bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diabetes Promotes Retinal Vascular Endothelial Cell Injury by Inducing CCN1 Expression
Authors: Li Haicheng , Li Ting , Wang Heting , He Xuemin , Li Ying , Wen Siying , Peng Rongdong , Nie Yuanpeng , Lu Yan , Yang He , Ye Yinong , Shi Guojun , Chen Yanming 
Published: August 2021

Purpose: Diabetic retinopathy (DR) is one of the most common diabetic microvascular complications. However, the pathogenesis of DR has not yet been fully elucidated. This study aimed to discover novel and key molecules involved in the pathogenesis of DR, which could potentially be targets for therapeutic DR intervention.Methods: To identify potential genes involved in the pathogenesis of DR, we analyzed the public database of neovascular membranes (NVMs) from patients with proliferative diabetic retinopathy (PDR) and healthy controls (HCs) (GSE102485, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE102485). Further, we compared these findings by performing RNA-sequencing analysis of peripheral blood mononuclear cells (PBMC) from patients with DR, control patients with non-complicated diabetes mellitus (DMC), and HCs. To determine the critical role of candidate genes in DR, knockdown or knockout was performed in human retinal vascular endothelial cells (HRVECs). The oxidative stress pathway, as well as tight junction integrity, was analyzed.Results: Transcriptional profiles showed distinct patterns between the NVMs of patients with DR and those of the HCs. Those genes enriched in either extracellular matrix (ECM)-receptor interaction or focal adhesion pathways were considerably upregulated. Both pathways were important for maintaining the integrity of retinal vascular structure and function. Importantly, the gene encoding the matricellular protein CCN1, a key gene in cell physiology, was differentially expressed in both pathways. Knockdown of CCN1 by small interfering RNA (siRNA) or knockout of CCN1 by the CRISPR-Cas9 technique in HRVECs significantly increased the levels of VE-cadherin, reduced the level of NADPH oxidase 4 (NOX4), and inhibited the generation of reactive oxygen species (ROS).Conclusion: The present study identifies CCN1 as an important regulator in the pathogenesis of DR. Increased expression of CCN1 stimulates oxidative stress and disrupts tight junction integrity in endothelial cells by inducing NOX4. Thus, targeting the CCN1/NOX4 axis provides a therapeutic strategy for treating DR by alleviating endothelial cell injury.
Active Faulting in Lake Constance (Austria, Germany, Switzerland) Unraveled by Multi-Vintage Reflection Seismic Data
Authors: Fabbri S.C. , Affentranger C. , Krastel S. , Lindhorst K. , Wessels M. , Madritsch Herfried , Allenbach R. , Herwegh M. , Heuberger S. , Wielandt-Schuster U. , Pomella H. , Schwestermann T. , Anselmetti F.S. 
Published: August 2021

Probabilistic seismic hazard assessments are primarily based on instrumentally recorded and historically documented earthquakes. For the northern part of the European Alpine Arc, slow crustal deformation results in low earthquake recurrence rates and brings up the necessity to extend our perspective beyond the existing earthquake catalog. The overdeepened basin of Lake Constance (Austria, Germany, and Switzerland), located within the North-Alpine Molasse Basin, is investigated as an ideal (neo-) tectonic archive. The lake is surrounded by major tectonic structures and constrained via the North Alpine Front in the South, the Jura fold-and-thrust belt in the West, and the Hegau-Lake Constance Graben System in the North. Several fault zones reach Lake Constance such as the St. Gallen Fault Zone, a reactivated basement-rooted normal fault, active during several phases from the Permo-Carboniferous to the Mesozoic. To extend the catalog of potentially active fault zones, we compiled an extensive 445 km of multi-channel reflection seismic data in 2017, complementing a moderate-size GI-airgun survey from 2016. The two datasets reveal the complete overdeepened Quaternary trough and its sedimentary infill and the upper part of the Miocene Molasse bedrock. They additionally complement existing seismic vintages that investigated the mass-transport deposit chronology and Mesozoic fault structures. The compilation of 2D seismic data allowed investigating the seismic stratigraphy of the Quaternary infill and its underlying bedrock of Lake Constance, shaped by multiple glaciations. The 2D seismic sections revealed 154 fault indications in the Obersee Basin and 39 fault indications in the Untersee Basin. Their interpretative linkage results in 23 and five major fault planes, respectively. One of the major fault planes, traceable to Cenozoic bedrock, is associated with a prominent offset of the lake bottom on the multibeam bathymetric map. Across this area, high-resolution single channel data was acquired and a transect of five short cores was retrieved displaying significant sediment thickness changes across the seismically mapped fault trace with a surface-rupture related turbidite, all indicating repeated activity of a likely seismogenic strike-slip fault with a normal faulting component. We interpret this fault as northward continuation of the St. Gallen Fault Zone, previously described onshore on 3D seismic data.
