bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of a novel method to detect clarithromycin-resistant Helicobacter pylori using a stool antigen test reagent
Authors: Kakiuchi Toshihiko , Hashiguchi Kazutoshi , Imamura Ichiro , Nakayama Aiko , Takamori Ayako , Okuda Masumi , Matsuo Muneaki 
Published: February 2020

Abstract
Background The resistance rate of Helicobacter pylori to clarithromycin (CAM) is high among the infected children in Japan; therefore, a new method for detecting CAM-resistant H. pylori using a less invasive technique is strongly desired. We aimed to confirm the clinical usefulness of our newly developed Nested polymerase chain reaction-QProbe (quenching probe) (Nested PCR-QP) method using stool specimens. Methods The first was an evaluation of our method using the residual solution of the H. pylori stool antigen test for adolescents, and the second was an evaluation of our method using culture testing for adults. Results Of the 57 middle school students with H. pylori , the Nested PCR-QP test results of 53 (90.3%) could be analyzed; 28 students were found to have CAM resistance mutations. The results indicating genetic mutation in 28 and no mutation in 23 students were consistent with those of PCR-direct sequencing. In the 23 adults who were diagnosed with H. pylori infection using the rapid urease test and culture testing, it was possible to use Nested PCR-QP for analyzing all 21 adults who tested positive in the stool H. pylori antigen test. The results obtained for all the 21 adults were consistent with those obtained via the drug susceptibility test. Conclusions Our novel method could be useful for non-invasively detecting CAM resistance mutations in H. pylori. This may help select an eradication drug to reduce eradication failure rates against H. pylori.
A Chinese Case Series of Schnitzler Syndrome and Complete Remission in One Tocilizumab-treated Patient
Authors: Yan Ruyu , Shen Min , Cao Wei , Liu Xinchao , Li Feng 
Published: February 2020

Abstract
Backgroud: Schnitzler syndrome (SchS) is a rare acquired systemic autoinflammatory disease. The major clinical features of SchS are urticarial rash and monoclonal gammopathy, accompanied by fever, joint pain and lymphadenopathy. There were few reports about SchS in Chinese population. Herein, we describe two patients with SchS in China. Methods: Two Chinese Han patients were diagnosed as SchS in our department from 2017 to 2019. Their phenotype and genotype were carefully documented and studied. We also conducted a systematic literature review about SchS. Results: There were one man and one woman with an average disease-onset age of 52. Recurrent fever and urticarial rash occurred in both of them during the febrile attacks and normalized in asymptomatic intervals. Other manifestations included arthritis/arthralgia, lymphadenopathy and hearing loss. Hepatic cirrhosis and epilepsy were seen in one patient. None of them had bone pain or family histories. Serum monoclonal IgM gammopathy was found in both patients. MyD88 gene mutation L258P was identified in one patient. They were treated with tocilizumab and tripterygium wilfordii Hook F (TwHF) respectively and both showed good response. Conclusions: The rarity and diversity of SchS makes it difficult to be recognized. The patient in our study was the first SchS with concomitant liver and neural damage. Anti-IL-6 agents and TwHF may be alternative therapies when anti-IL-1 therapy is unresponsive or unavailable.
Comparison of Personal and Shared Frameshift Neoantigen Vaccines in a Mouse Mammary Cancer Model.
Authors: Peterson Milene , Murphy Sierra Nicole , Lainson John , Zhang Jian , Shen Luhui , Diehnelt Chris W , Johnston Stephen Albert 
Published: February 2020

