bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of suicidal behaviour and violent crime following antidepressant medication: a Danish cohort study
Authors: Osler M. , Wium‐Andersen M. K. , Wium‐Andersen I. K. , Gronemann F. H. , Jørgensen M. B. , Rozing M. P. 
Published: September 2019

ObjectiveTo examine the incidence of suicidal and violent behaviour following initiation of antidepressant medication.MethodCohorts of 997 911 conscripts and 95 794 patients with a first‐time affective disorder were followed for purchase of antidepressant medication, suicide, suicide attempts and conviction for violent crime in Danish registries between 1997 through 2015. Incidence of outcomes was estimated for the first 28 days, 28–365 days or later after initiation of antidepressants or study entry.ResultsOf 16.5% of conscripts and 73.7% of patients with affective disorders initiated antidepressant medication. Incidence of suicide was 3–4 times higher during the first 28 days after initiation compared to the rates in the following year in both cohorts. A similar trend was seen among the untreated patients with affective disorders, whereas suicide incidence was stable at a low level among conscripts not treated with antidepressants. Incidence of attempted suicide was highest during the 28 days before and after initiation of antidepressants, while rates of violent crime were similar before and after initiation. These trends in incidence were independent of class of antidepressant.ConclusionHigher rates of suicidal behaviour in the weeks following initiation of antidepressant medication probably reflect disease severity and a delay in mood response.
Fathers’ alcohol use and suicidal behaviour in offspring during youth and young adulthood
Authors: Landberg J. , Danielsson A.‐K. , Hemmingsson T. 
Published: September 2019

ObjectiveTo examine the association between various indicators of father's alcohol use and suicidal behaviour in offspring during youth and young adulthood.MethodsThe study is based on a cohort of 68 910 Swedish citizens who were born between 1970 and 1985 and have fathers who participated in conscription for compulsory military training in 1969/70. Information on fathers’ alcohol use was collected during conscription. Offspring was followed for suicide attempts or completed suicides (through linkage with national registers) from age 12 to end of follow‐up in 2008.ResultsAfter adjustment for confounders, the hazard ratio (HR) for offspring to fathers who were heavy drinkers was 1.4 (95% CI 1.02, 1.93) while the associations turned non‐significant for offspring to fathers who often drank into intoxication, HR 1.14 (0.68, 1.90). The highest risk for suicidal behaviour was found for offspring to fathers who had been apprehended for drunkenness two times or more, or with an alcohol‐related hospitalization, with adjusted HRs of 2.1 (1.4, 3,14) and 1.9 (1.27, 2,85) respectively.ConclusionFathers’ alcohol use is associated with increased risk of suicidal behaviour among offspring in youth and young adulthood.
Three‐dimensional computed tomographic examination of pelvic cavity in Van Cats and its morphometric investigation
Authors: Yilmaz Osman , Soyguder Zafer , Yavuz Alpaslan , Dundar Ilyas 
Published: September 2019

AbstractThis study was carried out to determine the morphometric values of the pelvic cavity, the cranial and caudal pelvic aperture by three‐dimensional (3D) reconstruction of the images obtained by computed tomography in adult Van Cats and to show the differences between these indicators in both genders. A total of 16 adult Van Cats, eight male and eight female, were used in the study. Animals were anesthetized with ketamine–xylazine combination and were scanned by computerized tomography. Images of the pelvic cavity were obtained. Three‐dimensional reconstruction of the pelvis was performed with three‐dimensional modelling program. Measurements of the diameters of the pelvic cavity, the cranial and caudal pelvic aperture were calculated from these images, and statistical analyzes were performed. Three‐dimensional modelling of the pelvic cavity of Van Cats were examined between males and females. The results showed that there were significant (p < .05) differences between measurement of the pelvic inclination, the medial transverse diameter, the caudal transverse diameter and the angle between ischiatic arch. In addition, the correlations between age and weight were found statistically significant (p < .05) with the dorsal transverse diameter, the intermediate transverse diameter and the caudal transverse diameter in males. On the other hand, the correlations of age were statistically significant (p < .01) with the cranial pelvic aperture and the caudal pelvic aperture in females. In conclusion, some biometric values of pelvic cavity were observed to be statistically different in Van Cats.
Trophoblasts promote induction of a regulatory phenotype in B cells that can protect against detrimental T cell–mediated inflammation
Authors: Guzman‐Genuino Ruth Marian , Dimova Tanya , You Yuan , Aldo Paulomi , Hayball John D. , Mor Gil , Diener Kerrilyn R. 
Published: September 2019