Geochemistry and Weathering Indices of Yedoma and Alas Deposits beneath Thermokarst Lakes in Central Yakutia
Authors: Ulrich Mathias , Jongejans Loeka L. , Grosse Guido , Schneider Birgit , Opel Thomas , Wetterich Sebastian , Fedorov Alexander N. , Schirrmeister Lutz , Windirsch Torben , Wiedmann Julia , Strauss Jens 
Published: August 2021

Ice- and organic-rich deposits of late Pleistocene age, known as Yedoma Ice Complex (IC), are widespread across large permafrost regions in Northeast Siberia. To reconstruct Yedoma IC formation in Central Yakutia, we analyzed the geochemistry, sedimentology, and stratigraphy of thawed and frozen deposits below two thermokarst lakes in different evolutionary stages (a mature alas lake and a initial Yedoma lake) from the Yukechi site in the Lena-Aldan interfluve. We focused on inorganic geochemical characteristics and mineral weathering in two ∼17 m long sediment cores to trace syngenetic permafrost aggradation and degradation over time. Geochemical properties, element ratios, and specific weathering indices reflect varying sedimentation processes and seasonal thaw depths under variable environmental conditions. Deeper thaw during the interstadial Marine Isotope Stage (MIS) 3 enabled increasing mineral weathering and initial thermokarst processes. Sedimentological proxies reflect high transport energy and short transport paths and mainly terrestrial sediment supply. The Yedoma formation resulted from fluvial, alluvial and aeolian processes. Low mean TOC contents in both cores contrast with Yedoma deposits elsewhere. Likely, this is a result of the very low organic matter content of the source material of the Yukechi Yedoma. Pronounced cryostructures and strongly depleted pore water stable isotopes show a perennially frozen state and preserved organic matter for the lower part of the Yedoma lake core, while changing permafrost conditions, conditions promoting weathering, and strong organic matter decomposition are suggested by our proxies for its middle and upper parts. For the alas lake core, less depleted water stable isotopes reflect the influence of recent precipitation, i.e. the infiltration of rain and lake water into the unfrozen ground. The FENG, MIA(R), and ICV weathering indices have proven to be promising proxies for the identification of conditions that promote mineral weathering to different degrees in the stratigraphy of the thawed and frozen Yedoma deposits, for which we assume a rather homogeneous chemical composition of the parent material. Our study highlights that the understanding of environmental conditions during Yedoma formation and degradation processes by specific geochemical proxies is crucial for assessing the potential decomposition and preservation of the frozen and unfrozen Yedoma inventories.
