bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic changes of angiopoietins and endothelial nitric oxide supply during fluid resuscitation for major gyn-oncological surgery: a prospective observation
Authors: Gehlen Jennifer , Klaschik Sven , Neumann Claudia , Keyver-Paik Mignon-Denise , Mustea Alexander , Soehle Martin , Frede Stilla , Velten Markus , Hoeft Andreas , Hilbert Tobias 
Published: January 2020

Abstract
Background
Despite goal-directed hemodynamic therapy, vascular function may deteriorate during surgery for advanced abdominal tumor masses. Fluid administration has been shown to be associated with distinct changes in serum levels of functional proteins. We sought to determine how serum total protein and angiopoietin (ANG) levels change during major abdominal tumor surgery. In addition, ex vivo endothelial nitric oxide synthase (eNOS) activation as well as NO bioavailability in vivo were assessed.

Methods
30 patients scheduled for laparotomy for late-stage ovarian or uterine cancer were prospectively included. Advanced hemodynamic monitoring as well as protocol-driven goal-directed fluid optimization were performed. Total serum protein, ANG-1, -2, and soluble TIE2 were determined pre-, intra-, and postoperatively. Phosphorylation of eNOS was assessed in microvascular endothelial cells after incubation with patient serum, and microvascular reactivity was determined in vivo by near-infrared spectroscopy and arterial vascular occlusion.

Results
Cardiac output as well as preload gradually decreased during surgery and were associated with a median total fluid intake of 12.8 (9.7–15.4) mL/kg*h and a postoperative fluid balance of 6710 (4113–9271) mL. Total serum protein decreased significantly from baseline (66.5 (56.4–73.3) mg/mL) by almost half intraoperatively (42.7 (36.8–51.5) mg/mL, p < 0.0001) and remained at low level. While ANG-1 showed no significant dilutional change (baseline: 12.7 (11.9–13.9) ng/mL, postop.: 11.6 (10.8 –13.5) ng/mL, p = 0.06), serum levels of ANG-2 were even increased postoperatively (baseline: 2.2 (1.6–2.6) ng/mL vs. postop.: 3.4 (2.3–3.8) ng/mL, p < 0.0001), resulting in a significant shift in ANG-2 to ANG-1 ratio. Ex vivo phosphorylation of eNOS was decreased depending on increased ANG-2 levels and ANG-2/1 ratio (Spearman r = − 0.37, p = 0.007). In vivo, increased ANG-2 levels were associated with impaired capillary recruitment and NO bioavailability (Spearman r = − 0.83, p = 0.01).

Conclusions
Fluid resuscitation-associated changes in serum vascular mediator profile during abdominal tumor surgery were accompanied by impaired eNOS activity ex vivo as well as reduced NO bioavailability in vivo. Our results may explain disturbed microvascular function in major surgery despite goal-directed hemodynamic optimization.
ALK expressed in a gastrointestinal stromal tumor harboring PDGFRA p. D842V mutation:a case report
Authors: Fan Jun , Yang Ming , Huang Bo , Wang Zhenkao , Luo Danju , Zhang Jiwei , Zhang Peng , Shi Heshui , Li Yan , Nie Xiu 
Published: January 2020

Abstract
Background
Gastrointestinal stromal tumors (GISTs) are the most common type of adult mesenchymal neoplasms. The events that drive GIST oncogenesis are primarily KIT or PDGFRA mutations, which lead to the susceptibility of these tumors to small-molecule tyrosine kinase inhibitors such as imatinib and sunitinib. However, previous studies have shown that patients with a PDGFRA D842V mutation in GISTs have a very low rate of response to imatinib treatment. Therefore, novel tyrosine kinase inhibitors (TKIs) are currently being evaluated in clinical trials to treat GISTs harboring a PDGFRA D842V mutation. Anaplastic lymphoma kinase (ALK) overexpression was not expected to be present in the GIST, and it has been used as a biomarker to distinguish GISTs from other types of mesenchymal tumors.

Case presentation
Here, we report a 37-year-old male patient who presented with a large mass in the right upper abdomen and was subsequently diagnosed with a GIST harboring a PDGFRA D842V mutation. We unexpectedly found that the GIST in this patient exhibited simultaneous ALK expression.

