bluuebunny/crossref_metadata_2025_split huggingface dataset:
Weight gain in patients with severe atopic dermatitis treated with dupilumab: a cohort study
Authors: Johansson Emma Kristin , Ivert Lina Ulrika , Bradley Baltzar , Lundqvist Maria , Bradley Maria 
Published: September 2020

Abstract
Background Dupilumab, targeting the interleukin-4α receptor and inhibiting the action of interleukin-4 and interleukin-13, was recently approved for treatment of moderate to severe atopic dermatitis. There is limited data on long-term effects and safety among patients with severe atopic dermatitis treated with dupilumab. Weight gain was observed among patients treated with dupilumab in our clinic. The aim was to describe weight change in a cohort study of patients with severe atopic dermatitis treated with dupilumab from baseline to follow-up after 12 months, and to analyze if weight change was associated with effect of treatment, reported appetite, and/or disturbed night sleep due to itching.Methods All patients with atopic dermatitis receiving systemic treatment at the Unit of Dermatology, Karolinska University Hospital, have been registered and monitored consecutively since January 2017. This cohort constituted all patients who started treatment on dupilumab or methotrexate between 10 January 2017 and 30 June 2019 with at least 6 months of follow-up within the study period. The following variables were monitored at start of and during treatment: Eczema Severity Score Index, Patient-Oriented Eczema Measure, visual analogue scale for pruritus 10cm, Montgomery-Åsberg Depression Rating Scale, Dermatology Life Quality Index, and weight. Data analyses were performed using two-sample Wilcoxon-Mann-Whitney rank-sum test, or the Wilcoxon matched-pairs sign-rank test with a p-value <0.05 considered as statistically significant.Results Patients treated with dupilumab (n=12) gained weight (mean 6.1 kg, range [0.1–18.0], p=0.002) after one year on treatment. The majority of patients showed a good response to treatment with dupilumab (n=11); at follow-up at 6, 9, or 12 months, they reached EASI-90 (n=6), EASI-75 (n=4), or EASI-50 (n=1). There was no significant association between weight gain and treatment response, reported appetite, or disturbed night-sleep due to itch. Patients treated with methotrexate showed no significant weight change (n=8). Conclusions To our knowledge, this is the first report on a possible association between weight gain and dupilumab treatment; the extent of the association is yet to be seen, as is the mechanism behind this finding.
Nosocomial Tuberculosis Transmission from 2006 to 2018 in Beijing Chest Hospital, China
Authors: Xie Zhongyao , Zhou Ning , Chi Yuqing , Huang Guofang , Wang Jingping , Gao Hui , Xie Na , Ma Qianhui , Yang Nan , Nie Wenjuan , Sun Zhaogang , Chu Naihui 
Published: September 2020

Abstract
Introduction: Strong evidence is lacking to support effectiveness of currently implemented tuberculosis infection prevention control (TB-IPC) measures for preventing nosocomial tuberculosis (TB) transmission. This 13-year analysis is the longest follow-up investigation to date to identify risk factors underlying nosocomial TB transmission. Methods: We monitored all staff of Beijing Chest Hospital each year from 2006 to 2018. Age, gender, duration, department, education, income, respirator, ultraviolet, and ventilation were chosen as variables. Univariate cox regression, correlation analysis, and multivariate cox regression were analyzed sequentially.Results: Using multivariable cox regression analysis, variables of income, ultraviolet germicidal irradiation (UVGI), natural ventilation and mechanical ventilation conferred significant protective effects, with odds ratios (ORs) of 0.499, 0.058, 0.003, and 0.015, respectively (P<0.05). Medical N95 respirator conferred an excellent protective effect, with an associated TB infection rate of 0%. Notably, inadequately maintained mechanical ventilation systems were less protective than natural ventilation systems.Conclusions: UVGI, adequate ventilation, and use of medical N95 respirator may be risk factors of nosocomial TB transmission.
Schistosoma mansoni-related periportal fibrosis; can we use APRI and PSDR levels in the real-time selection of patients for targeted endoscopy in a resource-limited setting? A case-control study
Authors: Gunda Daniel W. , Mtui Elizabeth F. , Manyiri Paulina M. , Majinge David C. , Kilonzo Semvua B. , Mazigo Humphrey D. , Kidenya Benson R. 
Published: September 2020

