bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic evidence for polyphyletic origins and interlineage gene flow within complex taxa: a case study of Picea brachytyla in the Qinghai‐Tibet Plateau
Authors: Ru Dafu , Mao Kangshan , Zhang Lei , Wang Xiaojuan , Lu Zhiqiang , Sun Yongshuai 
Published: April 2016

AbstractHybridization and introgression are believed to play important roles in plant evolution. However, few empirical studies have been designed to clarify the ways in which these processes complicate taxonomic delimitation. Recent phylogenetic studies based on a number of different DNA fragments have indicated that Picea brachytyla in the eastern Qinghai‐Tibet Plateau is polyphyletic, a finding that contrasts with traditional taxonomy based on morphological traits. We aimed to test this conflict using transcriptomic data from 26 trees collected from multiple localities for this and related species. Our phylogenomic analyses suggest that the sampled trees of P. brachytyla cluster into two distinct lineages corresponding to the two taxonomically recognized intraspecific varieties: var. brachytyla and var. complanata. However, var. complanata nested within Picea likiangensis and was sister to one of its three varieties, while var. brachytyla comprised an isolated lineage. The polyphyletic origin hypothesis was further supported by likelihood tree comparisons using Akaike's information criterion (AIC) and by coalescent analyses under the snapp model. However, our abba‐baba and ∂a∂i analyses suggest that gene flow between these two independently evolved lineages has been extensive and bidirectional. Introgression, as well as parallel evolution in the arid habitats common to both lineages, may have given rise to their morphological similarity. Our study highlights the importance of genomic evidence and the use of newly developed coalescent analysis methods for clarifying the evolutionary complexity of certain plant taxa.
Population genomic evidence for adaptive differentiation in the Baltic Sea herring
Authors: Guo Baocheng , Li Zitong , Merilä Juha 
Published: April 2016

AbstractDetecting and estimating the degree of genetic differentiation among populations of highly mobile marine fish having pelagic larval stages is challenging because their effective population sizes can be large, and thus, little genetic drift and differentiation is expected in neutral genomic sites. However, genomic sites subject to directional selection stemming from variation in local environmental conditions can still show substantial genetic differentiation, yet these signatures can be hard to detect with low‐throughput approaches. Using a pooled RAD‐seq approach, we investigated genomewide patterns of genetic variability and differentiation within and among 20 populations of Atlantic herring in the Baltic Sea (and adjacent Atlantic sites), where previous low‐throughput studies and/or studies based on few populations have found limited evidence for genetic differentiation. Stringent quality control was applied in the filtering of 1 791 254 SNPs, resulting in a final data set of 68 182 polymorphic loci. Clear differentiation was identified between Atlantic and Baltic populations in many genomic sites, while differentiation within the Baltic Sea area was weaker and geographically less structured. However, outlier analyses – whether including all populations or only those within the Baltic Sea – uncovered hundreds of directionally selected loci in which variability was associated with either salinity, temperature or both. Hence, our results support the view that although the degree of genetic differentiation among Baltic Sea herring populations is low, there are many genomic regions showing elevated divergence, apparently as a response to temperature‐ and salinity‐related natural selection. As such, the results add to the increasing evidence of local adaptation in highly mobile marine organisms, and those in the young Baltic Sea in particular.
Role of environmental exposures and filaggrin mutations on associations of ethnic origin with risk of childhood eczema. The Generation R Study
Authors: Elbert Niels J. , Duijts Liesbeth , den Dekker Herman T. , Jaddoe Vincent W. V. , Sonnenschein‐van der Voort Agnes M. M. , de Jongste Johan C. , Pasmans Suzanne G. M. A. 
Published: April 2016

