bluuebunny/crossref_metadata_2025_split huggingface dataset:
ICU-Mortality in Old and Very Old Patients Suffering From Sepsis and Septic Shock
Authors: Bruno Raphael Romano , Wernly Bernhard , Mamandipoor Behrooz , Rezar Richard , Binnebössel Stephan , Baldia Philipp Heinrich , Wolff Georg , Kelm Malte , Guidet Bertrand , De Lange Dylan W. , Dankl Daniel , Koköfer Andreas , Danninger Thomas , Szczeklik Wojciech , Sigal Sviri , van Heerden Peter Vernon , Beil Michael , Fjølner Jesper , Leaver Susannah , Flaatten Hans , Osmani Venet , Jung Christian 
Published: July 2021

Purpose: Old (&gt;64 years) and very old (&gt;79 years) intensive care patients with sepsis have a high mortality. In the very old, the value of critical care has been questioned. We aimed to compare the mortality, rates of organ support, and the length of stay in old vs. very old patients with sepsis and septic shock in intensive care.Methods: This analysis included 9,385 patients, from the multi-center eICU Collaborative Research Database, with sepsis; 6184 were old (aged 65–79 years), and 3,201 were very old patients (aged 80 years and older). A multi-level logistic regression analysis was used to fit three sequential regression models for the binary primary outcome of ICU mortality. A sensitivity analysis in septic shock patients (n = 1054) was also conducted.Results: In the very old patients, the median length of stay was shorter (50 ± 67 vs. 56 ± 72 h; p &lt; 0.001), and the rate of a prolonged ICU stay was lower (&gt;168 h; 9 vs. 12%; p &lt; 0.001) than the old patients. The mortality from sepsis was higher in very old patients (13 vs. 11%; p = 0.005), and after multi-variable adjustment being very old was associated with higher odds for ICU mortality (aOR 1.32, 95% CI 1.09–1.59; p = 0.004). In patients with septic shock, mortality was also higher in the very old patients (38 vs. 36%; aOR 1.50, 95% CI 1.10–2.06; p = 0.01).Conclusion: Very old ICU-patients suffer from a slightly higher ICU mortality compared with old ICU-patients. However, despite the statistically significant differences in mortality, the clinical relevance of such minor differences seems to be negligible.
Alteration of N6-Methyladenosine RNA Profiles in Cisplatin-Induced Acute Kidney Injury in Mice
Authors: Li Can-Ming , Li Ming , Zhao Wen-Bo , Ye Zeng-Chun , Peng Hui 
Published: July 2021

Aim: To identify the alterations of N6-methyladenosine (m6A) RNA profiles in cisplatin-induced acute kidney injury (Cis-AKI) in mice.Materials and Methods: The total level of m6A and the expression of methyltransferases and demethylases in the kidneys were measured. The profiles of methylated RNAs were determined by the microarray method. Bioinformatics analysis was performed to predict the functions.Results: Global m6A levels were increased after cisplatin treatment, accompanied by the alterations of Mettl3, Mettl14, Wtap, Fto, and Alkbh5. A total of 618 mRNAs and 98 lncRNAs were significantly differentially methylated in response to cisplatin treatment. Bioinformatics analysis indicated that the methylated mRNAs predominantly acted on the metabolic process.Conclusion: M6A epitranscriptome might be significantly altered in Cis-AKI, which is potentially implicated in the development of nephrotoxicity.
Phenotypic and Functional Analyses of B7S1 in Ovarian Cancer
Authors: Cai Dongli , Wang Fang , Wang Changgang , Jin Liping 
Published: July 2021

Background: Although programmed death (PD) ligand 1 (PD-L1)/PD-1 inhibitors show potent and durable antitumor effects in a variety of tumors, their efficacy in patients with OvCa is modest. Thus, additional immunosuppressive mechanisms beyond PD-L1/PD-1 need to be identified.Methods: The mRNA expression profiles of OvCa patients were obtained from The Cancer Genome Atlas (TCGA) database. The expression and clinical characteristics of VTCN1 (encoding B7S1) in OvCa were analyzed. The molecular interaction network, Gene Ontology (GO) analysis and Gene set enrichment analysis (GSEA) were used to functionally annotate and predict signaling pathways of VTCN1 in OvCa. Moreover, 32 treatment-naïve patients with OvCa were recruited to assess B7S1 expression. The cytotoxic immune phenotypes in distinct subgroups were analyzed.Results: B7S1 expression was increased in tumor sections compared with that in normal tissues from OvCa patients at both the mRNA and protein levels. VTCN1 expression was significantly correlated with the mRNA expression levels of several other co-inhibitory immune checkpoints. B7S1 protein was found to be highly expressed in CD45+CD68+ myeloid cells, whereas its putative receptor was expressed in CD8+ tumor-infiltrating lymphocytes (TILs). Furthermore, expression of B7S1 in antigen-presenting cells (APCs) was significantly correlated with the cytolytic function of CD8+ TILs. Functional annotations indicated that VTCN1 was involved in regulating T cell-mediated immune responses and participated in the activation of a variety of classic signaling pathways related to the progression of human cancer.Conclusion: In OvCa, B7S1 was highly expressed and may initiate dysfunction of CD8+ TILs, which could be targeted for cancer immunotherapy.
High Prevalence of Early Parkinson's Disease in Patients With Subtle Parkinsonian Signs
Authors: Sasaki Shoichi 
Published: July 2021

