bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wingless-related integration site (WNT) signaling is activated during the inflammatory response upon cardiac surgery: A translational study
Authors: Krüger Bernard D. , Hofer Gilles E. , Rudiger Alain , Spahn Gabriela H. , Braun Julia , Bettex Dominique , Schoedon Gabriele , Spahn Donat R. 
Published: November 2022

ObjectiveCardiac surgery and the use of cardiopulmonary bypass initiate a systemic inflammatory response. Wingless-related integration site (WNT) signaling is part of the innate immunity and has been attributed a major role in the regulation of inflammation. In preclinical research, WNT-5a may sustain an inflammatory response and cause endothelial dysfunction. Our aim was to investigate WNT signaling after cardiac surgery and its association with postoperative inflammation (Clinicaltrials.gov, NCT04058496).MethodsIn this prospective, single-center, observational study, 64 consecutive patients for coronary artery bypass grafting (CABG) ± valve surgery were assigned into three groups: off-pump CABG (n = 28), on-pump CABG (n = 16) and combined valve-CABG surgery (n = 20). Blood samples were acquired before surgery, at intensive care unit (ICU) admission and 4, 8, and 48 h thereafter. Plasma concentrations of WNT-5a and its antagonists Secreted frizzled-related protein 1 (sFRP-1), Secreted frizzled-related protein 5 (sFRP-5), and WNT inhibitory factor 1 (WIF-1) were determined by enzyme-linked immunosorbent assay. In addition, plasma concentrations of six inflammatory cytokines were measured by multiplex immunoassay. Parameters were analyzed for evolution of plasma concentration over time, interactions, intergroup differences, and association with clinical outcome parameters.ResultsAt baseline, WNT-5a, sFRP-1, and WIF-1 were present in a minimal concentration, while sFRP-5 was elevated. A higher baseline value of WNT-5a, sFRP-5, and WIF-1 resulted in higher subsequent values of the respective parameter. At ICU admission, WNT-5a and sFRP-5 reached their maximum and minimum value, respectively. WIF-1 decreased over time and was lowest 8 h after surgery. sFRP-1 changed minimally over time. While WNT-5a returned to the baseline within 48 h, sFRP-5 and WIF-1 did not reach their baseline value at 48 h. Of the investigated WNT system components, only WIF-1 partially reflected the severity of surgery. WNT-5a and WIF-1 had an impact on postoperative fluid balance and noradrenaline requirement.ConclusionWNT-5a, sFRP-5, and WIF-1 are part of the systemic inflammatory response after cardiac surgery. WNT-5a peaks immediately after cardiac surgery and returns to baseline within 48 h, presumably modulated by its antagonist sFRP-5. Based on this translational study, WNT-5a antagonism may be further investigated to assess potentially beneficial effects in patients with a dysregulated inflammation after cardiac surgery.
A case study of pillar extraction techniques based on strip-filling and second-mining method
Authors: Hao Jian , Chen Anfa , Li Xuelong , Bian Hua , Shi Yongkui , Wang Xin , Zhao Jiali , Liu Haojie 
Published: November 2022

Strip coal pillars caused by strip mining are widely distributed in China. Over time, strip coal pillars are posing more potential hazards as their stability decreases; therefore, it becomes increasingly important to recover coal pillars without damaging the ground surface. In this paper, strip-filling and second-mining technique is adopted to probe into an optimal scheme for mine goafs. Construction waste was one type of the materials used for backfilling, which was taken to underground from the surface with a pumping system. Jisuo Coal Mine of Tengzhou, Shandong province was taken as the object of study. Through theoretical calculation and on-site survey, we set a re-mining scheme to control rock stratum stability, i.e., 8-m-wide backfilling for the first time and 4-m-wide backfilling for the second time; moreover, the ground pressure behavior and subsidence of working surface were monitored and a contour map of surface subsidence was thus mapped. In-situ practice indicated that the underground pressure from coal pillars was transmitted to the backfilling materials, the maximum normal stress of which was 5 MPa, so it was sufficient for the backfilling strip to support the weight of overlying strata; the maximum value of roof-to-floor convergence of backfilled mining face is 45 mm, the maximum surface subsidence 44mm, the maximum inclination value 0.65 mm/m, the maximum surface curvature 0.018 mm/m2, and the maximum horizontal deformation 0.16 mm/m. The filling body in the original goafs plays the role of “pier”. By the monitoring data of subsidence, its surface deformation value was less than that of buildings suffering from grade I damage, which verified the feasibility of strip-filling and second-mining scheme. The success in this technique provides reliable technical and theoretical support for mines with similar conditions.
Sensitivity of sheltered mudflats to wind events
Authors: Zhu Qin , Nie Wei , Zhu Zhenchang , Cai Yanpeng , Yang Zhifeng 
Published: November 2022