AbstractProblemA successful outcome to pregnancy is critically dependent on the initiation of maternal immune tolerance before embryo implantation. Cells of embryonic origin that come in contact with the uterine microenvironment can exert influence over the phenotype and function of immune cells to facilitate robust implantation; however, what influence they may have on B cells remains unknown. In this study, we investigate the effect of human trophoblast cells on B‐cell phenotype and the subsequent effect on peri‐implantation events.Method of studyWe cultured purified human B cells with the first‐trimester human trophoblast cell line Swan 71 to investigate trophoblast‐B‐cell interactions and utilized trophoblast spheroids in an in vitro implantation model of migration and invasion.ResultsTrophoblast‐educated B cells or TE‐B cells were found to consist of B cells in committed lineages such as plasmablasts and memory B cells, as well as increased proportions in subsets of CD24hiCD27+ regulatory B cells and CD19+IL‐10+ B cells. Conditioned media from the TE‐B cells showed reduced production of pro‐inflammatory cytokines that influenced the T‐cell proliferation and cytokine production. Using trophoblast spheroids, we assessed the role of TE‐B cells in trophoblast invasion and migration. Our results demonstrate a protective effect of TE‐B‐conditioned media against deleterious inflammation as evidenced by survival of the trophoblast spheroid in the presence of an immune assault and promotion of a migratory phenotype.ConclusionWe posit that trophoblast‐mediated education of B cells leads to their acquisition of properties capable of modulating inflammation in the uterine environment during the peri‐implantation period.
Evaluation of IL8 pathway on the ocular surface: new insights in patients with ocular mucous membrane pemphigoid
Authors: Bruscolini Alice , Lambiase Alessandro , Segatto Marco , La Cava Maurizio , Nebbioso Marcella , Sacchetti Marta 
Published: September 2019

AbstractPurposeTo evaluate the expression of IL8/CXCL8 cytokine and its receptor CXCR1 in tear film and ocular surface of patients with ocular mucous membrane pemphigoid (oMMP).MethodsTen patients with oMMP in the quiescent phase, 20 patients with primary Sjogren syndrome (pSS) and 13 age‐ and sex‐matched healthy controls (HCs) were included in this study. All patients undergone complete eye examination including lacrimal function tests and ocular surface staining assessed by ocular staining score. Ocular mucous membrane pemphigoid (oMMP) staging according to Mondino classification and dry eye severity grade according to Dry Eye Workshop 2007 classification were recorded. Tear samples and conjunctival epithelium were collected. IL‐8 tear concentration was measured by enzyme‐linked immunosorbent assay, and conjunctival IL8 was analysed by Western blot; conjunctival expression of CXCR1 was evaluated by immunohistochemistry. Il‐8 and CXCR1 expression in oMMP patients were compared with HCand pSS patients and correlated with ocular clinical findings.ResultsTear levels of IL‐8 were significantly increased in patients with oMMP (260.1 ± 70 pg/ml) when compared to both HCs (98.5 ± 71.35 pg/ml; p = 0.001) and patients with pSS (96.3 ± 87.5 pg/ml; p = 0.001). Conjunctival expression of IL8 and CXCR1 was significantly increased in oMMP patients when compared to both healthy subjects and pSS patients.ConclusionThe significant increase of tear and conjunctival IL8 and CXCR1 levels in patients with oMMP when compared to healthy subjects and patients with Sjogren syndrome suggests that changes of IL8 pathway are specific of oMMP and may represent a potential biomarker of the disease and/or therapeutic target.
In situ ruminal degradation and in vitro fermentation characteristics, and antioxidative activities of the lotus rhizome
Authors: Asano Sanae , Aoki Kohei , Kaizuka Yuna , Kobayashi Yuhi , Watanabe Kenta , Kato Chizuko , Saito Chihiro , Nishimura Syuichi , Kato Toshiaki , Takagi Motonori , Kajikawa Hiroshi 
Published: September 2019

