bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic hypersensitivity pneumonitis in the southeastern United States: an assessment of how clinicians reached the diagnosis
Authors: Gu Jessie P. , Tsai Chen-Liang , Wysham Nicholas G. , Huang Yuh-Chin T. 
Published: February 2020

Abstract
Background
Chronic hypersensitivity pneumonitis (cHP) is a disease caused by exposure to inhaled environmental antigens. Diagnosis of cHP is influenced by the awareness of the disease prevalence, which varies significantly in different regions, and how clinicians utilize relevant clinical information. We conducted a retrospective study to evaluate how clinicians in the Southeast United States, where the climate is humid favoring mold growth, diagnosed cHP using items identified in the international modified Delphi survey of experts, i.e., environmental exposure, CT imaging and lung pathology,

Methods
We searched Duke University Medical Center database for patients over the age of 18 with a diagnosis of cHP (ICD-9 code: 495) between Jan. 1, 2008 to Dec. 31, 2013 using a query tool, Duke Enterprise Data Unified Content Explorer (DEDUCE).

Results
Five hundred patients were identified and 261 patients had cHP confirmed in clinic notes by a pulmonologist or an allergist. About half of the patients lived in the Research Triangle area where our medical center is located, giving an estimated prevalence rate of 6.5 per 100,000 persons. An exposure source was mentioned in 69.3% of the patient. The most common exposure sources were environmental molds (43.1%) and birds (26.0%). We used Venn diagram to evaluate how the patients met the three most common cHP diagnostic criteria: evidence of environmental exposures (history or precipitin) (E), chest CT imaging (C) and pathology from lung biopsies (P). Eighteen patients (6.9%) met none of three criteria. Of the remaining 243 patients, 135 patients (55.6%) had one (E 35.0%, C 3.3%, P 17.3%), 81 patients (33.3%) had two (E + C 12.3%, E + P 17.3%, C + P 4.9%), and 27 patients (11.1%) had all three criteria (E + C + P). Overall, 49.4% of patients had pathology from lung biopsy compared to 31.6% with CT scan.

Conclusions
Environmental mold was the most common exposure for cHP in the Southeast United States. Lung pathology was available in more than half of cHP cases in our tertiary care center, perhaps reflecting the complexity of referrals. Differences in exposure sources and referral patterns should be considered in devising future diagnostic pathways or guidelines for cHP.
Validity of computed tomographic measurements and morphological comparison of cubital tunnel in idiopathic cubital tunnel syndrome
Authors: Lee Sang Ki , Hwang Seok Young , Choy Won Sik 
Published: February 2020

Abstract
Background
Ulnar neuropathy is a common reason for referral to hand surgeons, and 10 to 30% of cubital tunnel syndrome (CuTS) is idiopathic. We hypothesized that the cause of idiopathic CuTS is in the bony structure.

Methods
We analyzed 79 elbows (39 idiopathic CuTS and 40 without CuTS symptom) using computed tomography and Materialize Mimics software to compare the differences between the two groups. We proposed a new bony cubital tunnel with a new boundary that could play a role in ulnar nerve compression symptom.

Results
The mean cubital tunnel volume was 1245.6 mm3 in all patients, 1180.6 mm3 in CuTS patients, and 1282.3 mm3 in the control group. A significant difference (p = 0.015) between two groups was found. Bony cubital tunnel cross-sectional area, cubital tunnel depth, and cubital tunnel angle also showed significant differences.

Conclusion
The shape of the bony cubital tunnel is an important cause of CuTS, and the normal variation of the volume and cross-sectional area of the cubital tunnel and cubital tunnel angle could influence the occurrence of idiopathic CuTS.
Evaluation of the hepatoprotective effect of Yigan mingmu oral liquid against acute alcohol-induced liver injury in rats
Authors: Mo Qigui , Zhou Gao , Xie Baibo , Ma Bingxin , Zang Xinyu , Chen Yuxin , Cheng Linyou , Zhou James Hua , Wang Youwei 
Published: February 2020

Abstract
Background
Yigan mingmu oral liquid (YGMM) is a herbal medicine based on a famous Chinese herbal formula that has been used for sore eyes for more than 400 years. Eye health is closely associated with the liver based on TCM. This study aimed to investigate the hepatoprotective effect of YGMM against acute liver injury induced by alcohol in rats.