Abstract
Background: It is widely hoped that personal cancer vaccines will extend the number of patients benefiting from checkpoint and other immunotherapies. However, it is clear creating such vaccines will be challenging. It requires obtaining and sequencing tumor DNA/RNA, predicting potentially immunogenic neoepitopes and manufacturing one-use vaccine. This process takes time and considerable cost. Importantly, most mutations will not produce an immunogenic peptide and many patient’s tumors do not contain enough DNA mutations to make a vaccine. We have discovered that Frameshift peptides (FSP) created from errors in the production of RNA rather than from DNA mutation are potentially a rich source of neoantigens for cancer vaccines. These errors are predictable, enabling the production of a FSP microarray. Previously we found that these microarrays can identify both personal and shared neoantigens.Methods: Here, we compared the performance of personal cancer vaccines (PCVs) with that of a shared antigen vaccine, termed Frameshift Antigen Shared Therapeutic (FAST) vaccine , using the 4T1 breast cancer model. Sera from 4T1-tumor bearing mice were assayed on the peptide microarray containing 200 FS neoantigens and for the PCV, the top 10 candidates were select and personal vaccines constructed and administrated to the respective mice. For the FAST, we selected the top 10 candidates with higher prevalence among all the mice challenged. Seven to 12-days challenged mice were immunized, combined or not with checkpoint inhibitor (CPI) (αPD-L1 and αCTLA-4). Primary and secondary tumor clearance and growth were evaluated as well as both cellular and humoral immune response against the vaccines targets by IFN-γ ELISPOT and ELISA. Lastly, we analyzed the immune response of the FAST-vaccinated mice by flow cytometry in comparison to control group.Results: We found that PCVs and FAST vaccines both reduced primary tumor incidence and growth as well as lung metastases when delivered as monotherapies or in combination with checkpoint inhibitor antibodies. Additionally, the FAST vaccine induces a robust and effective T-cell response.Conclusions: These results suggest that FSPs produced from RNA-based errors are potent neoantigens that could enable production of off-the-shelf shared antigen vaccines for solid tumors with efficacy comparable to that of PCVs.
The Genotoxin Colibactin Shapes Gut Microbiota in Mice
Authors: Tronnet Sophie , Floch Pauline , Lucarelli Laetitia , Gaillard Deborah , Martin Patricia , Serino Matteo , Oswald Eric 
Published: February 2020

Abstract
Background : The genotoxin colibactin produced by resident bacteria of the gut microbiota may have tumorigenic effect by inducing DNA double strand breaks in host cells. Yet, the effect of colibactin on gut microbiota composition and functions remains unknown.Results: To address this point, we designed an experiment in which pregnant mice were colonized with: i) a commensal E. coli strain, ii) a commensal E. coli strain plus a genotoxic E. coli strain, iii) a commensal E. coli strain plus a non-genotoxic E. coli mutant strain unable to produce mature colibactin. Then, we analysed the gut microbiota in pups at day 15 and day 35 after birth. At day 15, mice that were colonized at birth with the genotoxic strain showed lower levels of Proteobacteria and belonging taxa, a modest effect on overall microbial diversity and no effect on gut microbiome. At day 35, mice that received the genotoxic strain showed lower Firmicutes and belonging taxa, together with a strong effect on overall microbial diversity and higher microbial functions related to DNA repair. Moreover, the genotoxic strain strongly affected gut microbial diversity evolution of receiving pups between day 15 and day 35.Conclusions: our data show that colibactin, beyond targeting the host, may also exerce its genotoxic effect on the gut microbiota.
The care-givers of patients with persistent vegetative state have a terrible life: the result of a qualitative study
Authors: Alimohammadi Ehsan , Arast Atefeh , Abdi Alireza 
Published: February 2020

Abstract
Background persistent vegetative state (PVS) is one of the results of traumatic brain injury. These patients are hospitalized for a long time, and need more cares. The caregivers are first members who provide care and have some challenges accordingly. With regards to a lack of information in this issue, the current study was conducted to explore Iranian care-givers experiences of caring for PVS patients following traumatic brain injury. Methods this study was conducted as a descriptive phenomenological study in 2019. Semi- structured interviews were done on caregivers of PVS in a center of trauma in Iran. The interviews were recorded and wrote verbatim, then analyzed using seven steps of Collazi with management of MAXQUDA software. Guba and Lincoln`s criteria were used in favor of rigor, including credibility, dependability, transferability, and confirmability.Results twelve people participated in the study and five themes, and ten subthemes extracted from 428 codes. The themes were “falling into tensions”, “seeking peace”, “imposed therapeutic duties”, “preserve connection” and ‘unheard sounds ”. Conclusion In this study, the caregivers of PVS experienced some injuries and familial crises. They wished peace by praying and drain their feelings, also did some imposed duties, and tried to address all the needs of patient. They assessed patients’ signs daily and some information gap, therefore, wanted to obtain them by relationship with staff. The caregivers communicated with patients and hoped to recovery of patients. They were complained of accommodations and lack of staff visits.
Late-Onset Famılıal Medıterranean Fever: Sıngle-Center Experıence And Lıterature Revıew
Authors: Aydin Okan , Egeli Bugra Han , Ozdogan Huri , Ugurlu Serdal 
Published: February 2020