Abstract
Background Schistosoma mansoni related hepatic fibrosis is usually associated with hemodynamic alteration with increased mortality due to bleeding varices. The diagnosis of varices before bleeding imposes a big challenge in resource-limited countries using endoscopy. Published evidence on the utility of non-invasive clinical tools in predicting the presence of varices among patients with S. mansoni related periportal fibrosis is still inadequate including Aspartate to platelet ratio index (APRI) and Platelet to splenic diameter ratio (PSDR) levels. This study describes the determinants of portal varices and assesses the potential utility of the APRI and PSDR level in the discrimination of portal varices among patients with S. mansoni related periportal fibrosis (PPF). Methods A case-control study using cross-sectional data was done among patients with Schistosoma mansoni related periportal fibrosis at Bugando Medical Centre, in Mwanza Tanzania. Socio-demographic, laboratory, ultrasound, and upper digestive endoscopic information were collected for analysis using STATA 13. The prevalence of varices was calculated and its associated factors were determined by logistic regression. The sensitivity and specificity of independent factors were determined to assess their potential utility in discriminating the presence of portal varices in patients with PPF.Results In total, 250 patients were included in this study, 109 (43.6%; 95%CI: 37.3-.49.9) of them had varices. On multivariate analysis the odds of having varices were independently increased among patients with higher APRI levels than 1.51, (AOR: 5.8; 95%CI: 3.1-11.1; p<0.001) and PSDR levels that were lower than 5700 (AOR: 5.9; 95%CI: 3.2-11.2; p<0.001). Both APRI and PSDR levels had significantly high sensitivity and specificity in predicting the presence of esophageal varices. However, the combined values of APRI and PSDR had higher specificity than any of the two markersConclusions This study indicates that varices are a common encounter among patients with S. mansoni related periportal fibrosis and it is independently associated with higher APRI and lower PSDR levels suggesting that these tools are potential discriminators of varices in this subgroup of patients. The reproducibility of these results should further be assessed longitudinally as potential non-invasive tools in selecting patients at high risk of having esophageal varices who could benefit from the targeted endoscopic intervention in a resource-limited setting like ours.
The efficacy of pancreatic juice cytology with liquid-based cytology for evaluating malignancy in patients with intraductal papillary mucinous neoplasm
Authors: Miyamoto Kazuya , Matsumoto Kazuyuki , Kato Hironari , Yoshida Ryuichi , Umeda Yuzo , Inoue Hirohumi , Tanaka Takehiro , Matsumi Akihiro , Saragai Yosuke , Fujii Yuki , Yamazaki Tatsuhiro , Uchida Daisuke , Tomoda Takeshi , Horiguchi Shigeru , Yagi Takahito , Okada Hiroyuki 
Published: September 2020

Abstract
Background: Pancreatic juice cytology (PJC) is a tool for diagnosing malignant intraductal papillary mucinous neoplasm (IPMN); however, the accuracy is insufficient using the conventional method. Liquid-based cytology (LBC) improves the cell recovery rate, and almost all cells can be evaluated. We evaluated the efficacy of PJC with LBC for malignant IPMN. Methods: We retrospectively analyzed 90 patients with suspected malignant IPMN who underwent PJC before pancreatectomy. PJC with smear and LBC methods was conducted in 52 patients (between June 2003 to December 2011) and 38 patients (between January 2012 to December 2018). Based on the imaging studies, all of the patients were classified according to the international consensus guidelines for IPMN revised in 2017.Results: Of the 90 patients, 43 (48%) had malignant IPMN (high-grade dysplasia or invasive carcinoma), and the remaining patients had non-malignant IPMN (intermediate- or low-grade dysplasia). LBC increased the accuracy of PJC for the diagnosis of malignant IPMN (smear method: 56% [29/52] vs. LBC method: 76% [29/38]; P = 0.044). In a multivariate analysis, LBC was a significant factor influencing the accurate diagnosis of PJC (odds ratio: 3.52; P = 0.021). Furthermore, LBC increased the accuracy of PJC for malignant IPMN in patients with worrisome features (smear method: 66% [19/29] vs. LBC method: 93% [14/15]; P = 0.043). Conclusions: LBC increases the accuracy of PJC for diagnosing malignant IPMN compared with the conventional smear method.
Functional biomarker signatures of circulating T-cells and its association with distinct clinical status of leprosy patients and their respective household contacts
Authors: Marçal Pedro Henrique Ferreira , Gama Rafael Silva , Pereira Lorena Bruna de Oliveira , Filho Olindo Assis Martins , Pinheiro Roberta Olmo , Sarno Euzenir Nunes , Moraes Milton Ozório , Fraga Lucia Alves de Oliveira 
Published: September 2020