Conclusions
This is the first case reported of a GIST with ALK expression. This rare phenomenon suggests that the diagnosis of a GIST cannot be excluded absolutely if a tumor exhibits ALK expression. In addition, ALK may be a potential therapeutic target for patients with imatinib-resistant stromal tumors.
Population-based analysis of curative therapies in stage II non-small cell lung cancer: the role of radiotherapy in medically inoperable patients
Authors: Moore Sara , Leung Bonnie , Wu Jonn , Ho Cheryl 
Published: January 2020

Abstract
Objectives
Curative intent therapy of stage II NSCLC may include surgical resection or definitive radiotherapy. Primary management with surgery or radiotherapy may be influenced by patient and disease characteristics. We sought to perform a comparison of patients receiving surgery or radical radiation therapy as their curative treatment, and explore the impact of known prognostic factors on outcome.

Materials and methods
A retrospective review was completed of all patients with stage II NSCLC referred to the BC Cancer Agency from 2005 to 2012. Cases were filtered to identify those receiving curative intent therapy including surgery or radiotherapy. Information was collected on known prognostic and predictive factors. The primary outcome measure was overall survival. We compared survival among patients receiving curative intent radiotherapy versus surgical intervention.

Results
A total of 535 patients were referred. Of these, 245 (46%) received curative intent surgery, 132 (25%) curative intent radiotherapy, and 158 (30%) did not receive curative therapy. There were significant differences between cohorts with respect to median age, histology, ECOG PS, smoking status, and weight loss. Median OS was significantly different between cohorts: 61.4 m surgery, 26.5 m curative RT, and 13.1 m non-curative therapy. In a case-matched analysis, median OS remained superior for surgery at 101.6 m vs 28.1 m for curative RT. In a multivariate analysis, ECOG PS, weight loss, and treatment cohort all influenced survival. Among patients receiving curative intent radiotherapy, the use of concurrent chemotherapy and RT dose > = 60Gy were associated with improved outcomes.

Conclusions
Among patients with stage II NSCLC, many are unable to undergo standard of care surgical resection. Radiotherapy provides an inferior yet still curative option in the management of inoperable patients. Further work is needed to optimize outcomes in this population.
Treatment planning comparison of volumetric modulated arc therapy employing a dual-layer stacked multi-leaf collimator and helical tomotherapy for cervix uteri
Authors: Panda S. , Swamidas J. , Chopra S. , Mangaj A. , Fogliata A. , Kupelian P. , Agarwal J. P. , Cozzi L. 
Published: January 2020

AbstractPurposeTo ascertain the dosimetric performance of a new delivery system (the Halcyon system, H) equipped with dual-layer stacked multi-leaf collimator (MLC) for risk-adapted targets in cervix uteri cancer patients compared to another ring-based system in clinical operation (Helical Tomotherapy, HT).MethodsTwenty patients were retrospectively included in a treatment planning study (10 with positive lymph nodes and 10 without). The dose prescription (45Gy to the primary tumour volume and a simultaneously integrated boost up to 55Gy for the positive patients) and the clinical planning objectives were defined consistently as recommended by an ongoing multicentric clinical trial. Halcyon plans were optimised for the volumetric modulated arc therapy. The plan comparison was performed employing the quantitative analysis of the dose-volume histograms.ResultsThe coverage of the primary and nodal target volumes was comparable for both techniques and both subsets of patients. The primary planning target volume (PTV) receiving at least 95% of the prescription isodose ranged from 97.2 ± 1.1% (node-negative) to 99.1 ± 1.2% (node-positive) for H and from 96.5 ± 1.9% (node-negative) to 98.3 ± 0.9% (node-positive) for HT. The uncertainty is expressed at one standard deviation from the cohort of patient per each group. For the nodal clinical target volumes, the dose received by 98% of the planning target volume ranged 55.5 ± 0.1 to 56.0 ± 0.8Gy for H and HT, respectively. The only significant and potentially relevant differences were observed for the bowels. In this case, V40Gyresulted 226.3 ± 35.9 and 186.9 ± 115.9 cm3for the node-positive and node-negative patients respectively for Halcyon. The corresponding findings for HT were: 258.9 ± 60.5 and 224.9 ± 102.2 cm3. On the contrary, V15Gyresulted 1279.7 ± 296.5 and 1557.2 ± 359.9 cm3for HT and H respectively for node-positive and 1010.8 ± 320.9 versus 1203.8 ± 332.8 cm3for node-negative.ConclusionThis retrospective treatment planning study, based on the dose constraints derived from the Embrace II study protocol, suggested the essential equivalence between Halcyon based and Helical Tomotherapy based plans for the intensity-modulated rotational treatment of cervix uteri cancer. Different levels of sparing were observed for the bowels with H better protecting in the high-dose region and HT in the mid-low dose regions. The clinical impact of these differences should be further addressed.
Radiotherapy alone for stage IE ocular adnexal mucosa-associated lymphoid tissue lymphomas: long-term results
Authors: Niwa Masanari , Ishikura Satoshi , Tatekawa Kotoha , Takama Natsuko , Miyakawa Akifumi , Kubota Toshinobu , Kato Eriko , Shibamoto Yuta 
Published: January 2020