AbstractWe evaluated the lotus rhizome as a potential ruminant feed by investigating its compositional properties, in situ degradation profile and in vitro fermentation characteristics with ruminal microbes, in comparison with cereal grains (corn, barley and wheat). The antioxidative activities in the lotus rhizome were also estimated. The soluble fraction of dry matter in lotus tuber was >70%, which was higher than those in the grains. The insoluble fraction in lotus tuber was not degraded by ruminal microbes in accord with a first‐order reaction. In an in vitro experiment, lotus tuber showed lower fermentation at 8 hr compared to the grains, but exhibited higher productions of gas and VFA at 48 hr along with a lower lactate and higher pH. The lower value of final lactate production in lotus tuber, indicating the metabolic capacity for lactate utilization retained, suggests a lower risk of ruminal acidosis compared to grains. Lotus rhizome had high antioxidant activities, with the foliar bud showing the strongest ferric reducing antioxidant power, followed in order by the apical bud, node, residual tuber, edible tuber, and nodal root. For ruminants, the lotus rhizome could thus be not only an energy feed but also the source of natural antioxidants.
Pneumonia: host susceptibility and shared genetics with pulmonary function and other traits
Authors: Khadzhieva M B , Kuzovlev A N , Salnikova L E 
Published: September 2019

Summary
Pneumonia is a common and severe infectious lung disease. Host genetics, together with underlying medical and lifestyle conditions, determine pneumonia susceptibility. We performed a secondary analysis of the results of two genome-wide studies for pneumonia in 23andMe participants (40 600 cases/90 039 controls) (Tian et al., 2017) and UK Biobank (BB) participants (12 614 cases/324 585 controls) (via the Global Biobank Engine) and used the GTEx database to correlate the results with expression quantitative trait loci (eQTLs) data in lung and whole blood. In the 23andMe pneumonia single nucleotide polymorphism (SNP) set, 177 genotyped SNPs in the human leukocyte antigen (HLA) region satisfied the genome-wide significance level, P ≤ 5·0E-08. Several target genes (e.g. C4A, VARS2, SFTA2, HLA-C, HLA-DQA2) were unidirectionally regulated by many HLA eSNPs associated with a higher risk of pneumonia. In lung, C4A transcript was up-regulated by 291 pneumonia risk alleles spanning the half the HLA region. Among SNPs correlated with the expression levels of SFTA2 and VARS2, approximately 75% overlapped: all risk alleles were associated with VARS2 up-regulation and SFTA2 down-regulation. To find shared gene loci between pneumonia and pulmonary function (PF), we used data from the Global Biobank Engine and literature on genome-wide association studies (GWAS) of PF in general populations. Numerous gene loci overlapped between pneumonia and PF: 28·8% in the BB data set and 49·2% in the 23andMe data set. Enrichment analysis within the database of Genotypes and Phenotypes (dbGaP) and National Human Genome Research Institute-European Bioinformatics Institute (NHGRI-EBI) Catalog of pneumonia and pneumonia/PF gene sets identified significant overlap between these gene sets and genes related to inflammatory, developmental, neuropsychiatric and cardiovascular and obesity-related traits.
Multi-component meningococcal serogroup B (MenB)-4C vaccine induces effective opsonophagocytic killing in children with a complement deficiency
Authors: van den Broek B , van Els C A C M , Kuipers B , van Aerde K , Henriet S S , de Groot R , de Jonge M I , Langereis J D , van der Flier M 
Published: September 2019

Summary
Vaccination against meningococcal serogroup B is recommended for patients with a complement deficiency; however, although immunogenicity in this patient group has been shown, efficacy has not yet been established. In this study, we collected serum from children with a complement deficiency in the alternative pathway or in late terminal pathway before and after vaccination with multi-component meningococcal serogroup B (MenB)-4C. MenB-4C is a multi-component, protein-based vaccine against MenB consisting of factor H-binding protein, Neisserial heparin-binding protein, Neisserial adhesion A and outer membrane vesicles containing Porin A. We assessed the vaccine immunogenicity and vaccine-mediated protection by a whole cell enzyme-linked immunosorbent assay with Neisseria meningitidis serogroup B strains H44/76, 5/99 and NZ98/254, which shows that vaccination induced antibody titers against meningococcus. We show that the classical serum bactericidal activity assay with exogenous serum indicates the presence of vaccine-induced antibodies and capacity to activate complement-mediated pathogen lysis. However, in children with a late terminal pathway deficiency, no complement-mediated pathogen lysis was observed when autologous serum was applied in the serum bactericidal activity assay, demonstrating a lack of serum bactericidal activity in children with complement deficiencies. However, MenB-4C vaccination still induced effective complement-dependent opsonophagocytic killing against N. meningitidis serogroup B in reconstituted whole blood with autologous serum from children with an alternative pathway or late terminal pathway deficiency. These findings support the recommendation to vaccinate all complement-deficient children against MenB.
Decision‐support tools for dynamic management
Authors: Welch Heather , Brodie Stephanie , Jacox Michael G. , Bograd Steven J. , Hazen Elliott L. 
Published: September 2019