AbstractBackgroundThe prevalence of childhood eczema varies considerably between ethnic groups. However, data from longitudinal studies remain scarce.MethodsWe examined the associations of ethnic origin with the development of eczema from birth until the age of 4 years, and whether known environmental and genetic risk factors explain these associations. This study was performed in a multiethnic population‐based prospective cohort among 5,082 children. Ethnic origin was based on the parents' country of birth. Data on physician‐diagnosed eczema were obtained by annual questionnaires. Information on environmental risk factors was mostly obtained by questionnaires. Filaggrin (FLG) mutations (2282del4, R2447X, R501X, and S3247X) were genotyped for 3,096 children. We used generalized estimating equation models to examine the associations of ethnic origin with the longitudinal odds of eczema at 6 months and 1, 2, 3, and 4 years of age overall and independently.ResultsCompared with Dutch children, Cape Verdean, Dutch Antillean, Surinamese‐Creole, and Surinamese‐Hindustani children had overall increased risks of eczema (OR (95%‐CI): 1.53 (1.15, 2.03), 1.60 (1.21, 2.12), 1.95 (1.56, 2.44), and 2.06 (1.65, 2.57), respectively). Effect estimates for the associations of Cape Verdean and Dutch Antillean origin with eczema became non‐significant after adjustment for genetic risk factors or both environmental and genetic risk factors, respectively. Surinamese‐Creole and Surinamese‐Hindustani children remained to have increased risks of eczema.ConclusionsCape Verdean, Dutch Antillean, Surinamese‐Creole, and Surinamese‐Hindustani children had increased risks of eczema in the first 4 years of life. Environmental and genetic risk factors partly weakened these associations.
Longitudinal pattern of multiplexed immunoglobulin E sensitization from prenatal stage to the first year of life
Authors: Wang Jiu‐Yao , Chen Chih‐Ann , Hou Yung‐I , Hsiao Wan‐Lin , Huang Ya‐Wen , Tsai Yu‐Ting , Tsai Hui‐Ju 
Published: April 2016

AbstractBackgroundThe longitudinal pattern of allergen‐specific IgE levels from the prenatal stage to early life has remained largely unexplored.MethodsOne‐hundred and three mother–infant pairs, which were part of an ongoing population‐based prospective birth cohort study of early childhood allergic diseases in Tainan, Taiwan, were included in this study. We examined the relationship of 20 allergen‐specific IgE levels with blood samples of mothers, cord blood, and infants at 12 months of age using Spearman rank correlation, Kenal τ and McNemar test, respectively.ResultsCertain degree of IgE sensitization against most 20 examined specific allergens was observed in blood samples of mothers, cord blood, and infants at 12 months of age. When we further examined the association between allergy‐related risk factors and atopy in infants at the first year of life, we found positive association between colic pain and atopy in infants at 12 months of age [adjusted odds ratios (AOR) = 3.51; 95% confidence interval (CI): 1.13–10.96; p = 0.03], and borderline significance between wheezing and atopy in infants at 12 months of age (AOR = 4.58; 95% CI: 0.89–23.50; p = 0.07).ConclusionThe findings from this study suggest that influence of maternal allergen‐specific IgE levels on infant immune response might occur at birth and then wane in infants at 12 months of age. Positive association of colic pain and wheezing with atopy in infants at 12 months of age provides supportive evidence for the ‘Allergy March' theory of allergy development in an Asian birth cohort.
Treating IgE‐mediated diseases via targeting IgE‐expressing B cells using an anti‐CεmX antibody
Authors: Liour Sean S. , Tom Andrew , Chan Yueh‐Hsuan , Chang Tse Wen 
Published: April 2016

AbstractTargeting the IgE pathway is a clinically validated strategy for treating IgE‐mediated diseases. Omalizumab, an anti‐IgE antibody, which binds to free IgE and prevents the binding of IgE to FcεRI on mast cells and basophils has been approved for severe persistent allergic asthma and chronic spontaneous (idiopathic) urticaria. The therapeutic efficacy of anti‐IgE has also been reported in allergic rhinitis, allergic bronchopulmonary aspergillosis, latex allergy, atopic dermatitis, allergic urticaria, anaphylaxis, and others. Anti‐CεmX, which binds to membrane‐bound IgE (mIgE) on IgE‐switched B cells, lyses mIgE‐expressing B lymphoblasts and prevents the allergen‐induced generation of IgE‐producing plasma cells, offers an alternative mechanism of intervening with the IgE inflammatory pathway. Because anti‐CεmX does not bind to free IgE, it can modulate the IgE pathway regardless of the serum IgE levels in treated patients. These unique pharmacologic mechanisms potentially enable anti‐CεmX to provide different clinical utilities from anti‐IgE and serve as a therapeutic and a prophylactic in some IgE‐mediated diseases, which are not adequately treated with current medicine.
The optimal immunosuppressive protocol for the portal vein infusion of PGE1 and methylprednisolone in pediatric liver transplantation for fulminant hepatic failure of unknown etiology
Authors: Yamada Yohei , Hoshino Ken , Irie Rie , Tomita Hirofumi , Kato Mototoshi , Shimojima Naoki , Fujino Akihiro , Hibi Taizo , Shinoda Masahiro , Obara Hideaki , Itano Osamu , Kawachi Shigeyuki , Tanabe Minoru , Sakamoto Michiie , Kitagawa Yuko , Kuroda Tatsuo 
Published: April 2016