Abstract
Background: Leprosy is a chronic infectious disease classified into two subgroups for therapeutic purposes: paucibacillary (PB) and multibacillary (MB), closely related to the host immune responses. In this context it is noteworthy looking for immunological biomarkers applicable as complementary diagnostic tools as well as a laboratorial strategy to follow-up leprosy household contacts. Methods: The main goal of the present study was to characterize the global cytokine signatures of CD4+ and CD8+ T-cells from leprosy patients with distinct clinical forms and their respective household contacts (HHC) upon in vitro antigen-specific stimuli. Short-term culture of peripheral blood mononuclear cells was done. After incubation, cells were harvested and prepared for surface and intracytoplasmic cytokine staining Results: The cytokine signature analysis demonstrated that leprosy patients presented a polyfunctional profile of T-cells subsets, with increased frequency of IFN-g+ T-cell subsets along with IL-10+ and IL-4+ from CD4+ T-cells. Moreover, L(PB) displayed a polyfunctional profile characterized by enhanced percentage of IFN-g+, IL-10+ and IL-4+ produced by most T-cell subsets, as compared to L(MB) that presented a more restricted cytokine functional profile mediated by IL-10+ and IL-4+ T-cells with minor contribution of IFN-g produced by CD4+ T-cells. Noteworthy was that HHC(MB) exhibited enhanced frequency of IFN-g+ T-cells, contrasting with HHC(PB) that presented a cytokine profile limited to IL-10 and IL-4. Conclusions: Together, our findings provide additional immunological features associated with leprosy and household contacts. These data provide evidence that biomarkers of immune response can be useful complementary diagnostic/prognostic tools as well as insights that household contacts should be monitored to access putative subclinical infection.
The Trends and Efficacy of Operation in the Treatment of Hepatocellular Carcinoma
Authors: Chen Lei , Chen Shi , Sun Tao , Yang Fan , Zheng Chuansheng 
Published: September 2020

Abstract
BackgroundOperation for the treatment of hepatocellular carcinoma (HCC) is limited. Recently, the possibility was advanced that operation (including surgery, transplantation, and ablation et, al) could be applied in HCC patients more widely. To address this issue, the trend in the use of operation and surgery for the treatment of HCC with time was analyzed. Additionally, whether patients gain a better survival benefit from surgery than other treatments was also evaluated.MethodsData from SEER registries were used to analyze the trends in the use operation and surgery for HCC and the survival benefits of these procedures. The study included patients between the ages of 35 and 84 years diagnosed as HCC between 2004 and 2015 (n=64019). Propensity score matching (PSM) analysis was used to reduce selection bias.Results From 2004 to 2015, the rate of operation for HCC decreased in the localized group (P<0.001), the regional and distant group (P<0.001). Surgery rate in the localized, regional, and distant group also declined (P=0.016, P=0.009, and P=0.018, respectively). Non-operation rate increased in the localized, regional, and distant group (all P<0.001). The median overall survival (mOS) of patients in the localized, regional group who underwent surgery was longer than that of patients with non-surgery operation and non-operation. Similar survival results were obtained in the analysis of patients with single tumor larger than 5 cm and 2-3 tumors larger than 3 cm. ConclusionAlthough surgery rate declined from 2004 to 2015 in all HCC patients, it might be used more widely in patients with localized and regional tumors. And the treatment of surgery in patients with single tumor larger than 5 cm or patients with 2-3 tumors larger than 3 cm was worth trying.
Influence of vitamin D binding protein polymorphism, demographics and lifestyle factors on vitamin D status of healthy Malaysian pregnant women
Authors: Lee Siew-Siew , Ling King-Hwa , Tusimin Maiza , Subramaniam Raman , Rahim Kartini Farah , Loh Su-Peng 
Published: September 2020

