bluuebunny/crossref_metadata_2025_split huggingface dataset:
Passive administration of purified secretory IgA from human colostrum induces protection against Mycobacterium tuberculosis in a murine model of progressive pulmonary infection
Authors: Alvarez Nadine , Otero Oscar , Camacho Frank , Borrero Reinier , Tirado Yanely , Puig Alina , Aguilar Alicia , Rivas Cesar , Cervantes Axel , Falero-Díaz Gustavo , Cádiz Armando , Sarmiento María E , Norazmi Mohd Nor , Hernández-Pando Rogelio , Acosta Armando 
Published: December 2019

AbstractBackgroundImmunoglobulin A is the most abundant isotype in secretions from mucosal surfaces of the gastrointestinal, respiratory and genitourinary tracts and in external secretions such as colostrum, breast milk, tears and saliva. The high concentration of human secretory IgA (hsIgA) in human colostrum strongly suggests that it should play an important role in the passive immune protection against gastrointestinal and respiratory infections.Materials and methodsHuman secretory IgA was purified from colostrum. The reactivity of hsIgA against mycobacterial antigens and its protective capacity against mycobacterial infection was evaluated.ResultsThe passive administration of hsIgA reduces the pneumonic area before challenge withM.tuberculosis. The intratracheal administration ofM. tuberculosispreincubated with hsIgA to mice greatly reduced the bacterial load in the lungs and diminished lung tissue injury.ConclusionsHsIgA purified from colostrum protects againstM. tuberculosisinfection in an experimental mouse model.
Presence of genes for type III secretion system 2 in Vibrio mimicus strains
Authors: Okada Natsumi , Matsuda Shigeaki , Matsuyama Junko , Park Kwon-Sam , de los Reyes Calvin , Kogure Kazuhiro , Honda Takeshi , Iida Tetsuya 
Published: December 2019

Abstract

Background
Vibrios, which include more than 100 species, are ubiquitous in marine and estuarine environments, and several of them e.g. Vibrio cholerae, V. parahaemolyticus, V. vulnificus and V. mimicus, are pathogens for humans. Pathogenic V. parahaemolyticus strains possess two sets of genes for type III secretion system (T3SS), T3SS1 and T3SS2. The latter are critical for virulence of the organism and be classified into two distinct phylogroups, T3SS2α and T3SS2β, which are reportedly also found in pathogenic V. cholerae non-O1/non-O139 serogroup strains. However, whether T3SS2-related genes are present in other Vibrio species remains unclear.

Results
We therefore examined the distribution of the genes for T3SS2 in vibrios other than V. parahaemolyticus by using a PCR assay targeting both T3SS2α and T3SS2β genes. Among the 32 Vibrio species tested in our study, several T3SS2-related genes were detected in three species, V. cholerae, V. mimicus and V. hollisae, and most of the essential genes for type III secretion were present in T3SS2-positive V. cholerae and V. mimicus strains. Moreover, both V. mimicus strains possessing T3SS2α and T3SS2β were identified. The gene organization of the T3SS2 gene clusters in V. mimicus strains was fundamentally similar to that of V. parahaemolyticus and V. cholerae in both T3SS2α- and T3SS2β-possessing strains.

Conclusions
This study is the first reported evidence of the presence of T3SS2 gene clusters in V. mimicus strains. This finding thus provides a new insight into the pathogenicity of the V. mimicus species.
A homeobox protein Phx1 regulates long-term survival and meiotic sporulation in Schizosaccharomyces pombe
Authors: Kim Ji-Yoon , Kwon Eun-Soo , Roe Jung-Hye 
Published: December 2019

Abstract

Background
In the fission yeast Schizosaccharomyces pombe, the phx1
+ (pombe homeobox) gene was initially isolated as a multi-copy suppressor of lysine auxotrophy caused by depletion of copper/zinc-containing superoxide dismutase (CuZn-SOD). Overproduction of Phx1 increased the synthesis of homocitrate synthase, the first enzyme in lysine biosynthetic pathway, which is labile to oxidative stress. Phx1 has a well conserved DNA-binding domain called homeodomain at the N-terminal region and is predicted to be a transcription factor in S. pombe. However, its role has not been revealed in further detail. Here we examined its expression pattern and the phenotype of its null mutant to get clues on its function.