Abstract
Background
To evaluate the long-term efficacy and toxicity of radiation therapy in patients with Stage IE primary ocular adnexal mucosa-associated lymphoid tissue lymphoma.

Methods
We designed a retrospective analysis to evaluate 81 patients with ocular adnexal mucosa-associated lymphoid tissue lymphoma treated with radiation therapy between 2006 and 2016. The median radiation dose was 30 Gy (range, 30–36 Gy in 15–18 fractions). Local control, progression-free survival, overall survival, and cumulative incidence of Grade 3 cataract were calculated by using the Kaplan–Meier method.

Result
The median follow-up time was 74 months (range, 4–157 months). The 5-year local control was 100%. Although local relapse was suspected in 3 patients after radiation therapy, 2 patients were pathologically diagnosed as IgG4-related inflammation and in 1 patient as intense inflammatory cell infiltration. The 5-year progression-free survival was 94.4%. Five patients had relapse at distant sites. The 5-year overall survival was 98.8%. Twenty patients had Grade 3 cataract. The 5-year cumulative incidences of Grade ≥ 3 and Grade ≥ 2 cataract for 58 patients treated without a lens shield were 38 and 40%, respectively. The incidence of Grade ≥ 3 cataract was 42% for 50 patients treated with 6-MV X-rays (estimated lens dose: 29 Gy) and 17% for 8 patients treated with 9-MeV electrons (estimated lens dose: 24 Gy).

Conclusions
Radiation therapy alone yielded excellent local control and long-term survival in Stage IE ocular adnexal mucosa-associated lymphoid tissue lymphoma. Long-term observation with careful attention to relapse at distant sites is necessary. In the case of suspected local relapse, IgG4-related disease should be carefully ruled out.
Towards European harmonisation of healthcare for patients with rare immune disorders: outcome from the ERN RITA registries survey
Authors:   on behalf of ERN RITA Council, Papa Riccardo , Cant Andrew , Klein Christoph , Little Mark A. , Wulffraat Nico M. , Gattorno Marco , Ruperto Nicolino 
Published: January 2020

AbstractThe Rare Immunodeficiency, AutoInflammatory and AutoImmune Disease (RITA) network is a European Research Network (ERN) that brings together the leading centres for rare immune disorders. On April 2018 an online survey was sent to all RITA members in order to facilitate the harmonization of data collection in rare immune disorders registries. Currently, as many as 52 different registries collect data on rare immune disorders, of whom 30 (58%) are dedicated primarily to autoimmune diseases, 15 (29%) to primary immunodeficiencies and 12 (23%) to autoinflammatory disorders. Improving data on patient safety, outcome, and quality of life measures is warranted to unfold the full potential of RITA registries.
The impact of high frequency oscillatory ventilation on mortality in paediatric acute respiratory distress syndrome
Authors: Wong Judith Ju-Ming , Liu Siqi , Dang Hongxing , Anantasit Nattachai , Phan Phuc Huu , Phumeetham Suwannee , Qian Suyun , Ong Jacqueline Soo May , Gan Chin Seng , Chor Yek Kee , Samransamruajkit Rujipat , Loh Tsee Foong , Feng Mengling , Lee Jan Hau ,   for the Pediatric Acute & Critical care Medicine Asian Network (PACCMAN)
Published: January 2020

Abstract
Background
High-frequency oscillatory ventilation (HFOV) use was associated with greater mortality in adult acute respiratory distress syndrome (ARDS). Nevertheless, HFOV is still frequently used as rescue therapy in paediatric acute respiratory distress syndrome (PARDS). In view of the limited evidence for HFOV in PARDS and evidence demonstrating harm in adult patients with ARDS, we hypothesized that HFOV use compared to other modes of mechanical ventilation is associated with increased mortality in PARDS.

