bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic vaccination for chronic hepatitis B: A systematic review and meta‐analysis
Authors: Lim Seng Gee , Agcaoili Jennielyn , De Souza Nurun Nisa Amatullah , Chan Edwin 
Published: February 2019

SummaryTherapeutic vaccines may be promising treatments for chronic hepatitis B (CHB), but their clinical efficacy and safety are unclear. We conducted a systematic review of the evidence for the efficacy and safety of therapeutic vaccines in CHB patients. We searched PubMed, EMBASE and Google Scholar from 1990 until present and abstracts from EASL, APASL and AASLD from 2012 to 2017 and selected randomized controlled trials of CHB patients, comparing therapeutic vaccines with no treatment or standard of care. The Cochrane Risk of Bias tool v2.0 and GRADE method were used. Analyses were stratified by hepatitis B e antigen (HBeAg) status and the comparator (therapeutic vaccines vs no treatment, or therapeutic vaccines + standard of care vs standard of care). Efficacy outcomes were HBeAg seroconversion, hepatitis B virus DNA reduction and hepatitis B virus surface antigen (HBsAg) loss, measured at the end of treatment or end of follow‐up. Effects were reported as risk differences with 95% confidence intervals using a random effects model. Fifteen studies were included. A wide variety of therapeutic vaccines were tested. For HBeAg clearance at the end of follow‐up, when comparing therapeutic vaccines vs no therapy, RD = 0.01, 95% CI −0.05 to 0.07, and when comparing therapeutic vaccines + standard of care vs standard of care, RD = 0.03, 95% CI −0.03 to 0.09. For HBVDNA reduction at the end of follow‐up, when comparing therapeutic vaccines vs no therapy, RD = −0.03, 95% CI −0.08 to 0.02, and when comparing therapeutic vaccines + standard of care, RD = 0.15, 95% CI 0.02‐0.28. There were only a few studies on HBsAg loss, and hence, the findings were inconclusive. The only efficacy finding was HBVDNA reduction at the end of follow‐up for therapeutic vaccines + standard of care vs standard of care; otherwise, therapeutic vaccines do not appear to be efficacious for the treatment of CHB, but were limited by few RCTs, suboptimal therapeutic vaccines and patient selection.
Genetic diversity of hepatitis D virus genotype‐1 in Europe allows classification into subtypes
Authors: Karimzadeh Hadi , Usman Zainab , Frishman Dmitrij , Roggendorf Michael 
Published: February 2019

SummaryHepatitis delta virus (HDV) is an RNA virus which leads to both acute and chronic forms of hepatitis. At present, HDV isolates have been classified into eight major genotypes distributed over different geographical regions. Recent increase in HDV sequences in Europe and worldwide has enabled us to revisit the taxonomic classification of HDV. A total of 116 large hepatitis delta antigen (L‐HDAg) nucleotide sequences and 13 full‐length HDV genome sequences belonging to genotype‐1 from our European cohort, as well as 621 L‐HDAg nucleotide sequences belonging to genotype‐1 to genotype‐8 retrieved from the GenBank NCBI were included in this study. All 116 isolates of our cohort and 341 of 621 isolates (60%) account for genotype‐1, while the remaining 40% of isolates were unevenly distributed across genotype‐2 to genotype‐8. Phylogenetic analysis of 98 L‐HDAg sequences selected after elimination of redundant sequences of all 737 isolates was performed to identify plausible subtypes within HDV genotype‐1. Pairwise genetic distances for L‐HDAg sequences were calculated to estimate the inter‐genotype and inter‐subtype differences. The HDV genotype‐1 isolates phylogenetically formed five distinct clusters (genotype 1a‐1e), each of them corresponding to a distinct geographic region. Two distinct subtypes for HDV genotype‐2 and ‐4 (ie ‐2a and ‐2b; ‐4a and ‐4b, respectively) could be identified based on isolate sequences from GenBank. The previously defined genotype‐1 to genotype‐8 have an inter‐genotypic difference of ≥10%, while the newly defined subtypes of genotype‐1, ‐2 and ‐4 show an inter‐subtype difference of ≥3% to <10% from the average diversity. In addition, we identified unique amino acid residues, known as specificity‐determining positions, amongst the proposed subtypes.
Biological basis for functional cure of chronic hepatitis B
Authors: Martinez Maria G. , Testoni Barbara , Zoulim Fabien 
Published: February 2019

