bluuebunny/crossref_metadata_2025_split huggingface dataset:
NOVA1-Mediated SORBS2 Isoform Promotes Colorectal Cancer Migration by Activating the Notch Pathway
Authors: Zhang Tao , Chen Sixia , Peng Yi , Wang Changgang , Cheng Xi , Zhao Ren , Liu Kun 
Published: October 2021

Background: Gene expression and alternative splicing (AS) can promote cancer development via complex mechanisms. We aimed to identify and verify the hub AS events and splicing factors associated with the progression of colorectal cancer (CRC).Methods: RNA-Seq data, clinical data, and AS events of 590 CRC samples were obtained from the TCGA and TCGASpliceSeq databases. Cox univariable and multivariable analyses, KEGG, and GO pathway analyses were performed to identify hub AS events and splicing factor/spliceosome genes, which were further validated in five CRCs.Results: In this study, we first compared differentially expressed genes and gene AS events between normal and tumor tissues. Differentially expressed genes were different from genes with differentially expressed AS events. Prognostic analysis and co-expression network analysis of gene expression and gene AS events were conducted to screen five hub gene AS events involved in CRC progression: EPB41L2, CELF2, TMEM130, VCL, and SORBS2. Using qRT-PCR, we also verified that the gene AS events SORBS2 were downregulated in tumor tissue, and gene AS events EPB41L2, CELF2, TMEM130, and VCL were upregulated in tumor tissue. The genes whose mRNA levels were significantly related to the five hub gene AS events were significantly enriched in the GO term of cell division and Notch signaling pathway. Further coexpression of gene AS events and alternative splicing factor genes revealed NOVA1 as a crucial factor regulating the hub gene AS event expression in CRC. Through in vitro experiments, we found that NOVA1 inhibited gene AS event SORBS2, which induced the migration of CRC cells via the Notch pathway.Conclusion: Integrated analysis of gene expression and gene AS events and further experiments revealed that NOVA1-mediated SORBS2 promoted the migration of CRC, indicating its potential as a therapeutic target.
Microbial Biofilm Decontamination on Dental Implant Surfaces: A Mini Review
Authors: Dhaliwal Jagjit Singh , Abd Rahman Nurul Adhwa , Ming Long Chiau , Dhaliwal Sachinjeet Kaur Sodhi , Knights Joe , Albuquerque Junior Rubens Ferreira 
Published: October 2021

IntroductionAfter insertion into the bone, implants osseointegrate, which is required for their long-term success. However, inflammation and infection around the implants may lead to implant failure leading to peri-implantitis and loss of supporting bone, which may eventually lead to failure of implant. Surface chemistry of the implant and lack of cleanliness on the part of the patient are related to peri-implantitis. The only way to get rid of this infection is decontamination of dental implants.ObjectiveThis systematic review intended to study decontamination of microbial biofilm methods on titanium implant surfaces used in dentistry.MethodsThe electronic databases Springer Link, Science Direct, and PubMed were explored from their inception until December 2020 to identify relevant studies. Studies included had to evaluate the efficiency of new strategies either to prevent formation of biofilm or to treat matured biofilm on dental implant surfaces.Results and DiscussionIn this systematic review, 17 different groups of decontamination methods were summarized from 116 studies. The decontamination methods included coating materials, mechanical cleaning, laser treatment, photodynamic therapy, air polishing, anodizing treatment, radiation, sonication, thermal treatment, ultrasound treatment, chemical treatment, electrochemical treatment, antimicrobial drugs, argon treatment, and probiotics.ConclusionThe findings suggest that most of the decontamination methods were effective in preventing the formation of biofilm and in decontaminating established biofilm on dental implants. This narrative review provides a summary of methods for future research in the development of new dental implants and decontamination techniques.
Randomized Evaluation of Beta Blocker and ACE-Inhibitor/Angiotensin Receptor Blocker Treatment for Post Infarct Angina in Patients With Myocardial Infarction With Non-obstructive Coronary Arteries: A MINOCA-BAT Sub Study Rationale and Design
Authors: Pasupathy Sivabaskari , Lindahl Bertil , Tavella Rosanna , Nordenskjöld Anna M. , Zeitz Christopher , Arstall Margaret , Worthley Matthew , Neil Christopher , Singh Kuljit , Turner Stuart , Rajwani Adil , Mooney John , Beltrame John F. 
Published: October 2021

