bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness and safety of vedolizumab in biologically naïve patients: A real‐world multi‐centre study
Authors: Macaluso Fabio Salvatore , Fries Walter , Renna Sara , Viola Anna , Muscianisi Marco , Cappello Maria , Guida Laura , Siringo Sebastiano , Camilleri Salvatore , Garufi Serena , Privitera Antonino Carlo , Belluardo Nunzio , Giangreco Emiliano , Bertolami Carmelo , Vassallo Roberto , Rizzuto Giulia , Orlando Rosalba , Ventimiglia Marco , Orlando Ambrogio ,   the Sicilian Network for Inflammatory Bowel Disease (SN‐IBD)
Published: August 2020

BackgroundBiologically naïve patients with inflammatory bowel disease treated with vedolizumab (VDZ) are largely underrepresented in real‐world cohorts. A multi‐centre, observational cohort study was performed on the effectiveness and safety of VDZ in biologically naïve subjects with Crohn’s disease (CD) and ulcerative colitis (UC).MethodsData of consecutive biologically naïve patients with CD and UC treated with VDZ from July 2016 to December 2019 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease.ResultsA total of 172 consecutive patients (CD: N  = 88; UC: N  = 84; median age 66.0 years) were included, with a median follow‐up of 58.8 weeks. After 14 weeks, a clinical response was reported in 68.2% of patients with CD and 67.9% of patients with UC treated with VDZ, including 45.5% patients in the CD group and 46.4% patients in the UC group who achieved steroid‐free remission. After 52 weeks, a clinical response was reported in 77.4% of CD and in 73.8% of UC patients treated with VDZ, including 59.7% patients in the CD group and 60.7% patients in the UC group who achieved steroid‐free remission.ConclusionsThis study demonstrates the effectiveness and safety of VDZ as a first‐line biological, particularly among elderly patients.
RAS/CBL mutations predict resistance to JAK inhibitors in myelofibrosis and are associated with poor prognostic features
Authors: Coltro Giacomo , Rotunno Giada , Mannelli Lara , Mannarelli Carmela , Fiaccabrino Sara , Romagnoli Simone , Bartalucci Niccolò , Ravenda Enrica , Gelli Eleonora , Sant’Antonio Emanuela , Patnaik Mrinal M. , Tefferi Ayalew , Vannucchi Alessandro M. , Guglielmelli Paola 
Published: August 2020

Abstract
The dysregulation of the JAK/STAT pathway drives the pathogenesis of myelofibrosis (MF). Recently, several JAK inhibitors (JAKis) have been developed for treating MF. Select mutations (MTs) have been associated with impaired outcomes and are currently incorporated in molecularly annotated prognostic models. Mutations of RAS/MAPK pathway genes are frequently reported in cancer and at low frequencies in MF. In this study, we investigated the phenotypic, prognostic, and therapeutic implications of NRASMTs, KRASMTs, and CBLMTs (RAS/CBLMTs) in 464 consecutive MF patients. A total of 59 (12.7%) patients had RAS/CBLMTs: NRASMTs, n = 25 (5.4%); KRASMTs, n = 13 (2.8%); and CBLMTs, n = 26 (5.6%). Patients with RAS/CBLMTs were more likely to present with high-risk clinical and molecular features. RAS/CBLMTs were associated with inferior overall survival compared with patients without MTs and retained significance in a multivariate model, including the Mutation-Enhanced International Prognostic Score System (MIPSS70) risk factors and cytogenetics; however, inclusion of RAS/CBLMTs in molecularly annotated prognostic models did not improve the predictive power of the latter. The 5-year cumulative incidence of leukemic transformation was notably higher in the RAS/CBLMT cohort. Among 61 patients treated with JAKis and observed for a median time of 30 months, the rate of symptoms and spleen response at 6 months was significantly lower in the RAS/CBLMT cohort. Logistic regression analysis disclosed a significant inverse correlation between RAS/CBLMTs and the probability of achieving a symptom or spleen response that was retained in multivariate analysis. In summary, our study showed that RAS/CBLMTs are associated with adverse phenotypic features and survival outcomes and, more important, may predict reduced response to JAKis.
Sustained fetal hematopoiesis causes juvenile death from leukemia: evidence from a dual-age–specific mouse model
Authors: Vara Nitza , Liu Yuqing , Yan Yan , Lensing Shelly Y. , Colorado Natalia , Robinson Delli , Zhang Jingliao , Zhang Xin , Peterson Erich A. , Baltz Nicholas J. , Zhou Daohong , Bertaina Alice , Johann Donald J. , Emanuel Peter D. , Liu Y. Lucy 
Published: August 2020