AbstractSpatial management is a valuable strategy to advance regional goals for nature conservation, economic development, and human health. One challenge of spatial management is navigating the prioritization of multiple features. This challenge becomes more pronounced in dynamic management scenarios, in which boundaries are flexible in space and time in response to changing biological, environmental, or socioeconomic conditions. To implement dynamic management, decision‐support tools are needed to guide spatial prioritization as feature distributions shift under changing conditions. Marxan is a widely applied decision‐support tool designed for static management scenarios, but its utility in dynamic management has not been evaluated. EcoCast is a new decision‐support tool developed explicitly for the dynamic management of multiple features, but it lacks some of Marxan's functionality. We used a hindcast analysis to compare the capacity of these 2 tools to prioritize 4 marine species in a dynamic management scenario for fisheries sustainability. We successfully configured Marxan to operate dynamically on a daily time scale to resemble EcoCast. The relationship between EcoCast solutions and the underlying species distributions was more linear and less noisy, whereas Marxan solutions had more contrast between waters that were good and poor to fish. Neither decision‐support tool clearly outperformed the other; the appropriateness of each depends on management purpose, resource‐manager preference, and technological capacity of tool developers.Article impact statement: Marxan can function as a decision‐support tool for dynamic management scenarios in which boundaries are flexible in space and time.
Topographic ruggedness and rainfall mediate geographic range contraction of a threatened marsupial predator
Authors: Moore Harry A. , Dunlop Judy A. , Valentine Leonie E. , Woinarski John C. Z. , Ritchie Euan G. , Watson David M. , Nimmo Dale G. 
Published: September 2019

AbstractAimSpecies range contractions are increasingly common globally. The niche reduction hypothesis posits that geographic range contractions are often patterned across space owing to heterogeneity in threat impacts and tolerance. We applied the niche reduction hypothesis to the decline of a threatened marsupial predator across northern Australia, the northern quoll (Dasyurus hallucatus).LocationNorthern Australia.MethodsWe assembled a database containing 3,178 historic and contemporary records for northern quolls across the extent of their distribution dating between 1778 and 2019. Based on these records, we estimated changes in the geographic range of the northern quoll using α‐hulls across four main populations. We then examined how range contractions related to factors likely to mediate the exposure, susceptibility, or tolerance of northern quolls to threats.ResultThe extent of range contractions showed an east–west gradient, most likely reflecting the timing of spread of introduced cane toads (Rhinella marina). There were clear changes in environmental characteristics within the contemporary compared to the historic geographic range, with the most substantial occurring in populations that have suffered the greatest range contractions. The contemporary range is comprised of higher quality habitats (measured using environmental niche models), characterized by higher topographical ruggedness and annual rainfall, and reduced distance to water, compared to the historic range.Main conclusionsChanges to range and niche likely reflect the capacity of complex habitats to ameliorate threats (namely predation and altered fire regimes), and access to resources that increase threat tolerance. This study highlights the multivariate nature of ecological refuges and the importance of high‐quality habitats for the persistence of species exposed to multiple threats. Our methods provide a useful framework which can be applied across taxa in providing valuable insight to management.
Effects of sodium‐glucose co‐transporter‐2 inhibitors in type 2 diabetes in women versus men
Authors: Rådholm Karin , Zhou Zien , Clemens Kristin , Neal Bruce , Woodward Mark 
Published: September 2019