Introduction: Myocardial infarction with non-obstructive coronary arteries (MINOCA) occurs in ~10% of all patients with acute myocardial infarction (AMI), with an over-representation amongst women. Remarkably, it is estimated that as many as 1 in 4 patients with MINOCA experience ongoing angina at 12 months despite having no flow-restricting stenoses in their epicardial arteries. This manuscript presents the rationale behind Randomized Evaluation of Beta Blocker and Angiotensin-converting enzyme inhibitors/Angiotensin Receptor Blocker Treatment (ACEI/ARB) for Post Infarct Angina in MINOCA patients—The MINOCA BAT post infarct angina sub study.Methods: This trial is a registry-based, randomized, parallel, open-label, multicenter trial with 2 × 2 factorial design. The primary aim is to determine whether oral beta blockade compared with no oral beta blockade, and ACEI/ARB compared with no ACEI/ARB, reduce post infarct angina in patients discharged after MINOCA without clinical signs of heart failure and with left ventricular ejection fraction ≥40%. A total of 664 patients will be randomized into four groups; (i) ACEI/ARB with beta blocker, (ii) beta blocker only, (iii) ACEI/ARB only, or (iv) neither ACEI/ARB nor beta blocker and followed for 12 months.Results: The trial is currently recruiting in Australia and Sweden. Fifty six patients have been recruited thus far. Both sexes were equally distributed (52% women and 48% men) and the mean age was 56.3 ± 9.9 years.Conclusions: It remains unclear whether conventional secondary preventive therapies are beneficial to MINOCA patients in regard to post infarct angina. Existing registry-based literature suggest cardioprotective agents are less likely to be used in MINOCA patients. Thus, results from this trial will provide insights for future treatment strategies and guidelines specific to MINOCA patients.
Effectiveness of Direct Oral Anticoagulants in Obese Adults With Atrial Fibrillation: A Systematic Review of Systematic Reviews and Meta-Analysis
Authors: Shaikh Fahad , Wynne Rochelle , Castelino Ronald L. , Inglis Sally C. , Ferguson Caleb 
Published: October 2021

Background: Atrial Fibrillation (AF) is the most common sustained cardiac arrhythmia. Obesity is an independent risk factor for AF. Anticoagulants have been strongly recommended by all international guidelines to prevent stroke. However, altered pathophysiology in obese adults may influence anticoagulant pharmacology. Direct oral anticoagulants (DOACs) in the context of obesity and AF have been examined in recent systematic reviews. Despite the similarities in included studies, their results and conclusions do not agree.Methods and Results: The protocol for this review was registered with PROSPERO (CRD42020181510). Seven key electronic databases were searched using search terms such as “atrial fibrillation,” “obese,*” “overweight,” “novel oral anticoagulant,” “direct oral anticoagulant,” “DOAC,” “NOAC,” “apixaban,” dabigatran,” “rivaroxaban,” and “edoxaban” to locate published and unpublished studies. Only systematic reviews with meta-analyses that examined the effect of DOACs in overweight or obese adults with AF, published in the English language, were included. A total of 9,547 articles were initially retrieved. After removing the duplicates, title and abstract review and full-text review, five articles were included in the systematic review. From these only RCTs were included in the meta-analyses. There was disagreement within the published systematic reviews on DOACs in obesity. The results from our meta-analysis did not show any significant difference between all body mass index (BMI) groups for all outcomes at both 12 months and for the entire trial duration. Non-significant differences were seen among the different types of DOACs.Conclusion: There was no difference between the BMI classes in any of the outcomes assessed. This may be due to the limited number of people in the trial that were in the obese class, especially obese class III. There is a need for large prospective trials to confirm which DOACs are safe and efficacious in the obese class III adults and at which dose.
Antithrombotic Therapy for Chronic Kidney Disease Patients With Concomitant Atrial Fibrillation and Coronary Artery Disease
Authors: Lee Kuo-Hua , Ou Shuo-Ming , Chu Yuan-Chia , Lin Yao-Ping , Tsai Ming-Tsun , Tarng Der-Cherng 
Published: October 2021

