bluuebunny/crossref_metadata_2025_split huggingface dataset:
Energy Balance After Sodium–Glucose Cotransporter 2 Inhibition
Authors: Ferrannini Giulia , Hach Thomas , Crowe Susanne , Sanghvi Arjun , Hall Kevin D. , Ferrannini Ele 
Published: July 2015

OBJECTIVE
Sodium–glucose cotransporter 2 (SGLT2) inhibitors cause substantially less weight loss than expected from the energy excreted via glycosuria. Our aim was to analyze this phenomenon quantitatively.

RESEARCH DESIGN AND METHODS
Eighty-six patients with type 2 diabetes (HbA1c 7.8 ± 0.8% [62 ± 9 mmol/mol], estimated glomerular filtration rate [eGFR] 89 ± 19 mL ⋅ min−1 ⋅ 1.73 m−2) received empagliflozin (25 mg/day) for 90 weeks with frequent (n = 11) assessments of body weight, eGFR, and fasting plasma glucose (FPG). Time-dependent glucose filtration was calculated as the product of eGFR and FPG; time-dependent glycosuria was estimated from previous direct measurements. The relation of calorie-to-weight changes was estimated using a mathematical model of human energy metabolism that simulates the time course of weight change for a given change in calorie balance and calculates the corresponding energy intake changes.

RESULTS
At week 90, weight loss averaged −3.2 ± 4.2 kg (corresponding to a median calorie deficit of 51 kcal/day [interquartile range (IQR) 112]). However, the observed calorie loss through glycosuria (206 kcal/day [IQR 90]) was predicted to result in a weight loss of –11.3 ± 3.1 kg, assuming no compensatory changes in energy intake. Thus, patients lost only 29 ± 41% of the weight loss predicted by their glycosuria; the model indicated that this difference was accounted for by a 13% (IQR 12) increase in calorie intake (269 kcal/day [IQR 258]) coupled with a 2% (IQR 5) increase in daily energy expenditure (due to diet-induced thermogenesis). This increased calorie intake was inversely related to baseline BMI (partial r = −0.34, P &lt; 0.01) and positively to baseline eGFR (partial r = 0.29, P &lt; 0.01).

CONCLUSIONS
Chronic glycosuria elicits an adaptive increase in energy intake. Combining SGLT2 inhibition with caloric restriction is expected to be associated with major weight loss.
Evidence-based Recommendations for the Management of Comorbidities in Rheumatoid Arthritis, Psoriasis, and Psoriatic Arthritis: Expert Opinion of the Canadian Dermatology-Rheumatology Comorbidity Initiative
Authors: Roubille Camille , Richer Vincent , Starnino Tara , McCourt Collette , McFarlane Alexandra , Fleming Patrick , Siu Stephanie , Kraft John , Lynde Charles , Pope Janet , Gulliver Wayne , Keeling Stephanie , Dutz Jan , Bessette Louis , Bissonnette Robert , Haraoui Boulos 
Published: July 2015

Objective.Comorbidities such as cardiovascular diseases (CVD), cancer, osteoporosis, and depression are often underrecognized in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), or psoriasis (PsO). Recommendations may improve identification and treatment of comorbidities. The Canadian Dermatology-Rheumatology Comorbidity Initiative reviewed the literature to develop practical evidence-based recommendations for management of comorbidities in patients with RA, PsA, and PsO.Methods.Eight main topics regarding comorbidities in RA, PsA, and PsO were developed. MEDLINE, EMBASE, and the Cochrane Library (1960–12/2012), together with abstracts from major rheumatology and dermatology congresses (2010–2012), were searched for relevant publications. Selected articles were analyzed and metaanalyses performed whenever possible. A meeting including rheumatologists, dermatologists, trainees/fellows, and invited experts was held to develop consensus-based recommendations using a Delphi process with prespecified cutoff agreement. Level of agreement was measured using a 10-point Likert scale (1 = no agreement, 10 = full agreement) and the potential effect of recommendations on daily clinical practice was considered. Grade of recommendation (ranging from A to D) was determined according to the Oxford Centre for Evidence-Based Medicine evidence levels.Results.A total of 17,575 articles were identified, of which 407 were reviewed. Recommendations were synthesized into 19 final recommendations ranging mainly from grade C to D, and relating to a large spectrum of comorbidities observed in clinical practice: CVD, obesity, osteoporosis, depression, infections, and cancer. Level of agreement ranged from 80.9% to 95.8%.Conclusion.These practical evidence-based recommendations can guide management of comorbidities in patients with RA, PsA, and PsO and optimize outcomes.
Genetic Variants of the NLRP3 Inflammasome Are Associated with Stroke in Patients with Rheumatoid Arthritis
Authors: Kastbom Alf , Ärlestig Lisbeth , Rantapää-Dahlqvist Solbritt 
Published: July 2015

