust blood supply chain.
Favorable outcomes of hematopoietic stem cell transplantation in children and adolescents with Diamond-Blackfan anemia
Authors: Strahm Brigitte , Loewecke Felicia , Niemeyer Charlotte M. , Albert Michael , Ansari Marc , Bader Peter , Bertrand Yves , Burkhardt Birgit , Da Costa Lydie M. , Ferster Alina , Fischer Alexandra , Güngör Tayfun , Gruhn Bernd , Hainmann Ina , Kapp Friedrich , Lang Peter , Müller Ingo , Schulz Ansgar , Szvetnik Amina , Wlodarski Marcin , Noellke Peter , Leblanc Thierry , Dalle Jean-Hugues 
Published: April 2020

AbstractDiamond-Blackfan anemia (DBA) is a congenital pure red cell aplasia associated with congenital abnormalities and cancer predisposition. Allogeneic hematopoietic stem cell transplantation (HSCT) can correct the hematological phenotype and is indicated in transfusion-dependent patients. In 70 children reported to the German DBA and French HSCT registries, HSCT was performed from 1985 to 2017. Median age at HSCT was 5.5 years (range, 0.9-17.3 years). Two-thirds of patients (64%) were transplanted from a matched sibling donor (MSD), and most procedures were performed after the year 1999 (73%). Primary engraftment was achieved in all patients. One patient developed secondary graft failure. Cumulative incidence of acute graft-versus-host disease (GVHD) was 24% for °II-IV (95% confidence interval [CI], 16% to 37%) and 7% for °III-IV (95% CI, 3% to 17%); cumulative incidence of chronic GVHD was 11% (95% CI, 5% to 22%). The probability of chronic GVHD-free survival (cGFS) was 87% (95% CI, 79% to 95%) and significantly improved over time (&lt;2000: 68% [95% CI, 47% to 89%] vs ≥2000: 94% [95% CI, 87% to 100%], P &lt; .01). cGFS was comparable following HSCT from a MSD and an unrelated donor (UD). Of note, no severe chronic GVHD or deaths were reported following MSD-HSCT after 1999. The difference of cGFS in children transplanted &lt;10 years of age compared with older patients did not reach statistical significance (&lt;10 years: 90% [95% CI, 81% to 99%] vs 10-18 years 78% [95% CI, 58% to 98%]). In summary, these data indicate that HSCT is efficient and safe in young DBA patients and should be considered if a MSD or matched UD is available. HSCT for transfusion dependency only must be critically discussed in older patients.
Baseline FDG-PET/CT detects bone marrow involvement in follicular lymphoma and provides relevant prognostic information
Authors: Nakajima Reiko , Moskowitz Alison J. , Michaud Laure , Mauguen Audrey , Batlevi Connie Lee , Dogan Ahmet , Schöder Heiko 
Published: April 2020

Abstract
In follicular lymphoma (FL), detection of bone marrow (BM) involvement (BMI) by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) improves the accuracy of staging vs BM biopsy (BMB) alone. Our objective was to determine the diagnostic utility of PET for BMI FL and the prognostic value of BMI by PET (positive PET result [PET+]). Records of patients (2002-2016) with PET and BMB at the time of initial treatment were reviewed. BMI was identified by positive BMB result (BMB+) and/or unifocal or multifocal BM FDG uptake on blindly reviewed PET scans with no corresponding CT abnormality (PET+). Among 261 patients, BMI was diagnosed in 78 patients (29.9%) by PET+, in 81 patients (31.0%) by BMB+, and in 113 patients (43.3%) by either PET+ or BMB+. PET+ upstaged 24 patients to stage IV, including 10 from stages I or II to stage IV. Median duration of follow-up was 6.0 years (range, 0-16.6 years). In univariate analysis, a high Follicular Lymphoma International Prognosis Index (FLIPI) score, PET+, and BMB+ correlated with shorter progression-free survival (PFS; all P ≤ .03), and high FLIPI, PET+, and combined PET+ and BMB+ with shorter overall survival (OS; all P ≤ .01). In multivariate analysis, PET+ was the only independent predictor of PFS, whereas high FLIPI score and PET+ predicted OS (P ≤ .03). Combined PET and BMB identify BMI more accurately than either BMB or PET alone, but BMB rarely adds critical information. For patients initiating treatment of FL, identification of BMI by PET is predictive of PFS and OS.
Hydrothermal Synthesis of Silver Decorated Reduced Graphene Oxide (rGO) Nanoflakes with Effective Photocatalytic Activity for Wastewater Treatment
Authors: Ikram Muhammad , Raza Ali , Imran Muhammad , Ul-Hamid Anwar , Shahbaz Atif , Ali Salamat 
Published: April 2020

