bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triglyceride-glucose index predicts adverse cardiovascular events in patients with diabetes and acute coronary syndrome
Authors: Wang Le , Cong Hong-liang , Zhang Jing-xia , Hu Yue-cheng , Wei Ao , Zhang Ying-yi , Yang Hua , Ren Li-bin , Qi Wei , Li Wen-yu , Zhang Rui , Xu Jing-han 
Published: June 2020

Abstract
Background
The triglyceride-glucose index (TyG index) has been regarded as a reliable alternative marker of insulin resistance and an independent predictor of cardiovascular outcomes. Whether the TyG index predicts adverse cardiovascular events in patients with diabetes and acute coronary syndrome (ACS) remains uncertain. The aim of this study was to investigate the prognostic value of the TyG index in patients with diabetes and ACS.

Methods
A total of 2531 consecutive patients with diabetes who underwent coronary angiography for ACS were enrolled in this study. Patients were divided into tertiles according to their TyG index. The primary outcomes included the occurrence of major adverse cardiovascular events (MACEs), defined as all-cause death, non-fatal myocardial infarction and non-fatal stroke. The TyG index was calculated as the ln (fasting triglyceride level [mg/dL] × fasting glucose level [mg/dL]/2).

Results
The incidence of MACE increased with TyG index tertiles at a 3-year follow-up. The Kaplan–Meier curves showed significant differences in event-free survival rates among TyG index tertiles (P = 0.005). Multivariate Cox hazards regression analysis revealed that the TyG index was an independent predictor of MACE (95% CI 1.201–1.746; P < 0.001). The optimal TyG index cut-off for predicting MACE was 9.323 (sensitivity 46.0%; specificity 63.6%; area under the curve 0.560; P = 0.001). Furthermore, adding the TyG index to the prognostic model for MACE improved the C-statistic value (P = 0.010), the integrated discrimination improvement value (P = 0.001) and the net reclassification improvement value (P = 0.019).

Conclusions
The TyG index predicts future MACE in patients with diabetes and ACS independently of known cardiovascular risk factors, suggesting that the TyG index may be a useful marker for risk stratification and prognosis in patients with diabetes and ACS.
Generalizability of sodium-glucose co-transporter-2 inhibitors cardiovascular outcome trials to the type 2 diabetes population: a systematic review and meta-analysis
Authors: Castellana Marco , Procino Filippo , Sardone Rodolfo , Trimboli Pierpaolo , Giannelli Gianluigi 
Published: June 2020

Abstract
Background
Cardiovascular outcome trials of sodium-glucose co-transporter-2 inhibitors (SGLT2i CVOTs) found the agents to be associated with clinical benefits in terms of cardiovascular and renal outcomes. We performed a meta-analysis to assess and compare the overall prevalence of eligibility for the enrollment criteria of CANVAS, DECLARE-TIMI 58, EMPA-REG OUTCOME, and VERTIS-CV among unselected patients with type 2 diabetes.

Methods
This meta-analysis was registered in PROSPERO (CRD42020172032). PubMed, CENTRAL, Scopus and Web of Science were researched in March 2020. Studies evaluating the prevalence of eligibility for each SGLT2i CVOT were selected. Endpoints were estimated using a random-effects model.

Results
Five studies, evaluating 1,703,519 patients with type 2 diabetes, were included. Overall, the prevalence of eligible patients according to the enrollment criteria of CANVAS, DECLARE-TIMI 58, EMPA-REG OUTCOME, and VERTIS-CV was 36.4%, 49.5%, 17.0% and 19.0%, respectively. In head-to-head comparisons, DECLARE-TIMI 58 was associated with the highest odds of eligibility (1.74 versus CANVAS, 5.15 versus EMPA-REG OUTCOME and 4.81 versus VERTIS-CV), followed by CANVAS and EMPA-REG OUTCOME/VERTIS-CV. A high heterogeneity was found for all the outcomes.

Conclusions
The present review showed that a considerable number of patients counseled in clinical practice could have been eligible for SGLT2i CVOTs. Particularly, dapagliflozin was shown to be the SGLT2i with the largest generalizability of findings from its CVOT according to the odds ratio of eligibility for the enrollment criteria among unselected patients with type 2 diabetes. Further country- or region-specific studies are needed to confirm the applicability of our results.
Type 2 diabetes mellitus increases the mortality risk after acute coronary syndrome treated with coronary artery bypass surgery
Authors: Ram Eilon , Sternik Leonid , Klempfner Robert , Iakobishvili Zaza , Fisman Enrique Z. , Tenenbaum Alexander , Zuroff Elchanan , Peled Yael , Raanani Ehud 
Published: June 2020

Abstract
Background
Type 2 diabetes mellitus (DM) is a risk factor for cardiovascular diseases and is common among patients undergoing coronary artery bypass grafting (CABG) surgery. The main objective of our study was to investigate the impact of DM type 2, and its treatment subgroups, on short- and long-term mortality in patients with acute coronary syndrome (ACS) who undergo CABG.

