bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of initial combination therapy with gemigliptin and metformin compared with monotherapy with either drug in patients with type 2 diabetes: A double‐blind randomized controlled trial (INICOM study)
Authors: Lim Soo , Han Kyung Ah , Yu JaeMyung , Chamnan Parinya , Kim Eun Sook , Yoon Kun‐Ho , Kwon Sam , Moon Min Kyong , Lee Kwan Woo , Kim Dong‐Jun , Kim Mikyung , Wongtanate Manaj , Kim Eun Young , Kim Sung‐Ho , Lee Moon‐Kyu ,   INICOM Study Group
Published: September 2016

BackgroundGemigliptin is a new dipeptidyl peptidase‐IV inhibitor. We investigated the efficacy and safety of initial combination therapy with gemigliptin and metformin compared with monotherapy with either drug in patients with type 2 diabetes (T2D).MethodsA total of 433 T2D patients with a glycosylated haemoglobin (HbA1c) level of 7.5% to 11.0% and a fasting plasma glucose (FPG) concentration <270 mg/dL were randomly assigned to 3 groups: (1) gemigliptin 50 mg qd + metformin 1000 to 2000 mg qd (titrated individually), (2) gemigliptin 50 mg qd, or (3) metformin 1000 to 2000 mg qd. The primary end‐point was the change in HbA1c level after 24 weeks. Secondary end‐points were the changes in FPG, insulin, proinsulin and C‐peptide levels. The percentages of responders who achieved an HbA1c level <7% (or <6.5%) were compared between treatment groups.ResultsBaseline HbA1c levels were 8.7% in all groups. The mean changes in HbA1c level from baseline to week 24 were −2.06%, −1.24% and −1.47% in the combination, gemigliptin monotherapy and metformin monotherapy groups, respectively. The 95% confidence intervals for between‐group differences in HbA1c changes were −1.02 to −0.63 in the combination group vs the gemigliptin group and −0.82 to −0.41 vs the metformin group, which confirmed the superiority of combination therapy. A significantly higher percentage of patients in the combination therapy group reached the target HbA1c level <7% (or <6.5%) compared with the monotherapy groups. No severe side effects were observed.ConclusionsIn T2D patients, the initial combination of gemigliptin and metformin had superior efficacy without safety concerns compared with monotherapy with either drug.
Evaluation of the efficacy, safety and glycaemic effects of evolocumab (AMG 145) in hypercholesterolaemic patients stratified by glycaemic status and metabolic syndrome
Authors: Blom Dirk J. , Koren Michael J. , Roth Eli , Monsalvo Maria Laura , Djedjos C. Stephen , Nelson Patric , Elliott Mary , Wasserman Scott M. , Ballantyne Christie M. , Holman Rury R. 
Published: September 2016

AimTo examine the lipid and glycaemic effects of 52 weeks of treatment with evolocumab.Materials and MethodsThe Durable Effect of PCSK9 Antibody Compared with Placebo Study (DESCARTES) was a 52‐week placebo‐controlled trial of evolocumab that randomized 905 patients from 88 study centres in 9 countries, with 901 receiving at least one dose of study drug. For this post‐hoc analysis, DESCARTES patients were categorized by baseline glycaemic status: type 2 diabetes, impaired fasting glucose (IFG), metabolic syndrome (MetS) or none of these. Monthly subcutaneous evolocumab (420 mg) or placebo was administered. The main outcomes measured were percentage change in LDL‐cholesterol (LDL‐C) at week 52 and safety.ResultsA total of 413 patients had dysglycaemia (120, type 2 diabetes; 293, IFG), 289 had MetS (194 also had IFG) and 393 had none of these conditions. At week 52, evolocumab reduced LDL‐C by >50% in all subgroups, with favourable effects on other lipids. No significant differences in fasting plasma glucose, HbA1c, insulin, C‐peptide or HOMA indices were seen in any subgroup between evolocumab and placebo at week 52. The overall incidence of new‐onset diabetes mellitus did not differ between placebo (6.6%) and evolocumab (5.6%); in those with baseline normoglycaemia, the incidences were 1.9% and 2.7%, respectively. Incidences of AEs were similar in evolocumab‐ and placebo‐treated patients.ConclusionsEvolocumab showed encouraging safety and efficacy at 52 weeks in patients with or without dysglycaemia or MetS. Changes in glycaemic parameters did not differ between evolocumab‐ and placebo‐treated patients within the glycaemic subgroups examined.
Search for protective factors for psychosis – a population‐based sample with special interest in unaffected individuals with parental psychosis
Authors: Keskinen Emmi , Marttila Riikka , Koivumaa‐Honkanen Heli , Moilanen Kristiina , Keinänen‐Kiukaanniemi Sirkka , Timonen Markku , Isohanni Matti , McGrath John , Miettunen Jouko , Jääskeläinen Erika 
Published: September 2016

