bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gastric per-oral endoscopic myotomy (G-POEM) for refractory gastroparesis: results from an international prospective trial
Authors: Vosoughi Kia , Ichkhanian Yervant , Benias Petros , Miller Larry , Aadam A Aziz , Triggs Joseph R , Law Ryan , Hasler William , Bowers Nicole , Chaves Dalton , Ponte-Neto Alberto M , Draganov Peter , Yang Dennis , El Halabi Maan , Sanaei Omid , Brewer Gutierrez Olaya Isabella , Bulat Robert Stephen , Pandolfino John , Khashab Mouen 
Published: March 2021

ObjectiveAlthough gastric per-oral endoscopic myotomy (G-POEM) is considered a promising technique for the management of refractory gastroparesis, high-quality evidence is limited. We prospectively investigated the efficacy and safety of G-POEM in unselected patients with refractory gastroparesis.DesignIn five tertiary centres, patients with symptomatic gastroparesis refractory to standard medical therapy and confirmed by impaired gastric emptying were included. The primary endpoint was clinical success, defined as at least one score decrease in Gastroparesis Cardinal Symptom Index (GCSI) with ≥25% decrease in two subscales, at 12 months. GCSI Score and subscales, adverse events (AEs) and 36-Item Short Form questionnaire of quality of life were evaluated at baseline and 1, 3, 6 and 12 months after G-POEM. Gastric emptying study was performed before and 3 months after the procedure.ResultsOf 80 enrolled patients, 75 patients (94%) completed 12-month follow-up. Clinical success at 12 months was 56% (95% CI, 44.8 to 66.7). GCSI Score (including subscales) improved moderately after G-POEM (p<0.05). In a regression model, a baseline GCSI Score >2.6 (OR=3.23, p=0.04) and baseline gastric retention >20% at 4 hours (OR=3.65, p=0.03) were independent predictors of clinical success at 12 months, as was early response to G-POEM at 1 month after therapy (OR 8.75, p<0.001). Mild procedure-related AEs occurred in 5 (6%) patients.ConclusionG-POEM is a safe procedure, but showed only modest overall effectiveness in the treatment of refractory gastroparesis. Further studies are required to identify the best candidates for G-POEM; unselective use of this procedure should be discouraged.Trial registration numberClinicalTrials.gov Registry NCT02732821.
Ratio of urinary N-terminal titin fragment to urinary creatinine is a novel biomarker for amyotrophic lateral sclerosis
Authors: Yamada Shinichiro , Hashizume Atsushi , Hijikata Yasuhiro , Ito Daisuke , Kishimoto Yoshiyuki , Iida Madoka , Koike Haruki , Hirakawa Akihiro , Katsuno Masahisa 
Published: March 2021

ObjectiveWe aimed to investigate the validity of urinary N-terminal titin fragment as a biomarker for amyotrophic lateral sclerosis (ALS).MethodsWe consecutively enrolled patients with ALS (n=70) and healthy controls (HC) (n=43). We assessed the urinary titin N-terminal fragment, urinary neurotrophin receptor p75 extracellular domain, serum neurofilament light chain (NfL), motor functional measurements and prognosis. We used urinary creatinine (Cr) levels to normalise the urinary levels of titin fragment.ResultsCompared with HC, patients with ALS had significantly increased urinary levels of titin N-terminal fragment normalised with Cr (titin/Cr) (ALS, 27.2 pmol/mg/dL; HC, 5.8 pmol/mg/dL; p<0.001), which were correlated with the scores of the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (r=−0.422, p<0.001). A Cox proportional hazards model demonstrated that the high urinary level of titin/Cr was a survival predictor in patients with ALS. Multivariate analysis of prognostic factors showed that the urinary titin/Cr and serum NfL were independent factors for poor prognosis.ConclusionsOur findings indicate that urinary N-terminal titin fragment is a non-invasive measure of muscle damage in ALS, which could be applied in disease monitoring and prediction of disease progression, in combination with serum NfL.
Small vessel disease burden and intracerebral haemorrhage in patients taking oral anticoagulants
Authors: Seiffge David J , Wilson Duncan , Ambler Gareth , Banerjee Gargi , Hostettler Isabel Charlotte , Houlden Henry , Shakeshaft Clare , Cohen Hannah , Yousry Tarek A , Al-Shahi Salman Rustam , Lip Gregory , Brown Martin M , Muir Keith , Jäger H.R , Werring David J 
Published: March 2021