Methods
The study included 1307 patients enrolled from the biennial Acute Coronary Syndrome Israeli Survey between 2000 and 2016, who were hospitalized for ACS and underwent CABG. Of them, 527 (40%) patients were with and 780 (60%) were without DM.

Results
Compared with the non-diabetic group, the diabetic group of patients comprised more women and had more comorbidities such as hypertension, dyslipidemia, renal impairment, peripheral vascular disease and prior ischemic heart disease. Overall 30-day mortality rate was similar between DM and non-DM patients (4.2% vs. 4%, p = 0.976). Ten-year mortality rate was higher in DM compared with non-diabetic patients (26.6% vs. 17.7%, log-rank p < 0.001), and higher in the subgroup of insulin-treated patients compared to non-insulin treated patients (31.5% vs. 25.6%, log-rank p = 0.019). Multivariable analysis showed that DM increased the mortality hazard by 1.61-fold, and insulin treatment among the diabetic patients increased the mortality hazard by 1.57-fold.

Conclusions
While type 2 DM did not influence the in-hospital mortality hazard, we showed that the presence of DM among patients with ACS referred to CABG, is a powerful risk factor for long-term mortality, especially when insulin was included in the diabetic treatment strategy.
Low expression of organic anion-transporting polypeptide 1B3 predicts a poor prognosis in hepatocellular carcinoma
Authors: Chen Shihan , Li Kun , Jiang Jiayun , Wang Xiaofei , Chai Yuelong , Zhang Chang , Deng Qingsong , Shuai Ling , Feng Kai , Ma Kuansheng , Zhang Leida 
Published: June 2020

Abstract
Objective
To detect the expression level of organic anion-transporting polypeptide 1B3 (OATP1B3) in hepatocellular carcinoma (HCC) and to determine the relationship between OATP1B3 expression, clinicopathological features, and prognosis.

Methods
Immunohistochemical (IHC) staining was performed to detect the expression of OATP1B3 in 131 HCC specimens and in 89 adjacent nontumorous tissues. Moreover, the expression levels of OATP1B3 in 30 pairs of tumor and matched adjacent nontumorous tissues were detected by quantitative real-time polymerase chain reaction, and 34 pairs of tumor and matched adjacent nontumorous tissues were detected by Western blotting. The χ2 test was applied to analyze the correlation between OATP1B3 expression and the clinical parameters of HCC patients. The prognostic value of OATP1B3 in HCC patients was estimated by Kaplan-Meier survival analysis and the Cox stepwise proportional hazards model.

Results
Compared with that in adjacent nontumorous tissues (25.8%, 23/89), OATP1B3 expression was significantly downregulated in tumor tissues (59.5%, 78/131) (P < 0.0001). Moreover, OATP1B3 expression was markedly correlated with tumor size, recurrence, tumor differentiation, and tumor node metastasis (TNM) stage (P < 0.05 for each). However, age, sex, tumor capsule status, HBsAg, cirrhosis, tumor number, vascular invasion, and serum alpha fetoprotein were not associated with OATP1B3 expression. The overall survival (OS) and disease-free survival (DFS) of HCC patients who had high expression of OATP1B3 were significantly longer than those of patients with low expression (33.0% vs 12.9%, P = 0.001; 18.8% vs 5.3%, P < 0.0001). Cox multivariate analysis showed that OATP1B3, invasion, and TNM stage (P < 0.05 for each) were independent prognostic factors of OS in HCC patients and that OATP1B3 and TNM stage (both P < 0.05) were independent prognostic factors of DFS in HCC patients.