AbstractGraphene oxide (GO) was obtained through modified hummers method, and reduced graphene oxide (rGO) was acquired by employing heat treatment. Various concentrations (2.5, 5, 7.5, and 10 wt. %) of silver (Ag) were incorporated in GO nanosheets by adopting hydrothermal approach. Synthesized Ag decorated rGO photocatalyst Ag/rGO was characterized using X-ray diffraction (XRD) to determine phase purity and crystal structure. XRD patterns showed the formation of GO to Ag/rGO. Molecular vibration and functional groups were determined through Fourier Transform Infrared spectroscopy (FTIR). Optical properties and a decrease in bandgap with insertion of Ag were confirmed with UV-Visible (Uv-Vis) spectrophotometer and photoluminescence (PL). Electronic properties and disorders in carbon structures were investigated through Raman spectroscopy that revealed the existence of characteristic bands (D and G). Surface morphology of prepared samples was examined with field emission scanning electron microscope (FESEM). Homogeneous distribution, size, and spherical shape of Ag NPs over rGO sheets were further confirmed with the help of high-resolution transmission electron microscope (HR-TEM). Dye degradation of doped and undoped samples was examined through Uv-Vis spectra. Experimental results indicated that photocatalytic activity of Ag@rGO enhanced with increased doping ratio owing to diminished electron-hole pair recombination. Therefore, it is suggested that Ag@rGO can be used as a beneficial and superior photocatalyst to clean environment and wastewater.
Evolution of emergency medical services in the Kingdom of Bahrain
Authors: Abuzeyad Feras H. , Al Qasim Ghada , Alqasem Leena , Al Farras Mudhaffar I. 
Published: April 2020

AbstractEmergency medical services (EMS) is crucial to any healthcare system, especially in urban countries. The Kingdom of Bahrain has always strived to develop healthcare services throughout the Kingdom including EMS. Like any other country, the Kingdom has gone through several stages in the provision of EMS. This article will focus on the development of EMS in the Kingdom and its evolution from a scattered hospital-based system to a unified system, which ensures ease of access for the population and speed of delivery to the healthcare facilities. The major focus will be the most recent national project which is the National Ambulance.
Basic biochemical characterization of cytosolic enzymes in thymidine nucleotide synthesis in adult rat tissues: implications for tissue specific mitochondrial DNA depletion and deoxynucleoside-based therapy for TK2-deficiency
Authors: Wang Liya , Sun Ren , Eriksson Staffan 
Published: April 2020

Abstract
Background
Deficiency in thymidine kinase 2 (TK2) or p53 inducible ribonucleotide reductase small subunit (p53R2) is associated with tissue specific mitochondrial DNA (mtDNA) depletion. To understand the mechanisms of the tissue specific mtDNA depletion we systematically studied key enzymes in dTMP synthesis in mitochondrial and cytosolic extracts prepared from adult rat tissues.

Results
In addition to mitochondrial TK2 a cytosolic isoform of TK2 was characterized, which showed similar substrate specificity to the mitochondrial TK2. Total TK activity was highest in spleen and lowest in skeletal muscle. Thymidylate synthase (TS) was detected in cytosols and its activity was high in spleen but low in other tissues. TS protein levels were high in heart, brain and skeletal muscle, which deviated from TS activity levels. The p53R2 proteins were at similar levels in all tissues except liver where it was ~ 6-fold lower. Our results strongly indicate that mitochondria in most tissues are capable of producing enough dTTP for mtDNA replication via mitochondrial TK2, but skeletal muscle mitochondria do not and are most likely dependent on both the salvage and de novo synthesis pathways.

Conclusion
These results provide important information concerning mechanisms for the tissue dependent variation of dTTP synthesis and explained why deficiency in TK2 or p53R2 leads to skeletal muscle dysfunctions. Furthermore, the presence of a putative cytosolic TK2-like enzyme may provide basic knowledge for the understanding of deoxynucleoside-based therapy for mitochondrial disorders.