ObjectiveWe investigated the contribution of small vessel disease (SVD) to anticoagulant-associated intracerebral haemorrhage (ICH).MethodsClinical Relevance of Microbleeds in Stroke-2 comprised two independent multicentre observation studies: first, a cross-sectional study of patients with ICH; and second, a prospective study of patients taking anticoagulants for atrial fibrillation (AF) after cerebral ischaemia. In patients with ICH, we compared SVD markers on CT and MRI according to prior anticoagulant therapy. In patients with AF and cerebral ischaemia treated with anticoagulants, we compared the rates of ICH and ischaemic stroke according to SVD burden score during 2 years follow-up.ResultsWe included 1030 patients with ICH (421 on anticoagulants), and 1447 patients with AF and cerebral ischaemia. Medium-to-high severity SVD was more prevalent in patients with anticoagulant-associated ICH (CT 56.1%, MRI 78.7%) than in those without prior anticoagulant therapy (CT 43.5%, p<0.001; MRI 64.5%, p=0.072). Leukoaraiosis and atrophy were more frequent and severe in ICH associated with prior anticoagulation. In the cerebral ischaemia cohort (779 with SVD), during 3366 patient-years of follow-up the rate of ICH was 0.56%/year (IQR 0.27–1.03) in patients with SVD, and 0.06%/year (IQR 0.00–0.35) in those without (p=0.001); ICH was independently associated with severity of SVD (HR 5.0, 95% CI 1.9 to 12.2,p=0.001), and was predicted by models including SVD (c-index 0.75, 95% CI 0.63 to 0.85).ConclusionsMedium-to-high severity SVD is associated with ICH occurring on anticoagulants, and independently predicts ICH in patients with AF taking anticoagulants; its absence identifies patients at low risk of ICH. Findings from these two complementary studies suggest that SVD is a contributory factor in ICH in patients taking anticoagulants and suggest that anticoagulation alone should no longer be regarded as a sufficient ‘cause’ of ICH.Trial registrationNCT02513316
Deciphering the Role of Intestinal Crypt Cell Populations in Resistance to Chemotherapy
Authors: Frau Carla , Jamard Catherine , Delpouve Gaspard , Guardia Gabriela D.A. , Machon Christelle , Pilati Camilla , Nevé Clémentine Le , Laurent-Puig Pierre , Guitton Jérôme , Galante Pedro A.F. , Penalva Luiz O. , Freund Jean-Noel , de la Fouchardiere Christelle , Plateroti Michelina 
Published: March 2021

Abstract

Intestinal crypts are composed of heterogeneous and highly plastic cell populations. Lgr5high-stem cells (SC) are responsible for homeostatic renewal, but other cells can revert to an SC-like phenotype to maintain epithelial integrity. Despite their distinct roles in orchestrating homeostasis, both populations have been designated as the putative “cell-of-origin” of colorectal cancer. However, their respective involvement in the emergence of drug-resistant cancer SCs (CSC), responsible for tumor relapse and associated with poor outcome of colorectal cancer, remains elusive. In this context, the intestinal SC/progenitor-marker Musashi1 (MSI1) is interesting as it plays important functions in intestinal homeostasis and is frequently overexpressed in human colorectal cancer. Therefore, our aims were: (i) to study the impact of chemotherapy on Lgr5-expressing and MSI1-expressing cell populations, (ii) to explore the effect of increased MSI1 levels in response to treatment, and (iii) to evaluate the relevance in human colorectal cancer. Engineered mouse models treated with the therapeutic agent 5-fluorouracil showed that upon increased MSI1 levels, Lgr5high SCs remain sensitive while Lgr5low progenitors reprogram to a drug-resistant phenotype. This resulted in the expansion of an MSI1-expressing cell subpopulation with improved resistance to DNA damage and increased detoxification, typical properties of dormant-CSCs that can reactivate after chemotherapy. Analysis in patients with colorectal cancer revealed a correlation between MSI1 levels and tumor grading, CSC phenotype, and chemoresistance. Altogether, these results shed new light on the biology and plasticity of normal crypt and cancer cell populations and also open new perspectives to target MSI1 to improve chemotherapy outcome.