Objective.Inflammasomes are intracellular protein complexes important for the production of pro-inflammatory cytokines. Studies have suggested that the NLRP3 inflammasome influences both the severity of rheumatoid arthritis (RA) and development of atherosclerosis. Therefore, we investigated whether functional genetic variants related to the NLRP3 inflammasome influence the risk of cardiovascular (CV) disease (CVD) in patients with RA.Methods.The incidence of CVD was assessed in 522 patients with established RA by a retrospective survey of medical records in combination with a 6-year prospective followup. NLRP3-Q705K and CARD8-C10X genotypes were analyzed in relation to CVD by logistic regression, adjusting for traditional risk factors, antirheumatic treatment, and age at the onset of RA.Results.Carriage of the NLRP3-Q705K minor allele was associated with an increased risk of stroke/transient ischemic attack (TIA; OR 2.01, 95% CI 1.0–4.1, p = 0.05), while CARD8-C10X was not associated with any type of CV event. Patients with ≥ 1 variant allele in both polymorphisms had an increased risk of CVD when compared with patients without variant alleles present in both polymorphisms (adjusted OR 3.05, 95% CI 1.42–6.54, p = 0.004). Stratification showed that this risk was confined to stroke/TIA (adjusted OR 5.09, 95% CI 2.27–11.44, p < 0.0001) and not to myocardial infarction (MI)/angina pectoris (adjusted OR 1.58, 95% CI 0.67–3.73). Risk estimates were consistently higher among female patients.Conclusion.Genetic variants of the NLRP3 inflammasome influence the risk of stroke/TIA, but not of MI/angina pectoris in Swedish patients with established RA.
Miscarriage and Stillbirth in Women with Rheumatoid Arthritis
Authors: Wallenius Marianne , Salvesen Kjell Å. , Daltveit Anne K. , Skomsvoll Johan F. 
Published: July 2015

Objective.To examine the risk of pregnancy loss in women with rheumatoid arthritis (RA).Methods.Cumulative numbers of early miscarriages (before gestational Week 12), late miscarriages (weeks 12–22), and stillbirths reported to the Medical Birth Registry of Norway in the period 1999–2009.Results.There were 1578 women with RA and 411,130 reference women included in the study. Relative risks of early and late miscarriage in women with RA versus references were 1.2 (95% CI 1.1–1.3) and 1.4 (95% CI 1.1–1.7), respectively. There was no difference in stillbirth.Conclusion.The risk of miscarriage was slightly higher among women with RA than in references.
Cutting Edge: A Natural Antisense Transcript, AS-IL1α, Controls Inducible Transcription of the Proinflammatory Cytokine IL-1α
Authors: Chan Jennie , Atianand Maninjay , Jiang Zhaozhao , Carpenter Susan , Aiello Daniel , Elling Roland , Fitzgerald Katherine A. , Caffrey Daniel R. 
Published: July 2015

Abstract
Natural antisense transcripts (NATs) are a class of long noncoding RNAs (lncRNAs) that are complementary to other protein-coding genes. Although thousands of NATs are encoded by mammalian genomes, their functions in innate immunity are unknown. In this study, we identified and characterized a novel NAT, AS-IL1α, which is partially complementary to IL-1α. Similar to IL-1α, AS-IL1α is expressed at low levels in resting macrophages and is induced following infection with Listeria monocytogenes or stimulation with TLR ligands (Pam3CSK4, LPS, polyinosinic-polycytidylic acid). Inducible expression of IL-1α mRNA and protein were significantly reduced in macrophages expressing shRNA that target AS-IL1α. AS-IL1α is located in the nucleus and did not alter the stability of IL-1α mRNA. Instead, AS-IL1α was required for the recruitment of RNA polymerase II to the IL-1α promoter. In summary, our studies identify AS-IL1α as an important regulator of IL-1α transcription during the innate immune response.
Identification of Teleost Skin CD8α+ Dendritic-like Cells, Representing a Potential Common Ancestor for Mammalian Cross-Presenting Dendritic Cells
Authors: Granja Aitor G. , Leal Esther , Pignatelli Jaime , Castro Rosario , Abós Beatriz , Kato Goshi , Fischer Uwe , Tafalla Carolina 
Published: July 2015

