bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epithelial and interstitial Notch1 activity contributes to the myofibroblastic phenotype and fibrosis
Authors: Hong Weilong , Zhang Ge , Lu Hong , Guo Yangyang , Zheng Shizhang , Zhu Hengyue , Xiao Yanyi , Papa Akuetteh Percy David , Wu Cunzao , Sun Linxiao , Chen Bicheng , Bai Yongheng 
Published: November 2019

Abstract

Background
Notch1 signalling is a stem-cell-related pathway that is essential for embryonic development, tissue regeneration and organogenesis. However, the role of Notch1 in the formation of myofibroblasts and fibrosis in kidneys following injury remains unknown.

Methods
The activity of Notch1 signalling was evaluated in fibrotic kidneys in CKD patients and in ureteral obstructive models in vivo and in cultured fibroblasts and TECs in vitro. In addition, the crosstalk of Notch1 with TGF-β1/Smad2/3 signalling was also investigated.

Results
Notch1 activity was elevated in fibrotic kidneys of rat models and patients with chronic kidney disease (CKD). Further study revealed that epithelial and interstitial Notch1 activity correlated with an α-SMA-positive myofibroblastic phenotype. In vitro, injury stimulated epithelial Notch1 activation and epithelial-mesenchymal transition (EMT), resulting in matrix deposition in tubular epithelial cells (TECs). Additionally, interstitial Notch1 activation in association with fibroblast-myofibroblast differentiation (FMD) in fibroblasts mediated a myofibroblastic phenotype. These TGF-β1/Smad2/3-dependent phenotypic transitions were abolished by Notch1 knockdown or a specific antagonist, DAPT, and were exacerbated by Notch1 overexpression or an activator Jagged-1-Fc chimaera protein. Interestingly, as a major driving force behind the EMT and FMD, TGF-β1, also induced epithelial and interstitial Notch1 activity, indicating that TGF-β1 may engage in crosstalk with Notch1 signalling to trigger fibrogenesis.

Conclusion
These findings suggest that epithelial and interstitial Notch1 activation in kidneys following injury contributes to the myofibroblastic phenotype and fibrosis through the EMT in TECs and to the FMD in fibroblasts by targeting downstream TGF-β1/Smad2/3 signalling.
Circ-ASH2L promotes tumor progression by sponging miR-34a to regulate Notch1 in pancreatic ductal adenocarcinoma
Authors: Chen Yan , Li Zhonghu , Zhang Mengyun , Wang Bo , Ye Jiaxin , Zhang Yang , Tang Di , Ma Dandan , Jin Weidong , Li Xiaowu , Wang Shuguang 
Published: November 2019

Abstract
Background
Circular RNAs (circRNAs) have recently been shown to play important roles in different tumors. However, their detailed roles and regulatory mechanisms in pancreatic ductal adenocarcinoma (PDAC) are not well understood. This study aimed to identify enriched circRNAs and detect their functions and mechanisms in PDAC cells and tissues.

Methods
circRNA-ASH2L (circ-ASH2L) was identified by circRNA microarray studies based on previous studies, and further detected in PDAC cells and samples by qRT-PCR. The functions of circ-ASH2L were identified by transwell, EdU, cell cycle or Tube formation assays. The regulatory mechanisms of circ-ASH2L were explored by WB, RIP, FISH, dual-luciferase assays, RNA pulldown or other assays.

Results
We identified a circRNA (circ-ASH2L) based on our previous studies, detected its expression in different malignant cells and found that circ-ASH2L was highly expressed in pancreatic cells or tumor tissues and correlated with tumor malignancy. Further studies revealed that circ-ASH2L promoted tumor invasion, proliferation and angiogenesis by regulating miR-34a, thus regulate Notch 1 expression. Circ-ASH2L served as a miRNA sponge for miR-34a and promoted tumor progression in vivo. Finally, we analyzed circ-ASH2L expression in clinical tissues and found that high circ-ASH2L expression was correlated with lymphatic invasion and TNM stage and was an independent risk factor for pancreatic patient survival.

Conclusions
circ-ASH2L play an important role in tumor invasion, and high circ-ASH2L may be a useful marker of PDAC diagnosis or progression.
Effective treatment of TNFα inhibitors in Chinese patients with Blau syndrome
Authors: Chen Jing , Luo Yi , Zhao Mengzhu , Wu Di , Yang Yunjiao , Zhang Wen , Shen Min 
Published: November 2019

Abstract

Objectives
Blau syndrome (BS) is a rare dominantly inherited autoinflammatory disorder associated with mutations in the nucleotide-binding oligomerization domain containing 2 (NOD2) gene. Biologic therapy of BS yielded diverse results. We aimed to evaluate clinical features and outcomes of Chinese patients with BS who were treated with tumor necrosis factor (TNF)α inhibitors.