AbstractAimTo find factors that are associated with not having psychotic illness in a prospective general population sample, with a special interest in individuals with parental psychosis.MethodsData from the Northern Finland Birth Cohort 1966 (n = 10 458) and several registers were used to detect individuals with and without parental psychosis. Altogether, 594 persons had parent(s) with psychosis and 48 of them also had psychosis subsequently. Variables related to pregnancy and birth, family and childhood, health and habits in adolescence, school performance and physical activity were studied to identify determinants of unaffected status among individuals with and without parental psychosis.ResultsIn the parental psychosis group, the unaffected persons had more likely a mother who was non‐depressed during pregnancy, and who worked outside the home or studied than among those who developed psychosis.ConclusionsProtective factors for psychosis were surprisingly few in this sample. These factors were related to the mother's non‐depressed mood and the mother's work outside the home or studies. This could relate to better health and functioning of a mother. This work highlights the need for more research on protective factors for psychosis in order to identify methods for prevention of psychosis.
Brazilian guidelines on hematopoietic stem cell transplantation in acute myeloid leukemia
Authors: Silla Lucia , Dulley Frederico , Saboya Rosaura , Kerbauy Fabio , de Moraes Arantes Adriano , Pezzi Annelise , Gross Luisa Grave , Paton Eduardo , Hamerschlak Nelson 
Published: September 2016

AbstractIntroduction/ObjectivesAcute myeloid leukemia (AML) accounts for 90% of all cases of acute leukemia in adults. In Brazil, the mortality from myeloid leukemia is 1.74/100 000 men and 1.37/100 000 women. Our aim was to review and update guidelines of the Brazilian Society of Bone Marrow Transplantation on indications of hematopoietic stem cell transplantation (HSCT) for the treatment AML.Conclusions(i) Allo‐HSCT is recommended for high‐risk AML (IA); (ii) allo‐HSCT is recommended for AML of intermediate risk (IA); (iii) allo‐HSCT is recommended for AML relapsed/refractory (C4); (iv) auto‐HSCT is recommended for AML after 1 consolidation (C4); (v) auto‐HSCT is recommended for AML in CR1 (higher than QT in the Brazilian experience) (C4); (vi) auto‐HSCT is accepted for AML M3 in second molecular complete remission (2B); (vii) peripheral blood instead of Bone Marrow HSC for advanced disease (2A); (viii) recommended conditioning protocols: Bu‐Cy/Bu‐Mel, Bu‐Flu, TBI‐Cy. In umbilical cord HSCT, consider ATG‐based protocols (2A); (ix) allogeneic HSCT for the treatment of AML can be used in patients between 60 and 80 yr with good performance status and the absence of significant comorbidities (C4).
Von Willebrand disease – the ‘Dos’ and ‘Don'ts’ in surgery
Authors: Miesbach Wolfgang , Berntorp Erik 
Published: September 2016

AbstractVon Willebrand disease (VWD) is the most common genetic bleeding disorder. VWD is caused by a deficiency or dysfunction of von Willebrand factor (VWF), a plasma protein that mediates the initial adhesion of platelets at sites of vascular injury and binds and stabilises coagulation factor VIII (FVIII) in the blood. Prophylaxis of surgical bleeding in patients with VWD requires consideration of the individual situation, including the type of procedure and the bleeding rate, before decisions about treatment type, dose, duration and adjunctive therapy with antifibrinolytics or antithrombotic prophylaxis can be made. Although desmopressin (DDAVP)‐stimulated release of endogenous VWD is an effective treatment strategy in many patients, plasma concentrates containing VWF are the preferred option for most patients undergoing surgical procedures. Recommendations for the management of surgery in patients with VWD are summarised, including the severity of VWD and the type of the surgical procedure.
Expression of key components of the RNAi machinery are suppressed in Apis mellifera that suffer a high virus infection
Authors: De Smet Lina , Ravoet Jorgen , Wenseleers Tom , de Graaf Dirk C. 
Published: September 2016