Nature of Volatile Organic Matter in Lake Sediments as a Reflection of Paleoclimate Changes Occurring at 4 ka in the Central Qaidam Basin
Authors: Lu Xiaohang , Zhang Yongsheng , Yi Lei , Ma Zhe , Su Weigang , Liu Xiaobao , Han Fengqing 
Published: August 2021

This study explores the paleoclimate changes around the 4 ka BP period in the central Qaidam Basin (QB), assessing the differences in spectral characteristics and organic composition of salt lake sediments under different climate change conditions. Sediment samples (10-m-depth profile) were collected from the middle of dry salt flats in East Taijinar Lake (China). Sediment organic matter (SOM) was assessed by Fourier transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry (GC-MS). Results showed a significant difference in the TOC content of sediments with different lithological characteristics. A lower TOC content in salt-bearing strata was attributed to the extreme sedimentary environment with minimal exogenous inputs. FTIR spectroscopy revealed that the SOM in sediments included aliphatic C, ketones and alcohols. Sediments of salt-bearing strata generally exhibited a rise in the content of ketone C=O groups and a decrease in aliphatic C, with an equal content of alcohols compared with silty sand. Therefore, exogenous OM and the content of TOC in silty sand strata are higher than in salt-bearing strata, indicating that the paleoclimate became warmer and wetter after 4 ka BP. GC-MS analysis showed a significant difference between the phenol and aldehyde content in different strata, further indicating that the paleoclimate changed from dry to relatively warm around 4 ka BP. Seven organic compound types were identified in SOM, including aldehydes, hydrocarbons, phenols, esters, ketones, alcohols, and furans. Different strata exhibited different distributions of organic compounds, with particularly high concentrations of aldehydes in salt-bearing strata and phenols in silty sand. Correlation analysis was performed between detrital minerals and OM types in all samples. Results showed a strong positive correlation between detrital minerals and phenols and a strong negative correlation between detrital minerals and aldehydes, with a negative correlation also identified between detrital minerals and ketones. Overall, the reduction in volatile organic compounds demonstrates that the paleoclimate changed from cooler and dry to wet and warm around the 4 ka BP period in the central QB, with the carbon preference index and n-alkane values further demonstrating these results. This study also confirms the importance of volatile organic compound monitoring to assess paleoclimate changes.
Vitamin D Deficiency as a Predictor of a High Prevalence of Coronary Artery Disease in Pancreas Transplant Candidates With Type 1 Diabetes
Authors: Buksińska-Lisik Małgorzata , Kwasiborski Przemysław J. , Ryczek Robert , Lisik Wojciech , Mamcarz Artur 
Published: August 2021

IntroductionPancreas transplantation is a high-risk procedure in terms of cardiovascular complications. Therefore, identification of all cardiovascular risk factors is crucial to prevent cardiovascular complications after pancreas transplantation. Vitamin D deficiency (VDD) appears to be a potential risk factor for coronary artery disease.ObjectiveTo determine the prevalence of VDD in pancreas transplant candidates, and further to examine the relationship between vitamin D and the prevalence of coronary artery disease and lipid profile parameters.Materials and MethodsThis is a prospective cross-sectional study. We enrolled consecutive patients with type 1 diabetes eligible for simultaneous pancreas-kidney transplantation or pancreas transplant alone. The laboratory tests included HbA1c, lipid profile, creatinine, and total 25-hydroxyvitamin D (25(OH)D). The diagnosis of coronary artery disease was based on coronary angiography.ResultsThe study population included 48 patients. VDD was revealed in 48% of patients and coronary artery disease in 35% of patients. The mean concentration of vitamin D in the entire cohort was 21.3 ± 9.48 ng/ml. The median value of 25(OH)D in patients with coronary artery disease was significantly lower than in patients without coronary artery disease (18.5 (11.6–21.5) vs. 24.8 (18.4–31.8) ng/ml, p = 0.018). There was a significant relationship between VDD and coronary artery disease (OR = 4.36; 95% confidence interval (CI): 1.22–15.64, p = 0.034). A patient’s odds of having coronary artery disease while having a sufficient level of vitamin D was 4.36 times lower than if the patient had VDD. There was a significant relationship between VDD and hypertension (OR = 5.91; 95% CI: 1.12–31.20, p = 0.039) and hemodialysis (OR = 4.25; 95% CI: 1.25–14.5, p = 0.023). There was no significant correlation between 25(OH)D and lipid profile.ConclusionsVDD is highly prevalent in pancreas transplant candidates with type 1 diabetes. There is a significant relationship between VDD and increased prevalence of coronary disease. The lack of any significant association between serum vitamin D and lipid profile suggests that the relationship between vitamin D and coronary artery disease results from other causes.