Abstract
It is not clear whether disrupted age-specific hematopoiesis contributes to the complex manifestations in leukemia patients who carry identical mutations, particularly in pediatric and adult patients with similar clinical characteristics. By studying a dual-age–specific mouse model, we demonstrate that (1) loss of Pten during the fetal-to-adult hematopoiesis switch (hematopoiesis switch) causes sustained fetal hematopoiesis, resulting in death in juvenile leukemia; (2) myeloid-biased hematopoiesis in juvenile mice is associated with the sustained fetal properties of hematopoietic stem cells (HSCs); (3) the age specificity of juvenile myelomonocytic leukemia depends on the copy number of Pten and Nf1; (4) single-allelic Pten deletion during the hematopoiesis switch causes constitutive activation of MAPK in juvenile mice with Nf1 loss of heterozygosity (LOH); and (5) Nf1 LOH causes monocytosis in juvenile mice with Pten haploinsufficiency but does not cause lethality until adulthood. Our data suggest that 1 copy of Pten is sufficient to maintain an intact negative-feedback loop of the Akt pathway and HSC function in reconstitution, despite MAPK being constitutively activated in juvenile Pten+/ΔNf1LOH mice. However, 2 copies of Pten are required to maintain the integrity of the MAPK pathway in juvenile mice with Nf1 haploinsufficiency. Our data indicate that previous investigations of Pten function in wild-type mice may not reflect the impact of Pten loss in mice with Nf1 mutations or other genetic defects. We provide a proof of concept that disassociated age-specific hematopoiesis contributes to leukemogenesis and pediatric demise.
Molecular profiling and risk classification of patients with myeloproliferative neoplasms and splanchnic vein thromboses
Authors: Debureaux Pierre-Edouard , Cassinat Bruno , Soret-Dulphy Juliette , Mora Barbara , Verger Emmanuelle , Maslah Nabih , Plessier Aurelie , Rautou Pierre-Emmanuel , Ollivier-Hourman Isabelle , De Ledinghen Victor , Goria Odile , Bureau Christophe , Siracusa Claudia , Valla Dominique , Giraudier Stephane , Passamonti Francesco , Kiladjian Jean-Jacques 
Published: August 2020

Abstract
Myeloproliferative neoplasms (MPNs) are the most frequent underlying causes of splanchnic vein thromboses (SVTs). MPN patients with SVTs (MPN-SVT) often have a unique presentation including younger age, female predominance, and low Janus kinase 2 (JAK2) mutation allele burden. This study aimed at identifying risk factors for adverse hematologic outcomes in MPN-SVT patients. We performed a retrospective study of a fully characterized cohort of MPN-SVT patients. The primary outcome was the incidence of evolution to myelofibrosis, acute leukemia, or death. Eighty patients were included in the testing cohort. Median follow-up was 11 years. Most of the patients were women with a mean age of 42 years and a diagnosis of polycythemia vera. The primary outcome was met in 13% of the patients and was associated with a JAK2V617F allele burden ≥50% (odds ratio [OR], 14.7) and presence of additional mutations in genes affecting chromatin/spliceosome (OR, 9). We identified high-risk patients (29% of the cohort) as those harboring at least 1 molecular risk factor: JAK2-mutant allele burden ≥50%, presence of chromatin/spliceosome/TP53 mutation. High-risk patients had worse event-free survival (81% vs 100%; P = .001) and overall survival at 10 years (89% vs 100%; P = .01) than low-risk patients. These results were confirmed in an independent validation cohort of 30 MPN-SVT patients. In conclusion, molecular profiling identified MPN-SVT patients with dismal outcome. In this high-risk population, a disease-modifying therapy should be taken into consideration to minimize the probability of transformation.
SHAMAN: a user-friendly website for metataxonomic analysis from raw reads to statistical analysis
Authors: Volant Stevenn , Lechat Pierre , Woringer Perrine , Motreff Laurence , Campagne Pascal , Malabat Christophe , Kennedy Sean , Ghozlane Amine 
Published: August 2020

Abstract
Background
Comparing the composition of microbial communities among groups of interest (e.g., patients vs healthy individuals) is a central aspect in microbiome research. It typically involves sequencing, data processing, statistical analysis and graphical display. Such an analysis is normally obtained by using a set of different applications that require specific expertise for installation, data processing and in some cases, programming skills.