The impact of waves on the morphological changes of sheltered mudflats is less well studied compared to that on open flats. To investigate the sensitivity of low-energy sheltered mudflats to hydrodynamics such as waves, we carried out in situ measurements of bed level, currents, and waves on the middle flat of a sheltered mudflat in a bay in southern China. Two 1-month measurements, March 26–26 April 2021, and July 8–8 August 2021, were performed for repetition. We found that the sheltered system was not as stable as it appeared. The maximum intratidal bed-level variation, ΔZ, was &lt;5 mm in calm conditions. However, wind speeds slightly highly than 3.0 m/s, under which significant wave height was approximately 0.1 m, triggered significant bed-level variation patterns, with ΔZ reaching up to 2 cm. Intratidal bed-level change patterns depend on the relative dominance of waves and currents: low τc (current-induced bed shear stress) and high τw (wave-induced bed shear stress) promote the generation and migration of bed ripples; comparable τc and τw, with medium-to-high values, lead to non-cyclic bed-level change patterns; high τc and high τw result in bed accumulation/degradation superimposed by bed ripple migration. From a long-term perspective, i.e. in the time scale of month to year, sheltered mudflats are stable systems, and their high sensitivity causes short-term significant bed-level variation. The sensitivity and stability of sheltered mudflats must be further investigated to explore the effects of human intervention and global climate change.
Comprehensive analyses of one-carbon metabolism related genes and their association with prognosis, tumor microenvironment, chemotherapy resistance and immunotherapy in lung adenocarcinoma
Authors: Zhou Ning , Tang Quanying , Yu Haochuan , Li Tong , Ren Fan , Zu Lingling , Chen Gang , Chen Jun , Xu Song 
Published: November 2022

Background: Lung adenocarcinoma (LUAD) is the most common type of lung cancer and is a global public health concern. One-carbon (1C) metabolism plays a crucial role in the occurrence and development of multiple cancer types. However, there are limited studies investigating 1C metabolism in LUAD. This study aims to evaluate the prognostic value of 1C metabolism-related genes in LUAD and to explore the potential correlation of these genes with gene methylation, the tumor microenvironment, and immunotherapy.Methods: We identified 26 1C metabolism-related genes and performed a Kaplan-Meier and Cox regression analysis to evaluate the prognostic value of these genes. Consensus clustering was further performed to determine the 1C metabolism-related gene patterns in LUAD. The clinical and molecular characteristics of subgroups were investigated based on consensus clustering. CIBERSORT and ssGSEA algorithms were used to calculate the relative infiltration levels of multiple immune cell subsets. The relationship between 1C metabolism-related genes and drug sensitivity to immunotherapy was evaluated using the CellMiner database and IMvigor210 cohort, respectively.Results: The expression levels of 23 1C metabolism-related genes were significantly different between LUAD tumor tissues and normal tissues. Seventeen of these genes were related to prognosis. Two clusters (cluster 1 and cluster 2) were identified among 497 LUAD samples based on the expression of 7 prognosis-related genes. Distinct expression patterns were observed between the two clusters. Compared to cluster 2, cluster 1 was characterized by inferior overall survival (OS) (median OS = 41 vs. 60 months, p = 0.00031), increased tumor mutation burden (15.8 vs. 7.5 mut/Mb, p &lt; 0.001), high expression of PD-1 (p &lt; 0.001) and PD-L1 (p &lt; 0.001), as well as enhanced immune infiltration. 1C metabolism-related genes were positively correlated with the expression of methylation enzymes, and a lower methylation level was observed in cluster 1 (p = 0.0062). Patients in cluster 1 were resistant to chemotherapy drugs including pemetrexed, gemcitabine, paclitaxel, etoposide, oxaliplatin, and carboplatin. The specific expression pattern of 1C metabolism-related genes was correlated with a better OS in patients treated with immunotherapy (median OS: 11.2 vs. 7.8 months, p = 0.0034).Conclusion: This study highlights that 1C metabolism is correlated with the prognosis of LUAD patients and immunotherapy efficacy. Our findings provide novel insights into the role of 1C metabolism in the occurrence, development, and treatment of LUAD, and can assist in guiding immunotherapy for LUAD patients.
Peak width of skeletonized mean diffusivity in cerebral amyloid angiopathy: Spatial signature, cognitive, and neuroimaging associations
Authors: Zanon Zotin Maria Clara , Schoemaker Dorothee , Raposo Nicolas , Perosa Valentina , Bretzner Martin , Sveikata Lukas , Li Qi , van Veluw Susanne J. , Horn Mitchell J. , Etherton Mark R. , Charidimou Andreas , Gurol M. Edip , Greenberg Steven M. , Duering Marco , Santos Antonio Carlos dos , Pontes-Neto Octavio M. , Viswanathan Anand 
Published: November 2022