Methods
Patients with PARDS from 10 paediatric intensive care units across Asia from 2009 to 2015 were identified. Data on epidemiology and clinical outcomes were collected. Patients on HFOV were compared to patients on other modes of ventilation. The primary outcome was 28-day mortality and secondary outcomes were 28-day ventilator- (VFD) and intensive care unit- (IFD) free days. Genetic matching (GM) method was used to analyse the association between HFOV treatment with the primary outcome. Additionally, we performed a sensitivity analysis, including propensity score (PS) matching, inverse probability of treatment weighting (IPTW) and marginal structural modelling (MSM) to estimate the treatment effect.

Results
A total of 328 patients were included. In the first 7 days of PARDS, 122/328 (37.2%) patients were supported with HFOV. There were significant differences in baseline oxygenation index (OI) between the HFOV and non-HFOV groups (18.8 [12.0, 30.2] vs. 7.7 [5.1, 13.1] respectively; p < 0.001). A total of 118 pairs were matched in the GM method which found a significant association between HFOV with 28-day mortality in PARDS [odds ratio 2.3, 95% confidence interval (CI) 1.3, 4.4, p value 0.01]. VFD was indifferent between the HFOV and non-HFOV group [mean difference − 1.3 (95%CI − 3.4, 0.9); p = 0.29] but IFD was significantly lower in the HFOV group [− 2.5 (95%CI − 4.9, − 0.5); p = 0.03]. From the sensitivity analysis, PS matching, IPTW and MSM all showed consistent direction of HFOV treatment effect in PARDS.

Conclusion
The use of HFOV was associated with increased 28-day mortality in PARDS. This study suggests caution but does not eliminate equivocality and a randomized controlled trial is justified to examine the true association.
Effect of Daesiho-tang on obesity with non-alcoholic fatty liver disease: a study protocol for a randomised, double-blind, placebo-controlled pilot trial
Authors: Han Kyungsun , Kwon Ojin , Park Hyo-ju , Jung So-Young , Yang Changsop , Son Chang-Gue 
Published: January 2020

Abstract
Background
The high prevalence of obesity and non-alcoholic fatty acid disease has become an important public health problem. Daesiho-tang (DST) is an herbal medicine widely used to treat obesity, metabolic syndrome and liver diseases. This pilot study will assess the feasibility of using DST in obese patients with a non-alcoholic fatty liver disease (NAFLD) prior to undertaking a full-scale clinical trial.

Methods/design
This is a study protocol for a randomised, double-blind, parallel-group, stratified, placebo-controlled pilot trial. We will recruit a total of 60 participants with NAFLD who have a body mass index ≥ 25 kg/m2. They will take either DST or placebo (3 g, three times daily) for 12 weeks with a 4-week follow-up period. The effects of DST will be evaluated by the mean change in body weight as the primary measurement and other secondary parameters (body composition, anthropometric measurements, blood tests, hepatic fat quantification through transient elastography and a physical symptoms questionnaire). Faecal samples will be collected before and after the intervention for a gut microbial analysis.

Discussion
In anticipation of conducting further large-scale trials, in this study we will explore the effect of DST on weight loss and obesity-related markers, along with NAFLD-related clinical parameters, in obese patients with NAFLD. Furthermore, it will provide insight into the DST pharmacological mechanism of action through a gut microbiome analysis.

Trial registration
Korean Clinical Trial Registry, KCT0003554. Registered on 25 February 2019.
Proteins involved in the biosynthesis of lipophosphoglycan in Leishmania: a comparative genomic and evolutionary analysis
Authors: Azevedo Lucas Gentil , de Queiroz Artur Trancoso Lopo , Barral Aldina , Santos Luciane Amorim , Ramos Pablo Ivan Pereira 
Published: January 2020

Abstract
Background
Leishmania spp. are digenetic parasites capable of infecting humans and causing a range of diseases collectively known as leishmaniasis. The main mechanisms involved in the development and permanence of this pathology are linked to evasion of the immune response. Crosstalk between the immune system and particularities of each pathogenic species is associated with diverse disease manifestations. Lipophosphoglycan (LPG), one of the most important molecules present on the surface of Leishmania parasites, is divided into four regions with high molecular variability. Although LPG plays an important role in host-pathogen and vector-parasite interactions, the distribution and phylogenetic relatedness of the genes responsible for its synthesis remain poorly explored. The recent availability of full genomes and transcriptomes of Leishmania parasites offers an opportunity to leverage insight on how LPG-related genes are distributed and expressed by these pathogens.

