bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absolute Eosinophil Count May be an Optimal Peripheral Blood Marker to Identify Risk of Immune-Related Adverse Events in Advanced Malignant Tumors Treated with PD-1/PD-L1 Inhibitors: A Retrospective Analysis.
Authors: Ma Yan , Ma Xiao , Wang Jingting , Wu Shanshan , Wang Jing , Cao Bangwei 
Published: October 2021

Abstract
Background

This study aimed to investigate the predictive values of serum biomarkers including absolute eosinophil count (AEC), neutrophil–lymphocyte ratio (NLR), and platelet–lymphocyte ratio (PLR) with respect to immune-related adverse events (irAEs) during anti-PD-1/PD-L1 inhibitor treatment in patients with advanced malignant tumors.
Methods

We retrospectively analyzed 95 patients with advanced cancer who were treated with anti-PD-1/PD-L1 inhibitors from January 1, 2017 to May 1, 2020, in our cancer center. We then analyzed associations between irAEs and anti-PD-1/PD-L1 inhibitor responses and evaluated the predictive values of serum biomarkers with respect to risk of irAEs.
Results

The incidence of irAEs was 55.8%. There were no statistically significant differences between the irAEs and no-irAEs groups in objective response rate (ORR) or disease control rate (DCR). However, landmark analysis showed that the irAEs group had better survival after 120 days following the initiation of anti-PD-1/PD-L1 inhibitor treatment, compared with the no-irAEs group. The incidences of irAEs were greater in the high-AEC and low-NLR groups than in the low-AEC and high-NLR groups. Univariate logistic analysis showed that low NLR, ECOG performance status (0–1), and high AEC were risk factors for irAEs. Multivariate logistic analysis showed that high AEC and good ECOG performance status were independent predictors for irAEs.
Conclusions

irAEs may be associated with a survival benefit. Baseline AEC is a strong predictor of irAEs in patients undergoing treatment with anti-PD-1/PD-L1 inhibitors.
The Diversity and Heterogeneity of TCR and BCR in Pan-Cancer
Authors: Li Bo , Zhang Jing , Guo Jin-dan , TANG Hui-xue , Hu Wen-xiang , XU Li-da , Chen Yu-bao 
Published: October 2021

Abstract
Background: With the development of the sequencing technology, RNA-seq is becoming more and more popular. The method of using RNA-seq technology to analyze the immune repertoire has the advantages of low sample demand, simple operation, and comprehensive information.Result: The RNA-seq data from public database were used to analyze and compare the TCR and BCR sequences of cancer and normal tissues in four types of cancers, including colon adenocarcinoma, lung adenocarcinoma, pancreatic adenocarcinoma and stomach adenocarcinoma. It was found that the clonal diversity of TCR among various types of cancer is different, and the variety of BCR between cancer tissues and healthy tissues is obvious. Based on the analysis of non-shared CDR3 sequences, the degree of the heterogeneity of TRB is: different cancer types> different individuals with same cancer> cancer tissues and paracancerous tissues of the same individual. Also, the correlation between the expression levels of the five main immune checkpoints genes and the count of TCR clones displayed various among different types of cancers.Conclusion: The results verify the advantage of RNA-seq analyzing in acquiring individual immune repertoire. Moreover, the heterogeneity of TCR in different cancers and the diversity of BCR in tumour and adjacent tissues shown in the results, provide hints at developing the strategies of tumour immunotherapy.
Operando electrochemical spectroscopic ellipsometry: Insights into electrochemical behavior of catalyst materials under realistic working conditions
Authors: Sachse René , Sahre Mario , Bernicke Michael , Bernsmeier Denis , Hodoroaba Vasile-Dan , Strasser Peter , Kraehnert Ralph , Hertwig Andreas 
Published: October 2021

Abstract
Large-scale hydrogen production using proton exchange membrane water electrolysis (PEM-EL) requires a drastic reduction in the current noble metal content of the electrodes. To achieve this, new analytical techniques for characterizing solid-liquid catalytic interfaces, applicable in operando under a variety of realistic operating conditions, are critical because they provide a deeper understanding of the relationships between catalyst state, structure, and catalytic performance. However, many analytical techniques cannot be applied in liquid environments at realistic potentials and current densities. We propose electrochemical spectroscopic ellipsometric analysis (ECSE), performed in realistic electrolysis cells, as a new analytical operando method for characterizing electrochemical reactions at solid-liquid interfaces under widely varying working conditions. The method is first validated on a platinum surface using ex-situ and operando ellipsometric analyses. Subsequently, the physico-chemistry of a mesoporous IrOx catalyst film under oxygen evolution reaction (OER) potentials was investigated, showing precise reversible and irreversible potential-dependent variations of a number of physical material properties relevant to catalysis.
Mountains to climb: on the role of seamounts in upwelling of deep ocean waters
Authors: Mashayek Ali , Gula Jonathan , Baker Lois , Garabato Alberto Naveira , Cimoli Laura , Riley James 
Published: October 2021