Evidence That the Etiology of Congenital Hypopituitarism Has a Major Genetic Component but Is Infrequently Monogenic
Authors: Jee Youn Hee , Gangat Mariam , Yeliosof Olga , Temnycky Adrian G. , Vanapruks Selena , Whalen Philip , Gourgari Evgenia , Bleach Cortney , Yu Christine H. , Marshall Ian , Yanovski Jack A. , Link Kathleen , Ten Svetlana , Baron Jeffrey , Radovick Sally 
Published: August 2021

PurposeCongenital hypopituitarism usually occurs sporadically. In most patients, the etiology remains unknown.MethodsWe studied 13 children with sporadic congenital hypopituitarism. Children with non-endocrine, non-familial idiopathic short stature (NFSS) (n= 19) served as a control group. Exome sequencing was performed in probands and both unaffected parents. A burden testing approach was used to compare the number of candidate variants in the two groups.ResultsFirst, we assessed the frequency of rare, predicted-pathogenic variants in 42 genes previously reported to be associated with pituitary gland development. The average number of variants per individual was greater in probands with congenital hypopituitarism than those with NFSS (1.1 vs. 0.21, mean variants/proband,P= 0.03). The number of probands with at least 1 variant in a pituitary-associated gene was greater in congenital hypopituitarism than in NFSS (62% vs. 21%,P= 0.03). Second, we assessed the frequency of rare, predicted-pathogenic variants in the exome (to capture undiscovered causes) that were inherited in a fashion that could explain the sporadic occurrence of the proband’s condition with a monogenic etiology (de novomutation, autosomal recessive, or X-linked recessive) with complete penetrance. There were fewer monogenic candidates in the probands with congenital hypopituitarism than those with NFSS (1.3 vs. 2.5 candidate variants/proband,P= 0.024). We did not find any candidate variants (0 of 13 probands) in genes previously reported to explain the phenotype in congenital hypopituitarism, unlike NFSS (8 of 19 probands,P= 0.01).ConclusionOur findings provide evidence that the etiology of sporadic congenital hypopituitarism has a major genetic component but may be infrequently monogenic with full penetrance, suggesting a more complex etiology.
Pan-Cancer Analysis of Genomic and Prognostic Characteristics Associated With Coronavirus Disease 2019 Regulators
Authors: Zhang Jian , Jiang Huali , Du Kunpeng , Xie Tao , Wang Baiyao , Chen Chengcong , Cen Bohong , Yuan Yawei , Ye Jiacai 
Published: August 2021

Background: Cancer patients are alleged to have poor coronavirus disease 2019 (COVID-19) outcomes. However, no systematic or comprehensive analyses of the role and mechanisms of COVID-19 receptor-related regulators in cancer are available.Methods: We comprehensively evaluated the genomic alterations and their clinical relevance of six COVID-19 receptor-related regulators [transmembrane serine protease 2 (TMPRSS2), angiotensinogen (AGT), angiotensin-converting enzyme 1 (ACE1), solute carrier family 6 member 19 (SLC6A19), angiotensin-converting enzyme 2 (ACE2), and angiotensin II receptor type 2 (AGTR2)] across a broad spectrum of solid tumors. RNA-seq data, single nucleotide variation data, copy number variation data, methylation data, and miRNA–mRNA interaction network data from The Cancer Genome Atlas (TCGA) of 33 solid tumors were analyzed. We assessed the sensitivities of drugs targeting COVID-19 receptor-related regulators, using information from the Cancer Therapeutics Response Portal database.Results: We found that there are widespread genetic alterations of COVID-19 regulators and that their expression levels were significantly correlated with the activity of cancer hallmark-related pathways. Moreover, COVID-19 receptor-related regulators may be used as prognostic biomarkers. By mining the genomics of drug sensitivities in cancer databases, we discovered a number of potential drugs that may target COVID-19 receptor-related regulators.Conclusion: This study revealed the genomic alterations and clinical characteristics of COVID-19 receptor-related regulators across 33 cancers, which may clarify the potential mechanism between COVID-19 receptor-related regulators and tumorigenesis and provide a novel approach for cancer treatments.