SummaryChronic hepatitis B (CHB) infection affects over 250 millon people worldwide and 800000 are expected to die yearly due to the development of hepatocellular carcinoma (HCC). Current antiviral therapies include nucleoside analogs (NAs) that target the viral retrotranscriptase inhibiting de novo viral production. Pegylated interferon (Peg‐IFN) is also effective in reducing the viral DNA load in serum. However, both treatments remain limited to control the infection, aiming for viral suppression and improving the quality of life of the infected patients. Complete cure is not possible due to the presence of the stable DNA intermediate covalently closed circular DNA (cccDNA). Attempts to achieve a functional cure are thus ongoing and novel targets and molecules, together with different combination therapies are currently in the pipeline for early clinical trials. In this review we discuss novel treatments both targeting directly and indirectly cccDNA. As we gain knowledge in the Hepatitis B virus (HBV) transcriptional control, and newer technologies emerge that could potentially allow the destruction of cccDNA, exciting new possibilities for curative therapies are discussed.
Resistant cutoff values and optimal scheme establishments for florfenicol against Escherichia coli with PK‐PD modeling analysis in pigs
Authors: Lei Zhixin , Liu Qianying , Khaliq Haseeb , Cao Jiyue , He Qigai 
Published: February 2019

AbstractFlorfenicol, a structural analog of thiamphenicol, has broad‐spectrum antibacterial activity against gram‐negative and gram‐positive bacteria. This study was conducted to investigate the epidemiological, pharmacokinetic–pharmacodynamic cutoff, and the optimal scheme of florfenicol against Escherichia coli (E. coli) with PK‐PD integrated model in the target infectious tissue. 220 E. coli strains were selected to detect the susceptibility to florfenicol, and a virulent strain P190, whose minimum inhibitory concentration (MIC) was similar to the MIC50 (8 μg/ml), was analyzed for PD study in LB and ileum fluid. The MIC of P190 in the ileum fluid was 0.25 times lower than LB. The ratios of MBC/MIC were four both in the ileum and LB. The characteristics of time‐killing curves also coincided with the MBC determination. The recommended dosages (30 mg/kg·body weight) were orally administrated in healthy pigs, and both plasma and ileum fluid were collected for PK study. The main pharmacokinetics (PK) parameters including AUC24 hr, AUC0–∞, Tmax, T1/2, Cmax, CLb, and Ke were 49.83, 52.33 μg*h/ml, 1.32, 10.58 hr, 9.12 μg/ml, 0.50 L/hr*kg, 0.24 hr−1 and 134.45, 138.71 μg*hr/ml, 2.05, 13.01 hr, 16.57 μg/ml, 0.18 L/hr*kg, 0.14 hr−1 in the serum and ileum fluid, respectively. The optimum doses for bacteriostatic, bactericidal, and elimination activities were 29.81, 34.88, and 36.52 mg/kg for 50% target and 33.95, 39.79, and 42.55 mg/kg for 90% target, respectively. The final sensitive breakpoint was defined as 16 μg/ml. The current data presented provide the optimal regimens (39.79 mg/kg) and susceptible breakpoint (16 μg/ml) for clinical use, but these predicted data should be validated in the clinical practice.
Primordial, thermal, and shock features of ordinary chondrites: Emulating bulk X‐ray diffraction using in‐plane rotation of polished thin sections
Authors: Imae Naoya , Kimura Makoto , Yamaguchi Akira , Kojima Hideyasu 
Published: February 2019

AbstractUsing an X‐ray diffractometer, powder‐like diffraction patterns were acquired from in‐plane rotation of polished thin sections (PTSs) of 60 ordinary chondrites (23 H, 21 L, and 16 LL), in order to explore the thermal and shock metamorphism and its modifications of primordial features. The olivine (Ol) 130 peak position shown as Bragg indices clearly correlates with the chemical group for equilibrated ordinary chondrites (EOCs), while the peak is split or broad for unequilibrated ordinary chondrites (UOCs). The intensity ratio of kamacite may be useful for distinguishing the chemical group between H and L‐LL, but it is not definite because of heterogeneous terrestrial weathering of kamacite, especially in H chondrites. The summed intensities of the orthoenstatite (Oen) 511 and 421 peaks positively correlates with the metamorphic sequence from 3 to 6, while that of clinoenstatite (Cen) 22 is inversely correlated. The shock stage positively correlates with the summed full width of half maximum values of the Oen 511 and 421 peaks and the FWHM of Ol 130 peak for each class. Significant amount of Oen (Pbca) transformed through Cen (C2/c) finally to Cen (P21/c) is stable at high pressure for shock stage S6 (Tenham and NWA 4719). The shock melted LL chondrite is characterized by the occurrence of Cen and abundant homogeneous olivine. The effects of both thermal and shock metamorphism are thus incorporated into the bulk X‐ray diffraction (XRD) data. The bulk XRD method is useful for determining the bulk mineralogy, resulting in the classification of ordinary chondrites. The method is also applicable to samples other than PTS.
Development of the peripheral and central venous catheter‐related bloodstream infection prevention knowledge and attitudes scale
Authors: Bakan Ayse B. , Arli Senay K. 
Published: February 2019