BackgroundPeak width of skeletonized mean diffusivity (PSMD) is a promising diffusion tensor imaging (DTI) marker that shows consistent and strong cognitive associations in the context of different cerebral small vessel diseases (cSVD).PurposeInvestigate whether PSMD (1) is higher in patients with Cerebral Amyloid Angiopathy (CAA) than those with arteriolosclerosis; (2) can capture the anteroposterior distribution of CAA-related abnormalities; (3) shows similar neuroimaging and cognitive associations in comparison to other classical DTI markers, such as average mean diffusivity (MD) and fractional anisotropy (FA).Materials and methodsWe analyzed cross-sectional neuroimaging and neuropsychological data from 90 non-demented memory-clinic subjects from a single center. Based on MRI findings, we classified them into probable-CAA (those that fulfilled the modified Boston criteria), subjects with MRI markers of cSVD not attributable to CAA (presumed arteriolosclerosis; cSVD), and subjects without evidence of cSVD on MRI (non-cSVD). We compared total and lobe-specific (frontal and occipital) DTI metrics values across the groups. We used linear regression models to investigate how PSMD, MD, and FA correlate with conventional neuroimaging markers of cSVD and cognitive scores in CAA.ResultsPSMD was comparable in probable-CAA (median 4.06 × 10–4 mm2/s) and cSVD (4.07 × 10–4 mm2/s) patients, but higher than in non-cSVD (3.30 × 10–4 mm2/s; p &lt; 0.001) subjects. Occipital-frontal PSMD gradients were higher in probable-CAA patients, and we observed a significant interaction between diagnosis and region on PSMD values [F(2, 87) = 3.887, p = 0.024]. PSMD was mainly associated with white matter hyperintensity volume, whereas MD and FA were also associated with other markers, especially with the burden of perivascular spaces. PSMD correlated with worse executive function (β = −0.581, p &lt; 0.001) and processing speed (β = −0.463, p = 0.003), explaining more variance than other MRI markers. MD and FA were not associated with performance in any cognitive domain.ConclusionPSMD is a promising biomarker of cognitive impairment in CAA that outperforms other conventional and DTI-based neuroimaging markers. Although global PSMD is similarly increased in different forms of cSVD, PSMD’s spatial variations could potentially provide insights into the predominant type of underlying microvascular pathology.
A ferroptosis-related gene signature associated with immune landscape and therapeutic response in osteosarcoma
Authors: Wang Xinxing , Xia Guang , Xiao Shilang , Wu Song , Zhang Lina , Huang Junjie , Zhang Wenxiu , Cao Xu 
Published: November 2022

BackgroundThe role of ferroptosis in tumor progression and immune microenvironment is extensively investigated. However, the potential value of ferroptosis regulators in predicting prognosis and therapeutic strategies for osteosarcoma (OS) patients remains to be elucidated.MethodsHere, we extracted transcriptomic and survival data from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) and Gene Expression Omnibus (GEO) to investigate the expression and prognostic value of ferroptosis regulators in OS patients. After comprehensive analyses, including Gene set variation analysis (GSVA), single-sample gene-set enrichment analysis (ssGSEA), Estimated Stromal and Immune cells in Malignant Tumor tissues using Expression (ESTIMATE), single-cell RNA sequencing, and biological experiments, our constructed 8-ferroptosis-regulators prognostic signature effectively predicted the immune landscape, prognosis, and chemoradiotherapy strategies for OS patients.ResultsWe constructed an 8-ferroptosis-regulators signature that could predict the survival outcome of OS. The signature algorithm scored samples, and high-scoring patients were more prone to worse prognoses. The tumor immune landscape suggested the positive relevance between risk score and immunosuppression. Interfering HILPDA and MUC1 expression would inhibit tumor cell proliferation and migration, and MUC1 might improve the ferroptosis resistance of OS cells. Moreover, we predicted chemoradiotherapy strategies of cancer patients following ferroptosis-risk-score groups.ConclusionDysregulated ferroptosis gene expression can affect OS progression by affecting the tumor immune landscape and ferroptosis resistance. Our risk model can predict OS survival outcomes, and we propose that HILPDA and MUC1 are potential targets for cancer therapy.
Utilization of functional MRI in the diagnosis and management of cervical cancer
Authors: Matani Hirsch , Patel Ankur K. , Horne Zachary D. , Beriwal Sushil 
Published: November 2022