AbstractViruses are one of the major threats for honeybees and until now more than 20 different viruses have been discovered. Viruses and their hosts are engaged in a continuous arms race in which viral defense mechanisms drive the adaptive evolution of host immune genes, which in turn results in counter‐adaptations of the viral immune antagonists. The honeybee immune responses to non‐viral pathogens have been extensively studied, but little is known about the antiviral responses. Recent evidence suggests that the main mechanism of antiviral defense in insects is the RNA interference (RNAi) pathway. Furthermore, there is evidence that some viruses suppress this RNAi pathway in order to evade antiviral immunity. In the present study, we test this hypothesis by comparing the gene expression levels of some key components of the RNAi response of honeybees that were naturally infected with at least five viruses with those who were infected with only two or three viruses using a colorimetric microarray developed in‐house, called BeeClinic, and subsequently confirmed by quantitative reverse‐transcription–polymerase chain reaction (qRT‐PCR). Our results show that key components of the RNAi pathway are indeed downregulated in highly infected bees. We were able to show that high virus loads suppress key RNAi components, which results in a counteraction of the host RNAi antiviral defense. As the RNAi is a primary defense against viruses, these findings shed new light on pathogen–host interactions and can help mitigate escalating colony losses worldwide.
Inhibitory effects of dietary soyasaponin on 2,4‐dinitrofluorobenzene‐induced contact hypersensitivity in mice
Authors: Nagano Takao , Katase Mitsuru , Tsumura Kazunobu , Saito Mineki , Matsuda Tsukasa 
Published: September 2016

AbstractSoyasaponins (SSs) abundant in soybean have anti‐inflammatory activities; however, their therapeutic effects on allergic contact dermatitis (ACD) remain unknown. To assess the effects of SS‐enriched diets on ACD, we used a mouse model of contact hypersensitivity (CHS). Mice were fed low‐dose or high‐dose SS‐containing diets for 3 weeks prior to CHS induction with 2,4‐dinitrofluorobenzene (DNFB). The low‐dose SS diet attenuated DNFB‐induced ear swelling and tissue oedema, and reduced the number of infiltrating Gr‐1‐positive myeloid cells. Low‐dose, but not high‐dose, SSs decreased chemokine (C‐X‐C motif) ligand 2 (CXCL2) and triggering receptor expressed on myeloid cells (TREM)‐1 production in ear tissues, compared to a control. Taxonomic 16S rRNA analysis revealed significant alterations in faecal microbiota caused by CHS, which were reversed by low‐dose SSs. The low‐dose SS and non‐CHS groups clustered together, while the high‐dose SS group split between CHS and non‐CHS clusters. Our results demonstrated that low‐dose SSs alleviated CHS symptoms by attenuating inflammation and improving the intestinal microbiota composition, suggesting that dietary SSs may have beneficial effects on ACD.
Characterization of the early local immune response to Ixodes ricinus tick bites in human skin
Authors: Glatz Martin , Means Terry , Haas Josef , Steere Allen C. , Müllegger Robert R. 
Published: September 2016

AbstractLittle is known about the immunomodulation by tick saliva during a natural tick bite in human skin, the site of the tick‐host interaction. We examined the expression of chemokines, cytokines and leucocyte markers on the mRNA levels and histopathologic changes in human skin biopsies of tick bites (n=37) compared to unaffected skin (n=9). Early tick‐bite skin lesions (<24 hours of tick attachment) were characterized by a predominance of macrophages and dendritic cells, elevated mRNA levels of macrophage chemoattractants (CCL2, CCL3, CCL4) and neutrophil chemoattractants (CXCL1, CXCL8), of the pro‐inflammatory cytokine, IL‐1β, and the anti‐inflammatory cytokine, IL‐5. In contrast, the numbers of lymphocytes and mRNA levels of lymphocyte cell markers (CD4, CD8, CD19), lymphocyte chemoattractants (CXCL9, CXCL10, CXCL11, CXCL13, CCL1, CCL22), dendritic cell chemoattractants (CCL20), and other pro‐ (IL‐6, IL‐12p40, IFN‐γ, TNF‐α) and anti‐inflammatory cytokines (IL‐4, IL‐10, TGF‐β) did not differ from normal skin. With longer tick attachment (>24 hours), the numbers of innate immune cells and mediators (not significantly) declined, whereas the numbers of lymphocytes (not significantly) increased. Natural tick bites by Ixodes ricinus ticks initially elicit a strong local innate immune response in human skin. Beyond 24 hours of tick attachment, this response usually becomes less, perhaps because of immunomodulation by tick saliva.
Should hidradenitis suppurativa/acne inversa best be renamed as “dissecting terminal hair folliculitis”?
Authors: Chen WenChieh , Plewig Gerd 
Published: September 2016