Results
Using a phylogenomics-based framework, we identified a catalog of genes involved in LPG biosynthesis across 22 species of Leishmania from the subgenera Viannia and Leishmania, as well as 5 non-Leishmania trypanosomatids. The evolutionary relationships of these genes across species were also evaluated. Nine genes related to the production of the glycosylphosphatidylinositol (GPI)-anchor were highly conserved among compared species, whereas 22 genes related to the synthesis of the repeat unit presented variable conservation. Extensive gain/loss events were verified, particularly in genes SCG1-4 and SCA1-2. These genes act, respectively, on the synthesis of the side chain attached to phosphoglycans and in the transfer of arabinose residues. Phylogenetic analyses disclosed evolutionary patterns reflective of differences in host specialization, geographic origin and disease manifestation.

Conclusions
The multiple gene gain/loss events identified by genomic data mining help to explain some of the observed intra- and interspecies variation in LPG structure. Collectively, our results provide a comprehensive catalog that details how LPG-related genes evolved in the Leishmania parasite specialization process.
A highly sensitive and specific workflow for detecting rare copy-number variants from exome sequencing data
Authors: Rajagopalan Ramakrishnan , Murrell Jill R. , Luo Minjie , Conlin Laura K. 
Published: January 2020

AbstractBackgroundExome sequencing (ES) is a first-tier diagnostic test for many suspected Mendelian disorders. While it is routine to detect small sequence variants, it is not a standard practice in clinical settings to detect germline copy-number variants (CNVs) from ES data due to several reasons relating to performance. In this work, we comprehensively characterized one of the most sensitive ES-based CNV tools, ExomeDepth, against SNP array, a standard of care test in clinical settings to detect genome-wide CNVs.MethodsWe propose a modified ExomeDepth workflow by excluding exons with low mappability prior to variant calling to drastically reduce the false positives originating from the repetitive regions of the genome, and an iterative variant calling framework to assess the reproducibility. We used a cohort of 307 individuals with clinical ES data and clinical SNP array to estimate the sensitivity and false discovery rate of the CNV detection using exome sequencing. Further, we performed targeted testing of theSTRCgene in 1972 individuals. To reduce the number of variants for downstream analysis, we performed a large-scale iterative variant calling process with random control cohorts to assess the reproducibility of the CNVs.ResultsThe modified workflow presented in this paper reduced the number of total variants identified by one third while retaining a higher sensitivity of 97% and resulted in an improved false discovery rate of 11.4% compared to the default ExomeDepth pipeline. The exclusion of exons with low mappability removes 4.5% of the exons, including a subset of exons (0.6%) in disease-associated genes which are intractable by short-read next-generation sequencing (NGS). Results from the reproducibility analysis showed that the clinically reported variants were reproducible 100% of the time and that the modified workflow can be used to rank variants from high to low confidence. Targeted testing of 30 CNVs identified inSTRC, a challenging gene to ascertain by NGS, showed a 100% validation rate.ConclusionsIn summary, we introduced a modification to the default ExomeDepth workflow to reduce the false positives originating from the repetitive regions of the genome, created a large-scale iterative variant calling framework for reproducibility, and provided recommendations for implementation in clinical settings.
An open-source video tracking system for mouse locomotor activity analysis
Authors: Zhang Chen , Li Haiwen , Han Renzhi 
Published: January 2020

AbstractObjectiveThe ability to accurately and efficiently quantify mouse locomotor activity is essential for evaluating therapeutic efficacy and phenotyping genetically modified mice, in particular for the research of neuromuscular diseases. Our objective is to develop a program for video tracking of mice and locomotion analysis.ResultsHere we describe a MATLAB program for video tracking of mice and locomotion analysis. The system is composed of a webcam, an open field, and a computer with MATLAB installed. Animal behavior is recorded by the webcam and the video is then analyzed for mouse position on each frame by a customized MATLAB code. The system has been tested for analyzing two or more mice simultaneously placed in individual chambers. The accumulative moving distance, velocity and thigmotaxis (percentage of time spending in the outer peripheral of the arena, which is commonly used as an index of anxiety) within a test period can be readily obtained. This system can be easily implemented in any laboratory as an in vivo locomotion assay to assess the neuromuscular abnormality of genetically modified animals and the impact of therapeutic interventions.