AbstractThe outcome of LTx in pediatric patients with FHF of unknown etiology remains inferior to that of LTx in pediatric patients with cholestatic diseases. A higher incidence of steroid‐resistant severe rejection has been increasingly recognized among the responsible factors. We assessed the efficacy of the administration of steroids and PGE1 via PVI in the management of LTx for FHF in pediatric patients. In our early cohort (1995–2007), seven patients who underwent LTx for FHF of unknown etiology were treated with conventional immunosuppressive therapy (calcineurin inhibitor and a steroid). Seven of eight grafts (one patient underwent re‐LTx) sustained CV and/or CPV associated with ACR, and four patients died of a graft failure or infectious complications that were associated with the treatment for rejection. Of note, the pathological incidence of CV/CPV was significantly higher in recipients with FHF of unknown etiology than in recipients with biliary cholestatic disease during the same study period (87.5% vs. 13.7%, p < 0.00001). From 2008, three patients underwent LTx for cryptogenic FHF with PVI and conventional IS. PVI was well tolerated, and no relevant severe complications were observed. More strikingly, the patients who received PVI overcame biopsy‐proven immunological events and are all currently doing well with excellent graft function after more than five yr. We conclude that PVI is technically safe and effective for preventing severe rejection in pediatric patients who undergo LTx for FHF of unknown etiology and that it does not increase the risk of fatal infectious complications.
Sex differences in renin response and changes of capillary diameters after renal ischemia/reperfusion injury
Authors: Csohány Rózsa , Prókai Ágnes , Sziksz Erna , Balicza‐Himer Leonóra , Pap Domonkos , Kosik Anna , Sugár Dániel , Vannay Ádám , Kis‐Petik Katalin , Fekete Andrea , Szabó Attila J. 
Published: April 2016

AbstractActivation of the RAS has a crucial role in the progression of ischemia/reperfusion‐associated CAD. The regulation of RAS differs in the two genders. However, the extent of gender differences and locations of renin production have not been revealed yet. We investigated in vivo the local renin production in the two genders during ischemia/reperfusion injury.In male and female Wistar rats, renal ischemia was induced followed by a reperfusion period of two, eight, 16, 24, or 48 h. We applied flow cytometry to measure renin content and multiphoton imaging to visualize renin granules and changes of peritubular diameters in vivo during ischemia/reperfusion.Renin content decreased in CD in the first eight h of reperfusion; however, after 16 h, its amount increased. In males, the production of renin was more pronounced, and the duration of vasoconstriction was longer with a subsequent phase of vessel hyperdilation compared to females.Renal ischemia/reperfusion injury induces renin response not only in the JGA, but also in the CD segment. Renin production is more explicit in males than in females which, via increased angiotensin II production, might explain the different dynamism of renal vessel regulation between the two genders.
Mortality risk and associated factors in HIV‐exposed, uninfected children
Authors: Arikawa Shino , Rollins Nigel , Newell Marie‐Louise , Becquet Renaud 
Published: April 2016