Results
Fluorescence from the Phx1-GFP expressed from a chromosomal fusion gene demonstrated that it is localized primarily in the nucleus, and is distinctly visible during the stationary phase. When we replaced the N-terminal homeobox domain of Phx1 with the DNA binding domain of Pap1, a well-characterized transcription factor, the chimeric protein caused the elevation of transcripts from Pap1-dependent genes such as ctt1

+
and trr1

+
, suggesting that Phx1 possesses transcriptional activating activity when bound to DNA. The amount of phx1

+
transcripts sharply increased as cells entered the stationary phase and was maintained at high level throughout the stationary phase. Nutrient shift down to low nitrogen or carbon sources caused phx1

+
induction during the exponential phase, suggesting that cells need Phx1 for maintenance function during nutrient starvation. The Δphx1 null mutant showed decreased viability in long-term culture, whereas overproduction of Phx1 increased viability. Decrease in long-term survival was also observed for Δphx1 under N- or C-starved conditions. In addition, Δphx1 mutant was more sensitive to various oxidants and heat shock. When we examined sporulation of the Δphx1/Δphx1 diploid strain, significant decrease in the formation of meiotic spores was observed.

Conclusions
Phx1 is a transcriptional regulator whose synthesis is elevated during stationary phase and by nutrient starvation in S. pombe. It supports long-term survival and stress tolerance against oxidation and heat, and plays a key role in the formation of meiotic spores.
A method of active case detection to target reservoirs of asymptomatic malaria and gametocyte carriers in a rural area in Southern Province, Zambia
Authors: Stresman Gillian H , Kamanga Aniset , Moono Petros , Hamapumbu Harry , Mharakurwa Sungano , Kobayashi Tamaki , Moss William J , Shiff Clive 
Published: December 2019

Abstract

Background
Asymptomatic reservoirs of malaria parasites are common yet are difficult to detect, posing a problem for malaria control. If control programmes focus on mosquito control and treatment of symptomatic individuals only, malaria can quickly resurge if interventions are scaled back. Foci of parasite populations must be identified and treated. Therefore, an active case detection system that facilitates detection of asymptomatic parasitaemia and gametocyte carriers was developed and tested in the Macha region in southern Zambia.

Methods
Each week, nurses at participating rural health centres (RHC) communicated the number of rapid diagnostic test (RDT) positive malaria cases to a central research team. During the dry season when malaria transmission was lowest, the research team followed up each positive case reported by the RHC by a visit to the homestead. The coordinates of the location were obtained by GPS and all consenting residents completed a questionnaire and were screened for malaria using thick blood film, RDT, nested-PCR, and RT-PCR for asexual and sexual stage parasites. Persons who tested positive by RDT were treated with artemether/lumefantrine (Coartem®). Data were compared with a community-based study of randomly selected households to assess the prevalence of asymptomatic parasitaemia in the same localities in September 2009.

Results
In total, 186 and 141 participants residing in 23 case and 24 control homesteads, respectively, were screened. In the case homesteads for which a control population was available (10 of the 23), household members of clinically diagnosed cases had a 8.0% prevalence of malaria using PCR compared to 0.7% PCR positive individuals in the control group (p = 0.006). The case and control groups had a gametocyte prevalence of 2.3% and 0%, respectively but the difference was not significant (p = 0.145).

Conclusions
This pilot project showed that active case detection is feasible and can identify reservoirs of asymptomatic infection. A larger sample size, data over multiple low transmission seasons, and in areas with different transmission dynamics are needed to further validate this approach.
The cross-sectional associations between sense of coherence and diabetic microvascular complications, glycaemic control, and patients' conceptions of type 1 diabetes
Authors: Ahola Aila J , Saraheimo Markku , Forsblom Carol , Hietala Kustaa , Groop Per-Henrik ,   the FinnDiane Study Group
Published: December 2019

Abstract

Background
Sense of coherence (SOC) has been associated with various self-care behaviours in the general population. As the management of type 1 diabetes heavily relies on self-management, the SOC concept could also prove important in this population. This paper is a report of a study conducted among patients with type 1 diabetes to assess the associations between SOC and glycaemic control, microvascular complications, and patients' conceptions of their disease.

Methods
Altogether 1,264 adult patients (45% men, age range 18-82 years) with type 1 diabetes participated in this cross-sectional study. SOC was evaluated using a 13-item SOC questionnaire. Standardized assays were used to determine HbA1c. Nephropathy status was based on albumin excretion rate and retinal laser-treatment was used as an indication of severe retinopathy. Patients' subjective conceptions of diabetes were studied using a questionnaire.

