bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulation and release of soluble fms‐like tyrosine kinase receptor 1 mediated by complement activation in human syncytiotrophoblast cells
Authors: Banadakoppa Manu , Balakrishnan Meena , Yallampalli Chandra 
Published: August 2018

ProblemAntiangiogenic molecule soluble fms‐like tyrosine kinase receptor 1 (sFLT1) released from trophoblast cells is associated with pregnancy‐specific hypertensive disorder pre‐eclampsia. Cause of elevated sFLT1 in pre‐eclampsia patients is not well understood. Despite evidence of excess systemic and placental complement activation in pre‐eclampsia patients, its role in pathophysiology is not clear. If the complement activation plays a role in upregulation and secretion of sFLT1 is not known.Method of studyHuman trophoblast cells were isolated from term placentas and allowed to syncytialize. Complement was activated in vitro at sublethal levels on syncytiotrophoblast cells. Effect of complement activation on expression and release of sFLT1 was assessed by comparing its levels in these cells with and without complement activation.ResultsSublethal level of complement activation on syncytialized human trophoblast cells induced upregulation of sFLT1 mRNA and protein. Complement also induced secretion of sFLT1 in a manner depending on degree of activation. Anaphylatoxins C3a induced upregulation but not the release of sFLT1. Release of terminal membrane attack complex (MAC) was associated with sFLT1 secretion.ConclusionComplement activation plays a major role in both the expression and secretion of sFLT1 from syncytial trophoblast cells. The terminal MAC complex is involved in its secretion. Increased levels of sFLT1 in pre‐eclampsia patients may be due to complement‐induced upregulation and secretion.
Multivariate Poisson hidden Markov models with a case study of modelling seismicity
Authors: Orfanogiannaki K. , Karlis D. 
Published: August 2018

SummaryWhile the literature on multivariate models for continuous data flourishes, there is a lack of models for multivariate counts. We aim to contribute to this framework by extending the well known class of univariate hidden Markov models to the multidimensional case, by introducing multivariate Poisson hidden Markov models. Each state of the extended model is associated with a different multivariate discrete distribution. We consider different distributions with Poisson marginals, starting from the multivariate Poisson distribution and then extending to copula based distributions to allow flexible dependence structures. An EM type algorithm is developed for maximum likelihood estimation. A real data application is presented to illustrate the usefulness of the proposed models. In particular, we apply the models to the occurrence of strong earthquakes (surface wave magnitude ≥5), in three seismogenic subregions in the broad region of the North Aegean Sea for the time period from 1 January 1981 to 31 December 2008. Earthquakes occurring in one subregion may trigger events in adjacent ones and hence the observed time series of events are cross‐correlated. It is evident from the results that the three subregions interact with each other at times differing by up to a few months. This migration of seismic activity is captured by the model as a transition to a state of higher seismicity.
Stillbirth and preterm birth and associated factors in one of the largest cities in central Vietnam
Authors: Giang Hoang Thi Nam , Bechtold‐Dalla Pozza Susanne , Tran Hoang Thi , Ulrich Sarah 
Published: August 2018

AbstractAimLittle is known about the rate of stillbirths, preterm births and associated risk factors in resource‐limited settings like Vietnam. This study reports those rates for Da Nang, which is one of the largest cities in central Vietnam.MethodsData on 20 762 births including stillbirths and preterm births and associated risk factors were prospectively collected from health facilities from April 2015 to March 2016.ResultsThe data represented 85% of the total births in Da Nang during the study period, and a stillbirth rate of 9.7 per 1000 live births was recorded. The preterm rate for live births was just under 5%. Independent factors associated with an increased risk of stillbirth and preterm births were mothers aged 35 plus, working as farmers, living in the provinces and a history of abortion. Mothers under 20 years with previous preterm births faced a higher risk of another preterm birth.ConclusionThe stillbirth and premature birth rates in Da Nang were higher than rates in high‐income countries. Developing registration programmes in Vietnam will provide improved data that will enable researchers and policymakers to identify strategies to reduce the number of stillbirths and premature births.
Effects of self‐regulatory skill usage on weight management behaviours: Mediating effects of induced self‐efficacy changes in non‐obese through morbidly obese women
Authors: Annesi James J. 
Published: August 2018