Abstract
Although fish constitute the most ancient animal group in which an acquired immune system is present, the presence of dendritic cells (DCs) in teleosts has been addressed only briefly, and the identification of a specific DC subset in teleosts remained elusive because of the lack of specific Abs. In mice, DCs expressing CD8α+ in lymphoid tissues have the capacity to cross-present extracellular Ags to T cells through MHC I, similarly to tissue-derived CD103+ DCs and the human CD141+ DC population. In the current study, we identified a large and highly complex subpopulation of leukocytes coexpressing MHC class II and CD8α. This CD8α+ MHC II+ DC-like subpopulation constituted ∼1.2% of the total leukocyte population in the skin, showing phenotypical and functional characteristics of semimature DCs that seem to locally regulate mucosal immunity and tolerance in a species lacking lymph nodes. Furthermore, we identified trout homologs for CD141 and CD103 and demonstrated that, in trout, this skin CD8+ DC-like subpopulation expresses both markers. To our knowledge, these results provide the first evidence of a specific DC-like subtype in nonimmune tissue in teleosts and support the hypothesis of a common origin for all mammalian cross-presenting DCs.
An Excess of the Proinflammatory Cytokines IFN-γ and IL-12 Impairs the Development of the Memory CD8+ T Cell Response to Chlamydia trachomatis
Authors: Zhang Xuqing , Starnbach Michael N. 
Published: July 2015

Abstract
The obligate intracellular bacterium Chlamydia trachomatis is the most common cause of bacterial sexually transmitted disease in the United States and the leading cause of preventable blindness worldwide. Transfer of cultured Chlamydia-specific CD8+ T cells or vaccination with recombinant virus expressing an MHC I–restricted Chlamydia Ag confers protection, yet surprisingly a protective CD8+ T cell response is not stimulated following natural infection. In this study, we demonstrate that the presence of excess IL-12 and IFN-γ contributes to poor memory CD8+ T cell development during C. trachomatis infection of mice. IL-12 is required for CD8+ T cell expansion but drives effector CD8+ T cells into a short-lived fate, whereas IFN-γ signaling impairs the development of effector memory cells. We show that transient blockade of IL-12 and IFN-γ during priming promotes the development of memory precursor effector CD8+ T cells and increases the number of memory T cells that participate in the recall protection against subsequent infection. Overall, this study identifies key factors shaping memory development of Chlamydia-specific CD8+ T cells that will inform future vaccine development against this and other pathogens.
Differentiation Kinetics of Blood Monocytes and Dendritic Cells in Macaques: Insights to Understanding Human Myeloid Cell Development
Authors: Sugimoto Chie , Hasegawa Atsuhiko , Saito Yohei , Fukuyo Yayoi , Chiu Kevin B. , Cai Yanhui , Breed Matthew W. , Mori Kazuyasu , Roy Chad J. , Lackner Andrew A. , Kim Woong-Ki , Didier Elizabeth S. , Kuroda Marcelo J. 
Published: July 2015

Abstract
Monocyte and dendritic cell (DC) development was evaluated using in vivo BrdU pulse-chase analyses in rhesus macaques, and phenotype analyses of these cells in blood also were assessed by immunostaining and flow cytometry for comparisons among rhesus, cynomolgus, and pigtail macaques, as well as African green monkeys and humans. The nonhuman primate species and humans have three subsets of monocytes, CD14+CD16−, CD14+CD16+, and CD14−CD16+ cells, which correspond to classical, intermediate, and nonclassical monocytes, respectively. In addition, there exist presently two subsets of DC, BDCA-1+ myeloid DC and CD123+ plasmacytoid DC, that were first confirmed in rhesus macaque blood. Following BrdU inoculation, labeled cells first appeared in CD14+CD16− monocytes, then in CD14+CD16+ cells, and finally in CD14−CD16+ cells, thus defining different stages of monocyte maturation. A fraction of the classical CD14+CD16− monocytes gradually expressed CD16+ to become CD16+CD14+ cells and subsequently matured into the nonclassical CD14−CD16+ cell subset. The differentiation kinetics of BDCA-1+ myeloid DC and CD123+ plasmacytoid DC were distinct from the monocyte subsets, indicating differences in their myeloid cell origins. Results from studies utilizing nonhuman primates provide valuable information about the turnover, kinetics, and maturation of the different subsets of monocytes and DC using approaches that cannot readily be performed in humans and support further analyses to continue examining the unique myeloid cell origins that may be applied to address disease pathogenesis mechanisms and intervention strategies in humans.
pVHL Negatively Regulates Antiviral Signaling by Targeting MAVS for Proteasomal Degradation
Authors: Du Juan , Zhang Dawei , Zhang Wei , Ouyang Gang , Wang Jing , Liu Xing , Li Shun , Ji Wei , Liu Wei , Xiao Wuhan 
Published: July 2015