Results
Higher SOC scores, reflecting stronger SOC, were associated with lower HbA1c values. Strong SOC was independently associated with reaching the HbA1c level <7.5%. Adjusting for diabetes duration, age at onset, socioeconomic status and HbA1c, weak SOC was associated with the presence of nephropathy among men, but not women. No associations were observed between SOC and severe retinopathy. Four dimensions describing patients' conceptions of HbA1c, complications, diabetes control and hypoglycaemia were formed from the diabetes questionnaire. Weak SOC was independently associated with worse subjective conceptions in the dimensions of HbA1c and hypoglycaemia. Furthermore among men, an association between weak SOC and the complications factor was observed.

Conclusion
Interventions to improve patients' SOC, if available, could improve patients' metabolic control and therefore also reduce the incidence of diabetic complications.
Immunological analysis of a Lactococcus lactis-based DNA vaccine expressing HIV gp120
Authors: Gram Gregers J , Fomsgaard Anders , Thorn Mette , Madsen Søren M , Glenting Jacob 
Published: December 2019

AbstractFor reasons of efficiencyEscherichia coliis used today as the microbial factory for production of plasmid DNA vaccines. To avoid hazardous antibiotic resistance genes and endotoxins from plasmid systems used nowadays, we have developed a system based on the food-gradeLactococcus lactisand a plasmid without antibiotic resistance genes. We compared theL. lactissystem to a traditional one inE. coliusing identical vaccine constructs encoding the gp120 of HIV-1. Transfection studies showed comparable gp120 expression levels using both vector systems. Intramuscular immunization of mice withL. lactisvectors developed comparable gp120 antibody titers as mice receivingE. colivectors. In contrast, the induction of the cytolytic response was lower using theL. lactisvector. Inclusion of CpG motifs in the plasmids increased T-cell activation more when theE. colirather than theL. lactisvector was used. This could be due to the different DNA content of the vector backbones. Interestingly, stimulation of splenocytes showed higher adjuvant effect of theL. lactisplasmid. The study suggests the developedL. lactisplasmid system as new alternative DNA vaccine system with improved safety features. The different immune inducing properties using similar gene expression units, but different vector backbones and production hosts give information of the adjuvant role of the silent plasmid backbone. The results also show that correlation between thein vitroadjuvanticity of plasmid DNA and its capacity to induce cellular and humoral immune responses in mice is not straight forward.
The effect of infliximab plus methotrexate on the modulation of inflammatory disease markers in juvenile idiopathic arthritis: analyses from a randomized, placebo-controlled trial
Authors: Visvanathan Sudha , Wagner Carrie , Marini Joseph C , Lovell Daniel J , Martini Alberto , Petty Ross , Cuttica Ruben , Woo Patricia , Espada Graciela , Gattorno Marco , Apaz Maria T , Baildam Eileen , Fasth Anders , Gerloni Valeria , Lahdenne Pekka , Quartier Pierre , Saurenmann Rotraud , Travers Suzanne , Mendelsohn Alan , Xu Stephen , Giannini Edward H , Ruperto Nicolino ,   the Paediatric Rheumatology INternational Trials Organization (PRINTO),   the Pediatric Rheumatology Collaborative Study Group (PRCSG)
Published: December 2019

Abstract

Background
We evaluated the effect of infliximab on markers of inflammation in patients with juvenile idiopathic arthritis (JIA).

Methods
In this randomized, placebo-controlled substudy, 122 patients with JIA received infliximab 3 mg/kg + methotrexate (MTX)(n = 60) or placebo + MTX (n = 62) at weeks 0, 2, and 6. At week 14, patients receiving placebo + MTX crossed over to infliximab 6 mg/kg + MTX; patients receiving infliximab 3 mg/kg + MTX continued treatment through week 44. Sera and plasma from eligible patients receiving infliximab 3 mg/kg + MTX (n = 34) and receiving placebo→infliximab 6 mg/kg +MTX (n = 38) were collected at weeks 0, 2, 14, 16, 28, and 52 and analyzed for inflammatory markers (IL-6, IL-12p40, ICAM-1, MMP-3, VEGF, TNF-α, and CRP).