Motor Dysfunction Questionnaire and Dopamine Transporter Imaging Composite Scale Improve Differentiating Dementia With Lewy Bodies From Alzheimer's Disease With Motor Dysfunction
Authors: Chiu Pai-Yi , Wei Cheng-Yu , Hung Guang-Uei , Wu Shey-Lin 
Published: August 2021

Objective: Characteristic parkinsonism is the major comorbidity of dementia with Lewy bodies (DLB). We aimed to differentiate DLB from Alzheimer's disease (AD) with motor dysfunction using a composite scale with a characteristic motor dysfunction questionnaire (MDQ) and dopamine transporter (DAT) imaging. It could help detect DLB easily in healthcare settings without movement disorder specialists.Methods: This is a two-phase study. In the design phase, seven questions were selected and composed of a novel MDQ. In the test phase, all participants with DLB, AD, or non-dementia (ND) control completed dementia and parkinsonism survey, the novel designed questionnaire, DAT imaging, and composite scales of MDQ and DAT. The cutoff scores of the MDQ, semiquantitative analysis of the striatal–background ratio (SBR) and visual rating of DAT, and the composite scale of MDQ and DAT for discriminating DLB from AD or ND were derived and compared.Results: A total of 277 participants were included in this study (126 with DLB, 86 with AD, and 65 with ND). Compared with the AD or ND groups, the DLB group showed a significantly higher frequency in all seven items in the MDQ and a significantly lower SBR. For discrimination of DLB from non-DLB with MDQ, SBR, and composite scale, the cutoff scores of 3/2, 1.37/1.38, and 6/5 were suggested for the diagnosis of DLB with the sensitivities/specificities of 0.91/0.72, 0.91/0.80, and 0.87/0.93, respectively. The composite scale significantly improved the accuracy of discrimination compared with either the MDQ or SBR.Conclusion: This study showed that the novel designed simple questionnaire was a practical screening tool and had similar power to DAT scanning to detect DLB. The questionnaire can be applied in clinical practice and population studies for screening DLB. In addition, the composite scale of MDQ and DAT imaging further improved the diagnostic accuracy, indicating the superiority of the dual-model diagnostic tool.