Abstract
Ocean turbulent mixing exerts an important control on the rate and structure of the overturning circulation.
Recent observational evidence suggests, however, that there could be a mismatch between the observed intensity of mixing integrated over basin or global scales, and the net mixing required to sustain the overturning's deep upwelling limb.
Here, we investigate the hitherto largely overlooked role of tens of thousands of seamounts in resolving this discrepancy. Dynamical theory indicates that seamounts may stir and mix deep waters by generating lee waves and topographic wake vortices. At low latitudes, this is enhanced by a layered vortex regime in the wakes.
We consider three case studies (in the equatorial zone, Southern Ocean and Gulf Stream) that are predicted by theory to be representative of, respectively, a layered vortex, barotropic wake, and hybrid regimes, and corroborate theoretical scalings of mixing in each case with a realistic regional ocean model. We then apply such scalings to a global seamount dataset and an ocean climatology to show that seamount-generated mixing makes a leading-order contribution to the global upwelling of deep waters. Our work thus brings seamounts to the fore of the deep-ocean mixing problem, and urges observational, theoretical and modeling efforts toward incorporating the seamounts' mixing effects in conceptual and numerical models of the ocean circulation.
Development And Evaluation of Transferosomal Gel Using Cephalexin.
Authors: Singh Vinay , Dharashivkar Sanket , Gaikwad Madhuri , Shaikh Shirin 
Published: October 2021

Abstract
Background: In the present research work transferosomal gel was developed for an effective treatment of skin infection using cephalexin as model drug. The Transferosomes were prepared by thin film hydration method using Phospholipon 90H as a Lipid, Sodium deoxycholate as a surfactant and the vesicles were characterized on the basis of entrapment efficiency, particle size, Zeta potential, shape, morphology, x-ray diffraction analysis and in-vitro drug release. The transfersomal gel was prepared by dispersion method using Carbopol 934 as a gelling agent and evaluated for spreadability, viscosity, pH, drug release, antimicrobial study and stability.Results: The entrapment efficiency of the optimized transferosomes was found to be 90.62% and the % Cumulative release of gel across the dialysis membrane was found to be 91.26% at the end of 24h. Conclusion: Vesicular system can be of great help in decreasing the burden of Bacterial infections and other infections around the globe.
WITHDRAWN: PLK1 is A Promising Biomarker for the Prognosis of Lung Adenocarcinoma
Authors: Wang Lina , Gao Man , Sun Dongjie , Wu Haitao , Lv Shuang , Qian Xiaoli , Li Yulin , Li Lisha 
Published: October 2021

Abstract
Background: As one of the commonly occurred lung cancer, over 40% of lung cancer are lung adenocarcinoma (LUAD) in the world. However, due to the lack of effective treatment method, the prognosis of this disease is poor. In this study, we identified a novel treatment target for LUAD. Differentially expressed genes (DEGs) were extracted from 551 LUAD cases in the Cancer Genome Atlas (TCGA) database and used for Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Gene set variation analysis (GSVA) and the CIBERSORT method were applied for the estimation of the biological pathways and the tumor-infiltrating immune cells (TICs). Protein-protein interaction (PPI) network and Cox regression analyses were conducted for the analysis of DEGs. Quantitative real-time PCR (qPCR) and immunoblotting were used for the validation of DEGs.Results: Genes related to cell cycle were sorted out. Positive association between cell cycle scores and clinical features including age, clinical stages and metastasis was found. Negative association between cell cycle scores and overall survival of LUAD patients was detected. In PPI and Cox analyses, PLK1 was estimated to be a factor for the prognostic predictions of LUAD patients. In LUAD patients, PLK1 was positively associated to the clinical stages and negatively associated to the overall survival. As suggested by CIBERSORT analysis, significant positive correlations were found between the transcription level of PLK1 and the function of CD8+ and activated memory CD4+ T cell. Meanwhile, significant negative correlation between the transcription level of PLK1 and activated natural killer cell was also found out. Moreover, PLK1 overexpression caused elevated immune cytotoxicity, including cytolytic activity score, IFN-γ score and IFN-γ level.Conclusions: PLK1 displayed robust correlations with key features of TICs related to the immune-microenvironment of cancer, and therefore was suggested as a promising biomarker for the prognostic prediction of LUAD.
QRS Fragmentation in Preserved Ejection Fraction Heart Failure: Functional Insights, Pathological Correlates, and Prognosis
Authors: Sung Kuo-Tzu , Chang Sheng-Hsiung , Chi Po-Ching , Chien Shih‐Chieh , Lo Chi‐In , Lin Chao‐Feng , Huang Wen‐Hung , Yun Chun‐Ho , Tsai Cheng-Ting , Su Cheng-Huang , Hou Charles Jia-Yin , Yeh Hung-I , Tsao Chin-Ho , Kuo Jen-Yuan , Hung Chung-Lieh 
Published: October 2021