Results
At week 2, decreases from baseline in IL-6, ICAM-1, MMP-3, TNF-α, and CRP were greater with infliximab versus placebo treatment, and with the exception of CRP, these differences were generally maintained through week 14. The decreases from baseline to week 52 in IL-6, ICAM-1, VEGF, MMP-3, and CRP and increases in IL-12p40 levels were larger in patients receiving placebo→infliximab 6 mg/kg +MTX versus infliximab 3 mg/kg + MTX treatment. Patients receiving infliximab 3 mg/kg+MTX who achieved an American College of Rheumatology Pediatric 30 (ACR-Pedi-30) response had significantly larger decreases from baseline in ICAM-1 (p = 0.0105) and MMP-3 (p = 0.0253) at week 2 and in ICAM-1 (p = 0.0304), MMP-3 (p = 0.0091), and CRP (p = 0.0011) at week 14 versus ACR-Pedi-30 nonresponders.

Conclusion
Infliximab + MTX attenuated several inflammatory markers in patients with JIA; larger decreases in ICAM-1, MMP-3, and CRP levels were observed in ACR-Pedi-30 responders versus nonresponders.

Trial Registration
NCT00036374
Effects of betaine on lipopolysaccharide-induced memory impairment in mice and the involvement of GABA transporter 2
Authors: Miwa Masaya , Tsuboi Mizuki , Noguchi Yumiko , Enokishima Aoi , Nabeshima Toshitaka , Hiramatsu Masayuki 
Published: December 2019

Abstract

Background
Betaine (glycine betaine or trimethylglycine) plays important roles as an osmolyte and a methyl donor in animals. While betaine is reported to suppress expression of proinflammatory molecules and reduce oxidative stress in aged rat kidney, the effects of betaine on the central nervous system are not well known. In this study, we investigated the effects of betaine on lipopolysaccharide (LPS)-induced memory impairment and on mRNA expression levels of proinflammatory molecules, glial markers, and GABA transporter 2 (GAT2), a betaine/GABA transporter.

Methods
Mice were continuously treated with betaine for 13 days starting 1 day before they were injected with LPS, or received subacute or acute administration of betaine shortly before or after LPS injection. Then, their memory function was evaluated using Y-maze and novel object recognition tests 7 and 10-12 days after LPS injection (30 μg/mouse, i.c.v.), respectively. In addition, mRNA expression levels in hippocampus were measured by real-time RT-PCR at different time points.

Results
Repeated administration of betaine (0.163 mmol/kg, s.c.) prevented LPS-induced memory impairment. GAT2 mRNA levels were significantly increased in hippocampus 24 hr after LPS injection, and administration of betaine blocked this increase. However, betaine did not affect LPS-induced increases in levels of mRNA related to inflammatory responses. Both subacute administration (1 hr before, and 1 and 24 hr after LPS injection) and acute administration (1 hr after LPS injection) of betaine also prevented LPS-induced memory impairment in the Y-maze test.

Conclusions
These data suggest that betaine has protective effects against LPS-induced memory impairment and that prevention of LPS-induced changes in GAT2 mRNA expression is crucial to this ameliorating effect.
Characterization of aberrant pathways across human cancers
Authors: Ylipää Antti , Yli-Harja Olli , Zhang Wei , Nykter Matti 
Published: December 2019

Abstract

Background
Cancer is a broad group of genetic diseases which account for millions of deaths worldwide each year. Cancers are classified by various clinical, pathological and molecular methods, but even within a well-characterized disease, there is a significant inter-patient variability in survival, response to treatment, and other parameters. Especially in molecular level, tumours of the same category can appear significantly dissimilar due to complex combinations of genetic aberrations leading to a similar malignancy. We extended the current classification methods by studying tumour heterogeneity at pathway level.

Methods
We computed the rate of alterations in 1994 pathways and 2210 tumours consisting of eight different cancers. Using gene set enrichment analysis, each sample was computed a pathway aberration profile that reflected its molecular state. The profiles were analysed together to infer the characteristic aberration rates for each pathway within each cancer. Subgroups of tumours defined by similar pathway aberrations were identified using clustering analyses. The pathway aberration and gene expression profiles of the subgroups were consecutively compared across all eight cancer types to search for similar tumours crossing the standard classification.

Results
We identified pathways and processes that were common to all cancers as well as traits that are unique to a cancer type or closely related cancers. Studying the gene expression patterns within the pathway context suggested potential alteration mechanisms. Clustering analysis revealed five clinically relevant subgroups of tumours in four cancers that exhibited significant differences in survival compared to others. The cross-cancer analysis of the subgroups resulted in the identification of tumours that shared potentially significant alterations.