Methods
Experimental rats were administered with silymarin and YGMM through the gastric gavage during the entire experiment. Starting from the 11th day, the rats were administered orally with 14 ml/kg Red Star Erguotou Liquor, a popular brand, at 4 h after the dose of silymarin (100 mg/kg) and YGMM (1, 2.5 and 5 ml/kg in low, middle and high dosage group, respectively) once a day for 4 weeks except for the rats in the normal group. Biochemical parameters, including ALT, AST, TB, TG, T-SOD, GSH, and MDA were detected to evaluate the protective effect of YGMM. Pathological changes were observed through histopathological examination.

Results
Treatment with YGMM exhibited a significant protective effect by reversing the biochemical parameters (ALT, AST, TB, TG, and GSH) and histopathological changes. Histopathological examination by Oil Red O Staining Solution showed that lipid droplets were significantly reduced in the silymarin and YGMM groups (p < 0.001) when compared to alcohol group.

Conclusions
YGMM exhibits a significant hepatoprotective activity against acute liver injury induced by alcohol in rats.
Study protocol for a randomized controlled trial: Qiliqiangxin in heart failUre: assESsment of reduction in morTality (QUEST)
Authors: Yao Wenming , Cheang Iokfai , Liao Shengen , Zhou Yanli , Zhou Fang , Xu Dongjie , Jia Zhenhua , Chang Liping , Zhang Haifeng , Li Xinli 
Published: February 2020

Abstract
Background
Qiliqiangxin (QLQX) capsule is a Traditional Chinese Medicine (TCM) that has been approved in China for the treatment of chronic heart failure (CHF). Our previous study showed with a background of standard HF treatment, QLQX capsules further reduced the levels of NT-proBNP and the incidence of composite cardiac events (CCEs) in CHF patients. This study aims to further assess the reduction in mortality when using QLQX compared with placebo for heart failure with reduced ejection fraction (HFrEF) patients.

Methods
This study is a randomized, double-blind, placebo-controlled, parallel-group, multi-center, event-driven clinical study of approximately 3080 patients for a targeted 620 events. Patients must have a diagnosis of heart failure for at least 3 months prior to screening. Patients will be randomized 1:1 to receive the placebo or QLQX in addition to their standard medications of CHF. The primary efficacy outcome event is a composite cardiovascular death and re-hospitalization due to the worsening of heart failure.

Discussion
The QUEST study is a randomized control study of TCM in chronic heart failure. It will determine the place of QLQX as an new treatment approach and provide additional and innovative information regarding TCM - and the specific used of QLQX in HFrEF.

Trial registration
The trial was registered at http://www.chictr.org.cn. ( Registration No.: ChiCTR1900021929); Date: 2019-03-16.
Structural modulation of gut microbiota during alleviation of non-alcoholic fatty liver disease with Gynostemma pentaphyllum in rats
Authors: Shen Shu-Hua , Zhong Ting-Yan , Peng Cui , Fang Jie , Lv Bin 
Published: February 2020

Abstract
Background
The current work aimed to assess whether Gynostemma pentaphyllum (GP), a Chinese herbal medicine, structurally modifies the gut microbiota in rats during non-alcoholic fatty liver disease (NAFLD) treatment.