Abstract

Backgrounds: Fragmented QRS (fQRS) morphology as a surrogate marker of the possible presence of myocardial scarring has been shown to confer a higher risk in patients with reduced ejection fraction heart failure. We aimed to investigate the pathophysiological correlates and prognostic implications of fQRS in patients with preserved ejection fraction heart failure (HFpEF). Methods and Results: We consecutively studied 960 patients with HFpEF (76.4±12.7 years, men: 37.2%). fQRS was assessed using a body surface electrocardiogram during hospitalization. QRS morphology was available and classified into three categories among 960 HFpEF subjects as non-fQRS, inferior fQRS, and anterior/lateral fQRS groups. Despite comparable clinical features in most baseline demographics among the three fQRS categories, anterior/lateral fQRS showed significantly higher BNP/troponin levels (both p<0.001), with both the inferior and anterior/lateral fQRS HFpEF groups demonstrating a higher degree of unfavorable cardiac remodeling, greater extent of myocardial perfusion defect, and slower coronary flow phenomenon (all p<0.05). Anterior/lateral fQRS HFpEF patients exhibited significantly altered cardiac structure/function and more impaired diastolic indices (all p<0.05). During a median of 657 days follow-up, the presence of anterior/lateral fQRS conferred a doubled HF re-admission risk (adjusted HR: 1.90, p<0.001), with both inferior and anterior/lateral fQRS having a higher risk of cardiovascular and all-cause death (all p<0.05) by using Cox regression models.Conclusions: The presence of fQRS in HFpEF was associated with more extensive myocardial perfusion defects and worsened mechanics, which possibly denotes a more severe involvement of cardiac damage. Early recognition in such HFpEF patients likely benefits from targeted therapeutic interventions.
Neutron-upscattering enhancement of the triple-alpha process
Authors: Bishop Jack , Parker Cody , Rogachev Grigory , Ahn Sunghoon , Koshchiy Evgeniy , Brandenburg Kristyn , Brune Carl , Charity Robert , Derkin Joseph , Dronchi Nicholas , Hamad Gulakhshan , Jones-Alberty Yenuel , Kokalova Tzanka , Massey Thomas , Meisel Zachary , Ohstrom Eva , Paneru Som , Saxena Mansi , Singh Nisha , Smith Robin , Sobotka Lee , Soltesz Douglas , Subedi Shiv Kumar , Voinov Alexander , Warren Justin , Wheldon Carl 
Published: October 2021

Abstract
The neutron inelastic scattering of carbon-12, populating the Hoyle state, is a reaction of interest 17 for the triple-alpha process. The inverse process (neutron upscattering) can enhance the Hoyle state’s decay rate to the bound states of 12 18 C, effectively increasing the overall triple-alpha reaction rate. 19 The cross section of this reaction is impossible to measure experimentally but has been determined 20 here at astrophysically-relevant energies for the first time using detailed balance. This cross section 21 will inform astrophysical models on the importance of neutron upscattering in neutron-rich stellar 22 environments. 23 Using a highly-collimated monoenergetic beam of neutrons incident on the Texas Active Target 24 Time Projection Chamber (TexAT TPC) filled with CO2 gas, the 3α-particles (arising from the decay 25 of the Hoyle state following inelastic scattering) were measured and a cross section was extracted 26 between En = 8.15 MeV and En = 10.0 MeV. The cross section above the threshold was dominated by a few resonances in 13 27 C around Ex = 13.5 MeV. This has a significant effect on the contribution 28 of neutron upscattering in stellar environments. 29 The neutron-upscattering enhancement is observed to be much smaller than previously expected. 30 For a temperature of 1 GK, the total enhancement factor, from upscattering to the ground state and 31 first-excited state, was seen to be 5, rising to around 46 at 10 GK thereby exceeding the contribution 32 from proton enhancement. The importance of the neutron-upscattering enhancement may therefore 33 not be significant aside from in very particular astrophysical sites (e.g. neutron star mergers).
Minimum Accepted Competency Examination: Test Item Analysis
Authors: McCrossan Paddy , Nicholson Alf , McCallion Naomi 
Published: October 2021