IntroductionImaging is integral part of cervical cancer management. Currently, MRI is used for staging, follow up and image guided adaptive brachytherapy. The ongoing IQ-EMBRACE sub-study is evaluating the use of MRI for functional imaging to aid in the assessment of hypoxia, metabolism, hemodynamics and tissue structure. This study reviews the current and potential future utilization of functional MRI imaging in diagnosis and management of cervical cancer.MethodsWe searched PubMed for articles characterizing the uses of functional MRI (fMRI) for cervical cancer. The current literature regarding these techniques in diagnosis and outcomes for cervical cancer were then reviewed.ResultsThe most used fMRI techniques identified for use in cervical cancer include diffusion weighted imaging (DWI) and dynamic contrast enhancement (DCE). DCE-MRI indirectly reflects tumor perfusion and hypoxia. This has been utilized to either characterize a functional risk volume of tumor with low perfusion or to characterize at-risk tumor voxels by analyzing signal intensity both pre-treatment and during treatment. DCE imaging in these situations has been associated with local control and disease-free survival and may have predictive/prognostic significance, however this has not yet been clinically validated. DWI allows for creation of ADC maps, that assists with diagnosis of local malignancy or nodal disease with high sensitivity and specificity. DWI findings have also been correlated with local control and overall survival in patients with an incomplete response after definitive chemoradiotherapy and thus may assist with post-treatment follow up. Other imaging techniques used in some instances are MR-spectroscopy and perfusion weighted imaging. T2-weighted imaging remains the standard technique used for diagnosis and radiation treatment planning. In many instances, it is unclear what additional information functional-MRI techniques provide compared to standard MRI imaging.ConclusionsFunctional MRI provides potential for improved diagnosis, prediction of treatment response and prognostication in cervical cancer. Specific sequences such as DCE, DWI and ADC need to be validated in a large prospective setting prior to widespread use. The ongoing IQ-EMBRACE study will provide important clinical information regarding these imaging modalities.
Collimating individual beamlets in pencil beam scanning proton therapy, a dosimetric investigation
Authors: Holmes Jason , Shen Jiajian , Patel Samir H. , Wong William W. , Foote Robert L. , Bues Martin , Liu Wei 
Published: November 2022

The purpose of this work is to investigate collimating individual proton beamlets from a dosimetric perspective and to introduce a new device concept, the spot scanning aperture (SSA). The SSA consists of a thin aperture with a small cylindrical opening attached to a robotics system, which allows the aperture to follow and align with individual beamlets during spot delivery. Additionally, a range shifter is incorporated (source-side) for treating shallow depths. Since the SSA trims beamlets spot by spot, the patient-facing portion of the device only needs to be large enough to trim a single proton beamlet. The SSA has been modelled in an open-source Monte-Carlo-based dose engine (MCsquare) to characterize its dosimetric properties in water at depths between 0 and 10 cm while varying the following parameters: the aperture material, thickness, distance to the water phantom, distance between the aperture and attached range shifter, and the aperture opening radius. Overall, the SSA greatly reduced spot sizes for all the aperture opening radii that were tested (1 – 4 mm), especially in comparison with the extended range shifter (ranger shifter placed at 30 cm from patient); greater than 50% when placed less than 10 cm away from the patient at depths in water less than 50 mm. The peak to entrance dose ratio and linear energy transfer was found to depend on the thickness of the aperture and therefore the aperture material. Neutron production rates were also investigated and discussed.
Development and Validation of a nomogram for forecasting survival of alcohol related hepatocellular carcinoma patients
Authors: Yan Tao , Huang Chenyang , Lei Jin , Guo Qian , Su Guodong , Wu Tong , Jin Xueyuan , Peng Caiyun , Cheng Jiamin , Zhang Linzhi , Liu Zherui , Kin Terence , Ying Fan , Liangpunsakul Suthat , Li Yinyin , Lu Yinying 
Published: November 2022