ObjectivesSelf‐regulation is thought to play a role in overcoming barriers to weight management behaviour changes. This research assessed the extent that relationship is manifested through associated changes in self‐efficacy, and effects based on degree of obesity.DesignData sets from three previous studies of the present research group were utilized. After assessment of change scores using repeated‐measures ANOVA, mediation and moderation analyses assessed effects of changes in self‐regulatory skill usage on changes in physical activity and fruit/vegetable intake through self‐efficacy changes. Moderating effects of BMI were then assessed.MethodsWomen with body compositions ranging from non‐obese (BMI < 30 kg/m2) to those with morbid obesity (BMI ≥ 40 kg/m2) were administered similar cognitive‐behavioural treatments, and assessed on theory‐based psychosocial and behavioural measures over 6 months.ResultsFrom baseline to Month 6, changes in self‐regulation for physical activity and eating, physical activity behaviours, fruit/vegetable intake, and self‐efficacy for controlled eating were significant in non‐obese women (n = 48) and women with Class 1 (n = 43), Class 2 (n = 70), and Class 3 (n = 48) obesity. Positive effects were smaller in exercise self‐efficacy. For each of the BMI‐based groups, changes in self‐efficacy significantly mediated the prediction of physical activity and fruit/vegetable intake by changes in self‐regulation. In aggregated data, BMI significantly moderated the prediction of change in physical activity (higher BMI associated with a stronger association), but not fruit/vegetable intake, within those models.ConclusionIncreasing self‐regulatory skills to overcome lifestyle barriers was found to be important for fostering improved weight loss behaviours, especially in the treatment of higher degrees of obesity in women.
Statement of contribution

What is already known on this subject?

Self‐efficacy is a malleable factor that predicts behaviour change within multiple theories.

Learned self‐regulatory skills may effectively deal with lifestyle barriers associated with improvements in weight management behaviours.

Increased physical activity and fruit/vegetable consumption predicts success with weight loss.

What does this study add?

Much of self‐regulation's effect on physical activity and eating behaviours is through its impact on self‐efficacy.

Weight management treatments should emphasize self‐regulatory skills development over simply health education.

Effects of interrelations of self‐regulation and self‐efficacy are more effective as female weight increases.
Switch from abiraterone plus prednisone to abiraterone plus dexamethasone at asymptomatic PSA progression in patients with metastatic castration‐resistant prostate cancer
Authors: Fenioux Charlotte , Louvet Christophe , Charton Emilie , Rozet Francois , Ropert Stanislas , Prapotnich Dominique , Barret Eric , Sanchez‐Salas Rafael , Mombet Annick , Cathala Nathalie , Joulia Marie‐Liesse , Molitor Jean‐Luc , Henriques Julie , Bonnetain Franck , Cathelineau Xavier , Bennamoun Mostefa 
Published: August 2018

ObjectiveTo evaluate the effects of switching from prednisone (P) to dexamethasone (D) at asymptomatic prostate‐specific antigen (PSA) progression in patients with metastatic castration‐resistant prostate cancer (mCRPC) treated with abiraterone acetate (AA).Materials and MethodsAmong 93 patients treated with AA between January 2013 and April 2016 in our institution, 48 consecutive asymptomatic patients with mCRPC, who experienced biochemical progression on treatment with AA+P 10 mg/day, were included. A corticosteroid switch to AA+D 0.5 mg/day at PSA increase was administered until radiological and/or clinical progression. The primary endpoint was progression‐free‐survival (PFS). A prognostic score based on independent prognostic factors was defined.ResultsThe median time to PSA progression on AA+P was 8.94 months. The median PFS on AA+D and AA+corticosteroids (P then D) was 10.35 and 20.07 months, respectively. A total of 56.25% of patients showed a decrease or stabilization in PSA levels after the switch. In univariate analysis, three markers of switch efficiency were significantly associated with a longer PFS: long hormone‐sensitivity duration (≥5 years; median PFS 16.62 vs 4.17 months, hazard ratio [HR] 0.30, 90% confidence interval [CI] 0.16–0.56); low PSA level at the time of switch (<50 ng/mL; median PFS 15.21 vs 3.86 months, HR 0.33, 90% CI 0.18–0.60); and short time to PSA progression on AA+P (<6 months; median PFS 28.02 vs 6.65 months, HR 0.41 (90% CI 0.21–0.81). In multivariate analysis, hormone sensitivity duration and PSA level were independent prognostic factors.ConclusionA steroid switch from P to D appears to be a safe and non‐expensive way of obtaining long‐term responses to AA in selected patients with mCRPC. A longer PFS has been observed in patients with previous long hormone sensitivity duration, and/or low PSA level and/or short time to PSA progression on AA+P.
Targeting the FOXM1‐regulated long noncoding RNA TUG1 in osteosarcoma
Authors: Li Yang , Zhang Tao , Zhang Yanhui , Zhao Xingkai , Wang Wenbo 
Published: August 2018