Abstract
BackgroundThe minimum accepted competency (MAC) examination in paediatrics was a set of MCQ’s designed to test undergraduate medical students on the most basic, ‘must know’ knowledge as determined by non-faculty paediatric clinicians. The faculty standard set the examination at a relatively difficult 41.2% with only two-thirds of students attaining this score (even though 96% of the same students passed their university paediatric examination). We will now describe the psychometric properties of the examination in a bid to explain these results and provide specific suggestions for future practiceMethodsThe methodology for designing the content, standard setting and administration of the MAC examination has already been described. The examination was set by three groups of undergraduate medical students and paediatric trainee doctors. Test item analysis was performed using difficulty index, discrimination index and Cronbach’s alpha.ResultsTest item difficulty between each group was positively correlated. Correlation of item difficulty with the standard set for each item showed a statistically significant positive relationship. However, for 10 of the items, the mean score did not even reach two standard deviations below the standard set by the faculty. Medical students outperformed the trainee doctors on three items. 18 of 30 items achieved a discrimination index >0.2. Cronbach’s alpha ranged from 0.22-0.59.ConclusionQuestions on respiratory paediatrics and seizures were answered poorly. Despite these topics being major topics within the curriculum, it is possible that the clinical emphasis in these non-faculty derived questions was juxtaposed with the factual recall often required for university examinations. Interestingly, for the questions on which the students performed better than the doctors, the questions were quite specific, and the answer found directly in the curriculum. This reflects how students learn with limited clinical experience and is a good example of assessment being a key driver of learning.The concept of a MAC examination to test basic medical knowledge is feasible and the study presented is an encouraging first step towards this method of assessment. This method is readily transferable to other medical (and allied health) specialties.
A gut feeling: how your gut and brain changes your risk and time preferences
Authors: Dantas Aline , Jiao Peiran , Sack Alexander , Bruggen Elisabeth , Schuhmann Teresa 
Published: October 2021

Abstract
Recent research has shown that the gut microbiota can influence the interaction between the central and the enteric nervous systems via the gut-brain axis (GBA). Animal models and human neuroimaging studies have revealed that changes in the gut microbiota affect neural activity in brain regions linked to basic emotional and cognitive processes. Whether the gut microbiota also affect human decision-making and, more specifically, risk and time preferences, however, remains largely unknown. Here, we examine the role of the gut-brain axis in decision-making in the face of risk and intertemporal choices. In a placebo-controlled double-blinded design, with two sessions separated by 28 days, during which participants received daily doses of probiotics (or a placebo), we investigate whether the prolonged and controlled intake of probiotics affects risk-taking behavior and intertemporal choices using incentivised economic tasks. We found a significant decrease in risk-taking behavior and an increase in future-oriented choices in the probiotics group as compared to the placebo group. These findings provided the first direct experimental evidence suggesting a potential functional role on the part of the microbiota-gut-brain axis in decision-making, creating a path for potential clinical applications and allowing for a better understanding of the underlying neural mechanisms of risk-taking behavior and intertemporal choices.
Effectiveness and Safety Evaluation of Microresection of Vestibular Schwannoma After Gamma Knife Treatment
Authors: Huang Bowen , Ren Yanming , Liu Xuesong , Lan Zhigang , Hui Xuhui , Ju Yan , Li Xuehan , Zhang Yuekang 
Published: October 2021

