bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Risk Threshold for Hemoglobin A1c Associated With Albuminuria: A Population-Based Study in China
Authors: Lian Hong , Wu Hongshi , Ning Jie , Lin Diaozhu , Huang Chulin , Li Feng , Liang Ying , Qi Yiqin , Ren Meng , Yan Li , You Lili , Xu Mingtong 
Published: May 2021

BackgroundDiabetic kidney disease (DKD) is a kind of common microvascular complication of diabetes. This study aims to explore the possible links between blood sugar level and albuminuria, providing the exact cut point of the “risk threshold” for blood glucose with DKD.MethodsThe relationship between blood glucose and albuminuria was modeled using linear and logistic regression in the REACTION study cohorts (N= 8932). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression model. Two-slope linear regression was used to simulate associations between blood glucose and ACR.ResultsWe found that the increase in ACR was accompanied by increased HbA1c, with a turning point at 5.5%. The positive correlation remained highly significant (P&lt;0.001) when adjusted for age, sex, marital status, education, smoking status, drinking status, BMI, waistline, SBP and DBP. In subgroup analyses including gender, obesity, hypertension, and smoking habits, the relationship was significant and stable.ConclusionsWe determined a risk threshold for HbA1c associated with albuminuria in a Chinese population over the age of 40. HbA1c ≥ 5.5% was positively and independently associated with ACR. These results suggest the necessity of early blood glucose control and renal function screening for DKD in at-risk populations.
Quotient of Waist Circumference and Body Mass Index: A Valuable Indicator for the High-Risk Phenotype of Obesity
Authors: Liu Xiao-cong , Huang Yu , Lo Kenneth , Huang Yu-qing , Chen Ji-yan , Feng Ying-qing 
Published: May 2021

ObjectiveMeasuring the body mass index (BMI) or waist circumference (WC) alone is insufficient for assessing possible health risks due to obesity. This study aimed to investigate whether the quotient of WC and BMI can be used as a proxy of the high-risk phenotype of obesity.MethodsData for analysis were derived from the National Health and Nutrition Examination Survey (NHANES 1999-2014). The Waist-BMI Ratio was defined as WC divided by BMI. The associations between Waist-BMI Ratio and mortality were estimated using Cox regression models. Restricted cubic spline and two-piecewise linear regression models were used to identify non-linear relationships. The discriminative abilities of different anthropometric measures were compared using receiver operating characteristic curves (ROC).ResultsThis study is based on data from 35557 adults (51.1% female, mean age 44.9 years). During an average follow-up of 101.8 months, 3680 participants died, including 807 of cardiovascular causes. In fully adjusted models, Waist-BMI Ratio was independently associated with overall (hazard ratio [HR], 1.78; 95% confidence interval [CI], 1.48-2.13) and cardiovascular (HR, 1.77; 95% CI, 1.25-2.52) mortality. Spline analyses revealed that dose-response relationships existed between Waist-BMI Ratio and death. The mortality risk rises dramatically above the cut-off point of the Waist-BMI Ratio (HR, 3.22; 95% CI, 2.43-4.26 for overall mortality and HR, 3.07; 95% CI, 1.71-5.52 for cardiovascular mortality). ROC curve analysis suggested that Waist-BMI Ratio was a better discriminator of mortality (AUC 0.637 for overall and 0.639 for cardiovascular mortality) than BMI, WC, and waist-to-height ratio (Delong’s test all P &lt;0.001).ConclusionsWaist-BMI Ratio was independently associated with overall and cardiovascular mortality in a J-shaped pattern, offering an immense potential risk marker for obesity in the clinical setting.
The GABAA Receptor Influences Pressure Overload-Induced Heart Failure by Modulating Macrophages in Mice
Authors: Bu Jin , Huang Shiyuan , Wang Jue , Xia Tong , Liu Hui , You Ya , Wang Zhaohui , Liu Kun 
Published: May 2021