Methods
A total of four patients with BS were diagnosed and treated with infliximab (IFX) at the Peking Union Medical College Hospital during 2015 to 2018 and were followed up for 18 months. All patients were systematically studied for treatment outcomes including the clinical manifestations and inflammatory markers. We also conducted a comprehensive literature review about TNFα inhibitor therapy in BS.

Results
Four BS patients were all Chinese Han, and three were women. The mean age of disease onset was 4 ± 3.5 years, and the mean time of diagnosis delay was 19 ± 11 years. All patients received IFX plus methotrexate, and all achieved clinical remission of skin lesions and polyarthritis rapidly, as well as normalization of erythrocyte sedimentation rate and C-reactive protein and improvements in inflammatory cytokines, patient visual analogue scale, physician global assessment, and Short Form (SF)-36, at the first follow-up of 6 months. The disease relapsed in two patients after they lengthened the interval of IFX and discontinued methotrexate. According to the 38 English-language publications, 62 patients with BS were reported who underwent TNFα inhibitor therapy, including IFX used in 31, adalimumab in 24, and etanercept in 7. IFX was well tolerated in 27 patients, while 2 still had uveitis, and the other 2 experienced an adverse drug reaction.

Conclusions
Early recognition and effective treatment of BS are very important to avoid irreversible organ damage. TNFα inhibitors such as IFX may be a promising approach for BS patients who have unsatisfactory response to corticosteroids and traditional disease-modifying antirheumatic drugs.
Long-term treatment with metformin in the prevention of fatty liver in Zucker diabetic fatty rats
Authors: Sui Yi , Kong Xianhe , Fan Rongrong , Ye Yanbin , Mai Haiyan , Zhuo Shuyu , Lu Wei , Ruan Peishan , Fang Shi , Yang Tao 
Published: November 2019

Abstract

Background
Treatment with metformin, the biguanide of hepatic insulin sensitizer, in patients with non-alcoholic fatty liver disease (NAFLD) has been reported with contradictory findings regarding the effectiveness on blood lipids and liver histology. In this study, we aimed to explore the preventive effects of metformin on NAFLD in Zucker diabetic fatty (ZDF) rats.

Methods
Male ZDF rats and Zucker lean rats aged 4–8 weeks were subjected to vehicle or metformin treatment for 6 months. Liver cDNA microarray assay, and protein semiquantitative and histological examinations were performed.

Results
Data demonstrated that ZDF rats developed hyperglycemia, hyperlipidemia, liver deficiency and hepatocyte degeneration. The metformin treatment significantly reduced post-load blood glucose levels, but not blood lipid profiles or liver enzyme levels. Hepatocyte degeneration was not attenuated after the treatment. The metformin-treated ZDF rats showed activation of AMP-activated protein kinase by Western blot and overexpression of cytochrome c oxidase by immunofluorescent microscopy. Gene expression microarray assay demonstrated that a panel of genes participating in glucose and lipid metabolisms were changed in the ZDF rats, and most of the altered genes involved in glucose and cholesterol metabolisms, but not those in fatty acid metabolisms, were corrected by the metformin treatment. No genes associated with inflammation, apoptosis, fibrosis, or cell death were overexpressed in the metformin-treated ZDF rats.

Conclusions
These results suggest that long-term metformin treatment presents no preventive effect for NAFLD in ZDF rats.
Exploring semantic deep learning for building reliable and reusable one health knowledge from PubMed systematic reviews and veterinary clinical notes
Authors: Arguello-Casteleiro Mercedes , Stevens Robert , Des-Diz Julio , Wroe Chris , Fernandez-Prieto Maria Jesus , Maroto Nava , Maseda-Fernandez Diego , Demetriou George , Peters Simon , Noble Peter-John M. , Jones Phil H. , Dukes-McEwan Jo , Radford Alan D. , Keane John , Nenadic Goran 
Published: November 2019