AbstractHidradenitis suppurativa/acne inversa is a diverse, enigmatic and distressful disease that has aroused growing interest in specialists from different disciplines. Both names describe its classical manifestations in the intertriginous regions and reflect the historical view of the disease definition, but cause confusions in the understanding of its pathogenesis and classification. In the light of the advance in clinical, histopathological and pathophysiological findings, we propose the term “dissecting terminal hair folliculitis” (DTHF) to characterize its disease nature as folliculitis instead of acneiform disease or apocrine gland disorder. DTHF attacks exclusively the terminal hair follicles in an overwhelming majority of adults, initiating from the fragile acroinfundibulum leading to a non‐infectious overreaction of innate immunity system with inflammation that may fiercely dissect and engulf all the surrounding tissues accompanied by secondary bacterial infections. Evidence indicates that perifolliculitis capitis abscedens et suffodiens and pilonidal disease are very likely regional variants of DTHF with the same pathogenesis. Treatment of DTHF remains frustrating. The benefit of biologics in targeting inflammation is so far non‐specific, palliative and inconsistent. Hair epilation and photodynamic therapy in treatment of the disease is questionable in consideration of the pathogenesis. Genetic and translational research, especially on the Notch signalling pathways, will yield breakthrough in the development of novel treatment modalities.
How to Attract an Audience at a Conference: Paper, Person or Place?
Authors: Günther Isabel , Grosse Melanie , Klasen Stephan 
Published: September 2016

Abstract
We analyze the drivers of audience size and the number of questions asked in parallel sessions at the annual conference of the German Economics Association. We find that the location of the presentation is at least as important for the number of academics attending a talk as the combined effect of the person presenting and the paper presented. Being a presenter in a late morning session on the second day of a conference, close to the place where coffee is served, significantly increases the size of the audience. When it comes to asking questions, location becomes less important, but smaller rooms lead to more questions being asked. Younger researchers and very senior researchers attract more questions and comments. There are also interesting gender effects. Women attend research sessions more diligently than men, but seem to ask fewer questions than men. Men are less likely to attend presentations on health, education, welfare and development economics than women. Our findings suggest that strategic scheduling of sessions could ensure better participation at conferences. Moreover, different behaviors of men and women at conferences might also contribute to the lack of women in senior scientist positions.
Evaluative Practices in Qualitative Management Research: A Critical Review
Authors: Symon Gillian , Cassell Catherine , Johnson Phil 
Published: September 2016

AbstractThis paper critically reviews commentaries on the evaluation and promotion of qualitative management research. The review identifies two disjunctures: between methodological prescriptions for epistemologically diverse criteria and management journal prescriptions for standardized criteria; and between the culturally dependent production of criteria and their positioning in editorials and commentaries as normative and objective. The authors’ critical social constructionist analysis surfaces underlying positivist assumptions and institutional processes in these commentaries, which they argue are producing (inappropriate) homogeneous evaluation criteria for qualitative research, marginalizing alternative perspectives, and disciplining individual qualitative researchers into particular normative practices. The authors argue that interventions to encourage more qualitative research need to focus as much on editorial, disciplinary and institutional practices as the practices of individual researchers, and they make recommendations for changes that may allow qualitative management research to develop in a more supportive context by recognizing philosophical diversity as legitimate.
Predicting survival in node‐positive prostate cancer after open, laparoscopic or robotic radical prostatectomy: A competing risk analysis of a multi‐institutional database
Authors: Schiavina Riccardo , Bianchi Lorenzo , Borghesi Marco , Briganti Alberto , Brunocilla Eugenio , Carini Marco , Terrone Carlo , Mottrie Alex , Dente Donato , Gacci Mauro , Gontero Paolo , Gurioli Alberto , Imbimbo Ciro , La Manna Gaetano , Marchioro Giansilvio , Milanese Giulio , Mirone Vincenzo , Montorsi Francesco , Morgia Giuseppe , Munegato Stefania , Novara Giacomo , Panarello Daniele , Porreca Angelo , Russo Giorgio I , Serni Sergio , Simonato Alchide , Urzì Daniele , Verze Paolo , Volpe Alessandro , Martorana Giuseppe 
Published: September 2016