Abstract
Introduction: Familial Mediterranean Fever (FMF) is an autoinflammatory disease characterized by recurrent fever and serositis attacks. The disease onset occurs before 20 years of age in 90% of patients. Rarely, the disease onset occurs after 40 years of age. Aim: We aimed to compare the patients with early and late-onset of disease. Methods: We did a retrospective analysis of 2020 patients registered in our FMF center in the years 2008-2017. Patients with disease onset after the age of 40 (Group 1) were collected. The control group (Group 2), disease onset before the age of 20, was randomly selected with twice amount of the study group. Demographic, clinical and genetic data were recorded. Results: Out of 2020 patients, 41 were in group 1 (2.02%). The male to female ratio was 1:1.7 in both groups. The delay of diagnosis was 5.6±5.75 years in group 1, 10.7±12.3 years in group 2. In terms of clinical features, the only significant difference between two groups belonged to fever seen in 26 (63.4%) patients in group 1 and 67 (81.7%) patients in group 2 (p=0,026). M694V mutation frequency was higher in group 2 whereas exon 2 mutation frequency was higher in group 1. The mean colchicine dose in the 6 months was 1.38±0.64 mg in group 1, 1.61±0.47 mg in group 2. Discussion: In patients with late disease onset, the results of decreased mean colchicine dose during the last 6 months, decreased fever ratio, and increased exon 2 mutation frequency might point out to mild disease severity. Keywords: Familial Mediterranean Fever, late-onset, early-onset, MEFV mutation, colchicine
Evaluation of WGS-subtyping methods for epidemiological surveillance of foodborne salmonellosis.
Authors: Mohammed Manal , Thapa Salina 
Published: February 2020

Abstract
Background: Salmonellosis is one of the most common foodborne diseases worldwide. Although human infection by non-typhoidal Salmonella (NTS) enterica subspecies enterica is associated primarily with a self-limiting diarrhoeal illness, invasive bacterial infections (such as septicaemia, bacteraemia and meningitis) were also reported. Human outbreaks of NTS were reported in several countries all over the world including developing as well as high-income countries. Conventional laboratory methods such as pulsed field gel electrophoresis (PFGE) do not display adequate discrimination and have their limitations in epidemiological surveillance. It is therefore very crucial to use accurate, reliable and highly discriminative subtyping methods for epidemiological characterisation and outbreak investigation. Methods: Here, we used different whole genome sequence (WGS)-based subtyping methods for retrospective investigation of two different outbreaks of Salmonella Typhimurium and Salmonella Dublin that occurred in 2013 in UK and Ireland respectively. Results: The core genome multilocus sequence typing (cgMLST) was discriminatory and separated the outbreak strains of Salmonella Dublin from the non-outbreak strains that were concordant with the epidemiological data however cgMLST could not discriminate between outbreak and non-outbreak strains of Salmonella Typhimurium, On the other hand, other WGS-based subtyping methods including multilocus sequence typing (MLST), ribosomal MLST (rMLST), whole genome MLST (wgMLST), clustered regularly interspaced short palindromic repeats (CRISPRs), prophage sequence profiling, antibiotic resistance profile and plasmid typing methods were less discriminatory. Conclusions: Foodborne salmonellosis is an important concern for public health therefore, it is crucial to use accurate, reliable and highly discriminative subtyping methods for epidemiological surveillance and outbreak investigation. The rapid development of next-generation sequencing (NGS) technology and bioinformatics tools have enabled WGS of any bacterial strain feasible. Various typing tools have been proposed by using WGS data but currently, the adoption of WGS-based methods have proved to be difficult due to lack of standardization. There are many layers on obtaining WGS data and there is need of standardization from the type of sequencers used to the bioinformatics analysis. Therefore, the emerging genetic analysis techniques should be combined with conventional phenotypic and molecular methods for routine surveillance and outbreak investigation until the WGS-based methods can be fully exploited, improved and standardized.
Recombinant PAL/PilE/FlaA DNA vaccine provides protective immunity against Legionella pneumophila in BALB/c mice
Authors: Chen Yingying , Yang Zehui , Dong Ying , Chen Yu 
Published: February 2020