Results
Here, we present SHAMAN, an interactive web application we developed in order to facilitate the use of (i) a bioinformatic workflow for metataxonomic analysis, (ii) a reliable statistical modelling and (iii) to provide the largest panel of interactive visualizations among the applications that are currently available. SHAMAN is specifically designed for non-expert users. A strong benefit is to use an integrated version of the different analytic steps underlying a proper metagenomic analysis. The application is freely accessible at http://shaman.pasteur.fr/, and may also work as a standalone application with a Docker container (aghozlane/shaman), conda and R. The source code is written in R and is available at https://github.com/aghozlane/shaman. Using two different datasets (a mock community sequencing and a published 16S rRNA metagenomic data), we illustrate the strengths of SHAMAN in quickly performing a complete metataxonomic analysis.

Conclusions
With SHAMAN, we aim at providing the scientific community with a platform that simplifies reproducible quantitative analysis of metagenomic data.
The reduction in CD8+PD-1+ T cells in liver histological tissue is related to Pegylated IFN-α therapy outcomes in chronic hepatitis B patients
Authors: Liu Ruyu , Chen Yanhui , Guo Jiang , Li Minghui , Lu Yao , Zhang Lu , Shen Ge , Wu Shuling , Chang Min , Hu Leiping , Hao Hongxiao , Zhang Henghui , Xie Yao 
Published: August 2020

AbstractBackgroundAntiviral therapy is recommended for patients with immune-active chronic hepatitis B (CHB) to decrease the risk of liver-related complications. However, the outcomes of the pegylated IFN-α (PEG-IFN-α) therapy vary among CHB patients. We aimed to identify factors that can influence the outcomes in CHB patients who received antiviral PEG-IFN-α monotherapy.MethodsThirty-two CHB patients who received PEG-IFN-α monotherapy were enrolled in this study. All of the patients underwent two liver biopsies at baseline and 6 months after the initiation of the therapy. CD8+T cells, CD4+T cells, CD68+mononuclear cells, and PD-1 levels in the 64 liver biopsy specimens were examined via immunofluorescence.ResultsThe overall median frequency of CD8+T cells in the liver tissues of 32 CHB patients significantly decreased at 6 months after the therapy initiation (p < 0.01). In the FIER (fibrosis and inflammation response with HBeAg seroconversion) group, CD8+PD-1+T cells significantly decreased at 6 months (p < 0.05), while CD8+PD-1−T cells had no significant difference. On the contrary, in the FIENR (no fibrosis and inflammation response and HBeAg seroconversion) group, CD8+PD-1−T cells significantly decreased after 6 months of PEG-IFN-α treatment (p < 0.05), while CD8+PD-1+T cells had no significant difference. In addition, the levels of CD68+mononuclear cells in the FIER group showed an overall increasing trend after treatment (p < 0.05).ConclusionsThe changes in the levels of CD8+PD-1+T cells and CD68+mononuclear cells may be related to the response to PEG-IFN-α therapy.
Screening of BRCA1/2 genes mutations and copy number variations in patients with high risk for hereditary breast and ovarian cancer syndrome (HBOC)
Authors: El Ansari Fatima Zahra , Jouali Farah , Marchoudi Nabila , Bennani Mohcine Mechita , Ghailani Naima Nourouti , Barakat Amina , Fekkak Jamal 
Published: August 2020

Abstract
Background
Hereditary breast and ovarian cancer (HBOC) is an autosomal dominant inherited cancer susceptibility disorder. Both BRCA1 and BRCA2 genes are considered as high penetrance genes of this syndrome. The identification of BRCA1/2 genetic alterations before cancer development, grant patients the chance to benefit from various medical cancer prevention approaches. Therefore, the appearance of recent advanced technologies in molecular analysis such as next generation sequencing has simplified full BRCA1/2 analysis.
Many attempts took place in hope of understanding the molecular germline spectrum of these two genes in Moroccan HBOC patients. However, most of the past projects focused only on young breast cancer cases, lacked ovarian cancer cases in their cohort and only a limited number of these studies were able to analyze the entire exons or copy number variations for both genes.
In attempt of gaining more information regarding the molecular profile of BRCA1/2 in HBOC, we conducted a study in which we analyze their molecular profile on selected Moroccan patients suspected of having HBOC syndrome.