Conclusions
The expression of OATP1B3 in HCC patients was significantly lower than that in adjacent nontumorous tissues. OATP1B3 expression may be a potential prognostic marker in HCC patients.
Chromosome 17p13 deletion is associated with an aggressive tumor phenotype in clear cell renal cell carcinoma
Authors: Eichenauer Till , Shadanpour Navid , Kluth Martina , Göbel Cosima , Weidemann Sören , Fraune Christoph , Büscheck Franziska , Hube-Magg Claudia , Möller-Koop Christina , Dahlem Roland , Fisch Margit , Rink Michael , Riechardt Silke , Burandt Eike , Bernreuther Christian , Minner Sarah , Simon Ronald , Sauter Guido , Wilczak Waldemar , Clauditz Till 
Published: June 2020

Abstract
Background
Deletions of 17p13 recurrently occur in renal cell carcinoma (RCC) but their prognostic role seems to be uncertain.

Methods
To determine prevalence, relationship with tumor phenotype, and patient prognosis, a tissue microarray containing samples from 1809 RCCs was evaluated using dual labeling fluorescence in situ hybridization (FISH) with 17p13 and chromosome 17 centromere probes.

Results
A 17p13 deletion was found in 72 of 1429 interpretable tumors. The frequency of 17p13 deletions varied greatly between RCC subtypes and was highest in chromophobe RCC (24/72; 33.3%). 17p13 deletions were also found in 35 (3.7%) of 946 clear cell RCC, 9 (4.3%) of 208 papillary RCC, 1 of 121 oncocytomas (0.8%), as well as in several rare cases of comprising 1 of 7 Xp11.2 translocation cancers, 1 of 3 collecting duct carcinomas, and 1 of 20 not otherwise specified (NOS) carcinomas. In clear cell carcinomas, 17p13 deletions revealed a strong and consistent association with higher Fuhrman, ISUP, and Thoenes grade (p < 0.0001 each), and linked to advanced tumor stage (p = 0.0168), large tumor diameter (p = 0.0004), distant metastases (p = 0.0077), cancer-specific survival (p = 0.0391), and recurrence-free survival (p = 0.0072). In multivariate analysis, 17p13 deletions showed in clear cell RCC a dependent prognostic role for established clinical-pathological parameters.

Conclusion
17p13 deletions have a dual role in RCC. They are associated with disease progression in clear cell RCC and possibly other subtypes and they are linked to the development of chromophobe RCC—a subtype with a particularly favorable prognosis.
Macrofollicular variant of papillary thyroid carcinoma with metastasis to femur
Authors: Candanedo-Gonzalez Fernando , Rodriguez-Orihuela Diana , Arista-Nasr Julian 
Published: June 2020

Abstract
Background
Macrofollicular variant of papillary thyroid carcinoma (MFV-PTC) is a rare subtype with histological features and an indolent clinical course that can be confused with nodular goiter or follicular adenoma. However, on rare occasions it may show more aggressive biological behavior. Only two cases of MFV-PTC with bone metastases have been reported previously. We describe the clinical-pathological characteristics of a man with MFV-PTC that developed femur metastasis. This the first case of MFV-PTC with femur metastases diagnosed histologically by means of an image-guided core needle biopsy in English literature.

Case presentation
A 33-year-old man presented two years earlier with swelling in the right neck associated with weight loss and pain in the left knee. Neck ultrasonography showed hyperechogenic and hypogenic nodular images in the thyroid’s right lobe. A fine needle aspiration biopsy specimen was initially interpreted as nodular hyperplasia. A CT showed a large tumor involving right thyroid lobe with trachea and vascular structures displaced to the right, and a total thyroidectomy was performed. Subsequently, a MRI of the knee confirmed the presence of a destructive tumor in the femur. A guided core-needle biopsy of the knee tumor showed the presence of metastatic MFV-PTC. Re-assessment of the histology from thyroidectomy was also consistent with MFV-PTC. A whole-body 18F-FDG PET/CT showed presence of lesions in the left anterior costal arch, metaphysis of the left femur and in the sternum handle. Therefore, he received 200 mCi radioactive iodine, and 40 Gy of radiotherapy to left costal arches and knee, which decreased his symptoms. Currently, after 10 months of follow-up, the patient is alive with bone tumor activity.

Conclusions
Our case supports the view that, on rare ocassions, MFV-PTC may show a more aggressive biological behavior than expected. The synchronous or asynchronous presence of one or more bone lesions, should raise the suspicion of metastasis. Given the suspicion, it is necessary to take a biopsy to confirm histologically. Only a careful analysis of the architectural and cytological characteristics of goiter or hyperplastic nodules will allow to recognize this rare variety of carcinoma.
Elevated serum TSH concentrations are associated with higher BMI Z-scores in southern Iranian children and adolescents
Authors: Habib Ashkan , Molayemat Mohadeseh , Habib Asadollah 
Published: June 2020

Abstract
Background
Subclinical hypothyroidism is defined as elevated TSH levels while T4 or FT4 levels are normal. Elevated TSH levels are linked with obesity in adults. In a recent meta-analysis in Iran, 6.1% of children below 18 had obesity. Due to the low number of studies on the subject in children we, designed the study to assess the relation between BMI Z-score and TSH levels in children and adolescence.