Methods
High-fat diet (HFD)-induced NAFLD rats were orally administered water decoction of GP or equal amounts of distilled water per day for 4 weeks. Liver tissues were examined by histopathological observation, while intestinal tissues were examined by both histopathological and ultrastructural observations. The levels of fasting blood glucose (FBG), fasting serum insulin (FINS), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), alanine transaminase (ALT) and aspartate transaminase (AST) were measured by enzymatic method. The levels of toll-like receptor 4 (TLR-4), tumor necrosis factor-alpha (TNF-α), interleukin-1-beta (IL-1β) and interleukin-6 (IL-6) in both serum and hepatic tissues were measured by RT-qPCR. The protein expression level of TLR-4 in hepatic tissues was detected by western blot. The gut microbiota was assessed by 16S rRNA-based microbiota analysis.

Results
GP maintained intestinal integrity and reversed gut dysbiosis in high-fat diet (HFD)-induced NAFLD rats. This also reduced the ratio of Firmicutes to Bacteroidetes, enriching the abundance of beneficial bacteria (Lactococcus spp.) and inhibiting the abundance of pathogenic bacteria (Ruminococcus spp.) in the gut. The levels of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6) and the expression of TLR4 were downregulated (P < 0.05), while the insulin resistance index, HOMA-IR showed improvement by GP treatment (P < 0.05). Liver function indicators (ALT and AST) were remarkably decreased (P < 0.01). Besides, GP treatment reduced TG and LDL-C levels (P < 0.05), and increased HDL-C level (P < 0.05) compared with NAFLD group.

Conclusion
The structural alterations of gut microbiota induced by GP are associated with NAFLD alleviation.
Stakeholder views on the acceptability of human infection studies in Malawi
Authors: Kapumba Blessings M. , Jambo Kondwani , Rylance Jamie , Gmeiner Markus , Sambakunsi Rodrick , Parker Michael , Gordon Stephen B. , Gooding Kate 
Published: February 2020

Abstract
Background
Human infection studies (HIS) are valuable in vaccine development. Deliberate infection, however, creates challenging questions, particularly in low and middle-income countries (LMICs) where HIS are new and ethical challenges may be heightened. Consultation with stakeholders is needed to support contextually appropriate and acceptable study design. We examined stakeholder perceptions about the acceptability and ethics of HIS in Malawi, to inform decisions about planned pneumococcal challenge research and wider understanding of HIS ethics in LMICs.

Methods
We conducted 6 deliberative focus groups and 15 follow-up interviews with research staff, medical students, and community representatives from rural and urban Blantyre. We also conducted 5 key informant interviews with clinicians, ethics committee members, and district health government officials.

Results
Stakeholders perceived HIS research to have potential population health benefits, but they also had concerns, particularly related to the safety of volunteers and negative community reactions. Acceptability depended on a range of conditions related to procedures for voluntary and informed consent, inclusion criteria, medical care or support, compensation, regulation, and robust community engagement. These conditions largely mirror those in existing guidelines for HIS and biomedical research in LMICs. Stakeholder perceptions pointed to potential tensions, for example, balancing equity, safety, and relevance in inclusion criteria.

Conclusions
Our findings suggest HIS research could be acceptable in Malawi, provided certain conditions are in place. Ongoing assessment of participant experiences and stakeholder perceptions will be required to strengthen HIS research during development and roll-out.
Use of smoking cessation pharmacotherapies during pregnancy is not associated with increased risk of adverse pregnancy outcomes: a population-based cohort study
Authors: Tran Duong Thuy , Preen David B. , Einarsdottir Kristjana , Kemp-Casey Anna , Randall Deborah , Jorm Louisa R. , Choi Stephanie K. Y. , Havard Alys 
Published: February 2020

Abstract
Background
Varenicline, bupropion and nicotine replacement therapy (NRT) are three effective pharmacotherapies for smoking cessation, but data about their safety in pregnancy are limited. We assessed the risk of adverse perinatal outcomes and major congenital anomalies associated with the use of these therapies in pregnancy in Australia.