Methods
In this study we obtained blood samples from 64 selected Moroccan patients, who suffered from Breast and/or ovarian cancer and had a strong family history for cancer. To analyze BRCA1/2 punctual variants and copy number variations, we used the Ion Personal Genome Machine (PGM) and Oncomine BRCA1/2 research assay panel. Afterward, we correlated the molecular results with the clinic-pathologic data using IBM SPSS Statistics ver 2.

Results
From the 64 selected cases, Forty-six had breast cancer, fifteen had ovarian cancer and three had both breast and ovarian cancer. The molecular analysis revealed that 18 patients from the 64 harbored a pathogenic variant (28%). Twelve had six different BRCA1 pathogenic variants and six had six different BRCA2 pathogenic variants. In this study, we report four pathogenic variants that to the best of our knowledge has never been reported in the Moroccan population before. Regarding copy number variation analysis, No CNV was detected in both genes for all the 64 successfully sequenced and analyzed patients in our cohort.

Conclusion
Work like the present has an important implication on public health and science. It is critical that molecular profiling studies are performed on underserved and understudied population like Morocco.
The association between protection motivation and hepatitis b vaccination intention among migrant workers in Tianjin, China: a cross-sectional study
Authors: Liu Cai , Nicholas Stephen , Wang Jian 
Published: August 2020

Abstract
Background
Migrant workers are a susceptible population to the hepatitis b virus (HBV) and a vulnerable spot in China’s immunization procedures. There is no free HBV immunization program for migrant workers in China, so understanding migrant workers’ motivation to receive the HBV vaccine is the first step in designing effective immunization policies.

Methods
A fully specified protection motivation theory (PMT) model of HBV vaccination intention among migrant workers was specified. Data were collected through a cross-sectional survey of 406 migrant workers in three migrant-dense industries in Tianjin, China. Principal component factor analysis was used to produce PMT factors and nested binary logistic regression modeling was applied to assess the associations between protection motivation and HBV vaccination intention of migrant workers.

Results
The nested binary logistic regression model suggested that the severity factor and self-efficacy factor were positively related to HBV vaccination intention (OR = 2.15, 95% CI: 1.25–3.71; OR = 2.75, 95% CI: 1.62–4.66) while the response costs was negatively related to the HBV vaccination motivation (OR = 0.50, 95% CI: 0.29–0.83). The socio-demographic variables showed that younger, married and good self-rated health status participants were statistically associated with the intention of taking the HBV vaccine. Sex, education level and income group were not significantly associated with vaccination intention. The migrant-industry variables showed that migrant location had a strong effect on migrant workers’ vaccination intention.

Conclusion
Socio-demographic, migrant-industry variables and PMT factors (severity, self-efficacy and response costs) were statistically associated with migrant workers’ intention to vaccinate. Our results suggest that health policy makers should provide more information to migrants on HBV severity; inform migrant workers on where, when and how to get the HBV vaccine; tap into work organizations as a location for vaccinations; and identify migrant worker subgroups for targeted interventions.
Socio-demographic correlates of first dose of measles (MCV1) vaccination coverage in India
Authors: Panda Basant Kumar , Mishra Suyash , Awofeso Niyi 
Published: August 2020

Abstract
Background
Between 2010 and 2018, measles-related mortality had halved in India mainly with effective measles vaccination campaigns and widespread coverage across the states and population subgroups. Despite the commendable vaccination coverage, 2.9 million children in India missed the first dose of measles vaccine (MCV1) in 2017, and many of those vaccinated were not vaccinated at the recommended age (i.e. between 9 and 12 months). This study analyzed pattern and correlates of MCV1 coverage and MCV1 administration at recommended age among children aged 12–23 months in India.

Methods
We used the official data from the recent round of National Family Health Survey (NFHS-4), a nationally representative cross-sectional household survey in India conducted in 2015–16. Descriptive statistics and logistic regression analysis were applied to ascertain the influence of specified socio-demographic variables affecting measles vaccination coverage in India.

Results
The study revealed the distinct variations in coverage of MCV1 between the districts of India. There were also major challenges with age recommended vaccination, with about 15% of eligible children not vaccinated within the recommended age range, attributable to several socio-demographic factors. Significantly, antenatal care utilization of mothers strongly influenced MCV1 coverage and age recommended MCV1 coverage in India. The study also identified that children who missed MCV1 had one or more adverse health risks such as malnutrition, anemia and diarrhea disease.