Abstract
Background: Legionella pneumophila (L.pneumophila), a Gram-negative small microorganism, causes hospital-acquired pneumonia especially in immunocompromised patients. Vaccination may be an effective method for preventing L.pneumophila infection. Therefore, it is necessary to develop a better vaccine against this disease. In this study, we developed a recombinant peptidoglycan-associated lipoprotein (PAL)/type IV pilin (PilE)/lagellin (FlaA) DNA vaccine and evaluated its immunogenicity and efficacy to protect against L.pneumophila infection.Results: According to the results, the expression of PAL, PilE, FlaA proteins and PAL/PilE/FlaA fusion protein in 293 cells was confirmed. Immunization with PAL/PilE/FlaA DNA vaccine resulted in highest IgG titer and strongest cytotoxic T-lymphocyte (CTL) response. Furthermore, the histopathological changes in lung tissues of mice challenged with a lethal dose of L.pneumophila were alleviated by PAL/PilE/FlaA DNA vaccine immunization. The production of T-helper-1 (Th1) cytokines (IFNγ, TGF-α, and IL-12), and Th2 cytokines (IL-4 and IL-10) were promoted in PAL/PilE/FlaA DNA vaccine group. Finally, immunized with PAL/PilE/FlaA vaccine raised the survival rate of mice to 100% after challenged with a lethal dose of L.pneumophila for 10 consecutive days.Conclusions: Our study suggests that the newly developed PAL/PilE/FlaA DNA vaccine stimulates strong humoral and cellular immune responses and may be a potential intervention of L.pneumophila infection.
Caloric restriction attenuates C57BL/6J mouse lung injury and systemic toxicity induced by real ambient particulate matter exposure
Authors: Li Daochuan , Chen Shen , Li Qiong , Chen Liping , Zhang Haiyan , Li Huiyao , Yu Dianke , Zhang Rong , Niu Yujie , Lu Shaoyou , Ye Lizhu , Zeng Xiaowen , Dong Guanghui , Chen Rui , Aschner Michael , Zheng Yuxin , Chen Wen 
Published: February 2020

Abstract
Background: Caloric restriction (CR) is known to improve health and extend life span in human beings. The effects of CR on adverse health outcomes in response to particulate matter (PM) exposure and the underlying mechanisms have yet to be defined. Results: Male C57BL/6J mice were fed with CR diet or ad libitum (AL) and exposed to PM for 4 weeks in a real-ambient PM exposure system located at Shijiazhuang, China, with a daily mean concentration (95.77 μg/m³) of PM 2.5. Compared to AL-fed mice, CR-fed mice attenuated PM-induced pulmonary injury and systemic toxicity characterized by reduction in oxidative stress, DNA damage and inflammation. Analysis of RNA sequencing revealed that several pulmonary pathways involved in production of ROS, cytokine production, and inflammatory cell activation were inactivated, while those mediating antioxidant generation and DNA repair were activated in CR-fed mice upon PM exposure. In addition, transcriptome analysis of murine livers revealed that CR led to induction of xenobiotic metabolism and detoxification pathways, corroborated by increased levels of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) and decreased cytotoxicity measured in an ex vivo assay. Conclusion: These novel results demonstrate, for the first time, that CR in mice confers resistance against pulmonary injuries and systemic toxicity induced by PM exposure. CR led to activation of xenobiotic metabolism and enhanced detoxification of PM-bound chemicals. These findings provide evidence that dietary intervention may afford therapeutic means to reduce the health risk associated with PM exposure. Keywords: Caloric restriction, particulate matter, pulmonary injury, systemic effects, RNA sequencing, xenobiotic metabolism.
Infection of highly insecticide-resistant malaria vector Anopheles coluzzii with an environment friendly entomopathogenic bacteria Chromobacterium violaceum reduces its survival, blood feeding propensity and fecundity
Authors: Gnambani Edounou Jacques , Bilgo Etienne , Sanou Adama , Dabire Roch K. , Diabate Abdoulaye 
Published: February 2020