BackgroundMyocardial macrophages have key roles in cardiac remodeling and dysfunction. The gamma-aminobutyric acid subtype A (GABAA) receptor was recently found to be distributed in macrophages, allowing regulation of inflammatory responses to various diseases. This study aimed to clarify the role of GABAA receptor-mediated macrophage responses in pressure overload-induced heart failure.Methods and ResultsC57BL/6J mice underwent transverse aortic constriction for pressure-overload hypertrophy (POH) and were intraperitoneally treated with a specific GABAA receptor agonist (topiramate) or antagonist (bicuculline). Echocardiography, histology, and flow cytometry were performed to evaluate the causes and effects of myocardial hypertrophy and fibrosis. Activation of the GABAA receptor by topiramate reduced ejection fraction and fractional shortening, enlarged the end-diastolic and end-systolic left ventricular internal diameter, aggravated myocardial hypertrophy and fibrosis, and accelerated heart failure in response to pressure overload. Mechanistically, topiramate increased the number of Ly6Clow macrophages in the heart during POH and circulating Ly6Chigh classic monocyte infiltration in late-phase POH. Further, topiramate drove Ly6Clow macrophages toward MHCIIhigh macrophage polarization. As a result, Ly6Clow macrophages activated the amphiregulin-induced AKT/mTOR signaling pathway, and Ly6ClowMHCIIhigh macrophage polarization increased expression levels of osteopontin and TGF-β, which led to myocardial hypertrophy and fibrosis. Conversely, GABAA receptor blockage with bicuculline reversed these effects.ConclusionsControl of the GABAA receptor activity in monocytes/macrophages plays an important role in myocardial hypertrophy and fibrosis after POH. Blockade of the GABAA receptor has the potential to improve pressure overload-induced heart failure.
Expression of the Carbohydrate Lewis Antigen, Sialyl Lewis A, Sialyl Lewis X, Lewis X, and Lewis Y in the Placental Villi of Patients With Unexplained Miscarriages
Authors: Ma Zhi , Yang Huixia , Peng Lin , Kuhn Christina , Chelariu-Raicu Anca , Mahner Sven , Jeschke Udo , von Schönfeldt Viktoria 
Published: May 2021

BackgroundLewis antigens such as Sialyl Lewis A (sLeA), Sialyl Lewis X (sLeX), Lewis X (LeX), and Lewis Y (LeY) are a class of carbohydrate molecules that are known to mediate adhesion between tumor cells and endothelium by interacting with its selectin ligands. However, their potential role in miscarriage remains enigmatic. This study aims to analyze the expression pattern of sLeA, sLeX, LeX, and LeY in the placental villi tissue of patients with a medical history of unexplained miscarriages.MethodsParaffin-embedded slides originating from placental tissue were collected from patients experiencing a miscarriage early in their pregnancy (6–13 weeks). Tissues collected from spontaneous (n = 20) and recurrent (n = 15) miscarriages were analyzed using immunohistochemical and immunofluorescent staining. Specimens obtained from legally terminated normal pregnancies were considered as control group (n = 18). Assessment of villous vessel density was performed in another cohort (n = 10 each group) of gestation ages-paired placenta tissue. Protein expression was evaluated with Immunoreactive Score (IRS). Statistical analysis was performed by using Graphpad Prism 8.ResultsExpression of sLeA, sLeX, LeX, and LeY in the syncytiotrophoblast was significantly upregulated in the control group compared with spontaneous and recurrent miscarriage groups. However, no prominent differences between spontaneous and recurrent miscarriage groups were identified. Potential key modulators ST3GAL6 and NEU1 were found to be significantly downregulated in the recurrent miscarriage group and upregulated in the spontaneous group, respectively. Interestingly, LeX and LeY expression was also detected in the endothelial cells of villous vessels in the control group but no significant expression in miscarriage groups. Furthermore, assessment of villous vessel density using CD31 found significantly diminished vessels in all size groups of villi (small villi &lt;200 µm, P = 0.0371; middle villi between 200 and 400 µm, P = 0.0010 and large villi &gt;400 µm, P = 0.0003). Immunofluorescent double staining also indicated the co-localization of LeX/Y and CD31.ConclusionsThe expression of four mentioned carbohydrate Lewis antigens and their potential modulators, ST3GAL6 and NEU1, in the placenta of patients with miscarriages was significantly different from the normal pregnancy. For the first time, their expression pattern in the placenta was illustrated, which might shed light on a novel understanding of Lewis antigens’ role in the pathogenesis of miscarriages.
Preservation of Gastrointestinal Mucosal Barrier Function and Microbiome in Patients With Controlled HIV Infection
Authors: Mak Gerald , Zaunders John J. , Bailey Michelle , Seddiki Nabila , Rogers Geraint , Leong Lex , Phan Tri Giang , Kelleher Anthony D. , Koelsch Kersten K. , Boyd Mark A. , Danta Mark 
Published: May 2021