ObjectivesTo investigate cancer‐specific mortality and other‐cause mortality in prostate cancer patients with nodal metastases.MethodsThe study included 411 patients treated with radical prostatectomy and pelvic lymph node dissection for prostate cancer with lymph node metastases at 10 tertiary care centers between 1995 and 2014. Kaplan–Meier analyses were used to assess cancer‐specific mortality‐free survival rates at 8 years' follow up in the overall population, and after stratifying patients according to clinical and pathological parameters. Uni‐ and multivariable competing risk Cox regression analyses were used to assess cancer‐specific mortality and other‐cause mortality. Finally, cumulative‐incidence plots were generated for cancer‐specific mortality and other‐cause mortality after stratifying patients according to the number of positive lymph nodes and the median age at surgery, according to the competing risks method.ResultsMen with prostate‐specific antigen ≤40 ng/mL and those with one to three positive lymph nodes showed higher cancer‐specific mortality‐free survival estimates as compared with their counterparts with prostate‐specific antigen >40 ng/mL and >3 metastatic lymph nodes, respectively (all P < 0.001). At multivariable Cox regression analyses, preoperative prostate‐specific antigen >40 ng/mL, >3 lymph node metastases and pathological Gleason score 8–10 were all independent predictors of cancer‐specific mortality (all P‐values ≤0.001). On competing risk analysis, when patients were stratified according to the number of positive lymph nodes (namely, ≤3 vs >3), the 8‐year cancer‐specific mortality rates were 27.4% versus 44.8% for patients aged <65 years, and 15.2% versus 52.6% for patients aged ≥65 years, respectively.ConclusionsThree positive lymph nodes represent the best prognostic cut‐off in node‐positive prostate cancer patients. In those individuals with >3 positive lymph nodes, the overall mortality rate is completely related to prostate cancer in young patients.
Retrospective observational analysis of the use of an architecturally unique dermal regeneration template (Derma Pure®) for the treatment of hard‐to‐heal wounds
Authors: Kimmel Howard , Gittleman Haley 
Published: September 2016

AbstractThe purpose of this analysis was to evaluate the use of DermaPure, a decellularised human skin allograft, in the treatment of a variety of challenging wounds. This retrospective observational analysis reviewed a total of 37 patients from 29 different wound clinics across the USA. Each patient received one application of DermaPure which was followed until complete closure. A statistical analysis was performed with the end point being complete healing. All wounds on average, had a duration of 56 weeks and healed in an average time of 10·58 weeks. Individual wound categories included diabetic foot ulcers, which healed in 8·21 weeks; venous leg ulcers, which healed in 11·29 weeks; and surgical/traumatic wounds, which healed in 11·8 weeks.
Biogeographical homogeneity of Caribbean coral reef benthos
Authors: Pawlik Joseph R. , Loh Tse‐Lynn 
Published: September 2016

AbstractCaribbean reef benthic assemblages have been considered biogeographically homogeneous at regional scales, but this concept was recently challenged by Williams et al. (2015, Journal of Biogeography, 42, 1327–1335). These authors concluded that benthic assemblages exhibit considerable biogeographical variability at regional and smaller scales, that rugosity and wave exposure play key roles in structuring assemblages, and that homogenization has yet to occur at a regional scale. We reassess their conclusions using recently published benthic and fish surveys that targeted sites either protected from fishing or intensively overfished. For sponges, regional variation in assemblages is mostly attributable to the removal of chemically undefended species by sponge‐eating fishes at sites protected from overfishing. We maintain that Caribbean benthic assemblages are remarkably homogeneous when compared to reefs in other tropical regions, and were likely more homogeneous before the localized effects of intensive fishing resulted in top‐down ecosystem alterations in benthic assemblages.