Methods
Perinatal data for 1,017,731 deliveries (2004 to 2012) in New South Wales and Western Australia were linked to pharmaceutical dispensing, hospital admission and death records. We identified 97,875 women who smoked during pregnancy; of those, 233, 330 and 1057 were exposed to bupropion, NRT and varenicline in pregnancy, respectively. Propensity scores were used to match exposed women to those who were unexposed to any smoking therapy (1:10 ratio). Propensity scores and gestational age at exposure were used to match varenicline-exposed to NRT-exposed women (1:1 ratio). Time-dependent Cox proportional hazards models estimated hazard ratios (HR) with 95% confidence intervals (95% CI) for any adverse perinatal event (a composite of 10 unfavourable maternal and neonatal outcomes) and any major congenital anomaly.

Results
The risk of any adverse perinatal event was not significantly different between bupropion-exposed and unexposed women (39.2% versus 39.3%, HR 0.93, 95% CI 0.73–1.19) and between NRT-exposed and unexposed women (44.8% vs 46.3%, HR 1.02, 95% CI 0.84–1.23), but it was significantly lower in women exposed to varenicline (36.9% vs 40.1%, HR 0.86, 95% CI 0.77–0.97). Varenicline-exposed infants were less likely than unexposed infants to be born premature (6.5% vs 8.9%, HR 0.72, 95% CI 0.56–0.92), be small for gestational age (11.4% vs 15.4%, HR 0.68, 95% CI 0.56–0.83) and have severe neonatal complications (6.6% vs 8.2%, HR 0.74, 95% CI 0.57–0.96). Among infants exposed to varenicline in the first trimester, 2.9% had a major congenital anomaly (3.5% in unexposed infants, HR 0.91, 95% CI 0.72–1.15). Varenicline-exposed women were less likely than NRT-exposed women to have an adverse perinatal event (38.7% vs 51.4%, HR 0.58, 95% CI 0.33–1.05).

Conclusions
Pregnancy exposure to smoking cessation pharmacotherapies does not appear to be associated with an increased risk of adverse birth outcomes. Lower risk of adverse birth outcomes in varenicline-exposed pregnancies is inconsistent with recommendations that NRT be used in preference to varenicline.
Identification of a Yarrowia lipolytica acetamidase and its use as a yeast genetic marker
Authors: Hamilton Maureen , Consiglio Andrew L. , MacEwen Kyle , Shaw A. Joe , Tsakraklides Vasiliki 
Published: February 2020

Abstract
Background
Yarrowia lipolytica is an oleaginous yeast that can be genetically engineered to produce lipid and non-lipid biochemicals from a variety of feedstocks. Metabolic engineering of this organism usually requires genetic markers in order to select for modified cells. The potential to combine multiple genetic manipulations depends on the availability of multiple or recyclable selectable markers.

Results
We found that Y. lipolytica has the ability to utilize acetamide as the sole nitrogen source suggesting that the genome contains an acetamidase gene. Two potential Y. lipolytica acetamidase gene candidates were identified by homology to the A. nidulans acetamidase amdS. These genes were deleted in the wild-type Y. lipolytica strain YB-392, and deletion strains were evaluated for acetamide utilization. One deletion strain was unable to grow on acetamide and a putative acetamidase gene YlAMD1 was identified. Transformation of YlAMD1 followed by selection on acetamide media and counterselection on fluoroacetamide media showed that YlAMD1 can be used as a recyclable genetic marker in Saccharomyces cerevisiae and Ylamd1Δ Y. lipolytica.