BackgroundWith the increasing incidence and prevalence of alcoholic liver disease, alcohol-related hepatocellular carcinoma has become a serious public health problem worthy of attention in China. However, there is currently no prognostic prediction model for alcohol-related hepatocellular carcinoma.MethodsThe retrospective analysis research of alcohol related hepatocellular carcinoma patients was conducted from January 2010 to December 2014. Independent prognostic factors of alcohol related hepatocellular carcinoma were identified by Lasso regression and multivariate COX proportional model analysis, and the nomogram model was constructed. The reliability and accuracy of the model were assessed using the concordance index(C-Index), receiver operating characteristic (ROC) curve and calibration curve. Evaluate the clinical benefit and application value of the model through clinical decision curve analysis (DCA). The prognosis was assessed by the Kaplan-Meier (KM) survival curve.ResultsIn sum, 383 patients were included in our study. Patients were stochastically assigned to training cohort (n=271) and validation cohort (n=112) according to 7:3 ratio. The predictors included in the nomogram were splenectomy, platelet count (PLT), creatinine (CRE), Prealbumin (PA), mean erythrocyte hemoglobin concentration (MCHC), red blood cell distribution width (RDW) and TNM. Our nomogram demonstrated excellent discriminatory power (C-index) and good calibration at 1-year, 3-year and 5- year overall survival (OS). Compared to TNM and Child-Pugh model, the nomogram had better discriminative ability and higher accuracy. DCA showed high clinical benefit and application value of the model.ConclusionThe nomogram model we established can precisely forcasting the prognosis of alcohol related hepatocellular carcinoma patients, which would be helpful for the early warning of alcohol related hepatocellular carcinoma and predict prognosis in patients with alcoholic hepatocellular carcinoma.
The effect of sodium-glucose cotransporter 2 inhibitors on biomarkers of inflammation: A systematic review and meta-analysis of randomized controlled trials
Authors: Wang Dongmei , Liu Jieying , Zhong Ling , Li Shunhua , Zhou Liyuan , Zhang Qian , Li Ming , Xiao Xinhua 
Published: November 2022

Aims: Inflammatory biomarkers may play vital roles in the pathophysiology of diabetes and diabetic cardiorenal complications. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have a potential cardiovascular and renal protective effect in type 2 diabetes. The aim of this meta-analysis was to quantify the effects of SGLT2 inhibitors on biomarkers of inflammation in randomized controlled trials (RCTs).Methods: PubMed, Cochrane Library, EMBASE, and Web of Science were searched for eligible RCTs of adults with type 2 diabetes (T2D) with no time limit (updated to 12 October 2022). The biomarkers selected included C-reactive protein (CRP), interleukin-6, tumor necrosis factor-alpha, leptin, adiponectin, ferritin, plasminogen activator inhibitor (PAI)-1, and vascular cell adhesion molecule-1. Data were analyzed using a random-effect model in Review Manager 5.4.Results: Thirty-four studies with 6,261 patients (68.6% male) were eligible for this meta-analysis. The mean age of the participants was 62.57(±11.13) years old, and the median treatment duration length with follow-up was 24 weeks. Generally, the included trials were of good methodological quality. The meta-analysis revealed that ferritin levels were significantly reduced in SGLT2 inhibitor treatment groups versus placebo or standard diabetes therapies (SMD: −1.21; 95% CI: −1.91, −0.52, p &lt; 0.001). The effects of CRP (SMD: 0.25; 95% CI: −0.47, −0.03, p = 0.02) and leptin (SMD: −0.22; 95% CI: −0.43, −0.01, p = 0.04) were reduced, and the effects of adiponectin were improved (SMD: 0.28; 95% CI: 0.15, 0.41, p &lt; 0.001) in placebo-controlled studies. PAI-1 levels were significantly reduced in studies controlled for diabetes therapies (SMD: −0.38; 95% CI: −0.61, −0.15, p = 0.001).Conclusion: This analysis provides strong evidence supporting anti-inflammatory effects of SGLT2 inhibitors in T2D subjects. The mechanisms and possible targets for the inflammation reducing and cardiorenal protective properties of SGLT2 inhibitors remain to be explored.