BackgroundDespite successful ART in people living with HIV infection (PLHIV) they experience increased morbidity and mortality compared with HIV-negative controls. A dominant paradigm is that gut-associated lymphatic tissue (GALT) destruction at the time of primary HIV infection leads to loss of gut integrity, pathological microbial translocation across the compromised gastrointestinal barrier and, consequently, systemic inflammation. We aimed to identify and measure specific changes in the gastrointestinal barrier that might allow bacterial translocation, and their persistence despite initiation of antiretroviral therapy (ART).MethodWe conducted a cross-sectional study of the gastrointestinal (GIT) barrier in PLHIV and HIV-uninfected controls (HUC). The GIT barrier was assessed as follows: in vivo mucosal imaging using confocal endomicroscopy (CEM); the immunophenotype of GIT and circulating lymphocytes; the gut microbiome; and plasma inflammation markers Tumour Necrosis Factor-α (TNF-α) and Interleukin-6 (IL-6); and the microbial translocation marker sCD14.ResultsA cohort of PLHIV who initiated ART early, during primary HIV infection (PHI), n=5), and late (chronic HIV infection (CHI), n=7) infection were evaluated for the differential effects of the stage of ART initiation on the GIT barrier compared with HUC (n=6). We observed a significant decrease in the CD4 T-cell count of CHI patients in the left colon (p=0.03) and a trend to a decrease in the terminal ileum (p=0.13). We did not find evidence of increased epithelial permeability by CEM. No significant differences were found in microbial translocation or inflammatory markers in plasma. In gut biopsies, CD8 T-cells, including resident intraepithelial CD103+ cells, did not show any significant elevation of activation in PLHIV, compared to HUC. The majority of residual circulating activated CD38+HLA-DR+ CD8 T-cells did not exhibit gut-homing integrins α4ß7, suggesting that they did not originate in GALT. A significant reduction in the evenness of species distribution in the microbiome of CHI subjects (p=0.016) was observed, with significantly higher relative abundance of the genus Spirochaeta in PHI subjects (p=0.042).ConclusionThese data suggest that substantial, non-specific increases in epithelial permeability may not be the most important mechanism of HIV-associated immune activation in well-controlled HIV-positive patients on antiretroviral therapy. Changes in gut microbiota warrant further study.
The Relationship Between Electrical Energy Delivered by Deep Brain Stimulation and Levodopa-Induced Dyskinesias in Parkinson's Disease: A Retrospective Preliminary Analysis
Authors: Prenassi Marco , Arlotti Mattia , Borellini Linda , Bocci Tommaso , Cogiamanian Filippo , Locatelli Marco , Rampini Paolo , Barbieri Sergio , Priori Alberto , Marceglia Sara 
Published: May 2021