AbstractBackgroundBecause of the necessities of modern medicine, catheters are frequently used for patients today. Mistakes made in catheter implementation frequently cause nosocomial infections.Aims and objectivesThe purpose of this study was to develop a scale to be used for the evaluation of nurses' knowledge and attitudes about peripheral and central venous catheter‐related bloodstream infection prevention.Design and methodsThis methodological study was conducted between July 2016 and December 2017, with 150 nurses who worked in intensive care units and surgical, internal and paediatric clinics in hospitals located in two different cities in the eastern part of Turkey and who consented to participate in the study.ResultsItem total correlation values of the scale ranged between 0.515 and 0.703. Correlation coefficient between the two measurements as a result of the test–retest reliability was found to be 0.64, and there was a linear relationship between the measurements. The Kaiser–Meyer–Olkin (KMO) value was found to be0.875, which indicates the adequacy of the sample. Barlett's test results indicated a correlation between the items (P < .01). Cronbach's alpha value of the scale was found to be 0.86.ConclusionsResults showed that the 5‐point Likert scale was formed with 14 items and two factors, which included “general precautions” and “catheter care.” Scale total score is obtained by collecting all the items. Higher scores indicate higher knowledge and attitudes. This scale could be used for assessing the knowledge and attitudes of nurses about peripheral and central venous catheter‐related bloodstream infection prevention precautions.Relevance to clinical practiceThe Peripheral and Central Venous Catheter‐Related Bloodstream Infection Prevention Knowledge and Attitudes Scale could be used for infection prevention in the assessment of the knowledge and attitudes of nurses with a view of preventing infections. The scale can be used in intensive care units and surgical, internal and paediatric clinics in order to assess nurses' knowledge and attitudes.
Necrotizing enterocolitis
Authors: Bellodas Sanchez Jenny , Kadrofske Mark 
Published: February 2019

AbstractNecrotizing enterocolitis (NEC) is an acute inflammatory disease of the intestine which primarily affects preterm infants and is a leading cause of morbidity and mortality in the neonatal intensive care unit. From a clinical standpoint, and during the early course of the disease, NEC can be difficult to distinguish from other diseases and conditions common to the preterm infant, and this warrants the need for specific disease biomarkers. The pathogenesis of NEC is only partly understood but likely involves an altered intestinal barrier immune response to feeding and the developing microbiome. Recent evidence points toward a role of the enteric nervous system in NEC pathogenesis. In this issue, Meister and colleagues use a rodent model of NEC to demonstrate that NEC is associated with diminished vagal tone, as determined by decreased high‐frequency heart rate variability (HF‐HRV), and altered myenteric nitrergic inhibitory neurotransmission. These results augment their previous findings that describe decreased HF‐HRV in human preterm infants with NEC. This mini‐review provides a brief summary of clinical and pathophysiologic aspects of NEC with focus on certain aspects of neurogastroenterology.
Comprehending international important Ramsar wetland documents using latent semantic topic model in kernel space
Authors: Lin Ping , Jiang Shanchao , Li Du , Zou Zhiyong , Chen Yongming 
Published: February 2019

AbstractThe kernel‐based statistical semantic topic model is introduced for comprehending three species of internationally important Ramsar wetland documents describing the Lashi Lake wetland in the Yunnan Province, the Yancheng wetland in the Jiangsu Province, and the Zoige wetland in the Sichuan Province of China. Latent Dirichlet allocation (LDA) features are used to represent the semantic components of wetland documents. Kernel principal component analysis (KPCA) maps the topic components to the kernel space to attain the low dimensional principal components. Support vector machines (SVMs) are used to comprehend the semantic distribution of distinct wetland documents in the kernel space. The LDA+KPCA+SVM algorithm reaches 77.0% training and 75.9% test accuracy and 0.902 training and 0.840 test mean average precision scores in the application of comprehending the wetland documents, respectively. The performance of the proposed kernel‐based model is superior to the traditional models of LDA+SVM and LDA+PCA+SVM.
Bcl‐2 is a prognostic marker and its silencing inhibits recurrence in ameloblastomas
Authors: Kim Jue Young , Kim Jinsun , Bazarsad Shadavlonjid , Cha In‐Ho , Cho Sung‐Won , Kim Jin 
Published: February 2019