Long noncoding RNAs (lncRNAs) play an important role in the proliferation and metastasis of osteosarcoma. Identification of the pathogenesis of osteosarcoma and development of new therapeutic strategies against osteosarcoma are urgently needed. In this study, we evaluated the expression of TUG1 (Taurine Upregulated Gene 1) in osteosarcoma tissues and selected it as our target for further analyses. In vitro, we found that TUG1 was upregulated by FOXM1 (Forkhead Box M1) in osteosarcoma cells. TUG1 accelerated osteosarcoma proliferation, migration, and invasion by competitively sponging miR‐219a‐5p, leading to upregulation of Phosphatidylinositol‐4, 5‐Bisphosphate 3‐Kinase Catalytic Subunit Alpha and activation of the protein kinase B (AKT) signaling pathway. In addition, the AKT pathway activation promoted TUG1 expression by upregulating the expression of FOXM1, forming a positive feedback loop in osteosarcoma. Furthermore, we designed and synthesized therapeutic locked nucleic acids targeting TUG1. The proliferation of osteosarcoma was significantly repressed. Hence, TUG1 may be a potential biomarker and therapeutic target for osteosarcoma.
Identification of gibberellin‐regulated protein as a new allergen in orange allergy
Authors: Inomata  Naoko , Miyakawa Mami , Ikeda Nobuyuki , Oda Kayoko , Aihara Michiko 
Published: August 2018

AbstractBackgroundTo date, three orange allergens have been reported. However, it is still unclear whether gibberellin‐regulated proteins (GRPs), identified as new allergens in other fruit allergies, are also involved in orange allergy.ObjectiveTo investigate the allergenicity of orange GRP and to determine the clinical characteristics of patients with orange allergy who are sensitized to orange GRP.MethodsWe enrolled 14 patients (four men, 10 women, mean age: 29.6 years) who were diagnosed with orange allergy based on relevant clinical history, positive skin test, and/or positive challenge test. Orange GRP (molecular weight: 6941.6 Da) was purified by ion‐exchange column chromatography. To test for orange GRP‐specific IgE, we performed ELISA, basophil activation tests, and skin prick tests. Cross‐reactivity of orange GRP with native peach allergen nPru p 7 and Japanese apricot nPru m 7 was analysed by ELISA inhibition assays. IgE specific for orange, grapefruit, and peach allergens rPru p 1, rPru p 3, and rPru p 4 was measured using ImmunoCAP.ResultsTwelve of the 14 patients (85.7%) were positive for orange GRP allergy in at least one test: 71.4% (10/14) were positive by ELISA, 50% (3/6) were positive in the basophil activation test, and 100% (4/4) were positive in the skin prick test. ELISA inhibition assays revealed cross‐reactivity of orange GRP with both nPru p 7 and nPru m 7. The patients showed variable positivity for specific IgE against orange, grapefruit, rPru p 1, rPru p 3, and rPru p 4 (57.1%, 71.4%, 7.1%, 0%, and 21.4%, respectively). The most frequent symptoms of orange GRP allergy were facial swelling and oropharyngeal symptoms.Conclusions and Clinical RelevanceOrange GRP may be involved in orange allergy and may be a cross‐reactive allergen between citrus fruits and the Rosaceae family of fruits.
Pathogen infections and primary biliary cholangitis
Authors: Tanaka A , Leung P S C , Gershwin M E 
Published: August 2018