AbstractSodium‐glucose co‐transporter‐2 (SGLT2) inhibitors prevent cardiovascular complications in type 2 diabetes. We aimed to study whether they have similar effects in women and men by summarizing the effects of SGLT2 inhibitors compared to placebo on vascular and safety outcomes stratified by sex. We included patients with type 2 diabetes enrolled in the EMPA‐REG OUTCOME, CANVAS Program, DECLARE TIMI‐58 and CREDENCE trials. There were no differences in the risk ratios between men and women, SGLT2 versus control (placebo), for vascular efficacy outcomes or death (all P for interaction ≥.12), with clear protection shown against major adverse cardiovascular events, heart failure, vascular death and total mortality. SGLT2 inhibitor treatment was also associated with similar relative risks in women and men for the safety outcomes of amputation, fracture, genital infection and urinary tract infection (all P for interaction ≥.17). SGLT2 inhibition provided similar protection against vascular risks and death, and similar risks of serious adverse events, for women and men.
Translocation (11;14) in newly diagnosed multiple myeloma, time to reclassify this standard risk chromosomal aberration?
Authors: Gran Charlotte , Uttervall Katarina , Borg Bruchfeld Johanna , Wallblom Ann , Alici Evren , Gahrton Gösta , Nahi Hareth 
Published: September 2019

AbstractObjectivesThe most common translocation in multiple myeloma (MM) is t(11;14)(q13;q32), and its importance as prognostic factor has been controversial. The aim was to analyze its prognostic value.MethodIn this retrospective study of 469 newly diagnosed myeloma patients, outcomes in patients with (11;14) and standard risk (t(11;14)SR) or high risk (t(11;14)HR) cytogenetics were compared to outcomes of patients without t(11;14) and SR (non‐t(11;14)SR) or HR (non‐t(11;14)HR), respectively.ResultsOverall progression‐free survival (PFS) was shorter in t(11;14)SR than non‐t(11;14)SR (median 28.9 vs 35.3 months); however, the difference was not significant (P = .2). Overall survival (OS) did not differ significantly between the groups. In the subgroup of patients that did not receive high‐dose treatment, PFS was shorter for t(11;14)SR compared to non‐t(11;14)SR, 10.6 vs 24.6 months (P = .01). Although OS were shorter for t(11,14)SR compared to non‐t(11;14)SR (5‐year OS 41.7% vs 63.8%), the difference was not significant (P = .1). In HDT patients, no significant difference was observed for OS or PFS between those with or without t(11;14).ConclusionThis study shows that t(11;14) is associated with poorer outcome in MM, particularly in non‐high‐dose‐treated SR patients. It should be considered an intermediate or high‐risk marker in these patients.
Mechanism of discrimination of isoleucyl‐tRNA synthetase against nonproteinogenic α‐aminobutyrate and its fluorinated analogues
Authors: Zivkovic Igor , Moschner Johann , Koksch Beate , Gruic‐Sovulj Ita 
Published: September 2019

Isoleucyl‐tRNA synthetase (IleRS) is a paradigm for understanding how specificity against smaller hydrophobic substrates evolved in both the synthetic and editing reactions. IleRS misactivates nonproteinogenic norvaline (Nva) and proteinogenic valine (Val), with a 200‐fold lower efficiency than the cognate isoleucine (Ile). Translational errors are, however, prevented by IleRS hydrolytic editing. Nva and Val are both smaller than Ile by a single methylene group. How does the removal of one additional methylene group affects IleRS specificity? We found that the nonproteinogenic α‐aminobutyrate (Abu) is activated 30‐fold less efficiently than Nva and Val, indicating that the removal of the second methylene group comes with a lower penalty. As with Nva and Val, discrimination against Abu predominantly originated from a higher KM. To examine whether increased hydrophobicity could compensate for the loss of van der Waals interactions, we tested fluorinated Abu analogues. We found that fluorination further hampered activation by IleRS, and even more so by the evolutionary‐related ValRS. This suggests that hydrophobicity is not a main driving force of substrate binding in these enzymes. Finally, a discrimination factor of 7100 suggests that IleRS is not expected to edit Abu. However, we found that the IleRS editing domain hydrolyzes Abu‐tRNAIle with a rate of 40 s−1 and the introduction of fluorine did not slow down the hydrolysis. This raises interesting questions regarding the mechanism of specificity of the editing domain and its evolution. Understanding what shapes IleRS specificity is also of importance for reengineering translation to accommodate artificial substrates including fluorinated amino acids.EnzymesIsoleucyl‐tRNA synthetase (EC 6.1.1.5), leucyl‐tRNA synthetase (EC 6.1.1.4), valyl‐tRNA synthetase (EC 6.1.1.9).