Conclusions
A socio-economic gradient exists in India’s MCV1 coverage, mediated by antenatal visits, education of mothers, and highlighted socio-demographic factors. Infection with measles was significantly correlated with greater anthropometric deficits among the study cohort, indicating a wider range of benefits from preventing measles infection. Eliminating morbidity and mortality from measles in India is feasible, although it will require efficient expanded program on immunization management, enhanced health literacy among mothers, continuing commitment from central state and district political authorities.
Factors affecting postoperative mortality of patients with insufficient union following osteoporotic vertebral fractures and impact of preoperative serum albumin on mortality
Authors: Ohba Tetsuro , Yokomichi Hiroshi , Koyama Kensuke , Tanaka Nobuki , Oda Kotaro , Haro Hirotaka 
Published: August 2020

Abtsract
Background
Numerous comparative studies of surgical procedures have focused on clinical and radiographical outcomes, as well as the effect of bone fragility on the outcome of spinal surgery; however, insights concerning a risk of mortality or morbidity have been limited. Additionally, the effect of surgical therapy on survival after vertebral compression fractures remains controversial. Our aim was to evaluate the preoperative factors that affected the long-term survival of patients who underwent spinal surgery for an insufficient union following osteoporotic vertebral fractures (OVF) and to determine postoperative mortality.

Methods
We retrospectively reviewed the cases of 105 consecutive patients who underwent spinal surgery for OVF. Mortality was estimated using the Kaplan-Meier method and a log-rank test. The preoperative backgrounds of patients were analyzed to determine which risk factors led to death among the OVF cases. Kaplan-Meier curves were used to estimate survival based on preoperative albumin levels of ≤3.5 g/dL (hypoalbuminemia) versus > 3.5 mg/dL.

Results
The mean follow-up time was 4.1 ± 0.8 years. Two years after surgery, percentage of patients who had died was 15%. The VAS scores and modified Frankel classification were significantly improved one year after surgery. The ratio of male-to-female was significantly higher for patients with OVF who died than for those who were still alive. No significant difference in mortality was observed among surgical procedures for OVF. The univariate analysis showed that male gender, serum albumin < 3.5 g/dl, creatinine clearance< 60 mg/dl, and the American Society of Anesthesiologists classificat0ion ≥3 were significant risk factors for postoperative mortality. Multivariate analysis revealed that only serum albumin ≤3.5 g/dL was a significant risk factor for long-term postoperative mortality of patients with OVF.

Conclusions
Preoperative hypoalbuminemia was associated with postoperative mortality following surgery for OVF.

Level of evidence
Level 3.
Effectiveness of blending E-learning with field trip on Chinese herbal medicine education: quasi-experimental study
Authors: Li Lei , Tam Chi Wing , Wang Ning , Cheung Fan , Zhou Qing , Zhang Cheng , Cheng Chien-shan , Xiong Lei , Feng Yibin 
Published: August 2020

Abstract
Background
Chinese Medicine education is part of professional medical training in Hong Kong. An important element of this is herbal medicine, which requires both theoretical and practical knowledge. A field trip programme was adopted to provide students with direct experience of medicinal plants studied in lectures. However, problems with the current programme were identified in learning outcome assessment and long-term knowledge management. To improve the teaching quality, a Moodle e-learning module was designed for augmentation. This study aimed to quantitatively evaluate the effectiveness of the Moodle module in supplementing the current field trip programme.

Methods
Prospective quasi-experiment. Participants were 49 year-2 students in the Bachelor of Chinese Medicine programme. A Moodle module including five online activities regarding two groups of herbal plants was integrated before and after the field trip. Fill-in-the-blank questions were used to assess the learning outcome. Also, a questionnaire was developed to collect student feedback as the secondary outcome.

Results
For herbal plants in Group A, the assessment score was higher in Moodle group (29.65 ± 5.0) than for the control group (21.65 ± 6.5) (P <  0.01). For herbal plants in Group B, the assessment score was higher for the Moodle group (28.68 ± 4.7) than for the control group (24.26 ± 7.7) (P <  0.01). The questionnaire results showed that students were satisfied with the Moodle platform.

Conclusions
A specially designed Moodle module may be effective in augmenting the field trip for Chinese herbal medicine education.