Background: Adaptive Deep Brain Stimulation (aDBS) is now considered as a new feasible and effective paradigm to deliver DBS to patients with Parkinson's disease (PD) in such a way that not only stimulation is personalized and finely tuned to the instantaneous patient's state, but also motor improvement is obtained with a lower amount of energy transferred to the tissue. Amplitude-controlled aDBS was shown to significantly decrease the amplitude-driven total electrical energy delivered to the tissue (aTEED), an objective measure of the amount of energy transferred by DBS amplitude to the patient's brain. However, there is no direct evidence of a relationship between aTEED and the occurrence of DBS-related adverse events in humans.Objective: In this work, we investigated the correlation of aTEED with the occurrence of levodopa-induced dyskinesias pooling all the data available from our previous experiments using aDBS and cDBS.Methods: We retrospectively analyzed data coming from 19 patients with PD undergoing surgery for STN-DBS electrode positioning and participating to experiments involving cDBS and aDBS delivery. Patients were all studied some days after the surgery (acute setting). The aTEED and dyskinesia assessments (Rush Dyskinesia Rating Scale, RDRS) considered in the Med ON-Stim ON condition.Results: We confirmed both that aTEED values and RDRS were significantly lower in the aDBS than in cDBS sessions (aTEED mean value, cDBS: 0.0278 ± 0.0011 j, vs. aDBS: 0.0071 ± 0.0003 j, p &lt; 0.0001 Wilcoxon's rank sum; normalized RDRS mean score, cDBS: 0.66 ± 0.017 vs. aDBS: 0.45 ± 0.01, p = 0.025, Wilcoxon's rank sum test). In addition, we found a direct significant correlation between aTEED and RDRS (ρ = 0.44, p = 0.0032, Spearman's correlation).Conclusions: Our results provide a first piece of evidence that aTEED is correlated to the amount of levodopa-induced dyskinesias in patients with PD undergoing STN-DBS, thus supporting the role of aDBS as feasible and safe alternative to cDBS.
C-reactive Protein for Stroke Detection in the Emergency Department in Patients With Dizziness Without Neurological Deficits
Authors: Hong Seok-In , Kim June-Sung , Bae Hong Jun , Kim Won Young 
Published: May 2021

Background: Stroke diagnosis can be challenging in patients with dizziness without neurologic deficits. The aim of this study was to evaluate the predictive value of C-reactive protein (CRP) for identifying acute stroke in such patients.Methods: Data from adult patients (&gt;18 years) admitted to the emergency department from August 2019 to February 2020 were evaluated. The study subjects were 1,188 patients presenting with dizziness without neurological deficits whose serum CRP level was measured within 2 h of arriving at the emergency department and who underwent brain magnetic resonance imaging. The relationship between CRP and acute stroke was analyzed using univariable and multivariable models.Results: Acute stroke was detected in 53 (4.4%) patients (40 with brain infarction, 10 with vertebrobasilar insufficiency, 2 with intracerebral hemorrhage, and 1 with subarachnoid hemorrhage). The CRP levels did not differ significantly between the acute stroke and non-stroke groups [0.10 (0.10–0.31) vs. 0.10 (0.10–0.16), P = 0.074]. The area under receiver operating characteristic curve of CRP for acute stroke was not statistically significant (0.567, P = 0.101). On multivariable analysis, the following variables were associated with acute stroke: age (odds ratio [OR], 1.041; 95% confidence interval [CI], 1.011–1.071), history of cerebrovascular accidents (OR, 1.823; 95% CI, 1.068–3.110), white blood cell count (OR, 1.126; 95% CI, 1.017–1.248), and hemoglobin (OR, 1.316; 95% CI, 1.056–1.640). However, CRP (P = 0.183) was not associated with acute stroke.Conclusion: Serum CRP levels do not have significant discriminative value for identifying acute stroke in patients with dizziness without definite neurologic deficits.
Flow Diversion for Intracranial Aneurysms Beyond the Circle of Willis
Authors: Yu Jinlu , Lv Xianli 
Published: May 2021