Background: Oral anticoagulants (OAC) plus antiplatelets is recommended for patients with atrial fibrillation (AF) and coronary artery disease (CAD) to reduce thromboembolism. However, there is limited evidence regarding antithrombotic therapy for patients with concomitant chronic kidney disease (CKD), AF, and CAD, especially those not undergoing percutaneous coronary intervention. We aimed to use real-world data assessing the efficacy and safety of antithrombotic regimens in this population.Methods: We used a single-center database of 142,624 CKD patients to identify those receiving antithrombotic therapy for AF and CAD between 2010 and 2018. Patients taking warfarin or direct OAC (DOAC) alone were grouped in the OAC monotherapy (n = 537), whereas those taking OAC plus antiplatelets were grouped in the combination therapy (n = 2,391). We conducted propensity score matching to balance baseline covariates. The endpoints were all-cause mortality, major adverse cardiovascular events, and major bleedings.Results: After 1:4 matching, the number of patients in OAC monotherapy and combination therapy were 413 and 1,652, respectively. Between the two groups, combination therapy was associated with higher risks for ischemic stroke (HR 2.37, CI 1.72–3.27), acute myocardial infarction (HR 6.14, CI 2.51–15.0), and hemorrhagic stroke (HR 3.57, CI 1.35–9.81). The results were consistent across CKD stages. In monotherapy, DOAC users were associated with lower risks for all-cause mortality, AMI, and gastrointestinal bleeding than warfarin, but the stroke risk was similar between the two subgroups.Conclusions: For patients with concomitant CKD, AF and CAD not undergoing PCI, OAC monotherapy may reduce stroke and AMI risks. DOAC showed more favorable outcomes than warfarin.
The Relationship Between Body Mass Index and In-Hospital Mortality in Patients Following Coronary Artery Bypass Grafting Surgery
Authors: Elbaz-Greener Gabby , Rozen Guy , Carasso Shemy , Kusniec Fabio , Yarkoni Merav , Marai Ibrahim , Strauss Bradley , Wijeysundera Harindra C. , Smart Frank W. , Erez Eldad , Alcalai Ronny , Planer David , Amir Offer 
Published: October 2021

Background: The association between Body Mass Index (BMI) and clinical outcomes following coronary artery bypass grafting (CABG) remains controversial. Our objective was to investigate the real-world relationship between BMI and in-hospital clinical course and mortality, in patients who underwent CABG.Methods: A sampled cohort of patients who underwent CABG between October 2015 and December 2016 was identified in the National Inpatient Sample (NIS) database. Outcomes of interest included in-hospital mortality, peri-procedural complications and length of stay. Patients were divided into 6 BMI (kg/m2) subgroups; (1) under-weight ≤19, (2) normal-weight 20–25, (3) over-weight 26–30, (4) obese I 31–35, (5) obese II 36–39, and (6) extremely obese ≥40. Multivariable logistic regression model was used to identify predictors of in-hospital mortality. Linear regression model was used to identify predictors of length of stay (LOS).Results: An estimated total of 48,710 hospitalizations for CABG across the U.S. were analyzed. The crude data showed a U-shaped relationship between BMI and study population outcomes with higher mortality and longer LOS in patients with BMI ≤ 19 kg/m2 and in patients with BMI ≥40 kg/m2 compared to patients with BMI 20–39 kg/m2. In the multivariable regression model, BMI subgroups of ≤19 kg/m2 and ≥40 kg/m2 were found to be independent predictors of mortality.Conclusions: A complex, U-shaped relationship between BMI and mortality was documented, confirming the “obesity paradox” in the real-world setting, in patients hospitalized for CABG.
Tomographic Image of Shear Wave Structure of NE India Based on Analysis of Rayleigh Wave Data
Authors: Kumar Amit , Kumar Naresh , Mukhopadhyay Sagarika , Klemperer Simon L. 
Published: October 2021