Significance:
This study unveils paradoxical roles for MSI1, underlining its importance in facilitating intestinal regeneration upon injury but also unraveling its new function in drug-resistant colorectal cancer stem cells.
Genome-Wide DNA Methylation Profiling of Esophageal Squamous Cell Carcinoma from Global High-Incidence Regions Identifies Crucial Genes and Potential Cancer Markers
Authors: Talukdar Fazlur Rahman , Soares Lima Sheila C. , Khoueiry Rita , Laskar Ruhina Shirin , Cuenin Cyrille , Sorroche Bruna Pereira , Boisson Anne-Claire , Abedi-Ardekani Behnoush , Carreira Christine , Menya Diana , Dzamalala Charles P. , Assefa Mathewos , Aseffa Abraham , Miranda-Gonçalves Vera , Jerónimo Carmen , Henrique Rui M. , Shakeri Ramin , Malekzadeh Reza , Gasmelseed Nagla , Ellaithi Mona , Gangane Nitin , Middleton Daniel R.S. , Le Calvez-Kelm Florence , Ghantous Akram , Roux Maria Leon , Schüz Joachim , McCormack Valerie , Parker M. Iqbal , Pinto Luis Felipe Ribeiro , Herceg Zdenko 
Published: March 2021

AbstractEpigenetic mechanisms such as aberrant DNA methylation (DNAme) are known to drive esophageal squamous cell carcinoma (ESCC), yet they remain poorly understood. Here, we studied tumor-specific DNAme in ESCC cases from nine high-incidence countries of Africa, Asia, and South America. Infinium MethylationEPIC array was performed on 108 tumors and 51 normal tissues adjacent to the tumors (NAT) in the discovery phase, and targeted pyrosequencing was performed on 132 tumors and 36 NAT in the replication phase. Top genes for replication were prioritized by weighting methylation results using RNA-sequencing data from The Cancer Genome Atlas and GTEx and validated by qPCR. Methylome analysis comparing tumor and NAT identified 6,796 differentially methylated positions (DMP) and 866 differential methylated regions (DMR), with a 30% methylation (Δβ) difference. The majority of identified DMPs and DMRs were hypermethylated in tumors, particularly in promoters and gene-body regions of genes involved in transcription activation. The top three prioritized genes for replication, PAX9, SIM2, and THSD4, had similar methylation differences in the discovery and replication sets. These genes were exclusively expressed in normal esophageal tissues in GTEx and downregulated in tumors. The specificity and sensitivity of these DNAme events in discriminating tumors from NAT were assessed. Our study identified novel, robust, and crucial tumor-specific DNAme events in ESCC tumors across several high-incidence populations of the world. Methylome changes identified in this study may serve as potential targets for biomarker discovery and warrant further functional characterization.Significance:This largest genome-wide DNA methylation study on ESCC from high-incidence populations of the world identifies functionally relevant and robust DNAme events that could serve as potential tumor-specific markers.
Structural Variants at theBRCA1/2Loci are a Common Source of Homologous Repair Deficiency in High-grade Serous Ovarian Carcinoma
Authors: Ewing Ailith , Meynert Alison , Churchman Michael , Grimes Graeme R. , Hollis Robert L. , Herrington C. Simon , Rye Tzyvia , Bartos Clare , Croy Ian , Ferguson Michelle , Lennie Mairi , McGoldrick Trevor , McPhail Neil , Siddiqui Nadeem , Dowson Suzanne , Glasspool Rosalind , Mackean Melanie , Nussey Fiona , McDade Brian , Ennis Darren , McMahon Lynn , Matakidou Athena , Dougherty Brian , March Ruth , Barrett J. Carl , McNeish Iain A. ,   for the Scottish Genomes Partnership, Biankin Andrew V. , Roxburgh Patricia , Gourley Charlie , Semple Colin A. 
Published: March 2021

AbstractPurpose:The abundance and effects of structural variation at BRCA1/2 in tumors are not well understood. In particular, the impact of these events on homologous recombination repair deficiency (HRD) has yet to be demonstrated.Experimental Design:Exploiting a large collection of whole-genome sequencing data from high-grade serous ovarian carcinoma (N = 205) together with matched RNA sequencing for the majority of tumors (N = 150), we have comprehensively characterized mutation and expression at BRCA1/2.Results:In addition to the known spectrum of short somatic mutations (SSM), we discovered that multi-megabase structural variants (SV) were a frequent, unappreciated source of BRCA1/2 disruption in these tumors, and we found a genome-wide enrichment for large deletions at the BRCA1/2 loci across the cohort. These SVs independently affected a substantial proportion of patients (16%) in addition to those affected by SSMs (24%), conferring HRD and impacting patient survival. We also detail compound deficiencies involving SSMs and SVs at both loci, demonstrating that the strongest risk of HRD emerges from combined SVs at both BRCA1 and BRCA2 in the absence of SSMs. Furthermore, these SVs are abundant and disruptive in other cancer types.Conclusions:These results extend our understanding of the mutational landscape underlying HRD, increase the number of patients predicted to benefit from therapies exploiting HRD, and suggest there is currently untapped potential in SV detection for patient stratification.
Natural Course of New‐Onset Postoperative Atrial Fibrillation after Noncardiac Surgery
Authors: Hyun Junho , Cho Min Soo , Nam Gi‐Byoung , Kim Minsoo , Do Ungjeong , Kim Jun , Choi Kee‐Joon , Kim You‐Ho 
Published: March 2021

Background
Postoperative atrial fibrillation (POAF) is common after cardiac surgery, but little is known about its incidence and natural course after noncardiac surgery. We evaluated the natural course and clinical impact of POAF and the long‐term impact of anticoagulation therapy in patients without a history of atrial fibrillation (AF) undergoing noncardiac surgery.