Background: Little is known about how frequently patients with a Unified Parkinson Disease Rating Scale part III (UPDRS-III) score of 3 or 4, including postural and action tremor, could be classified into early Parkinson's disease (PD).Objective: To examine the prevalence of early PD in patients with subtle parkinsonian signs (rest tremor, postural tremor, and rigidity) without bradykinesia, having a UPDRS-III score of 3 or 4.Methods: Parkinsonism was assessed using UPDRS-III based on both the United Kingdom PD Society Brain Bank criteria and the Movement Disorder Society PD criteria. Ninety patients with a UPDRS-III score of 3 or 4, including postural tremor, were evaluated by 123I-FP-CIT SPECT (DaTscan), brain MRI, the Mini-Mental State Examination, and smell test. Some patients were additionally examined by 123I-metaiodobenzylguanidine myocardial scintigraphy or 123I-N-isopropyl-p-iodoamphetamine SPECT.Results: Seventy-five [mean age (standard deviation): 76.9 (8.1)] out of 90 patients (83.3%) showed abnormal findings on DaTscan imaging: 57 out of 75 (76.0%) showed a reduced specific binding ratio (SBR) accompanied by an egg shape pattern (n = 37, 49.3%) or a mixed type pattern (n = 14, 18.7%), both reduced SBR and increased asymmetry index (AI) with a normal shape (n = 4, 5.3%), and reduced SBR only (n = 2, 2.7%); 18 (24.0%) showed an egg shape pattern or a mixed type pattern without reduced SBR. In other words, 69 out of 75 patients (92.0%) showed either an egg shape or a mixed type pattern with or without reduced SBR. All patients were free of dementia, and their olfactory function was significantly impaired compared with controls (n = 141) on the odor-stick identification test for Japanese (p &lt; 0.0001).Conclusions: The prevalence of patients with subtle parkinsonian signs having a UPDRS-III score of 3 or 4, including postural tremor, is unexpectedly high in daily clinical practice, and most of these patients could be categorized into mild early-stage PD.
Sex Differences in the Association Between Obesity and Cognitive Impairment in a Low-Income Elderly Population in Rural China: A Population-Based Cross-Sectional Study
Authors: Guo Dandan , Zhang Xin , Zhan Changqing , Lin Qiuxing , Liu Jie , Yang Qiaoxia , Tu Jun , Ning Xianjia , Wang Jinghua , Song Yijun 
Published: July 2021

Background: Obesity is a potentially modifiable risk factor for cognitive impairment. However, sex-specific relationships between obesity and cognitive impairment in late life remain unclear.Objective: We aimed to assess sex differences in the association between various obesity parameters and cognitive impairment in a low-income elderly population in rural China.Methods: A population-based cross-sectional study was conducted to collect basic information from elderly residents aged 60 years and older from April 2014 to August 2014 in rural areas of Tianjin, China. Obesity parameters, including body mass index (BMI) and waist circumference (WC), and Mini Mental State Examination scores were measured, and the relationships between these variables were assessed.Results: A total of 1,081 residents with a mean age of 67.70 years were enrolled in this study. After adjusting for age, educational attainment, smoking status, drinking status, physical exercise participation, and the presence of diabetes and hyperlipidemia, blood pressure group; a high BMI was found to be associated with an increased prevalence of cognitive impairment in elderly women. Each 1-unit increase in BMI was associated with a 5.9% increase in the prevalence of cognitive impairment. WC was related to the prevalence of cognitive impairment in elderly men, and each 1-cm increase in WC was associated with a 4.0% decrease in the prevalence of cognitive impairment. However, there were no significant associations between WC and cognitive function in women or between BMI and cognitive impairment in men.Conclusion: A greater WC was positively associated with better cognitive function in low-income elderly men in rural China, whereas a higher BMI was associated with an increased risk of cognitive impairment in elderly women, independent of sociodemographic, lifestyle, and health-related comorbid factors. Our results suggest weight management of elderly women in rural China may have cognitive benefits. However, randomized controlled trials would be needed to confirm causality.
Peripheral Nerve Focused Ultrasound Lesioning—Visualization and Assessment Using Diffusion Weighted Imaging
Authors: Walker Matthew R. , Zhong Jidan , Waspe Adam C. , Piorkowska Karolina , Nguyen Lananh N. , Anastakis Dimitri J. , Drake James M. , Hodaie Mojgan 
Published: July 2021