Abstract
PURPOSEWe aimed to explored the influence of preoperative gamma knife treatment on the clinical effect of microsurgical resection of vestibular schwannoma.METHODSThe patients who underwent vestibular schwannoma resection in our hospital between November 2010 and December 2019 were retrospectively collected. According to retrospectively collected data, the patients who met the inclusion and exclusion criteria were defined as group A. The 1:3 ratio design was adopted in this study to select the group B that was not subjected to gamma knife treatment in the same period. The pre/postoperative clinical manifestations, neurological function grade, postoperative complications, tumor recurrence and increase were collected and compared between the two groups.RESULTSThere were 40 patients in group A and 120 patients in group B. At the last follow-up, the number of patients with poor facial nerve function was 15 (39.5%) in group A and 25 (21.2%) in group B (P = 0.025). In group A and group B, disequilibrium occurred in 14 patients and 17 patients respectively after operation (P=0.003). 7 patients caught the pulmonary infection in group A and 3 patients had a pulmonary infection in group B (P=0.03) after operation. CONCLUSIONSwhen a patient with vestibular schwannoma undergoes microsurgical surgery, the preoperative history of gamma knife treatment will make a recovery from postoperative facial paralysis difficult for the patients, making them more prone to suffer from postoperative disequilibrium and postoperative pulmonary infection.
Differential Expression of Circulating MiRNAs After Alemtuzumab Induction Therapy in Lung Transplantation
Authors: Benazzo Alberto , Bozzini Sara , Auner Sophia , Berezhinskiy Hatice Oya , Watzenboeck Martin L. , Schwarz Stefan , Schweiger Thomas , Klepetko Walter , Wekerle Thomas , Hoetzenecker Konrad , Meloni Federica , Jaksch Peter 
Published: October 2021

Abstract
Alemtuzumab is a monoclonal antibody targeting CD52, used as induction therapy after lung transplantation (LTx). Its engagement produces a long-lasting immunodepletion; however, the mechanisms driving cell reconstitution are poorly defined. We hypothesized that miRNAs are involved in this process. The expression of a set of miRNAs, cytokines and co-signaling molecules was measured with RT-qPCR and flow cytometry in prospectively collected serum samples of LTx recipients, after alemtuzumab or no induction therapy. Twenty-six LTx recipients who received alemtuzumab and twenty-seven matched LTx recipients without induction therapy were included in the analysis. One year after transplantation four miRNAs were differentially regulated: miR-23b (p=0.05) miR-146 (p=0.04), miR-155 (p<0.001) and miR-486 (p<0.001). Expression of 3 miRNAs changed within the alemtuzumab group: miR-146 (p<0.001), miR-155 (p<0.001) and miR-31 (p<0.001). Levels of IL-13, IL-4, IFN-γ, BAFF, IL-5, IL-9, IL-17F, IL-17A and IL-22 were different one year after transplantation compared to baseline. In no-induction group, concentration of sCD27, sB7.2 and sPD-L1 increased overtime. Expression of miR-23b, miR-146, miR-486, miR-155 and miR-31 was different in LTx recipients who received alemtuzumab compared to recipients without induction therapy. The observed cytokine pattern suggested proliferation of specific B cell subsets in alemtuzumab group and co-stimulation of T-cells in no-induction group.
Comparative Efficacy and Safety of Novel Therapeutic Drugs for Chronic Heart Failure: A Systematic Review and Network Meta-Analysis
Authors: Wu Honghui , Wen Yalu , Huang Jukai , Zhang Li , Yang Xiaohui 
Published: October 2021

Abstract
Recently, several novel therapeutic drugs (NTDs) were found to have therapeutic potential in treating chronic heart failure (CHF). This network meta-analysis aimed to compare and rank different NTDs in patients with CHF. We searched Medline/PubMed, Embase and Cochrane Library of Clinical Trials database through February 9, 2021, for RCTs comparing the NTDs with standard of care (SOC) in adult patients with CHF. Trials of angiotensin receptor-neprilysin inhibitor (ARNI), sodium-glucose transporter 2 (SGLT2) inhibitors, ivabradine, non-steroidal mineralcorticoid receptor antagonists (MRA), soluble guanylate cyclase (SGC) stimulators and cardiac myosin activators (CMA) were included. We performed a Bayesian network meta-analysis to indirectly compare the mortality, HF hospitalization and adverse events of the NTDs. Thirty-three studies enrolling 63614 patients were included in this analysis. The results showed none of the NTDs was associated with a significant superiority in reducing all-cause mortality, composite outcome of cardiovascular mortality or HF hospitalization and HF hospitalization alone. For cardiovascular mortality alone, ARNI was superior to ivabradine and CMA, while SGLT2 inhibitors were superior to CMA. For adverse events, SGLT2 inhibitors were associated with a lower risk of serious adverse events than ivabradine and CMA. ARNI and SGLT2 inhibitors were recommended as better choices in reducing CV mortality, while SGLT2 inhibitors performed better regarding serious adverse event.