AbstractBackgroundDeep Learning opens up opportunities for routinely scanning large bodies of biomedical literature and clinical narratives to represent the meaning of biomedical and clinical terms. However, the validation and integration of this knowledge on a scale requires cross checking with ground truths (i.e. evidence-based resources) that are unavailable in an actionable or computable form. In this paper we explore how to turn information about diagnoses, prognoses, therapies and other clinical concepts into computable knowledge using free-text data about human and animal health. We used a Semantic Deep Learning approach that combines the Semantic Web technologies and Deep Learning to acquire and validate knowledge about 11 well-known medical conditions mined from two sets of unstructured free-text data: 300 K PubMed Systematic Review articles (the PMSB dataset) and 2.5 M veterinary clinical notes (the VetCN dataset). For each target condition we obtained 20 related clinical concepts using two deep learning methods applied separately on the two datasets, resulting in 880 term pairs (target term, candidate term). Each concept, represented by an n-gram, is mapped to UMLS using MetaMap; we also developed a bespoke method for mapping short forms (e.g. abbreviations and acronyms). Existing ontologies were used to formally represent associations. We also create ontological modules and illustrate how the extracted knowledge can be queried. The evaluation was performed using the content within BMJ Best Practice.ResultsMetaMap achieves an F measure of 88% (precision 85%, recall 91%) when applied directly to the total of 613 unique candidate terms for the 880 term pairs. When the processing of short forms is included, MetaMap achieves an F measure of 94% (precision 92%, recall 96%). Validation of the term pairs with BMJ Best Practice yields precision between 98 and 99%.ConclusionsThe Semantic Deep Learning approach can transform neural embeddings built from unstructured free-text data into reliable and reusable One Health knowledge using ontologies and content from BMJ Best Practice.
Natural language processing for disease phenotyping in UK primary care records for research: a pilot study in myocardial infarction and death
Authors: Shah Anoop D. , Bailey Emily , Williams Tim , Denaxas Spiros , Dobson Richard , Hemingway Harry 
Published: November 2019

Abstract

Background
Free text in electronic health records (EHR) may contain additional phenotypic information beyond structured (coded) information. For major health events – heart attack and death – there is a lack of studies evaluating the extent to which free text in the primary care record might add information. Our objectives were to describe the contribution of free text in primary care to the recording of information about myocardial infarction (MI), including subtype, left ventricular function, laboratory results and symptoms; and recording of cause of death. We used the CALIBER EHR research platform which contains primary care data from the Clinical Practice Research Datalink (CPRD) linked to hospital admission data, the MINAP registry of acute coronary syndromes and the death registry. In CALIBER we randomly selected 2000 patients with MI and 1800 deaths. We implemented a rule-based natural language engine, the Freetext Matching Algorithm, on site at CPRD to analyse free text in the primary care record without raw data being released to researchers. We analysed text recorded within 90 days before or 90 days after the MI, and on or after the date of death.

Results
We extracted 10,927 diagnoses, 3658 test results, 3313 statements of negation, and 850 suspected diagnoses from the myocardial infarction patients. Inclusion of free text increased the recorded proportion of patients with chest pain in the week prior to MI from 19 to 27%, and differentiated between MI subtypes in a quarter more patients than structured data alone. Cause of death was incompletely recorded in primary care; in 36% the cause was in coded data and in 21% it was in free text. Only 47% of patients had exactly the same cause of death in primary care and the death registry, but this did not differ between coded and free text causes of death.

Conclusions
Among patients who suffer MI or die, unstructured free text in primary care records contains much information that is potentially useful for research such as symptoms, investigation results and specific diagnoses. Access to large scale unstructured data in electronic health records (millions of patients) might yield important insights.
On extended interpolative Ćirić–Reich–Rus type F-contractions and an application
Authors: Mohammadi Babak , Parvaneh Vahid , Aydi Hassen 
Published: November 2019

Abstract
The goal of this work is to introduce an extended interpolative Ćirić–Reich–Rus type contraction by the approach of Wardowski. We establish some related fixed point results (for single and multivalued-mappings). Some examples are presented to illustrate the main result. Moreover, we give an application to integral equations.
Improving exposure for transoral oropharyngeal surgery with the floor of mouth window: A cadaveric feasibility study
Authors: Chung Jeffson , Bender-Heine Adam , Lambert H. Wayne 
Published: November 2019