Method
This cross-sectional study was performed in a pediatric endocrinology clinic in Shiraz. Children aged between 2 to 18 years that came to the clinic for routine growth assessment follow up from January till April 2018 were considered. 850 children including 365 boys and 485 girls were included.

Results
Prevalence of subclinical hypothyroidism is increased in higher BMI groups. 9.9, 13.8, 17.2 and 20.5% of underweight, healthy weight, overweight and obese had subclinical hypothyroidism respectively. Obese and overweight participants had higher odds of subclinical hypothyroidism than those who were not (OR:1.649, P = 0.010, CI95% 1.126–2.413). On the other hand, Subclinical hypothyroid participants had higher odds of overweight or obesity than those who were euthyroid (OR:1.650, P = 0.010, CI95% 1.128–2.413). When TSH is set as a dependent value, TSH level is increased (β = 0.126, r = 0.125, P = 0.001) with an increase in BMI Z-score. When BMI Z-score is set as a dependent value, BMI Z-score is increased (β = 0.113, r = 0.243, P = 0.001) with an increase in TSH level.

Conclusion
BMI Z-score and elevated TSH levels are positively correlated however studies should be performed on establishing the causality.
The dynamics of biomarkers across the clinical spectrum of Alzheimer’s disease
Authors: Hadjichrysanthou Christoforos , Evans Stephanie , Bajaj Sumali , Siakallis Loizos C. , McRae-McKee Kevin , de Wolf Frank , Anderson Roy M. ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: June 2020

Abstract
Background
Quantifying changes in the levels of biological and cognitive markers prior to the clinical presentation of Alzheimer’s disease (AD) will provide a template for understanding the underlying aetiology of the clinical syndrome and, concomitantly, for improving early diagnosis, clinical trial recruitment and treatment assessment. This study aims to characterise continuous changes of such markers and determine their rate of change and temporal order throughout the AD continuum.

Methods
The methodology is founded on the development of stochastic models to estimate the expected time to reach different clinical disease states, for different risk groups, and synchronise short-term individual biomarker data onto a disease progression timeline. Twenty-seven markers are considered, including a range of cognitive scores, cerebrospinal (CSF) and plasma fluid proteins, and brain structural and molecular imaging measures. Data from 2014 participants in the Alzheimer’s Disease Neuroimaging Initiative database is utilised.

Results
The model suggests that detectable memory dysfunction could occur up to three decades prior to the onset of dementia due to AD (ADem). This is closely followed by changes in amyloid-β CSF levels and the first cognitive decline, as assessed by sensitive measures. Hippocampal atrophy could be observed as early as the initial amyloid-β accumulation. Brain hypometabolism starts later, about 14 years before onset, along with changes in the levels of total and phosphorylated tau proteins. Loss of functional abilities occurs rapidly around ADem onset. Neurofilament light is the only protein with notable early changes in plasma levels. The rate of change varies, with CSF, memory, amyloid PET and brain structural measures exhibiting the highest rate before the onset of ADem, followed by a decline. The probability of progressing to a more severe clinical state increases almost exponentially with age. In accordance with previous studies, the presence of apolipoprotein E4 alleles and amyloid-β accumulation can be associated with an increased risk of developing the disease, but their influence depends on age and clinical state.

Conclusions
Despite the limited longitudinal data at the individual level and the high variability observed in such data, the study elucidates the link between the long asynchronous pathophysiological processes and the preclinical and clinical stages of AD.
Simultaneous determination of the metabolites of the herbicide metazachlor in agricultural crops by LC–MS/MS
Authors: Park Ji-Su , Lee Han Sol , Cho Sung Min , Lee Su Jung , Shin Hye-Sun , Shim Jae-Han , Yun Sang Soon , Jung Yong-hyun , Oh Jae-ho 
Published: June 2020