SummaryPrimary biliary cholangitis (PBC) is a multi-factorial disease caused by the interaction of both genetic predisposition and environmental triggers. Bacterial infection has been investigated most intensively, both epidemiologically and experimentally, as a prime environmental aetiology in PBC. The association of recurrent history of urinary tract infection (UTI) with PBC has been frequently confirmed by several large-scale, case–control studies, despite variation in geographic area or case-finding methods. Escherichia coli is a predominant pathogen in most cases with UTI. Animal studies and molecular mimicry analysis between the human and E. coli E2 subunit of the 2-oxo-acid dehydrogenase complexes demonstrated that E. coli infection is a key factor in breaking immunological tolerance against the mitochondria, resulting in the production of anti-mitochondrial autoantibodies (AMA), the disease-specific autoantibodies of PBC. Novosphingobium aromaticivorans, a ubiquitous xenobiotic-metabolizing bacterium, is another candidate which may be involved in the aetiology of PBC. Meanwhile, improved environmental hygiene and increased prevalence of PBC, especially in males, may argue against the aetiological role of bacterial infection in PBC. Multiple mechanisms can result in the loss of tolerance to mitochondrial autoantigens in PBC; nonetheless, bacterial infection is probably one of the dominant pathways, especially in female patients. Notably, there is a rising prevalence of male patients with PBC. With increasing exposure to environmental xenobiotics in both genders, studies directed towards identifying the environmental culprit with systematically designed case–control studies are much needed to further determine the environmental factors and role of bacterial infections in PBC.
Immunogenicity of meningococcal polysaccharide ACWY vaccine in primary immunized or revaccinated adults
Authors: Ferlito C , Biselli R , Cattaruzza M S , Teloni R , Mariotti S , Tomao E , Salerno G , Peragallo M S , Lulli P , Caporuscio S , Autore A , Bizzarro G , Germano V , Biondo M I , Picchianti Diamanti A , Salemi S , Nisini R , D'Amelio R 
Published: August 2018

Summary
Meningococcal polysaccharide (Men-Ps) vaccine immunogenicity following either primary immunization or revaccination in adults was evaluated. The study population consisted of subjects who have received tetravalent Men-Ps vaccine once (group 1) or at least twice, with a 2–6 dose range (group 2). Human leucocyte antigen (HLA)-typing was performed by polymerase chain reaction and specific immunoglobulin (Ig)G was measured by enzyme-linked immunosorbent assay. Nine months post-immunization, the percentages of individuals with levels of anti-Men-Ps IgG ≥ 2 µg/ml were comparable in both groups, with the exception of anti-Men-PsW135 IgG, which were significantly higher in group 2. The percentage of subjects doubling IgG levels at 9 months was significantly higher in group 1. The high baseline anti-Men-Ps antibody levels negatively influenced the response to revaccination, suggesting a feedback control of specific IgG. The calculated durability of anti-Men-Ps IgG was 2·5–4·5 years, depending on the Men-Ps, following a single vaccine dose. No interference by other vaccinations nor HLA alleles association with immune response were observed. This study confirms that Men-Ps vaccine in adults is immunogenic, even when administered repeatedly, and underlines the vaccine suitability for large-scale adult immunization programmes that the higher costs of conjugate vaccines may limit in developing countries.
Comorbidities and complications of polycystic ovary syndrome: An overview of systematic reviews
Authors: Gilbert Emily W. , Tay Chau T. , Hiam Danielle S. , Teede Helena J. , Moran Lisa J. 
Published: August 2018

SummaryBackgroundPolycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting reproductive‐aged women with adverse reproductive, metabolic and psychological outcomes. It has a complex pathophysiology and therefore requires a multidiscipline clinical approach. However, there remains limited research synthesizing the broad clinical implications of PCOS which would assist clinicians in the management of PCOS.ObjectiveTo summarize and appraise methodological quality of systematic reviews and meta‐analyses evaluating complications and comorbidities associated with PCOS.MethodsA literature search from MEDLINE, EMBASE, CINAHL PLUS and PROSPERO was performed until 15 September 2017. Article selection, data extraction and quality appraisal of included reviews using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) tool were performed in duplicate. A narrative synthesis of the findings was conducted.ResultsTwenty‐three reviews were included. All reviews were of low (n = 2) to moderate quality (n = 21). PCOS was associated with adverse pregnancy outcomes (n = 2), impaired glucose tolerance (n = 6), insulin resistance (n = 6), increased risk of type 2 diabetes (n = 1), cardiovascular disease (n = 10), metabolic syndrome (n = 2), psychological stress (n = 7), endometrial cancer (n = 1) and vitamin D deficiency (n = 1). Obesity exacerbates many of these outcomes.ConclusionsThere is a large body of reliable evidence for adverse metabolic outcomes and smaller, but consistent evidence for psychological issues in PCOS. We identified a shortage of systematic reviews regarding pregnancy outcomes of PCOS and significant gaps in knowledge of the association between PCOS and subclinical hyperthyroidism, vitamin D levels and cancers which future studies could aim to address.
Glucose and lipid metabolism, bone density, and body composition in individuals with Williams syndrome
Authors: Shaikh Sofia , Waxler Jessica L. , Lee Hang , Grinke Kathy , Garry Jamie , Pober Barbara R. , Stanley Takara L. 
Published: August 2018