Methods and Results

We retrospectively analyzed the database of Asan Medical Center (Seoul, Korea) to identify patients who developed new‐onset POAF after undergoing noncardiac surgery between January 2006 and January 2016. The main outcomes were AF recurrence, thromboembolic event, and major bleeding during follow‐up. Of 322 688 patients who underwent noncardiac surgery, 315 patients (mean age, 66.4 years; 64.4% male) had new‐onset POAF with regular rhythm monitoring after discharge. AF recurred in 53 (16.8%) during 2 years of follow‐up. Hypertension (hazard ratio, 2.12;
P
=0.02), moderate‐to‐severe left atrial enlargement (hazard ratio, 2.33;
P
=0.007) were independently associated with recurrence. Patients with recurrent AF had higher risks of thromboembolic events (11.2% versus 0.8%;
P
<0.001) and major bleeding (26.9% versus 4.1%;
P
<0.001) than those without recurrence. Patients with recurrent AF and without anticoagulation were especially predisposed to thromboembolic events (
P
<0.001). Overall, anticoagulation therapy was not significantly associated with thromboembolic events (1.4% versus 2.5%,
P
=0.95).

Conclusions
AF recurred in 16.8% of patients with POAF after noncardiac surgery. AF recurrence was associated with higher risks of adverse clinical outcomes. Considering the high risk of anticoagulation‐related bleeding, the benefits of routine anticoagulation should be carefully weighed in this population. Active surveillance for AF recurrence is warranted.
Factors Related to Major Bleeding After Ticagrelor Therapy: Results from the TICO Trial
Authors: Cho Jae Young , Lee Seung‐Yul , Yun Kyeong Ho , Kim Byeong‐Keuk , Hong Sung‐Jin , Ko Jum Suk , Rhee Sang Jae , Oh Seok Kyu , Shin Dong‐Ho , Ahn Chul‐Min , Kim Jung‐Sun , Ko Young‐Guk , Choi Donghoon , Hong Myeong‐Ki , Jang Yangsoo 
Published: March 2021

Background
There is a lack of data on factors that are related to clinically relevant bleeding after ticagrelor treatment. We investigated the clinical and procedural factors related to major bleeding in patients with acute coronary syndrome treated with ticagrelor after coronary stent implantation.

Methods and Results

From the TICO (Ticagrelor Monotherapy After 3 Months in Patients Treated With New Generation Sirolimus‐Eluting Stent for Acute Coronary Syndrome) randomized trial, a total of 2660 patients were included for the present study. Patients with major bleeding, defined by TIMI (Thrombolysis in Myocardial Infarction) major or Bleeding Academic Research Consortium type 3 or 5, were compared with those without major bleeding. On the basis of multivariable and receiver operating characteristic curve analyses, weight ≤65 kg, hemoglobin ≤12 g/dL, and estimated glomerular filtration rate <60 mL/min per 1.73 m
2
were associated with an increased risk of major bleeding. In contrast, 3‐month aspirin therapy with continued ticagrelor (versus 12‐month aspirin and ticagrelor) was associated with a decreased risk of major bleeding. The lower risk of a net adverse clinical event (a composite of TIMI major bleeding and major adverse cardiac and cerebrovascular events) in patients treated with 3‐month aspirin therapy reported from the TICO trial remained valid in patients with any of these risk factors (hazard ratio, 0.59; 95% CI, 0.39–0.90;
P
interaction
=0.74).

Conclusions
Low body weight, anemia, and chronic kidney disease were risk factors for major bleeding after ticagrelor therapy. Early aspirin discontinuation had a net clinical benefit among patients with a bleeding risk.