The major scientific purpose of this work is to evaluate the geodynamic processes involved in the development of tectonic features of NE India and its surroundings. In this work, we have obtained tomographic images of the crust and uppermost mantle using inversion of Rayleigh waveform data to augment information about the subsurface gleaned by previous works. The images obtained reveal a very complicated tectonic regime. The Bengal Basin comprises a thick layer of sediments with the thickness increasing from west to east and a sudden steepening of the basement on the eastern side of the Eocene Hinge zone. The nature of the crust below the Bengal Basin varies from oceanic in the south to continental in the north. Indo-Gangetic and Brahmaputra River Valleys comprise ∼5–6-km-thick sediments. Crustal thickness in the higher Himalayas and southern Tibet is ∼70 km but varies between ∼30 and ∼40 km in the remaining part. Several patches of low-velocity medium present in the mid-to-lower crust of southern Tibet along and across the major rifts indicate the presence of either partially molten materials or aqueous fluid. Moho depth decreases drastically from west to east across the Yadong-Gulu rift indicating the complex effect of underthrusting of the Indian plate below the Eurasian plate. Crust and upper mantle below the Shillong Massif and Mikir Hills are at a shallow level. This observation indicates that tectonic forces contribute to the uprising of the Massif.
Beyond Vertical Point Accuracy: Assessing Inter-pixel Consistency in 30 m Global DEMs for the Arid Central Andes
Authors: Purinton Benjamin , Bookhagen Bodo 
Published: October 2021

Quantitative geomorphic research depends on accurate topographic data often collected via remote sensing. Lidar, and photogrammetric methods like structure-from-motion, provide the highest quality data for generating digital elevation models (DEMs). Unfortunately, these data are restricted to relatively small areas, and may be expensive or time-consuming to collect. Global and near-global DEMs with 1 arcsec (∼30 m) ground sampling from spaceborne radar and optical sensors offer an alternative gridded, continuous surface at the cost of resolution and accuracy. Accuracy is typically defined with respect to external datasets, often, but not always, in the form of point or profile measurements from sources like differential Global Navigation Satellite System (GNSS), spaceborne lidar (e.g., ICESat), and other geodetic measurements. Vertical point or profile accuracy metrics can miss the pixel-to-pixel variability (sometimes called DEM noise) that is unrelated to true topographic signal, but rather sensor-, orbital-, and/or processing-related artifacts. This is most concerning in selecting a DEM for geomorphic analysis, as this variability can affect derivatives of elevation (e.g., slope and curvature) and impact flow routing. We use (near) global DEMs at 1 arcsec resolution (SRTM, ASTER, ALOS, TanDEM-X, and the recently released Copernicus) and develop new internal accuracy metrics to assess inter-pixel variability without reference data. Our study area is in the arid, steep Central Andes, and is nearly vegetation-free, creating ideal conditions for remote sensing of the bare-earth surface. We use a novel hillshade-filtering approach to detrend long-wavelength topographic signals and accentuate short-wavelength variability. Fourier transformations of the spatial signal to the frequency domain allows us to quantify: 1) artifacts in the un-projected 1 arcsec DEMs at wavelengths greater than the Nyquist (twice the nominal resolution, so &gt; 2 arcsec); and 2) the relative variance of adjacent pixels in DEMs resampled to 30-m resolution (UTM projected). We translate results into their impact on hillslope and channel slope calculations, and we highlight the quality of the five DEMs. We find that the Copernicus DEM, which is based on a carefully edited commercial version of the TanDEM-X, provides the highest quality landscape representation, and should become the preferred DEM for topographic analysis in areas without sufficient coverage of higher-quality local DEMs.
Association Between Estrogen Receptors and GATA3 in Bladder Cancer: A Systematic Review and Meta-Analysis of Their Clinicopathological Significance
Authors: Bernardo Carina , Monteiro Fátima L. , Direito Inês , Amado Francisco , Afreixo Vera , Santos Lúcio L. , Helguero Luisa A. 
Published: October 2021