Abstract
Background: Vitamin D deficiency (VDD) has been related to vitamin D binding protein (GC) gene polymorphism, demographics and lifestyle factors in different populations. However, previous studies only focused on demographic and lifestyle factors or genetic factors alone. Therefore, this cross-sectional study aimed to assess the association between GC gene polymorphism, demographics and lifestyle factors with VDD among Malaysian pregnant women.Method: Information on demographic characteristics, dietary vitamin D intake from supplement and food, time spent outdoors, skin type and clothing were collected using questionnaire. Plasma total 25-hydroxyvitamin D (25OHD) levels were measured using a Ultra-High-Performance Chromatography (UHPLC). Maternal GC single nucleotide polymorphisms (SNPs) (rs4588 and rs7041) were determined using restriction fragment length polymorphism (RFLP) technique.Results: Results showed that 50.2% of pregnant women were vitamin D deficient (25OHD <30 nmol/L). VDD (25OHD <30 nmol/L) was significantly associated with age, veiled clothing, maternal vitamin D intakes, from both food and supplements, and GC rs7041(and GC diplotypes). In contrast to previous studies that reported for non-pregnant population, significant positive association was found between CC genotype for SNP GC rs7041, GC 1s-1s and GC If-2 with risk of VDD (25OHD <30 nmol/L). Conclusions: The high prevalence of maternal VDD found in this study suggests the need for urgent development and implementation of vitamin D supplementation or fortification strategies to reduce VDD among pregnant women. The discrepancy in the association between GC rs7041 gene polymorphism and VDD reflects the variation in the factors associated with VDD in pregnancy compared to non-pregnant state
Beagle dog 90-day oral toxicity study of a novel coccidiostat – ethanamizuril
Authors: Zhang Keyu , Wang Xiaoyang , Wei Shuya , Wang Chunmei , Wang Mi , Liu Yingchun , Zhang Lifang , Xue Feiqun , Tang Shusheng 
Published: September 2020

Abstract
Background: Triazine coccidiostats are widely used in chickens and turkeys for coccidiosis control. Ethanamizuril is a novel triazine compound that exhibits anticoccidial activity in poultry. To support the safety assessment of the new potent anticoccidial agent, the subchronic toxicity of ethanamizuril was studied in beagle dogs administered ethanamizuril by diet at doses of 12, 60 or 300 mg/kg/day for 90 days.Results: Ethanamizuril was well tolerated at low and middle dosages and there were no ethanamizuril related effects on survival, clinical observations, clinical pathology parameters, organs weight, macroscopic or microscopic evaluations. The ethanamizuril related changes were limited to effects on food consumption and histologic changes of kidneys in the 300 mg/kg/day group in both sexes. However, the characteristic toxicities of ethanamizuril in kidneys are recoverable in convalescence dogs of 300 mg/kg/day group. Conclusions: Therefore, the no-observed-adverse-effect level (NOAEL) was considered to be 60 mg/kg/day, the middle dosage level tested. These results add to the safety database for ethanamizuril with potential for use as a novel coccidiostat.
Uncovering fungal community composition in natural habitat of Ophiocordyceps sinensis using high-throughput sequencing and culture-dependent approaches
Authors: Zhang Chuanbo , Ren Chao-Hui , Wang Yan-Li , Wang Qi-Qi , Wang Yun-Sheng , Weng Qing-Bei 
Published: September 2020

Abstract
Background: The fungal communities inhabiting natural Ophiocordyceps sinensis play critical ecological roles in alpine meadow ecosystem, contribute to infect host insect, influence the occurrence of O. sinensis, and are repertoire of potential novel metabolites discovery. However, a comprehensive understanding of fungal communities of O. sinensis remain elusive. Therefore, the present study aimed to unravel fungal communities of natural O. sinensis using combination of high-throughput sequencing and culture-dependent approaches. Results: A total of 280,519 high-quality sequences, belonging to 5 fungal phyla, 15 classes, 41 orders, 79 families, 112 genera, and 352 putative operational taxonomic units (OTUs) were obtained from natural O. sinensis using high-throughput sequencing. Among of which, 43 genera were identified in external mycelial cortices, Ophiocordyceps, Sebacinia, Archaeorhizomyces were predominant genera with the abundance of 95.86%, 1.14%, 0.85%, respectively. A total of 66 genera were identified from soil microhabitat, Inocybe, Archaeorhizomyces, unclassified Thelephoraceae, Tomentella, Thelephora, Sebacina, unclassified Ascomycota, unclassified Fungi were predominant genera with an average abundance of 53.32%, 8.69%, 8.12%, 8.12%, 7.21%, 4.6%, 3.08% and 3.05%, respectively. The fungal communities in external mycelial cortices were significantly distinct from the soil microhabitat. Meanwhile, seven types of culture media were used to isolate culturable fungi at 16°C, resulted in 77 fungal strains isolated by rDNA ITS sequence analysis, belonging to 33 genera, including Ophiocordyceps, Trichoderma, Cytospora, Truncatella, Dactylonectria, Isaria, Cephalosporium, Fusarium, Cosmospora and Paecilomyces, etc.. Among all culturable fungi, Mortierella and Trichoderma were predominant genera. Conclusions: The significantly differences and overlap in fungal community structure between two approaches highlight that the integration of high-throughput sequencing and culture-dependent approaches would generate more information. Our result reveal a comprehensive understanding of fungal community structure of natural O. sinensis, provide new insight into O. sinensis associated fungi, and support that microbiota of natural O. sinensis is an untapped source for novel bioactive metabolites discovery.
Efficacy and cardiovascular safety of the new estrogen-free contraceptive pill containing 4 mg drospirenone alone in a 24/4 regime.
Authors: Palacios Santiago , Colli Enrico , REGIDOR PEDRO ANTONIO 
Published: September 2020