Abstract
The von Hippel–Lindau (VHL) gene is a well-defined tumor suppressor linked to human heredity cancer syndromes. As a component of the VHL-elongin B/C E3 ligase complex, pVHL performs its tumor function by targeting proteins for proteasomal degradation. It is largely unknown whether pVHL functions in antiviral immunity. In this article, we identify that pVHL negatively regulates innate antiviral immunity, which acts mainly by inducing degradation of mitochondrial antiviral-signaling protein (MAVS, also known as Cardif, IPS-1, or VISA). Overexpression of pVHL abrogated the cellular response to viral infection, whereas knockdown of pVHL exerted the opposite effect. pVHL targeted the K420 residue of MAVS to catalyze the formation of K48-linked polyubiquitin chains, leading to proteasomal degradation of MAVS. After viral infection, Mavs levels remained low in wild type zebrafish embryos but became much higher in vhl-deficient (vhl−/−) zebrafish embryos. Higher MAVS levels correlated with a greatly exaggerated antiviral response. In this work, we demonstrate that pVHL exhibits a previously unknown role in innate antiviral immunity.
NK Cell and Ig Interplay in Defense against Herpes Simplex Virus Type 1: Epistatic Interaction of CD16A and IgG1 Allotypes of Variable Affinities Modulates Antibody-Dependent Cellular Cytotoxicity and Susceptibility to Clinical Reactivation
Authors: Moraru Manuela , Black Laurel E. , Muntasell Aura , Portero Francisca , López-Botet Miguel , Reyburn Hugh T. , Pandey Janardan P. , Vilches Carlos 
Published: July 2015

Abstract
HSV-1 latently infects most humans, causing a variable clinical picture that depends, in part, on host genetic factors. Both IgG and its cellular FcRs, CD16A and CD32A–C (encoded by FCGR3A and FCGR2A–C, respectively, on chromosome 1), display polymorphisms that could affect their defensive function. Of potential relevance are a FCGR3A dimorphism resulting in CD16A-valine/phenylalanine-158 allotypes with different IgG affinity, variations conditioning NK cell expression of CD32B or CD32C, and IgG1 H chain (IGHG1) and kappa-chain (IGKC) polymorphisms determining allotypes designated G1m and Km. In this study, we assessed the contribution of Ig genetic variations and their interaction with FcR polymorphism to HSV-1 susceptibility, as well as their impact on NK cell–mediated Ab-dependent cellular cytotoxicity (ADCC). Our results show an epistatic interaction between IGHG1 and FCGR3A such that the higher affinity CD16A-158V/V genotype associates with an asymptomatic course of HSV-1 infection only in homozygotes for G1m3. Furthermore, CD16A-158V and G1m3 allotypes enhanced ADCC against opsonized HSV-1–infected fibroblasts. Conversely, Km allotypes and CD32B or CD32C expression on NK cells did not significantly influence HSV-1 susceptibility or ADCC. NK cells degranulating against immune serum-opsonized HSV-1–infected fibroblasts had heterogeneous phenotypes. Yet, enhanced ADCC was observed among NK cells showing a differentiated, memory-like phenotype (NKG2CbrightNKG2A−CD57+FcRγ−), which expand in response to human CMV. These results extend our knowledge on the importance of immunogenetic polymorphisms and NK cell–Ab interplay in the host response against HSV-1 and point to the relevance of interactions between immune responses elicited during chronic coinfection by multiple herpesviruses.
Perspectives in musculoskeletal injury management by traditional bone setters in Ashanti, Ghana
Authors: Edusei Anthony K. , Owusu-Ansah Frances E. , Dogbe Joslin A. , Morgan Julia , Sarpong Kofi 
Published: July 2015