Conclusions
These findings add to our understanding of Y. lipolytica nitrogen utilization and expand the set of genetic tools available for engineering this organism, as well as S. cerevisiae.
RETRACTED ARTICLE: Exosome-mediated lncRNA AFAP1-AS1 promotes trastuzumab resistance through binding with AUF1 and activating ERBB2 translation
Authors: Han Mingli , Gu Yuanting , Lu Pengwei , Li Jingyi , Cao Hui , Li Xiangke , Qian Xueke , Yu Chao , Yang Yunqing , Yang Xue , Han Na , Dou Dongwei , Hu Jianguo , Dong Huaying 
Published: February 2020

Abstract
Background
Although trastuzumab provides significant clinical benefit for HER2-positive breast cancers, responses are limited by the emergence of resistance. Recent evidence suggests that long noncoding RNAs (lncRNAs) play important roles in tumorigenesis and chemoresistance. However, the regulatory mechanism of lncRNAs in trastuzumab resistance is not well established to date. In this research, we identified the differentially expressed lncRNA and investigated its regulatory role in trastuzumab resistance of breast cancer.

Methods
LncRNA microarray and qRT-PCR were performed to identify the dysregulated lncRNAs. Transmission electron microscopy, differential ultracentrifugation and qRT-PCR were used to verify the existence of exosomal AFAP1-AS1 (actin filament associated protein 1 antisense RNA 1). Bioinformatics prediction, RNA fluorescence in situ hybridization (RNA-FISH) and immunoprecipitation assays were performed to identify the direct interactions between AFAP1-AS1 and other associated targets, such as AU-binding factor 1 (AUF1) and ERBB2. Finally, a series gain- or loss-functional assays were done to prove the precise role of AFAP1-AS1 in trastuzumab resistance.

Results
AFAP1-AS1 was screened out due to its higher expression in trastuzumab-resistant cells compared to sensitive cells. Increased expression of AFAP1-AS1was associate with poorer response and shorter survival time of breast cancer patients. AFAP1-AS1 was upregulated by H3K27ac modification at promoter region, and knockdown of AFAP1-AS1 reversed trastuzumab resistance. Moreover, extracellular AFAP1-AS1 secreted from trastuzumab resistant cells was packaged into exosomes and then disseminated trastuzumab resistance of receipt cells. Mechanically, AFAP1-AS1 was associated with AUF1 protein, which further promoted the translation of ERBB2 without influencing the mRNA level.

Conclusion
Exosomal AFAP1-AS1 could induce trastuzumab resistance through associating with AUF1 and promoting ERBB2 translation. Therefore, AFAP1-AS1 level may be useful for prediction of trastuzumab resistance and breast cancer treatment.
Cut and paste: temperature-enhanced cotyledon micrografting for Arabidopsis thaliana seedlings
Authors: Bartusch Kai , Trenner Jana , Melnyk Charles W. , Quint Marcel 
Published: February 2020

AbstractBackgroundCotyledon micrografting represents a useful tool for studying the central role of cotyledons during early plant development, especially their interplay with other plant organs with regard to long distance transport. While hypocotyl micrografting methods are well-established, cotyledon micrografting is still inefficient. By optimizing cotyledon micrografting, we aim for higher success rates and increased throughput in the model speciesArabidopsis thaliana.ResultsWe established a cut and paste cotyledon surgery procedure on a flat and solid but moist surface which improved handling of small seedlings. By applying a specific cutting and joining pattern, throughput was increased up to 40 seedlings per hour. The combination of short-day photoperiods and low light intensities for germination and long days plus high light intensities, elevated temperature and vertical plate positioning after grafting significantly increased ‘ligation’ efficiency. In particular high temperatures affected success rates favorably. Altogether, we achieved up to 92% grafting success inA. thaliana. Reconnection of vasculature was demonstrated by transport of a vasculature-specific dye across the grafting site. Phloem and xylem reconnection were completed 3–4 and 4–6 days after grafting, respectively, in a temperature-dependent manner. We observed that plants with grafted cotyledons match plants with intact cotyledons in biomass production and rosette development.ConclusionsThis cut and paste cotyledon-to-petiole micrografting protocol simplifies the handling of plant seedlings in surgery, increases the number of grafted plants per hour and greatly improves success rates forA. thalianaseedlings. The developed cotyledon micrografting method is also suitable for other plant species of comparable size.
Non-invasive prenatal test to screen common trisomies in twin pregnancies
Authors: Motevasselian Mahtab , Saleh Gargari Soraya , Younesi Sarang , Pooransari Parichehr , Saadati Pourandokht , Mirzamoradi Masoomeh , Savad Shahram , Taheri Amin Mohammad Mahdi , Modarresi Mohammad-Hossein , Afrakhteh Maryam , Ghafouri-Fard Soudeh 
Published: February 2020