Background Transoral robotic and laser surgery is rising in popularity due to the increasing incidence of Human Papilloma Virus (HPV) related oropharyngeal cancer. However, adequate exposure of the tongue base remains a major hurdle in many cases. This study introduces a novel surgical technique called the Floor of Mouth Window, which can be used to improve tongue base exposure at the time of transoral surgery. Methods This is a preclinical anatomic cadaver study. Seven fresh cadavers were used for this study. Exposure of the tongue base was compared between conventional mouth gags – the Feyh-Kastenbauer and McIvor – and our novel procedure, the Floor of Mouth Window. Exposure was compared subjectively using endoscopic and extracorporeal photographs, as well as objective measurements of inter-incisor distance, and oral cavity volume. Results The exposure achieved by the Floor of Mouth Window technique was superior to the mouth gags. Inter-incisor distance and oral cavity volume measurements were all more favorable with the Floor of Mouth Window. This technique allowed for successful transoral laser tongue base and tonsil resection without the use of gags or scopes. Conclusion The Floor of Mouth Window is an adjunctive procedure that simply and reliably improved exposure for transoral oropharyngeal surgery in this cadaveric feasibility study. This improved exposure may help increase the adoption of transoral surgery and reduce the number of aborted cases due to anatomic limitations.
First in-orbit results of the vector magnetic field measurement of the High Precision Magnetometer onboard the China Seismo-Electromagnetic Satellite
Authors: Zhou Bin , Cheng Bingjun , Gou Xiaochen , Li Lei , Zhang Yiteng , Wang Jindong , Magnes Werner , Lammegger Roland , Pollinger Andreas , Ellmeier Michaela , Xiao Qi , Zhu Xinghong , Yuan Shigeng , Yang Yanyan , Shen Xuhui 
Published: November 2019

Abstract
The High Precision Magnetometer (HPM) is one of the main payloads onboard the China Seismo-Electromagnetic Satellite (CSES). The HPM consists of two Fluxgate Magnetometers (FGM) and the Coupled Dark State Magnetometer (CDSM), and measures the magnetic field from DC to 15 Hz. The FGMs measure the vector components of the magnetic field; while the CDSM detects the magnitude of the magnetic field with higher accuracy, which can be used to calibrate the linear parameters of the FGM. In this paper, brief descriptions of measurement principles and performances of the HPM, ground, and in-orbit calibration results of the FGMs are presented, including the thermal drift and magnetic interferences from the satellite. The HPM in-orbit vector data calibration includes two steps: sensor non-linearity corrections based on on-ground calibration and fluxgate linear parameter calibration based on the CDSM measurements. The calibration results show a reasonably good stability of the linear parameters over time. The difference between the field magnitude calculated from the calibrated FGM components and the magnitude directly measured by the CDSM is just 0.5 nT (1σ) when the linear parameters are fitted separately for the day- and the night-side. Satellite disturbances have been analyzed including soft and hard remanence as well as magnetization of the magnetic torquer, radiation from the Tri-Band Beacon, and interferences from the rotation of the solar wing. A comparison shows consistency between the HPM and SWARM magnetic field data. Observation examples are introduced in the paper, which show that HPM data can be used to survey the global geomagnetic field and monitor the magnetic field disturbances in the ionosphere.
Determinants of p14/ARF methylation in healthy females: association with reproductive and non-reproductive risk factors of breast cancer
Authors: Ezzat Ghada M. , El-Shoeiby Mahmoud H. 
Published: November 2019

Abstract

Background
DNA methylation is associated with the risk factors of breast cancer. However, the impact of the reproductive and non-reproductive risk factors of breast cancer on p14/ARF methylation is not well known. Therefore, we investigated the relationships between p14/ARF methylation percentage and risk factors of breast cancer including age, family history, obesity, and reproductive risk factors in 120 breast cancer-free subjects; 60 women with a first-degree family history of breast cancer and 60 age-matched women with no family history of breast cancer. Extracted DNA from the whole blood was bisulfite-treated by EZ DNA modification kit. Quantitative methylation of p14/ARF was analyzed by methylation-specific PCR then methylation percentage of p14/ARF was calculated.

Results
P14/ARF methylation percentage was not related to any of the risk factors of breast cancer except age. Our study showed that p14/ARF methylation percentage was significantly higher in females with age ≥ 40 years than in females with age <  40 years (p=0.029). Also, a positive significant correlation between the p14/ARF methylation percentage and age was detected (r = 0.285, p = 0.014). Furthermore, univariate regression analysis showed that the age is independently associated with high p14/ARF methylation percentage (β = 1. 46, p = 0.029).