AbstractObjectiveWith increasing maternal antiretroviral treatment (ART), the number of children newly infected with HIV has declined. However, the possible increased mortality in the large number of HIV‐exposed, uninfected (HEU) children may be of concern. We quantified mortality risks among HEU children and reviewed associated factors.MethodsSystematic search of electronic databases (PubMed, Scopus). We included all studies reporting mortality of HEU children to age 60 months and associated factors. Relative risk of mortality between HEU and HIV‐unexposed, uninfected (HUU) children was extracted where relevant. Inverse variance methods were used to adjust for study size. Random‐effects models were fitted to obtain pooled estimates.ResultsA total of 14 studies were included in the meta‐analysis and 13 in the review of associated factors. The pooled cumulative mortality in HEU children was 5.5% (95% CI: 4.0–7.2; I2 = 94%) at 12 months (11 studies) and 11.0% (95% CI: 7.6–15.0; I2 = 93%) at 24 months (four studies). The pooled risk ratios for the mortality in HEU children compared to HUU children in the same setting were 1.9 (95% CI: 0.9–3.8; I2 = 93%) at 12 months (four studies) and 2.4 (95% CI: 1.1–5.1; I2 = 93%) at 24 months (three studies).ConclusionCompared to HUU children, mortality risk in HEU children was about double at both age points, although the association was not statistically significant at 12 months. Interpretation of the pooled estimates is confounded by considerable heterogeneity between studies. Further research is needed to characterise the impact of maternal death and breastfeeding on the survival of HEU infants in the context of maternal ART, where current evidence is limited.
Impact of Fluoroquinolone Exposure Prior to Tuberculosis Diagnosis on Clinical Outcomes in Immunocompromised Patients
Authors: Lee Ju Young , Lee Hyun Jung , Kim Yong Kyun , Yu Shinae , Jung Jiwon , Chong Yong Pil , Lee Sang-Oh , Choi Sang-Ho , Shim Tae Sun , Kim Yang Soo , Woo Jun Hee , Kim Sung-Han 
Published: April 2016

ABSTRACT

There have been concerns about an association of fluoroquinolone (FQ) use prior to tuberculosis (TB) diagnosis with adverse outcomes. However, FQ use might prevent clinical deterioration in missed TB patients, especially in those who are immunocompromised, until they receive definitive anti-TB treatment. All adult immunocompromised patients with smear-negative and culture-positive TB at a tertiary care hospital in Korea over a 2-year period were included in this study. Long-term FQ (≥7 days) use was defined as exposure to FQ for at least 7 days prior to TB diagnosis. A total of 194 patients were identified: 33 (17%) in the long-term FQ group and 161 (83%) in the comparator, including a short-term FQ group (
n
= 23), non-FQ group (
n
= 78), and a group receiving no antibiotics (
n
= 60). Patients in the long-term FQ group presented with atypical chest radiologic pattern more frequently than those in the comparator (77% [24/31] versus 46% [63/138];
P
= 0.001). The median time from mycobacterial test to positive mycobacterial culture appeared to be longer in the long-term FQ group (8.1 weeks versus 7.7 weeks;
P
= 0.09), although the difference was not statistically significant. Patients in the long-term FQ group were less likely to receive empirical anti-TB treatment (55% versus 74%;
P
= 0.03). The median time from mycobacterial test to anti-TB therapy was longer in the long-term FQ group (4.6 weeks versus 2.2 weeks;
P
< 0.001), but there was no significant difference in FQ resistance (0% versus 3%;
P
> 0.99) or in the 30-day (6% versus 6%;
P
> 0.99) or 90-day (12% versus 12%;
P
> 0.99) mortality rate between the two groups. FQ exposure (≥7 days) prior to TB diagnosis in immunocompromised patients appears not to be associated with adverse outcomes.
Excellent outcome of minimal residual disease-defined low-risk patients is sustained with more than 10 years follow-up: results of UK paediatric acute lymphoblastic leukaemia trials 1997–2003
Authors: Bartram Jack , Wade Rachel , Vora Ajay , Hancock Jeremy , Mitchell Chris , Kinsey Sally , Steward Colin , Moppett John , Goulden Nick 
Published: April 2016

BackgroundMinimal residual disease (MRD) is defined as the presence of sub-microscopic levels of leukaemia. Measurement of MRD from bone marrow at the end of induction chemotherapy (day 28) for childhood acute lymphoblastic leukaemia (ALL) can highlight a large group of patients (>40%) with an excellent (>90%) short-term event-free survival (EFS). However, follow-up in recent published trials is relatively short, raising concerns about using this result to infer the safety of further therapy reduction in the future.MethodsWe examined MRD data on 225 patients treated on one of three UKALL trials between 1997 and 2003 to assess the long-term (>10 years follow-up) outcome of those patients who had low-risk MRD (<0.01%) at day 28.ResultsOur pilot data define a cohort of 53% of children with MRD <0.01% at day 28 who have an EFS of 91% and long-term overall survival of 97%. Of 120 patients with day-28 MRD <0.01% and extended follow-up, there was one death due to treatment-related toxicity, one infectious death while in complete remission, and four relapse deaths.ConclusionsThe excellent outcome for childhood ALL in patients with MRD <0.01% after induction chemotherapy is sustained for more than 10 years from diagnosis. This supports the potential exploration of further reduction of therapy in this group, in an attempt to reduce treatment-related mortality and late effects.
Mortality and complications in 3495 children with isolated ventricular septal defects
Authors: Jortveit Jarle , Leirgul Elisabeth , Eskedal Leif , Greve Gottfried , Fomina Tatiana , Døhlen Gaute , Tell Grethe S , Birkeland Sigurd , Øyen Nina , Holmstrøm Henrik 
Published: April 2016

