bluuebunny/crossref_metadata_2025 huggingface dataset:
Propofol Suppresses Microglia Inflammation by Targeting TGM2/NF-κB Signaling
Authors: Hou Yuanyuan , Xiao Xi , Yu Wei , Qi Sihua
Published: August 2021

Background. Propofol is a known intravenous hypnotic drug used for induction and maintenance of sedation and general anesthesia. Emerging studies also reveal a neuroprotective effect of propofol in diverse diseases of neuronal injuries via modulating microglia activation. In this study, we aimed to uncover the downstream targets of propofol in this process. Methods. RNA sequencing analysis to identify genes implicated in the propofol-mediated neuroprotective effect. Quantitative real-time PCR, enzyme-linked immunosorbent assay, and Western blotting analysis were performed to analyze inflammatory gene expression, cytokine levels, and TGM2. BV2 cells and primary microglia were used for functional verification and mechanism studies. Results. The multifunctional enzyme transglutaminase 2 (TGM2) was identified as a putative functional mediator of propofol. TGM2 was significantly upregulated in lipopolysaccharide- (LPS-) primed BV2 cells. Genetic silencing of TGM2 abolished LPS-induced microglial activation. Notably, gain-of-function experiments showed that the proinflammatory effects of TGM2 were dependent on its GTP binding activity instead of transamidase activity. Then, TGM2 was revealed to activate the NF-κB signaling pathway to facilitate microglial activation. Propofol can inhibit TGM2 expression and NF-κB signaling in BV2 cells and primary microglia. Ectopic expression of TGM2 or constitutively active IKKβ (CA-IKKβ) can compromise propofol-induced anti-inflammatory effects. Conclusions. Our findings suggest that TGM2-mediated activation of NF-κB signaling is an important mechanism in the propofol-induced neuroprotective effect that prevents microglial activation.
Time‐ and Quantile‐Varying Causality between Investor Attention and Bitcoin Returns: A Rolling‐Window Causality‐in‐Quantiles Approach
Authors: Hang Jianqin , Zhang Xu
Published: August 2021

This study proposes a novel approach that incorporates rolling‐window estimation and a quantile causality test. Using this approach, Google Trends and Bitcoin price data are used to empirically investigate the time‐varying quantile causality between investor attention and Bitcoin returns. The results show that the parameters of the causality tests are unstable during the sample period. The results also show strong evidence of quantile‐ and time‐varying causality between investor attention and Bitcoin returns. Specifically, our results show that causality appears only in high volatility periods within the time domain, and causality presents various patterns across quantiles within the quantile domain.
Flow of Brinkman Fluid with Heat Generation and Chemical Reaction
Authors: Ramzan M. , Un Nisa Zaib , Ahmad M. , Nazar M.
Published: August 2021

Unsteady magnetohydrodynamics (MHD) flow of fractionalized Brinkman‐type fluid over a vertical plate is discussed. In the model of problem, additional effects such as heat generation/absorption and chemical reaction are also considered. The model is solved by using the Caputo fractional derivative. The governing dimensionless equations for velocity, concentration, and temperature profiles are solved using the Laplace transform method and compared graphically. The effects of different parameters like fractional parameter, heat generation/absorption Q, chemical reaction R, and magnetic parameter M are discussed through numerous graphs. Furthermore, comparison among ordinary and fractionalized velocity fields are also drawn. From the figures, it is observed that chemical reaction and magnetic field have decreasing effect on velocity profile, whereas thermal radiation and mass Grashof numbers have increasing effect on the velocity of the fluid.
Mortality and Its Associated Factors among Hospitalized Heart Failure Patients : The Case of South West Ethiopia
Authors: Meshesha Meiraf Daniel , Kabthymer Robel Hussen , Abafogi Mohammed Mecha
Published: August 2021