Background: Few reports have shown the therapeutic outcomes of flow diversion (FD) for intracranial aneurysms beyond the circle of Willis, and the efficacy of this technique remains unclear.Materials and methods: A retrospective study was performed on 22 consecutive patients, diagnosed with intracranial aneurysms beyond the circle of Willis, and treated with pipeline embolization device (PED) (Medtronic, Irvine, California, USA) between January 2015 and December 2019.Result: The 22 patients were between 16 and 66 years old (mean 44.5 ± 12.7 years), and six patients were male (27.3%, 6/22). Twenty-two patients had 23 aneurysms. The 23 aneurysms were 3–25 mm in diameter (12.2 ± 7.1 mm on average). The diameter of the parent artery was 1.3–3.0 mm (2.0 ± 0.6 mm on average). The 23 aneurysms were located as follows: 17 (73.9%, 17/23) were in the anterior circulation, and 6 (26.1%, 6/23) were in the posterior circulation. PED deployment was technically successful in all cases. Two overlapping PEDs were used to cover the aneurysm neck in 3 cases. One PED was used to overlap the two tandem P1 and P2 aneurysms. Other cases were treated with single PED. Coil assistance was used to treat 7 aneurysms, including 4 recurrent aneurysms and 3 new cases requiring coiling assistance during PED deployment. There were no cases of complications during PED deployment. All patients were available at the follow-up (mean, 10.9 ± 11.4 months). All patients presented with a modified Rankin Score (mRS) of 0. During angiographic follow-up, complete embolization was observed in 22 aneurysms in 21 patients, and one patient had subtotal embolization with the prolongation of stasis in the arterial phase.Conclusion: PED deployment for intracranial aneurysms beyond the circle of Willis is feasible and effective, with high rates of aneurysm occlusion.
Is the Middle Meningeal Artery the Optimal Path for Dural Arteriovenous Fistula Embolization?
Authors: Su Han , Xu Kan , Wang Yiheng , Yu Jinlu 
Published: May 2021

Background: The middle meningeal artery (MMA) is the optimal arterial path for endovascular treatment (EVT) of dural arteriovenous fistulas (DAVFs). However, the details are not completely understood.Materials and Methods: We performed a retrospective study of patients who were admitted to the First Hospital of Jilin University with a diagnosis of cranial DAVF with involvement of the MMA as a feeding artery. On the basis of the arterial path chosen and the role of the MMA in the first EVT procedure, EVT was divided into three types (I–III), each of which was further divided into two subclasses (a and b). The degree of embolization was analyzed.Result: The 104 included patients ranged in age from 13 to 80 years (mean, 53.6 ± 11.8 years). There were 48 cases of hemorrhage (46.2%, 48/104). Complete embolization was achieved in the first procedure in 64.4% of cases, and success was eventually achieved using EVT (the first attempt or a subsequent attempt) in 74.1% of cases. EVT caused complications in 6.7% of cases. A modified Rankin scale score of 0 or 1 was achieved in 78.8% of patients. Statistical analyses revealed that type Ia and IIb EVTs had the lowest complete embolization rates, but no difference was found between type Ia and IIb EVTs. Types IIa and III EVT had the highest complete embolization rates. Most cases had a good prognosis.Conclusion: These findings elucidate the features of the different EVT classes defined by the first EVT procedure and the role of the MMA. The delivery of treatment via slim and tortuous MMA branches increased the failure rate of EVT. A thick, straight MMA branch is the optimal path for treatment.
Substantia Nigra Radiomics Feature Extraction of Parkinson’s Disease Based on Magnitude Images of Susceptibility-Weighted Imaging
Authors: Ren Qingguo , Wang Yihua , Leng Shanshan , Nan Xiaomin , Zhang Bin , Shuai Xinyan , Zhang Jianyuan , Xia Xiaona , Li Ye , Ge Yaqiong , Meng Xiangshui , Zhao Cuiping 
Published: May 2021