BackgroundEstrogen receptors alpha (ERα) and beta (ERβ) and the cooperating protein GATA-binding factor 3 (GATA3) have been implicated in bladder carcinogenesis and tumour progression. GATA3 and ER have been functionally linked in the establishment of luminal fate in breast tissue, but to date their relationship in bladder cancer has not been established. This information will be useful to advance diagnostic and prognostic markers.AimTo determine the relationship between the expression of ERα, ERβ and GATA3 in bladder cancer, disclose their prognostic and diagnostic value and their association with clinicopathological characteristics.MethodsA comprehensive literature search in PubMed database was performed for all immunohistochemical studies of ERα, ERβ and/or GATA3 in bladder cancer patients. We selected eligible studies in accordance with the PRISMA guidelines and evaluated methodological quality and risk of bias based on quality criteria from the reporting recommendations for tumour MARKer (REMARK) prognostic studies. Risk of bias assessment was performed using Review Manager 5. R software was used for all statistical analysis, the packages used were meta and dmetar for the standard meta-analysis, and netmeta for the network meta-analysis.ResultsThirteen studies were eligible for ERα, 5 for ERβ and 58 for GATA3 meta-analysis. Low grade tumours showed significantly lower ERα expression. GATA3 was widely expressed in bladder tumours, especially urothelial carcinomas, with higher expression of GATA3 in low grade and low stage tumours. Data was insufficient to determine the prognostic value of either ERα or ERβ, but GATA3-positivity was associated with higher recurrence free survival. A negative correlation between ERα or ERβ positivity and GATA3 expression was disclosed. Additionally, several sources of heterogeneity were identified, which can be used to improve future studies.ConclusionThe clinicopathological value of ERα and ERβ was inconclusive due to low availability of studies using validated antibodies. Still, this meta-analysis supports GATA3 as good prognostic marker. On the contrary, ERα-positivity was associated to higher grade tumours; while ERα and ERβ were inversely correlated with GATA3 expression. Considering that it has previously been shown that bladder cancer cell lines have functional ERs, this suggests that ERα could be activated in less differentiated cells and independently of GATA3. Therefore, a comprehensive analysis of ERα and ERβ expression in BlaCa supported by complete patient clinical history is required for the identification of BlaCa subtypes and subgroups of patients expressing ERα, to investigate if they could benefit from treatment with hormonal therapy.Systematic Review RegistrationProspero, CRD42021226836.
Treatment Modality and Risk of Heart Failure in Patients With Long-Standing Graves’ Disease: A Nationwide Population-Based Cohort Study
Authors: Song Eyun , Kim Mina , Park Sojeong , Park Min Jeong , Kim Jung A. , Roh Eun , Yu Ji Hee , Kim Nam Hoon , Seo Ji A. , Kim Sin Gon , Kim Nan Hee , Choi Kyung Mook , Baik Sei Hyun , Yoo Hye Jin 
Published: October 2021

BackgroundOptimal treatment for persistent Graves’ disease following 12–18 months of treatment with anti-thyroid drugs (ATDs) is unclear. Given the increased risk of cardiovascular morbidity and mortality with hyperthyroidism, assessing the risk of cardiovascular events associated with different treatment modalities after the conventional ATD course would be valuable in determining the appropriate next-line therapy.MethodsThis retrospective cohort study included data from the Korean National Health Insurance database of 16,882 patients with newly diagnosed hyperthyroidism who received primary ATD treatment for 24 months. Patients were categorized based on the treatment they received after receiving ATD for 24 months: continued ATD for at least 12 more months (ATD group), radioiodine ablation (RIA) with remission (RIA group 1), and RIA without remission (RIA group 2). The incidence and risk of heart failure (HF), the leading cause of cardiovascular mortality in hyperthyroidism, were compared between patients and age-and sex-matched controls.ResultsThere were 16,516 (97.8%) patients in the ATD group, 230 (1.4%) in RIA group 1, and 136 (0.8%) in RIA group 2. Compared to that of controls, a significant difference in the cumulative incidence of HF was observed according to second-line treatment modality after adjusting for covariates; the risk was highest in patients in RIA group 2, with a hazard ratio (HR) of 2.54 (95% confidence interval (CI) 1.60–4.03), followed by those in the ATD group, with an HR of 1.23 (95% CI 1.20–1.36). Patients in RIA group 1 were not at an increased risk of HF compared to their matched controls (HR 0.77; 95% CI 0.38–1.54). When patients in the ATD group were further classified by the duration of ATD treatment at one-year intervals, the risk of HF was higher in patients with longer ATD use (p for linear trend &lt; 0.001).ConclusionsIn patients with long-standing hyperthyroidism treated with conventional duration of ATD therapy, the risk of HF was attenuated by RIA with remission of hyperthyroidism and increased as ATD was required for longer duration. To reduce the risk of HF, resolution of hyperthyroidism with RIA should be considered in patients with long-standing Graves’ disease.