AbstractObjectivesRecent years have witnessed a shift from invasive methods of prenatal screening to non-invasive strategies. Accordingly, non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma has gained a considerable deal of interest from both geneticists and obstetricians. Efficacy of this method in identification of common aneuploidies has been extensively assessed in singleton pregnancies. However, a limited number of studies have addressed the twin pregnancies. In this context, the present study is aimed at identification of the efficacy of NIPT in twin pregnancies.MethodsNIPT was performed on twin pregnancies to screen trisomies 13, 18 and 21. Pregnant women referring to Nilou Clinical Laboratory between March 2016 and December 2018 were included in this research.ResultsIn the current study, a total 356 twin pregnancies were screened in search for trisomies 13, 18 and 21. 6 cases exhibited positive NIPT results in which the presence of trisomies 13, 18 and 21 was confirmed by fetal karyotype in 1, 2 and 2 cases, respectively. One twin pregnancy showed normal karyotype. The combined false-positive rate for these trisomies was 0.28%. No false negative case was observed. The combined sensitivity and specificity of NIPT in twin pregnancies were 100 and 99.7%, respectively.ConclusionThe results of the current study verify the feasibility, sensitivity and specificity of NIPT in twin pregnancies.
CD73 sustained cancer-stem-cell traits by promoting SOX9 expression and stability in hepatocellular carcinoma
Authors: Ma Xiao-Lu , Hu Bo , Tang Wei-Guo , Xie Su-Hong , Ren Ning , Guo Lin , Lu Ren-Quan 
Published: February 2020

Abstract
Background
Aberrant AKT activation contributes to cancer stem cell (CSC) traits in hepatocellular carcinoma (HCC). We previously reported that CD73 activated AKT signaling via the Rap1/P110β cascade. Here, we further explored the roles of CD73 in regulating CSC characteristics of HCC.

Methods
CD73 expression modulations were conducted by lentiviral transfections. CD73+ fractions were purified by magnetic-based sorting, and fluorescent-activated cell sorting was used to assess differentiation potentials. A sphere-forming assay was performed to evaluate CSC traits in vitro, subcutaneous NOD/SCID mice models were generated to assess in vivo CSC features, and colony formation assays assessed drug resistance capacities. Stemness-associated gene expression was also determined, and underlying mechanisms were investigated by evaluating immunoprecipitation and ubiquitylation.

Results
We found CD73 expression was positively associated with sphere-forming capacity and elevated in HCC spheroids. CD73 knockdown hindered sphere formation, Lenvatinib resistance, and stemness-associated gene expression, while CD73 overexpression achieved the opposite effects. Moreover, CD73 knockdown significantly inhibited the in vivo tumor propagation capacity. Notably, we found that CD73+ cells exhibited substantially stronger CSC traits than their CD73– counterparts. Mechanistically, CD73 exerted its pro-stemness activity through dual AKT-dependent mechanisms: activating SOX9 transcription via c-Myc, and preventing SOX9 degradation by inhibiting glycogen synthase kinase 3β. Clinically, the combined analysis of CD73 and SOX9 achieved a more accurate prediction of prognosis.

Conclusions
Collectively, CD73 plays a critical role in sustaining CSCs traits by upregulating SOX9 expression and enhancing its protein stability. Targeting CD73 might be a promising strategy to eradicate CSCs and reverse Lenvatinib resistance in HCC.