Objectives: Magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive targeted tissue ablation technique that can be applied to the nervous system. Diffusion weighted imaging (DWI) can visualize and evaluate nervous system microstructure. Tractography algorithms can reconstruct fiber bundles which can be used for treatment navigation and diffusion tensor imaging (DTI) metrics permit the quantitative assessment of nerve microstructure in vivo. There is a need for imaging tools to aid in the visualization and quantitative assessment of treatment-related nerve changes in MRgFUS. We present a method of peripheral nerve tract reconstruction and use DTI metrics to evaluate the MRgFUS treatment effect.Materials and Methods: MRgFUS was applied bilaterally to the sciatic nerves in 6 piglets (12 nerves total). T1-weighted and diffusion images were acquired before and after treatment. Tensor-based and constrained spherical deconvolution (CSD) tractography algorithms were used to reconstruct the nerves. DTI metrics of fractional anisotropy (FA), and mean (MD), axial (AD), and radial diffusivities (RD) were measured to assess acute (&lt;1–2 h) treatment effects. Temperature was measured in vivo via MR thermometry. Histological data was collected for lesion assessment.Results: The sciatic nerves were successfully reconstructed in all subjects. Tract disruption was observed after treatment using both CSD and tensor models. DTI metrics in the targeted nerve segments showed significantly decreased FA and increased MD, AD, and RD. Transducer output power was positively correlated with lesion volume and temperature and negatively correlated with MD, AD, and RD. No correlations were observed between FA and other measured parameters.Conclusions: DWI and tractography are effective tools for visualizing peripheral nerve segments for targeting in non-invasive surgical methods and for assessing the microstructural changes that occur following MRgFUS treatment.
Reliability and Validity of Alzheimer's Disease Screening With a Semi-automated Smartphone Application Using Verbal Fluency
Authors: Kwon Soon Jai , Kim Hye Sung , Han Ji Hyun , Bae Jong Bin , Han Ji Won , Kim Ki Woong 
Published: July 2021

Introduction: This study aimed to examine the reliability and validity of Alzheimer's disease (AD) screening with a self-administered categorical verbal fluency test using a semi-automated Android application (app; tCVFT). Furthermore, its diagnostic accuracy concerning AD was compared with both that of a conventional categorical verbal fluency test (cCVFT) administered by a health professional and the Mini-Mental State Examination (MMSE).Materials and Methods: Participants included 100 community-dwelling patients with early AD, whose Clinical Dementia Rating was either 0.5 or 1, and a further 100 sex-matched cognitively normal controls. The internal consistency and test-retest reliability of the tCVFT weighted sum score (tCVFT-WS) was examined using Cronbach's alpha and Pearson's correlation analyses (adjusted for age and education), respectively. The concurrent validity of the tCVFT-WS was examined by testing its correlations with the cCVFT weighted sum score (cCVFT-WS) and MMSE using Pearson's correlation tests. The diagnostic accuracies for early AD of the tCVFT-WS, cCVFT-WS, and MMSE were estimated and compared using receiver operating characteristic (ROC) analyses.Results: The tCVFT-WS exhibited strong internal consistency (Cronbach's alpha = 0.79). However, its test-retest reliability was moderate (r = 0.54) owing to the low test-retest reliability of the second-half responses. The patient group exhibited a higher tCVFT-WS than the control group (p &lt; 0.001). Correlations between the tCVFT-WS, cCVFT-WS, and MMSE were significant. The tCVFT-WS's area under the ROC curve for AD was 0.861. At its optimal cutoff, the sensitivity and specificity for AD were 0.78 and 0.77, respectively.Conclusions: The self-administered tCVFT-WS, using an Android app, proved valid and reliable at distinguishing people with early AD from cognitively normal controls.
Treatment of Intracranial Aneurysms Using the New Silk Vista Flow Diverter: Safety Outcomes at Short-Term Follow-Up
Authors: Pumar José M. , Mosqueira Antonio , Olier Jorge , Rodriguez-Fernandez Claudio , Vega Pedro , Gonzalez-Diaz Eva 
Published: July 2021