AbstractTo manage the safety of the herbicide metazachlor, analytical methods are required for the determination of metazachlor metabolites in agricultural crops. Herein, a liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed for the simultaneous determination of metazachlor metabolites (479M04, 479M08, and 479M16) in various agricultural commodities. After extraction using acetonitrile and adjusting the pH to 3, the samples were purified using a hydrophilic–lipophilic balance cartridge. The matrix-matched calibration curves (0.002–0.2 μg/mL) were linear (r2 > 0.99). For validation, recovery tests were carried out at three fortification levels (limit of quantification (LOQ), 10 LOQ, and 50 LOQ) in various agricultural samples. The recoveries of 479M04, 479M08, and 479M16 were 79.6–113.0, 76.9–97.7, and 79.1–102.1%, respectively, with relative standard deviation values of less than 17.0%. Furthermore, inter-laboratory testing was conducted to validate the method. All the values corresponded to the criteria of both the CODEX (CAC/GL 40-1993, 2003) and Ministry of Food and Drug Safety guidelines. Therefore, the proposed LC–MS/MS method can be used as an analytical method for the determination of metazachlor.
Climate mediates continental scale patterns of stream microbial functional diversity
Authors: Picazo Félix , Vilmi Annika , Aalto Juha , Soininen Janne , Casamayor Emilio O. , Liu Yongqin , Wu Qinglong , Ren Lijuan , Zhou Jizhong , Shen Ji , Wang Jianjun 
Published: June 2020

AbstractBackgroundUnderstanding the large-scale patterns of microbial functional diversity is essential for anticipating climate change impacts on ecosystems worldwide. However, studies of functional biogeography remain scarce for microorganisms, especially in freshwater ecosystems. Here we study 15,289 functional genes of stream biofilm microbes along three elevational gradients in Norway, Spain and China.ResultsWe find that alpha diversity declines towards high elevations and assemblage composition shows increasing turnover with greater elevational distances. These elevational patterns are highly consistent across mountains, kingdoms and functional categories and exhibit the strongest trends in China due to its largest environmental gradients. Across mountains, functional gene assemblages differ in alpha diversity and composition between the mountains in Europe and Asia. Climate, such as mean temperature of the warmest quarter or mean precipitation of the coldest quarter, is the best predictor of alpha diversity and assemblage composition at both mountain and continental scales, with local non-climatic predictors gaining more importance at mountain scale. Under future climate, we project substantial variations in alpha diversity and assemblage composition across the Eurasian river network, primarily occurring in northern and central regions, respectively.ConclusionsWe conclude that climate controls microbial functional gene diversity in streams at large spatial scales; therefore, the underlying ecosystem processes are highly sensitive to climate variations, especially at high latitudes. This biogeographical framework for microbial functional diversity serves as a baseline to anticipate ecosystem responses and biogeochemical feedback to ongoing climate change.
Three-dimensional magnetotelluric numerical simulation of realistic geologic models
Authors: Ansari SeyedMasoud , Schetselaar Ernst , Craven James , Farquharson Colin 
Published: June 2020

We have developed a workflow for constructing realistic mesh-based magnetotelluric (MT) models from 3D geologic models. The routine is developed for unstructured meshes that adapt to the complex shapes of geologic bodies including 3D surfaces and volumes in realistic modeling scenarios. The methodology is applied to the complexly altered Lalor volcanogenic massive sulfide deposit in Manitoba, Canada. The host rock envelope of the Lalor deposit is compartmentalized into lithostratigraphic units leading to a watertight model. This model then is meshed into unstructured tetrahedral meshes suitable for synthetic geophysical modeling of the MT method. Subsequently, two 3D resistivity models are generated from wireline logs: (1) a host rock background model in which each tetrahedral cell is attributed with the average resistivity of each lithostratigraphic unit and (2) a heterogeneous background-ore model in which the resistivity values of the cells are resampled from a 3D curvilinear grid model, generated by computing sequential Gaussian simulations from the resistivity data for each unit of a 3D lithofacies model produced by categorical kriging. To calculate the synthetic response of this model for MT, a numerical-modeling code is developed based on solving the vector-scalar potential formulation of the electromagnetic diffusion equation using the finite-element method on unstructured meshes. After validating the numerical method for the Commemi test model, the MT response of the Lalor model is investigated. A reasonable agreement is observed between the survey field data and the data synthesized from our constructed heterogeneous model. Using an investigation of the inductive and galvanic parts, we conclude with the ideal frequency range for detecting the ore deposit. We also conclude with and visualize the importance of regional-scale alteration zones around the ore deposits and model inhomogeneities in boosting the detectability of the ore formations through feeding electrical currents as a result of galvanic field dominance at depth.