Registration

URL:
https://www.clinicaltrials.gov/
. Unique Identifier: NCT02494895.
Early Season Hurricane Risk Assessment: Climate-Conditioned HITS Simulation of North Atlantic Tropical Storm Tracks
Authors: Nakamura Jennifer , Lall Upmanu , Kushnir Yochanan , Harr Patrick A. , McCreery Kyra 
Published: March 2021

AbstractWe present a hurricane risk assessment model that simulates North Atlantic Ocean tropical cyclone (TC) tracks and intensity, conditioned on the early season large-scale climate state. The model, Cluster-Based Climate-Conditioned Hurricane Intensity and Track Simulator (C3-HITS), extends a previous version of HITS. HITS is a nonparametric, spatial semi-Markov, stochastic model that generates TC tracks by conditionally simulating segments of randomly varying lengths from the TC tracks contained in NOAA’s Best Track Data, version 2, dataset. The distance to neighboring tracks, track direction, TC wind speed, and age are used as conditioning variables. C3-HITS adds conditioning on two early season, large-scale climate covariates to condition the track simulation: the Niño-3.4 index, representing the eastern equatorial Pacific Ocean sea surface temperature (SST) departure from climatology, and main development region, representing tropical North Atlantic SST departure from climatology in the North Atlantic TC main development region. A track clustering procedure is used to identify track families, and a Poisson regression model is used to model the probabilistic number of storms formed in each cluster, conditional on the two climate covariates. The HITS algorithm is then applied to evolve these tracks forward in time. The output of this two-step, climate-conditioned simulator is compared with an unconditional HITS application to illustrate its prognostic efficacy in simulating tracks during the subsequent season. As in the HITS model, each track retains information on velocity and other attributes that can be used for predictive coastal risk modeling for the upcoming TC season.
Simulation and Projection of Summer Convective Afternoon Rainfall Activities over Southeast Asia in CMIP6 Models
Authors: Huang Wan-Ru , Chang Ya-Hui , Deng Liping , Liu Pin-Yi 
Published: March 2021

AbstractConvective afternoon rainfall (CAR) events, which tend to generate a local rainfall typically in the afternoon, are among the most frequently observed local weather patterns over Southeast Asia during summer. Using satellite precipitation estimations as an observational base for model evaluation, this study examines the applicability of ten global climate models provided by the sixth phase of the Coupled Model Intercomparison Project (CMIP6) in simulating the CAR activities over Southeast Asia. Analyses also focus on exploring the characteristics and maintenance mechanisms of related projections of CAR activities in the future. Our analyses of the historical simulation indicate that EC-Earth3 and EC-Earth3-Veg are the two best models for simulating CAR activities (including amount, frequency, and intensity) over Southeast Asia. Analyses also demonstrate that EC-Earth3 and EC-Earth3-Veg outperform their earlier version (i.e., EC-Earth) in CMIP5 owing to the increase in its spatial resolution in CMIP6. For future projections, our examinations of the differences in CAR activities between the future (2071–2100, under the ssp858 run) and the present (1985–2014, under historical run) indicate that CAR events will become fewer but more intense over most land areas of Southeast Asia. Possible causes of the projected increase (decrease) in CAR intensity (frequency) are attributed to the projected increase (decrease) in the local atmospheric humidity (sea breeze convergence and daytime thermal instability). These findings provide insight into how the local weather/climate over Southeast Asia is likely to change under global warming.
Evaluating the 2019 NARO-APCC Joint Crop Forecasting Service Yield Forecasts for Northern Hemisphere Countries
Authors: Iizumi Toshichika , Shin Yonghee , Choi Jaewon , van der Velde Marijn , Nisini Luigi , Kim Wonsik , Kim Kwang-Hyung 
Published: March 2021

AbstractForecasting global food production is of growing importance in the context of globalizing food supply chains and observed increases in the frequency of climate extremes. The National Agriculture and Food Research Organization–Asia-Pacific Economic Cooperation Climate Center (NARO-APCC) Crop Forecasting Service provides yield forecasts for global cropland on a monthly basis using seasonal temperature and precipitation forecasts as the main inputs, and 1 year of testing the operation of the service was recently completed. Here we evaluate the forecasts for the 2019 yields of major commodity crops by comparing with the reported yields and forecasts from the European Commission’s Joint Research Centre (JRC) and the U.S. Department of Agriculture (USDA). Forecasts for maize, wheat, soybean, and rice were evaluated for 20 countries located in the Northern Hemisphere, including 39 crop-producing states in the United States, for which 2019 reported yields were already publicly available. The NARO-APCC forecasts are available several months earlier than the JRC and USDA forecasts. The skill of the NARO-APCC forecasts was good in absolute terms, but the forecast errors in the NARO-APCC forecasts were almost always larger than those of the JRC and USDA forecasts. The forecast errors in the JRC and USDA forecasts decreased as the harvest approached, whereas those in the NARO-APCC forecasts were rather stable over the season, with some exceptions. Although this feature seems to be a disadvantage, it may turn into an advantage if skillful forecasts are achievable in the earlier stages of a season. We conclude by discussing relative advantages and disadvantages and potential ways to improve global yield forecasting.