Abstract
Background: A new estrogen-free contraceptive has been approved by both the FDA and more than 15 European authorities. It is composed of drospirenone (DRSP) at a dosage of 4 mg in a regimen 24/4. The molecule is known to have anti-gonadotropic, anti-mineralocorticoid, anti-estrogenic, and antiandrogenic properties. The purpose of these clinical trials with a new estrogen-free contraceptive was to introduce a contraceptive method with high efficacy and showing a profile with low cardiovascular risks.Methods: Three European and American multicenter clinical trials have been conducted in more than 2,500 patients and more than 25,000 cycles, not only demonstrating an excellent efficacy (Pearl Index of 0.73) but also investigating possible cardiovascular risks. In the USA study, 422 participants (41.9 %) had a risk factor for VTE, while in the European studies, 261 patients (16.6 %) had at least one VTE risk factor. Amount of arterial and venous thromboembolic events, hemostasiological data, blood pressure development, and ECG data were evaluated. Results: No single case of VTE was documented, no changes in hemastosiological parameters were observed, a small decrease in RR in patients with pretreatment values between 130 and 140 and/or 85 to 90 mm HG and no influence on ECG parameters were observed.Conclusions: The introduction of a new estrogen-free contraceptive with 4 mg of non-micronized drospirenone in a 24/4-day regimen expands contraception options for women as not only a high efficacy could be demonstrated during clinical trials but also a very high cardiovascular safety profile was observed even in women with cardiovascular risk factors.EudraCT registration numbers: 2010-021787-15 & 2011-002396-42. Clincaltrials.gov: NCT02269241
Transcriptome analysis reveals underlying immune response mechanism of fungal (Penicillium oxalicum) disease in Gastrodia elata Bl. f. glauca S. Chow (Orchidaceae)
Authors: Wang Yanhua , Gao Yugang , Zang Pu , Xu Yue 
Published: September 2020

Abstract
Background: Gastrodia elata Bl. f. glauca S. Chow is a medicinal plant. G. elata f. glauca is unavoidably infected by pathogens in their growth process. In previous work, we have successfully isolated and identified Penicillium oxalicum from fungal diseased tubers of G. elata f. glauca. As a widespread epidemic, this fungal disease seriously affected the yield and quality of G. elata f. glauca. We speculate that the healthy G. elata f. glauca might carry resistance genes, which can resist against fungal disease. In this study, healthy and fungal diseased mature tubers of G. elata f. glauca from Changbai Mountain area were used as experimental materials to help us find the potential resistance genes against fungal disease.Results: A total of 7540 differentially expressed Unigenes (DEGs) were identified (FDR<0.01, log2FC>2). The current study screened 10 potential resistance genes. They were attached to transcription factors (TFs) in plant hormone signal transduction pathway and plant pathogen interaction pathway, including WRKY22, GH3, TIFY/JAZ, ERF1, WRKY33, TGA. In addition, four of these genes were closely related to jasmonic acid signaling pathway.Conclusions: The immune response mechanism of fungal disease in G. elata f. glauca is a complex biological process, involving plant hormones such as ethylene, jasmonic acid, salicylic acid and disease-resistant transcription factors such as WRKY, TGA.