Background: Flow diverters are widely used as the first endovascular treatment option for complex brain aneurysms due to their high percentage of occlusion and low morbi-mortality. The Silk Vista device is a new generation of flow diverters designed to facilitate full visibility, improve apposition to the vessel wall, and enhance navigability. Indeed, its greatest advantage is that it enables the easier navigation of stents between 3.5 and 4.75 mm through a 0.021 microcatheter. The objective of this study was to evaluate the safety and effectiveness of Silk Vista systems for treating cerebral aneurysms.Methods: This prospective observational study included 25 consecutive patients with 27 wide-necked unruptured aneurysms treated with SILK Vista who were retrospectively analyzed for safety and efficacy.Results: Endovascular treatment was successfully performed in all patients. The final morbidity and mortality rates were both 0.0%. Short-term (3–5 months) angiographic follow-up revealed 21 complete occlusions and 6 near-complete occlusions. No significant parent artery stenosis was observed.Conclusions: This report demonstrates the efficacy of Silk Vista in treating brain aneurysms, although longer experiences should be carried out to confirm our results.
Association of Sarcopenia With Toxicity and Survival in Postoperative Recurrent Esophageal Squamous Cell Carcinoma Patients Receiving Chemoradiotherapy
Authors: Xu Ying-Ying , Zhou Xi-Lei , Yu Chang-Hua , Wang Wan-Wei , Ji Fu-Zhi , He Dong-Cheng , Zhu Wei-Guo , Tong Yu-Suo 
Published: July 2021

BackgroundSarcopenia has been associated with treatment-related toxicities and poor survival in cancer patients. Our aim was to investigate the prevalence of sarcopenia in postoperative recurrent esophageal squamous cell carcinoma (ESCC) patients receiving chemoradiotherapy (CRT) and evaluate associations with treatment-related toxicity and prognosis.MethodsOne hundred and eighty-four patients with postoperative locoregional recurrent ESCC receiving CRT between January 2014 and December 2016 were included. The skeletal muscle area (SMA) was measured at the third lumbar vertebra level. Sarcopenia was defined as skeletal muscle index (SMI = SMA/height2) less than 47.24/cm2/m2 for men and 36.92/cm2/m2 for women. Association of sarcopenia with overall survival (OS) was analyzed using univariate and multivariate cox regression models.ResultsSarcopenia was observed in 94 of 184 (51.1%) patients. Sarcopenic patients had significantly higher rates of grade 3-4 toxicities compared to those without sarcopenia (36.2% vs 21.1%, p = 0.034). The survival rate at 12 and 24 months was 36.2% and 3.2% in the sarcopenic patients and 57.8% and 17.8% in the non-sarcopenic patients (p &lt; 0.001). Multivariate cox regression analysis showed that sarcopenia was significantly associated with decreased OS (HR = 1.729, 95% CI 1.231-2.428, p = 0.002).ConclusionsSarcopenia is an independent indicator of poor survival in postoperative locoregional recurrent ESCC patients treated with CRT. Early nutritional interventions before treatment may improve the prognosis.
Molecular Interplays Between Cell Invasion and Radioresistance That Lead to Poor Prognosis in Head-Neck Cancer
Authors: You Guo-Rung , Chang Joseph T. , Li Yan-Liang , Chen Yin-Ju , Huang Yu-Chen , Fan Kang-Hsing , Chen Yen-Chao , Kang Chung-Jan , Cheng Ann-Joy 
Published: July 2021