Background: The popularity of the services of traditional bone setters (TBS) in Ghana as an alternative health care requires exploration and documentation of the perspectives of providers and users. Objective: To explore and document the perspectives of providers and users of the services of TBS in the management of musculoskeletal injuries in the Ashanti region, Ghana. Methods: From the social constructivist and qualitative approach, in-depth interviews were used to explore the perspectives of eight TBS and 16 users of their services, selected purposively through snowballing. Thematic content analysis (TCA) was employed. Results: High recovery rate, warm reception, prompt attention, and the relatively lower charges, are reported to motivate the patronage of the services of TBS for the management of fractures in the legs, arms, ribs, joint bones dislocations, waist and spinal cord problems. The TBS combined traditional and orthodox procedures, using plant and animal-based materials, beliefs, spirituality (God-given) and physical therapy in the management of musculoskeletal injuries. No adverse experience was reported by either the providers or users of the traditional management methods.Conclusion: With plant and animal-based materials, TBS are observed to combine traditional and orthodox procedures to confidently manage musculoskeletal injuries to the satisfaction of their highly motivated patrons. Although over 60% of the TBS attribute the healing power behind their practice to God, the rest do not discount the role of spiritual therapy. Further studies expanded to include the perspectives of non-users of the services of the TBS will authenticate the findings of this study.
Literature Discussions as Mangles of Practice: Sociological Theories of Emergence and/in Dialogic Learning Events
Authors: Kamberelis George , McGinley William , Welker Alyson 
Published: July 2015

In this report, we argue that some of the most productive and edifying kinds of literature discussions among certain ages/grade levels may be best understood as “mangles of practice” (Pickering, 1995). Mangles of practice involve the coalescence of planned and contingent forces, and they produce emergent or self-organizing transformations of ongoing social activities, as well as unpredictable outcomes or products. Indeed, the discussions we studied had these characteristics. They often involved both planned and contingent actions and reactions by individual, social, cultural, and material agents and agencies. As such, they were emergent phenomena about which we could seldom predict what precise collections, collisions, and collusions of actions and reactions would occur within them or what the effects of these collections, collisions, and collusions would be. In spite of (or more likely because of) their unpredictability, these discussions were extremely dynamic knowledge-producing activities. Given this social fact, we think our findings contribute significantly to understanding the lineaments and potentials of dialogic pedagogy, which deepens students’ learning and development. More specifically, when teachers successfully prompt and engage students in more robustly dialogic talk that promotes text-to-life connections, life-to text connections, linkages to non-school knowledge (like that of popular culture), etc., then students often reap a wide variety of benefits with respect to their abilities to engage in genuine inquiry, to reason and argue for particular interpretations, to evaluate complex human actions and decisions, and to develop principled social, cultural, and moral equipment for living their own lives.
Role of Pharmacovigilance in India: An overview
Authors: Suke Sanvidhan G , Kosta Prabhat , Negi Harsh 
Published: July 2015

Pharmacovigilance (PV) plays a key role in the healthcare system through assessment, monitoring and discovery of interactions amongst drugs and their effects in human. Pharmaceutical and biotechnological medicines are designed to cure, prevent or treat diseases; however, there are also risks particularly adverse drug reactions (ADRs) can cause serious harm to patients. Thus, for safety medication, ADRs monitoring required for each medicine throughout its life cycle, during development of drug such as pre-marketing including early stages of drug design, clinical trials, and post-marketing surveillance. PV is concerns with the detection, assessment, understanding and prevention of ADRs. Pharmacogenetics and pharmacogenomics are an indispensable part of the clinical research. Variation in the human genome is a cause of variable response to drugs and susceptibility to diseases are determined, which is important for early drug discovery to PV. Moreover, PV has traditionally involved in mining spontaneous reports submitted to national surveillance systems. The research focus is shifting toward the use of data generated from platforms outside the conventional framework such as electronic medical records, biomedical literature, and patient-reported data in health forums. The emerging trend in PV is to link premarketing data with human safety information observed in the post-marketing phase. The PV system team obtains valuable additional information, building up the scientific data contained in the original report and making it more informative. This necessitates an utmost requirement for effective regulations of the drug approval process and conscious pre and post approval vigilance of the undesired effects, especially in India. Adverse events reported by PV system potentially benefit to the community due to their proximity to both population and public health practitioners, in terms of language and knowledge, enables easy contact with reporters by electronically. Hence, product safety PV helps to the patients get well, and to manage optimally, or ideally avoid, illness is a collective responsibility of industry, drug regulators, and clinicians and other healthcare professionals. This review summarized objectives and methodologies used in PV with critical overview of existing PV in India, challenges to overcome and future prospects with respect to Indian context.Keywords: Pharmacovigilance; Adverse drug reaction; Clinical trials; Pharmacogenomics; Data mining; Indian Pharmacopoeia Commission