The Roles of Magnetic Resonance-Guided Focused Ultrasound in Pain Relief in Patients With Bone Metastases: A Systemic Review and Meta-Analysis
Authors: Han Xiaying , Huang Runzhi , Meng Tong , Yin Huabin , Song Dianwen 
Published: August 2021

ObjectiveCancer pain, the most common skeleton-related event of bone metastases, significantly disturbs patients’ life. MRI-guided focused ultrasound (MRgFUS) is a therapeutic option to relieve pain; however, its efficacy and safety have not been fully explored. Therefore, we aim to conduct a meta-analysis on studies reporting MRgFUS for patients with bone metastases.MethodsRandomized controlled trials (RCT) and non-RCTs on MRgFUS treatment for patients with bone metastases were collected using PubMed, MEDLINE In-Process (US National Library of Medicine), National Institutes of Health (US National Library of Medicine), Embase (Elsevier), Web of Science, CINAHL, and the Cochrane Library between August 2007 and September 2019. Data on quantitative pain assessment before/after MRgFUS, response rate, and complication were extracted and analyzed.ResultsFifteen eligible studies with 362 patients were selected in this meta-analysis. The average pain score was 6.74 (95% CI: 6.30–7.18) at baseline, 4.15 (95% CI: 3.31–4.99) at 0–1 week, 3.09 (95% CI: 2.46–3.72) at 1–5 weeks, and 2.28 (95% CI: 1.37–3.19) at 5–14 weeks. Compared with baseline, the pain improvement at 0–1 week was 2.54 (95% CI: 1.92–3.16, p &lt; 0.01), at 1–5 weeks was 3.56 (95% CI: 3.11–4.02, p &lt; 0.01), and at 5–14 weeks was 4.22 (95% CI: 3.68–4.76, p &lt; 0.01). Change from baseline in OMEDD at 2 weeks after treatment was −15.11 (95% CI: −34.73, 4.50), at 1 month after treatment was −10.87 (95% CI: −26.32, 4.58), and at 3 months after treatment was −5.53 (95% CI: −20.44, 9.38). The overall CR rate was 0.36 (95% CI: 0.24–0.48), PR rate was 0.47 (95% CI: 0.36–0.58), and NR rate was 0.23 (95% CI: 0.13–0.34). Among 14 studies including 352 patients, 93 (26.4%) patients with minor complications and 5 (1.42%) patients with major complications were recorded.ConclusionThis meta-analysis identifies MRgFUS as a reliable therapeutic option to relieve cancer pain for patients with metastatic bone tumors with controllable related complications.
Impact of Surgical Approach on Surgical Resection Quality in Mid- and Low Rectal Cancer, A Bayesian Network Meta-Analysis
Authors: Wang Xiaojie , Zheng Zhifang , Yu Qian , Ghareeb Waleed M. , Lu Xingrong , Huang Ying , Huang Shenghui , Lin Shuangming , Chi Pan 
Published: August 2021

AimTo evaluate the evidence concerning the quality of surgical resection in laparoscopic (LapTME), robotic (RobTME) and transanal (TaTME) total mesorectal excision for mid-/low rectal cancer.MethodsA systematic literature search of the PubMed, EMBASE and Cochrane Central Register of Controlled Trials databases was performed. A Bayesian network meta-analysis was utilized to compare surgical resection involved in these 3 surgical techniques by using ADDIS software. Rates of positive circumferential resection margins (CRMs) were the primary endpoint.ResultsA total of 34 articles, 2 randomized clinical trials (RCTs) and 32 non-RCTs, were included in this meta-analysis. Pooled data showed CRM positivity in 114 of 1763 LapTME procedures (6.5%), 54 of 1051 RobTME procedures (5.1%) and 60 of 1276 TaTME procedures (4.7%). There was no statistically significant difference among these 3 surgical approaches in terms of CRM involvement rates and all other surgical resection quality outcomes. The incomplete mesorectal excision rates were 9.6% (69/720) in the LapTME group, 1.9% (11/584) in the RobTME group and 5.6% (45/797) in the TaTME group. Pooled network analysis observed a higher but not statistically significant risk of incomplete mesorectum when comparing both LapTME with RobTME (OR = 1.99; 95% CI = 0.48-11.17) and LapTME with TaTME (OR = 1.90; 95% CI = 0.99-5.25). By comparison, RobTME was most likely to be ranked the best or second best in terms of CRM involvement, complete mesorectal excision, rate of distal resection margin (DRM) involvement and length of DRMs. In addition, RobTME achieved a greater mean tumor distance to the CRM than TaTME. It is worth noting that TaTME was most likely to be ranked the worst in terms of CRM involvement for intersphincteric resection of low rectal cancer.ConclusionOverall, RobTME was most likely to be ranked the best in terms of the quality of surgical resection for the treatment of mid-/low rectal cancer. TaTME should be performed with caution in the treatment of low rectal cancer.