SummaryObjectiveWe assessed body composition, bone mineral density (BMD), glucose and lipids in Williams syndrome (WS), a rare microdeletion disorder.DesignIndividuals with WS had outpatient assessment at Massachusetts General Hospital. Controls were selected from the National Health and Nutrition Examination Survey (NHANES 2005‐2006).PatientsA total of 22 individuals with WS, each matched by age, sex and race to four NHANES controls.MeasurementsBlood sampling, oral glucose tolerance test, dual‐energy X‐ray absorptiometry scan.ResultsWS and control groups were 59% female and 29 ± 8 years old. Compared to controls, individuals with WS were shorter but had similar body weight, with more fat and less lean mass. Per cent body fat was higher in WS even after adjusting for BMI (+2.1% [95% CI 0.4, 3.9%]). Four WS patients had abnormal lower extremity fat accumulation resembling lipedema. HbA1c (+0.5% [0.2, 0.7]) and 2‐hour glucose (+68 mg/dL [44, 93]) were higher in WS vs controls, differences which persisted after adjusting for BMI. Fasting glucose was comparable between groups. LDL (−18 mg/dL [−35, −2]) and triglycerides (−45 mg/dL [−87, −2]) were significantly lower in WS. Whole‐body BMD was significantly lower (−0.15 g/cm2 [−0.20, −0.11]) in WS, and this remained true controlling for height (−0.06 g/cm2 [−0.11, −0.02]). Vitamin D was <30 ng/mL in 81% of those with WS.ConclusionsOn average, adults with WS have increased fat, decreased lean mass, impaired glucose homeostasis and reduced BMD. Clinical efforts to build muscle and bone mass, and to ensure vitamin D sufficiency, are warranted. Genotype–phenotype research efforts are also warranted.
Progranulin is a novel biomarker for predicting an acute exacerbation of chronic obstructive pulmonary disease
Authors: Chen Xiaoyan , Liu Jinguo , Zhu Mengchan , Hu Bijie , Bai Fengxi , Jin Wenting , Zhou Jian , Chen Cuicui , Song Yuanlin , Pan Jue 
Published: August 2018

AbstractBackgroundProgranulin is a pleiotropic glycosylated protein precursor that plays an important role in inflammation. Limited data exist regarding the role of progranulin in the acute exacerbation of chronic obstructive pulmonary disease (AECOPD).ObjectivesThe study is to assess the efficiency of progranulin as a circulating biomarker of AECOPD.MethodsThe plasma progranulin levels were measured and compared in patients with AECOPD (n = 52), patients with stable COPD (n = 56), and healthy controls (n = 36). In patients with AECOPD, plasma progranulin levels were measured repeatedly on the last day of hospitalization. Demographical data, pulmonary function, and laboratory parameters were recorded.ResultsPatients with AECOPD had higher plasma progranulin levels than both stable COPD patients and healthy controls (158.77 ± 48.17, 109.00 ± 25.05, 93.67 ± 14.71 ng/mL, respectively; P < .001). In patients with AECOPD, the plasma progranulin levels significantly decreased on the last day of hospitalization compared with those on the first day of hospitalization (138.51 ± 44.68 vs. 158.77 ± 48.17 ng/mL, P = .042). The progranulin levels were negatively correlated to FEV1%pred but positively correlated to neutrophil‐to‐lymphocyte ratio and C‐reactive protein in all patients with COPD. Multivariate logistic regression and ROC analysis revealed progranulin (odds ratio 1.05, 95% confidence interval 1.03‐1.08, P < .001) as an independent predictor of AECOPD, with an area under the curve of 0.82.ConclusionsProgranulin may be a valuable blood biomarker of AECOPD and progranulin may be involved in the pathogenesis of AECOPD by disturbing inflammatory responses.