BackgroundCancer metastasis and recurrence after radiotherapy are the significant causes of poor prognosis in head-neck cancer (HNC). Clinically, it is commonly found that patients with either condition may accompany the outcome of the other. We hypothesized that HNC cells might exhibit a cross-phenotypic attribute between cell invasion and radioresistance. To discover effective biomarkers for the intervention of aggressive cancer at one time, the potential molecules that interplay between these two phenotypes were investigated.Materials and MethodsThree isogenic HNC cell sublines with high invasion or radioresistance properties were established. Transcriptomic and bioinformatic methods were used to globally assess the phenotypic-specific genes, functional pathways, and co-regulatory hub molecules. The associations of gene expressions with patient survival were analyzed by Kaplan-Meier plotter, a web-based tool, using the HNSCC dataset (n=500). The molecular and cellular techniques, including RT-qPCR, flow cytometry, cell invasion assay, and clonogenic survival assay, were applied.ResultsThe phenotypic crosstalk between cell invasion and radioresistance was validated, as shown by the existence of mutual properties in each HNC subline. A total of 695 genes was identified in associations with these two phenotypes, including 349 upregulated and 346 downregulated in HNC cells. The focal adhesion mechanism showed the most significant pathway to co-regulate these functions. In the analysis of 20 up-regulatory genes, a general portrait of correlative expression was found between these phenotypic cells (r=0.513, p=0.021), and nine molecules exhibited significant associations with poor prognosis in HNC patients (HR&gt;1, p&lt;0.050). Three hub genes were identified (ITGA6, TGFB1, and NDRG1) that represented a signature of interplayed molecules contributing to cell invasion, radioresistance and leading to poor prognosis. The ITGA6 was demonstrated as a prominent biomarker. The expression of ITGA6 correlated with the levels of several extracellular and apoptotic/anti-apoptotic molecules. Functionally, silencing ITGA6 suppressed cell migration, invasion, and attenuated radioresistance in HNC cells.ConclusionsA panel of interplay molecules was identified that contribute to cell invasion and radioresistance, leading to poor prognosis. These panel molecules, such as ITGA6, may serve as predictive markers of radioresistance, prognostic markers of metastasis, and molecular therapeutic targets for refractory HNC.
Modulation of Astrocytic Glutamine Synthetase by Endocannabinoid 2-Arachidonoylglycerol in JNK-Independent Pathway
Authors: Wang Jing , Wang Shenghong , Zhang Hua 
Published: July 2021

Background and Objective: The glutamine synthetase (GS), an astrocyte-specific enzyme, plays an important role in neuroprotection through the glutamate/glutamine shuttle and can be modulated by endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) through extracellular signal-regulated protein kinase ½ (ERK1/2) and p38 signaling pathways. However, the role of c-Jun N-terminal kinase (JNK) signaling pathway in the modulation of GS in astrocytes by 2-AG is not clear.Materials and Methods: The expression of GS and JNK in astrocytes following the exposure to lipopolysaccharide (LPS) was examined with Western blotting and immunochemistry.Results: The results revealed that short-term exposure to LPS activated GS and increased phosphorylation of JNK in astrocytes in a time-dependent manner. Treatment with 2-AG reversed the changes in GS but had no effect on the activation of JNK.Conclusions: These findings suggest that the activation of JNK induced by LPS is not involved in the modulation of astrocytic GS by 2-AG.
The Association Between STX1B Polymorphisms and Treatment Response in Patients With Epilepsy
Authors: Wang Shitao , Zhou Liang , He Chenglu , Wang Dan , Cai Xuemei , Yu Yanying , Chen Liling , Lu Di , Bian Ligong , Du Sunbing , Wu Qian , Han Yanbing 
Published: July 2021

Background: Epilepsy is a debilitating brain disease with complex inheritance and frequent treatment resistance. However, the role of STX1B single nucleotide polymorphisms (SNPs) in epilepsy treatment remains unknown.Objective: This study aimed to explore the genetic association of STX1B SNPs with treatment response in patients with epilepsy in a Han Chinese population.Methods: We first examined the associations between STX1B SNPs and epilepsy in 1000 Han Chinese and the associations between STX1B SNPs and drug-resistant epilepsy in 450 subjects. Expression quantitative trait loci analysis was then conducted using 16 drug-resistant epileptic brain tissue samples and results from the BrainCloud database (http://eqtl.brainseq.org).Results: The allelic frequencies of rs140820592 were different between the epilepsy and control groups (p = 0.002) after Bonferroni correction. The rs140820592 was associated with significantly lower epilepsy risk among 1,000 subjects in the dominant model after adjusting for gender and age and Bonferroni correction (OR = 0.542, 95%CI = 0.358–0.819, p = 0.004). The rs140820592 also conferred significantly lower risk of drug-resistant epilepsy among 450 subjects using the same dominant model after adjusting for gender and age and Bonferroni correction (OR = 0.260, 95%CI = 0.103–0.653, p = 0.004). Expression quantitative trait loci analysis revealed that rs140820592 was associated with STX1B expression level in drug-resistant epileptic brain tissues (p = 0.012), and this result was further verified in the BrainCloud database (http://eqtl.brainseq.org) (p = 2.3214 × 10–5).Conclusion: The STX1B rs140820592 may influence the risks of epilepsy and drug-resistant epilepsy by regulating STX1B expression in brain tissues.