Conclusion
Among healthy females, the age is strongly linked to the peripheral p14/ARF methylation percentage. The present study suggests that p14/ARF methylation is not associated with other breast cancer risk factors. These results need oncoming research on a large cohort to define the interactions between p14/ARF methylation and the risk factors of breast cancer.
Assessing asylum seekers, refugees and undocumented migrants
Authors: Waterman Lauren Z. , Katona Cara , Katona Cornelius 
Published: November 2019

SummaryIdentifying the causes of psychiatric and physical symptoms in asylum seekers, refugees and other migrants and making definitive diagnoses can be challenging. Ethical and legal challenges in the UK include the likely deterrent effects of upfront charging for National Health Service (NHS) services. This paper focuses on the fictitious case of an asylum seeker presenting to a mental health service in England, highlighting some of the difficulties in assessing and treating this patient group and providing advice to clinicians on clinical and practical management. Current NHS entitlements for migrants are summarised and a list is presented in the online supplement of non-governmental organisations that can provide further support.
A Randomized, Placebo-Controlled Double-Blind Trial of a Closed-Loop Glucagon System for Postbariatric Hypoglycemia
Authors: Mulla Christopher M , Zavitsanou Stamatina , Laguna Sanz Alejandro Jose , Pober David , Richardson Lauren , Walcott Pamela , Arora Ipsa , Newswanger Brett , Cummins Martin J , Prestrelski Steve J , Doyle Francis J , Dassau Eyal , Patti Mary Elizabeth 
Published: November 2019

Abstract

Background
Postbariatric hypoglycemia (PBH) can threaten safety and reduce quality of life. Current therapies are incompletely effective.

Methods
Patients with PBH were enrolled in a double-blind, placebo-controlled, crossover trial to evaluate a closed-loop glucose-responsive automated glucagon delivery system designed to reduce severe hypoglycemia. A hypoglycemia detection and mitigation algorithm was embedded in the artificial pancreas system connected to a continuous glucose monitor (CGM, Dexcom) driving a patch infusion pump (Insulet) filled with liquid investigational glucagon (Xeris) or placebo (vehicle). Sensor/plasma glucose responses to mixed meal were assessed during 2 study visits. The system delivered up to 2 doses of study drug (300/150 μg glucagon or equal-volume vehicle) if triggered by the algorithm. Rescue dextrose was given for plasma glucose &lt;55 mg/dL or neuroglycopenia.

Results
Twelve participants (11 females/1 male, age 52 ± 2, 8 ± 1 years postsurgery, mean ± SEM) completed all visits. Predictive hypoglycemia alerts prompted automated drug delivery postmeal, when sensor glucose was 114 ± 7 vs 121 ± 5 mg/dL (P = .39). Seven participants required rescue glucose after vehicle but not glucagon (P = .008). Five participants had severe hypoglycemia (&lt;55 mg/dL) after vehicle but not glucagon (P = .03). Nadir plasma glucose was higher with glucagon vs vehicle (67 ± 3 vs 59 ± 2 mg/dL, P = .004). Plasma glucagon rose after glucagon delivery (1231 ± 187 vs 16 ± 1 pg/mL at 30 minutes, P = .001). No rebound hyperglycemia occurred. Transient infusion site discomfort was reported with both glucagon (n = 11/12) and vehicle (n = 10/12). No other adverse events were observed.

Conclusion
A CGM-guided closed-loop rescue system can detect imminent hypoglycemia and deliver glucagon, reducing severe hypoglycemia in PBH.

Clinical Trials Registration
NCT03255629
Mark1 regulates distal airspace expansion through type I pneumocyte flattening in lung development
Authors: Fumoto Katsumi , Takigawa-Imamura Hisako , Sumiyama Kenta , Yoshimura Shige H. , Maehara Natsumi , Kikuchi Akira 
Published: November 2019

ABSTRACT
During the later stages of lung development, two types of pneumocytes, cuboidal type II (AECII) and flattened type I (AECI) alveolar epithelial cells, form distal lung saccules. Here, we highlight how fibroblasts expressing MAP-microtubule affinity regulating kinase 1 (Mark1) are required for the terminal stages of pulmonary development, called lung sacculation. In Mark1-knockout (KO) mice, distal sacculation and AECI flattening are significantly impaired. Fetal epithelial cells generate alveolar organoids and differentiate into pneumocytes when co-cultured with fibroblasts. However, the size of organoids decreased and AECI flattening was impaired in the presence of Mark1 KO fibroblasts. In Mark1 KO fibroblasts themselves, cilia formation and the Hedgehog pathway were suppressed, resulting in the loss of type I collagen expression. The addition of type I collagen restored AECI flattening in organoids co-cultured with Mark1 KO fibroblasts and rescued the decreased size of organoids. Mathematical modeling of distal lung sacculation supports the view that AECI flattening is necessary for the proper formation of saccule-like structures. These results suggest that Mark1-mediated fibroblast activation induces AECI flattening and thereby regulates distal lung sacculation.