AbstractObjectivesAmeloblastomas are the most common odontogenic epithelial tumors with high recurrence rate. The aim of this study was to identify apoptosis‐related genes with recurrence of ameloblastomas and to evaluate its feasibility as a prognostic marker and as a target molecule preventing from recurrence.Materials and MethodsPublic microarray data were analyzed. To evaluate their expression in ameloblastoma patients, immunohistochemical staining was performed in 89 human ameloblastoma tissues. Quantitative PCR was performed by use of ameloblastoma cell line (AM‐1). Fluorescence activated cell sorting analysis and western blotting were conducted following transfection with siRNA. Further, AM‐1 cells were implanted in the renal subcapsular layer of immunodeficient mice.ResultsMicroarray data analysis revealed that osteoprotegerin (OPG) and B‐cell lymphoma 2 (Bcl‐2) were the two most upregulated genes in ameloblastoma. Only Bcl‐2 expression was significantly (p = 0.020) associated with recurrence in conservative treatment group (n = 17) among 89 patients. Silencing of Bcl‐2 increased apoptosis in AM‐1 cells in vitro and inhibited tumor nodule formation of AM‐1 cells in vivo.ConclusionThese results suggest that Bcl‐2 expression is a useful biomarker to predict recurrence of ameloblastomas, and as a therapeutic target molecule to prevent recurrence of ameloblastoma.
Do traditional fermented foods protect against infantile atopic dermatitis
Authors: Celik Velat , Beken Burcin , Yazicioglu Mehtap , Ozdemir Pinar Gokmirza , Sut Necdet 
Published: February 2019

AbstractBackgroundEnvironmental and dietary factors during pregnancy may affect development of infantile atopic dermatitis (AD). This study analyzed whether maternal consumption of selected Turkish fermented foods (FF) and other factors during pregnancy affect the development of AD during the first 2 years of life.MethodsEighty‐four children with physician‐diagnosed AD (aged between 2 and 24 months) and mothers, and 56 similarly aged, healthy children and mothers were studied. Physician‐administered questionnaires retrospectively surveyed maternal consumption of FF during pregnancy. The intake frequency of 8 selected Turkish FF was classified as either (1) daily or (2) less than daily. Other possible demographic and environmental risk factors were also analyzed.ResultsDaily maternal consumption of yogurt, fermented olive, and cheese in the control group was significantly higher than the AD group (P < 0.001, P = 0.017, and P = 0.011, respectively). Exposure to environmental tobacco smoking (ETS) was more common in the AD group than the control group (P = 0.025). In multivariate logistic regression analysis, maternal ETS exposure during pregnancy was associated with increased risk of infantile AD, and daily consumption of yogurt was associated with a reduced risk (odds ratio [OR]: 2.60, 95% confidence interval [CI]: 1.11‐6.1, and OR: 0.22, CI: 0.09‐0.54, respectively). The diversity of consumed FF during pregnancy was found to have a protective effect against infantile AD (OR: 0.27, CI: 0.14‐0.53).ConclusionsDaily maternal intake of yogurt and diversity of consumed Turkish FF during pregnancy may reduce the risk of AD. Maternal tobacco smoke exposure is associated with increased risk of infantile AD.
Sublingual immunotherapy alters salivary IgA and systemic immune mediators in timothy allergic children
Authors: Huoman Johanna , Papapavlou Georgia , Pap Anna , Alm Johan , Nilsson Lennart J. , Jenmalm Maria C. 
Published: February 2019