Conclusions
This study represents the first effort to extend the molecular characterizations towards pathway level descriptions across the family of cancers. In addition to providing a proof-of-concept for single sample pathway aberration analysis in this context, we present a comprehensive pathway aberration dataset that can be used to study pathway aberration patterns within or across cancers. Significant similarities between subgroups of different cancers on pathway and gene expression levels provide interesting hypotheses for understanding variable drug response, or transferring treatments across diseases by identifying common druggable pathways or genes, for example.
Biomarkers of disease differentiation: HCV recurrence versus acute cellular rejection
Authors: Gehrau Ricardo , Mas Valeria , Archer Kellie , Maluf Daniel 
Published: December 2019

Abstract
The wound-healing process induced by chronic hepatitis C virus (HCV) infection triggers liver damage characterized by fibrosis development and finally cirrhosis. Liver Transplantation (LT) is the optimal surgical treatment for HCV-cirrhotic patients at end-stage liver disease. However, acute cellular rejection (ACR) and HCV recurrence disease represent two devastating complications post-LT. The accurate differential diagnosis between both conditions is critical for treatment choice, and similar histological features represent a challenge for pathologists. Moreover, the HCV recurrence disease severity is highly variable post-LT. HCV recurrence disease progression is characterized by an accelerated fibrogenesis process, and almost 30% of those patients develop cirrhosis at 5-years of follow-up. Whole-genome gene expression (WGE) analyses through well-defined oligonucleotide microarray platforms represent a powerful tool for the molecular characterization of biological process. In the present manuscript, the utility of microarray technology is applied for the ACR and HCV-recurrence biological characterization in post-LT liver biopsy samples. Moreover, WGE analysis was performed to identify predictive biomarkers of HCV recurrence severity in formalin-fixed paraffin-embedded liver biopsies prospectively collected.
Development of a novel DNA sequencing method not only for hepatitis B virus genotyping but also for drug resistant mutation detection
Authors: Wang Fanjun , Lu Lili , Yu Changshun , Lv Zhanwu , Luo Xuelian , Wan Chao , Hu Zhaohui , Zhu Qinyi , Deng Youping , Zhang Chuyu 
Published: December 2019

Abstract

Background
In HBV-infected patients, different genotypes of the hepatitis B virus influence liver disease progression and response to antiviral therapy. Moreover, long-term antiviral therapy will eventually select for drug-resistant mutants. Detection of mutations associated to antiviral therapy and HBV genotyping are essential for monitoring treatment of chronic hepatitis B patients.

Results
In this study, a simple method of partial-S gene sequencing using a common PCR amplification was established for genotyping clinical HBV isolates sensitively, which could detect the drug-resistant mutations successfully at the same time.

Conclusions
The partial S gene sequencing assay developed in this study has potential for application in HBV genotyping and drug resistant mutation detection. It is simpler and more convenient than traditional S gene sequencing, but has nearly the same sensitivity and specificity when compared to S gene sequencing.
A single-tube allele specific-polymerase chain reaction to detect T315I resistant mutation in chronic myeloid leukemia patients
Authors: Wongboonma Wanwisa , Thongnoppakhun Wanna , Auewarakul Chirayu U 
Published: December 2019

Abstract

Background

BCR-ABL kinase domain (KD) mutation is the major mechanism contributing to suboptimal response to tyrosine kinase inhibitors (TKI) in BCR-ABL-positive chronic myeloid leukemia (CML) patients. T315I mutation, as one of the most frequent KD mutations, has been shown to be strongly associated with TKI resistance and subsequent therapeutic failure. A simple and sensitive method is thus required to detect T315I mutation at the earliest stage.

Methods
A single-tube allele specific-polymerase chain reaction (AS-PCR) method was developed to detect T315I mutation in a mixture of normal and mutant alleles of varying dilutions. Denaturing high performance liquid chromatography (DHPLC) and direct sequencing were performed as a comparison to AS-PCR.

Results
T315I mutant bands were observed in the mixtures containing as low as 0.5-1% of mutant alleles by AS-PCR. The detection sensitivity of DHPLC was around 1.5-3% dilution whereas sequencing analysis was unable to detect below 6.25% dilution.

Conclusion
A single-tube AS-PCR is a rapid and sensitive screening method for T315I mutation. Detection of the most resistant leukemic clone in CML patients undergoing TKI therapy should be feasible with this simple and inexpensive method.