Abstract
Background This is now a concern that malaria eradication will not be achieved without the introduction of novel control tools. Microbiological control might be able to make a greater contribution to vector control in the future. The interactions between bacteria and mosquito make mosquito microbiota really promising from a disease control perspective. Here, we studied the impact of Chromobacterium violaceum infections isolated from both larvae and adult of wild caught Anopheles gambiae s.l. mosquitoes in Burkina Faso on mosquito survival, blood feeding and fecundity propensy.Methods To assess entomopathogenic effects of C. violaceum infection on mosquitoes, three different types of bioassays were performed in laboratory. These bioassays were the impact of C.violaceum infection on mosquito survival, blood feeding and fecundity, respectively. During bioassays mosquitoes were infected through the well-established system of cotton ball soaked with 6% glucose containing C.violaceum.Results C. violaceum kills pyrethroid resistant mosquitoes An. coluzzii (LT80 of 8.78 ± 0.18 at 10 8 bacteria cell/ml of sugar meal). Interestingly, this bacterium had other negative effects on mosquito lifespan by significantly reducing (~59%, P<0.001) the mosquito feeding willingness from day 4-post infection (~81% would seek a host to blood feed) to 9- day post infection (22 ± 4.62% would seek a host to blood feed). Moreover, C. violaceum considerably jeopardized the egg laying (~16 eggs laid /mosquitoes with C. violaceum infected mosquitoes vs ~129 eggs laid / mosquitoes with control mosquitoes) and hatching of mosquitoes (A reduction of ~22 % of hatching rate with C. violaceum infected mosquitoes). Compared to the bacterial uninfected mosquitoes, mosquitoes infected with C. violaceum showed indeed significantly higher retention rates of immature eggs and follicles.Conclusion These data showed important properties of Burkina Faso C. violaceum strains , which are highly virulent against insecticide resistant Anopheles coluzzii , and reduce both mosquito blood feeding and fecundity propensities. However, additional studies as the sequencing of C. violaceum genome and the potential toxins secreted will certainly provide useful information render it a potential candidate for the biological control strategies of malaria and other disease vectors.
Oxytocin Use in Trial of Labor after Cesarean and Its Relationship with Risk of Uterine Rupture in Women with One Previous Cesarean Section: A Meta-analysis of Observational Studies.
Authors: ZHANG Huan , LIU Haiyan , LUO Shouling , Gu Weirong 
Published: February 2020

Abstract
Background Trial of labor after a previous cesarean delivery (TOLAC) has helped to reduce the rate of cesarean section (CS). But the increased rate of adverse outcomes limites the spread of TOLAC. The most serious one is the risk of symptomatic uterine rupture, which is possibly associated with oxytocin. This meta-analysis was to evaluate the risk association between oxytocin use and uterine rupture in TOLAC. Methods Multiple electronic databases (PubMed, Embase, Web of Science, and Google Scholar) were searched for case-control or cross-sectional studies about TOLAC, oxytocin and uterine rupture, which were published between January 1986 and October 2019. The bias-corrected Hedge's g was calculated as the effect size using the random-effects model. The risk of bias was evaluated by the Newcastle-Ottawa Scale (NOS). Quality of the evidence was assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) certainty ratings system. Results There were 14 studies meeting inclusion criteria including 48457 women undergoing TOLAC. The pooled rate of VBAC and rate of uterine rupture in spontaneous labor were 74.3% and 0.7%. And the pooled rate of VBAC and rate of uterine rupture in induction labor were 60.7% and 2.2%. The women with spontaneous labor had significantly higher rate of VBAC (p=0.0032) and lower rate of uterine rupture (p=0.0003) than that with induction labor. The pooled rates of uterine rupture in women using oxytocin and women not using oxytocin in TOLAC were 1.4% and 0.5%. There was significant difference between these two groups (p=0.0002). Conclusions In TOLAC, women with induction labor had higher risk of uterine rupture than that with spontaneous labor. Oxytocin use may increase the risk. So simplified and standardized intrapartum management, precise procotol and cautiously monitoring of oxytocin in TOLAC are necessary.