BackgroundVentricular septal defects (VSDs) are the most common congenital heart defects (CHDs). Previous studies indicate an increased risk of endocarditis, aortic regurgitation, left ventricular outflow tract obstructions, pulmonary hypertension, arrhythmias and sudden death in patients with isolated VSDs. The present nationwide cohort study reports mortality and cardiac complications requiring hospitalisation or intervention in children with isolated VSDs.Methods and resultsMedical information concerning all 943 871 live births in Norway in 1994–2009 was retrieved from the Medical Birth Registry of Norway, the Cardiovascular Disease in Norway project, the Oslo University Hospital's Clinical Registry of Congenital Heart Defects and the Norwegian Cause of Death Registry. Isolated VSDs were identified in 3495 children without known chromosomal aberrations or extracardiac malformations. Surgical or catheter-based treatment of VSD was performed in 181 (5.2%) cases. Twelve (0.3%) children with VSDs died before 2013. There was no operative mortality, and no excess mortality in children with isolated VSDs compared with children without VSDs (adjusted HR 0.8 (0.5 to 1.4), p=0.48). The following conditions were recorded as possible cardiac complications of the VSDs: endocarditis in 3 children (0.9‰), aortic regurgitation in 12 children (3.4‰), left ventricular outflow tract obstructions in no children (0.0‰), pulmonary hypertension in 1 child (0.3‰) and arrhythmias in 16 children (4.6‰).ConclusionsThe entire group of children with isolated VSDs had a favourable prognosis without excess mortality. Cardiac complications requiring hospitalisation or intervention, including endocarditis, aortic regurgitation, left ventricular outflow tract obstructions, pulmonary hypertension and arrhythmias, were infrequent during childhood.Trial registration numberNCT02026557.
BeAM value: an indicator of the need to initiate and intensify prandial therapy in patients with type 2 diabetes mellitus receiving basal insulin
Authors: Zisman Ariel , Morales Francienid , Stewart John , Stuhr Andreas , Vlajnic Aleksandra , Zhou Rong 
Published: April 2016

IntroductionIn patients with type 2 diabetes mellitus (T2DM) with uncontrolled glycemia despite ongoing upward titration of basal insulin, targeting postprandial hyperglycemia may be required. Nevertheless, the point at which basal insulin is fully optimized and postprandial glucose (PPG) should be targeted with additional treatment remains unclear. We report here on the BeAM value (difference between bedtime and morning blood glucose values) as an indicator of the need to target PPG.MethodsThis study had 3 stages: exploratory, main, and proof-of-concept analyses. For the exploratory and main analyses, data were pooled from phase 3 trials in adults with T2DM adding basal insulin to oral antidiabetic drugs (OADs). The main analysis included only patients who did not reach A1C ≤7.0% (53 mmol/mol) at week 24. The proof-of-concept analysis used pooled data from phase 3 trials in adults with T2DM adding insulin glargine and a single insulin glulisine injection to OADs.ResultsIn patients undergoing basal insulin titration, BeAM value increased over 24 weeks (27.8–61.7 mg/dL, n=1188; 32.6–71.2 mg/dL, n=553; exploratory and main analyses, respectively). There were significant correlations between week 24 BeAM value and postprandial contribution to hyperglycemia (Pearson's correlation coefficient (r)=0.375, p<0.001; r=0.396, p<0.001; exploratory and main analyses, respectively). When PPG was targeted (proof-of-concept analysis), the BeAM value reduced from 77.0 to 40.4 mg/dL (n=299).ConclusionsThe BeAM value described in this study is a simple, easy-to-calculate value that may identify patients with T2DM using basal insulin that need targeting of postprandial control rather than advancing basal insulin dose.