BackgroundIt is reported that radiomic features extracted from quantitative susceptibility mapping (QSM) had promising clinical value for the diagnosis of Parkinson’s disease (PD). We aimed to explore the usefulness of radiomics features based on magnitude images to distinguish PD from non-PD controls.MethodsWe retrospectively recruited PD patients and controls who underwent brain 3.0T MR including susceptibility-weighted imaging (SWI). A total of 396 radiomics features were extracted from the SN of 95 PD patients and 95 non-PD controls based on SWI. Intra-/inter-observer correlation coefficients (ICCs) were applied to measure the observer agreement for the radiomic feature extraction. Then the patients were randomly grouped into training and validation sets in a ratio of 7:3. In the training set, the maximum correlation minimum redundancy algorithm (mRMR) and the least absolute shrinkage and selection operator (LASSO) were conducted to filter and choose the optimized subset of features, and a radiomics signature was constructed. Moreover, radiomics signatures were constructed by different machine learning models. Area under the ROC curves (AUCs) were applied to evaluate the predictive performance of the models. Then correlation analysis was performed to evaluate the correlation between the optimized features and clinical factors.ResultsThe intro-observer CC ranged from 0.82 to 1.0, and the inter-observer CC ranged from 0.77 to 0.99. The LASSO logistic regression model showed good prediction efficacy in the training set [AUC = 0.82, 95% confidence interval (CI, 0.74–0.88)] and the validation set [AUC = 0.81, 95% CI (0.68–0.91)]. One radiomic feature showed a moderate negative correlation with Hoehn-Yahr stage (r = −0.49, P = 0.012).ConclusionRadiomic predictive features based on SWI magnitude images could reflect the Hoehn-Yahr stage of PD to some extent.
Exploration of the Tumor-Suppressive Immune Microenvironment by Integrated Analysis in EGFR-Mutant Lung Adenocarcinoma
Authors: Li Teng , Pang Xiaocong , Wang Junyun , Wang Shouzheng , Guo Yiying , He Ning , Xing Puyuan , Li Junling 
Published: May 2021

BackgroundClinical evidence has shown that few non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations can benefit from immunotherapy. The tumor immune microenvironment (TIME) is a significant factor affecting the efficacy of immunotherapy. However, the TIME transformational process in EGFR-mutation patients is unknown.MethodsThe mRNA expression and mutation data and lung adenocarcinoma (LUAD) clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Profiles describing the immune landscape of patients with EGFR mutations were characterized by differences in tumor mutation burden (TMB), ESTIMATE, CIBERSORT, and microenvironment cell populations-counter (MCP-counter).ResultsIn total, the TCGA data for 585 patients were analyzed. Among these patients, 98 had EGFR mutations. The TMB was lower in the EGFR group (3.94 mut/Mb) than in the KRAS mutation group (6.09 mut/Mb, P &lt; 0.001) and the entire LUAD (6.58 mut/Mb, P &lt; 0.001). The EGFR group had a lower population of activated immune cells and an even higher score of immunosuppressive cells. A further inter-group comparison showed that differences in the TMB and tumor-infiltrating lymphocytes were only found between patients with oncogenic mutations and unknown mutation. Meanwhile, there were more myeloid dendritic cells (DCs) in EGFR 19del than in L858R-mutation patients and in common mutation patents than in uncommon mutation patients (P &lt; 0.05). Additionally, we established a D score, where D = MCP-counter score for cytotoxic T lymphocytes (CTLs)/MCP-counter score for myeloid DCs. Further analysis revealed that lower D scores indicated immune suppression and were negatively related to several immunotherapy biomarkers.ConclusionsThe TIME of EGFR mutant NSCLC was immunosuppressive. Myeloid DCs gradually increased in EGFR 19del, L858R, and uncommon mutations. The potential role of CTLs and DCs in the TIME of patients requires further investigation.