AbstractBackgroundImmunomodulatory effects of sublingual immunotherapy on systemic and mucosal mediators in allergic children are largely unexplored. The aim of this study was to investigate allergy‐related cytokine and chemokine levels, as well as IgA‐responses upon a 3‐year treatment with timothy grass pollen sublingual immunotherapy in children with allergic rhinoconjunctivitis.MethodsFrom children included in the GRAZAX® Asthma Prevention study, blood and saliva samples were analyzed at inclusion, after 3 years of treatment, and 2 years after treatment ending. By means of Luminex and ELISA methodologies, allergy‐related cytokines and chemokines were measured in plasma samples and allergen‐stimulated peripheral blood mononuclear cell supernatants. Furthermore, studies of total, secretory, and Phl p 1–specific salivary IgA antibodies were performed using the same methods.ResultsGRAZAX®‐treated children exhibited significantly higher levels of Phl p 1–specific salivary IgA and serum IgG4, along with significantly lower skin prick test positivity, after 3 years of treatment and 2 years after treatment cessation. Additionally, plasma levels of the Th1‐associated chemokines CXCL10 and CXCL11 were significantly higher in treated than untreated children at these time points. Timothy‐induced ratios of IL‐5/IL‐13 over IFN‐γ were significantly decreased after 3 years with active treatment, as were symptoms of allergic rhinitis in terms of both severity and visual analogue scale scores. However, no consistent correlations were found between the clinical outcomes and immunologic parameters.ConclusionPhleum pratense sublingual immunotherapy in grass pollen allergic children modulates the immune response in the oral mucosa as well as systemically—by increasing Th1‐responses, decreasing Th2‐responses, and inducing immunoregulatory responses—all signs of tolerance induction.
Dissection of coleoptile elongation in japonica rice under submergence through integrated genome‐wide association mapping and transcriptional analyses
Authors: Nghi Khac Nhu , Tondelli Alessandro , Valè Giampiero , Tagliani Andrea , Marè Caterina , Perata Pierdomenico , Pucciariello Chiara 
Published: February 2019

AbstractRice is unique among cereals for its ability to germinate not only when submerged but also under anoxic conditions. Rice germination under submergence or anoxia is characterized by a longer coleoptile and delay in radicle emergence. A panel of temperate and tropical japonica rice accessions showing a large variability in coleoptile length was used to investigate genetic factors involved in this developmental process. The ability of the Khao Hlan On rice landrace to vigorously germinate when submerged has been previously associated with the presence of the trehalose 6 phosphate phosphatase 7 (TPP7) gene. In this study, we found that, in the presence of TPP7, polymorphisms and transcriptional variations of the gene in coleoptile tissue were not related to differences in the final coleoptile length under submergence. In order to find new chromosomal regions associated with the different ability of rice to elongate the coleoptile under submergence, we used genome‐wide association study analysis on a panel of 273 japonica rice accessions. We discovered 11 significant marker–trait associations and identified candidate genes potentially involved in coleoptile length. Candidate gene expression analyses indicated that japonica rice genotypes possess complex genetic elements that control final coleoptile length under low oxygen.
First report of successful transplantation of a pediatric donor liver graft after hypothermic machine perfusion
Authors: Werner Maureen J. M. , van Leeuwen Otto B. , de Jong Iris E. M. , Bodewes Frank A. J. A. , Fujiyoshi Masato , Luhker Olaf C. , Scheenstra René , de Vries Yvonne , de Kleine Ruben H. J. , Porte Robert J. 
Published: February 2019

AbstractOne of the main limiting factors in pediatric liver transplantation is donor availability. For adults, DCD liver grafts are increasingly used to expand the donor pool. To improve outcome after DCD liver transplantation, ex situ machine perfusion is used as an alternative organ preservation strategy, with the supplemental value of providing oxygen to the graft during preservation. We here report the first successful transplantation of a pediatric DCD liver graft after hypothermic oxygenated machine perfusion. The full‐size liver graft was derived from a 13‐year‐old, female DCD donor and was end‐ischemic pretreated with dual hypothermic oxygenated machine perfusion. Arterial and portal pressures were set at 18 and 4 mm Hg, slightly lower than protocolized settings for adult livers. During 2 hours of machine perfusion, portal and arterial flows increased from 100 to 210 mL/min and 30 to 63 mL/min, respectively. The pretreated liver graft was implanted in a 16‐year‐old girl with progressive familial intrahepatic cholestasis type 2. Postoperative AST, ALT, and prothrombin time normalized within a week. The recipient quickly recovered and was discharged from the hospital after 18 days. One year after transplantation, she is in excellent condition with a completely normal liver function and histology. This case is the first report of successful transplantation of a pediatric DCD liver graft after hypothermic oxygenated machine perfusion and illustrates the potential role of ex situ machine perfusion in expanding the donor pool and improving outcome after pediatric liver transplantation.