Background. Hospital case fatality among those with heart failure in Africa ranges from 9% to 12.5%. An integrated approach to identify those who are at high risk and implementing specific treatment strategies is of great importance for a better outcome. Objective. The aim of this study is to assess the mortality rate and its associated factors among hospitalized heart failure patients at the Jimma University Medical Center (JUMC), south west Ethiopia. Method. A hospital-based retrospective cross-sectional study design was conducted among 252 patients admitted with heart failure during the study period who were sampled and enrolled in to the study. A simple random sampling technique was used to select the study participants by using their medical registration number as the sampling frame. Data were collected using a pretested questionnaire. The collected data were entered into EpiData software and exported to SPSS version 20 for cleaning and analysis. A binary logistic regression model was used. Adjusted and crude odds ratio with 95% CI were used. A

P

value less than 0.05 was used to declare statistical significance. Results. The prevalence of in-hospital mortality was found to be 21.29%. Cardiogenic shock AOR: 0.016 (95% CI: 0.001–0.267), complication at admission AOR: 5.25 (95% CI: 1.28–21.6), and ejection fraction (<30) AOR: 0.112 (95% CI: 0.022–0.562) were found to be significantly associated factors. Conclusion. The in-hospital mortality rate among admitted heart failure patients is unacceptably high. Due emphasis should be given on the identified associated factors to reduce the mortality.
Interactive Virtual Reality Touring System: A Case Study of Shulin Ji’an Temple in Taiwan
Authors: Lo Jung-Hua , Wu Shih-Da , You Min-Jie
Published: August 2021

Most current tour guiding methods for Taiwanese temples employ graphic webpage frameworks combined with captioned pictures for introduction. This type of tour guiding lacks interactive presence. In addition, the audience may not be able to focus on browsing webpages or learn essential information from the introduction. This study adopted the Delphi method to evaluate the current developed system. This system was aimed at designing VR-based interaction that differs from conventional tour guiding methods to aid users in viewing the display space from their viewpoints. Users cannot only control camera view angles but also select the paths and guiding information as if they were walking in the temple. The analysis results revealed that, in general, the users perceived VR tour guiding as convenient and easy to use. The display and content of the tour guiding system presented clear information to the users, aiding them in gaining further understanding of the introduced item. Finally, the study results can serve as a reference for design research on VR applications in tour guiding.
Research on Classification of COVID-19 Chest X-Ray Image Modal Feature Fusion Based on Deep Learning
Authors: Ji Dongsheng , Zhang Zhujun , Zhao Yanzhong , Zhao Qianchuan
Published: August 2021

Most detection methods of coronavirus disease 2019 (COVID-19) use classic image classification models, which have problems of low recognition accuracy and inaccurate capture of modal features when detecting chest X-rays of COVID-19. This study proposes a COVID-19 detection method based on image modal feature fusion. This method first performs small-sample enhancement processing on chest X-rays, such as rotation, translation, and random transformation. Five classic pretraining models are used when extracting modal features. A global average pooling layer reduces training parameters and prevents overfitting. The model is trained and fine-tuned, the machine learning evaluation standard is used to evaluate the model, and the receiver operating characteristic (ROC) curve is drawn. Experiments show that compared with the classic model, the classification method in this study can more effectively detect COVID-19 image modal information, and it achieves the expected effect of accurately detecting cases.
An Efficient Surrogate-Based Optimization Method for BWBUG Based on Multifidelity Model and Geometric Constraint Gradients
Authors: Zhang Daiyu , Zhang Bei , Wang Zhidong , Zhu Xinyao
Published: August 2021

Performing shape optimization of blended-wing-body underwater glider (BWBUG) can significantly improve its gliding performance. However, high-fidelity CFD analysis and geometric constraint calculation in traditional surrogate-based optimization methods are expensive. An efficient surrogate-based optimization method based on the multifidelity model and geometric constraint gradient information is proposed. By establishing a shape parameterized model, deriving analytical expression of geometric constraint gradient, constructing multifidelity surrogate model, the calculation times of high-fidelity CFD model and geometric constraints are reduced during the shape optimization process of BWBUG, which greatly improve the optimization efficiency. Finally, the effectiveness and efficiency of the proposed method are verified by performing the shape optimization of a BWBUG and comparing with traditional surrogate-based optimization methods.
Building Thermal Comfort Research Based on Energy‐Saving Concept
Authors: Xue Feiran , Zhao Jingyuan
Published: August 2021

Under the trend of building green and comfortable development, effective control of building energy consumption has become one of the problems that countries are actively facing to solve. People’s demand for residential buildings has changed from the past survival type to a comfortable and livable type. The high level of heating energy consumption is worthy of in‐depth study. In order to reduce energy consumption, realize the mapping of energy‐saving concepts in buildings, and understand the energy consumption of different building materials and the influence of external factors on human thermal comfort, this book has conducted research on building thermal comfort based on energy‐saving concepts. First of all, this article introduces the concept and application mode of energy‐saving concepts in buildings and the concept of thermal comfort and the SET index of standard effective temperature, including the two‐node model and the algorithm involved in the Fanger heat balance equation. In the experimental part, a model based on the concept of energy saving was designed to predict and analyze the energy consumption and thermal comfort effects of the building. In the analysis part, a comprehensive analysis of the effects of temperature, humidity, wind speed, and gender on thermal comfort, methods to improve thermal comfort, cumulative load changes with the heat transfer coefficient of windows, and the effects of windows of different materials on energy consumption was performed. At the same temperature, the wind speed is different, and the degree of heat sensation is also different. When the wind speed is 0.18 m/s and the temperature is 28°C, the thermal sensation is 0.32, and the human sensation is close to neutral. When the wind speed increases to 0.72 m/s, the heat sensation drops to −0.45, and the human body feels neutral and cool. It can be seen that the increase in wind speed has a certain compensation effect on the thermal sensation of the human body. When the wind speed does not change, increase the air temperature. For example, when the wind speed is 0.72 m/s, the temperature is 28°C, and the thermal sensation is −0.45, and when the temperature is increased to 29°C, the thermal sensation is 0.08, which shows that the temperature is improving the thermal sensation of the human body which has a certain offsetting effect. By studying the thermal comfort of buildings based on energy‐saving concepts, it is possible to obtain the effect of external factors on thermal comfort, thereby optimizing building materials and using building materials with lower heat transfer coefficients to reduce heating energy consumption.
Downregulation of PART1 Inhibits Proliferation and Differentiation of Hep3B Cells by Targeting hsa-miR-3529-3p/FOXC2 Axis
Authors: Weng Zhicheng , Peng Jianyang , Wu Weida , Zhang Chunsheng , Zhao Jianfeng , Gao Hongbin
Published: August 2021

Background. Long noncoding RNAs (lncRNAs) are an important subtype of noncoding RNAs (ncRNAs) and microRNA sponges regulate protein-coding gene expression. The lncRNA prostate androgen-regulated transcript 1 (PART1) was implicated in the process of several cancer pathogeneses. However, studies on the regulation of PART1 expression and its mechanism in liver cancer are lacking. Methods. qRT-PCR and western blot were used to detect PART1 levels in liver cancer serums and cell lines. Cell proliferation, migration, and invasion were detected using CCK8 assays, cell clones, and transwell assays. Interaction between PART1 and miR-3529-3p and forkhead box protein C2 (FOXC2) was confirmed using dual-luciferase reporter assays. Results. We revealed that expression levels of PART1 and FOXC2 are significantly upregulated and the miR-3529-3p expression level significantly decreases in the serum while high expression level of PART1 is positively associated with tumour size, BCLC stage, and TNM stage. shRNA of PART1 can significantly reduce the ability of cell migration and invasion by regulating AKT signalling associated with the reduction of MMP-2 and MMP-9 protein expression. Dual-luciferase reporter assays showed that PART1 can sponge miR-3529-3p, which targets FOXC2 in liver cancer cells. The promoting or suppressing effect of PART1 for Hep3B cell proliferation, invasion, and migration is revised by miR-3529-3p mimics and inhibitors. Conclusion. Results showed that downregulation of PART1 can partially inhibit proliferation and differentiation by targeting hsa-miR-3529-3p/FOXC2 axis.
Coupling Interaction of Surrounding Soil-Buried Pipeline and Additional Stress in Subsidence Soil
Authors: Ding Yahong , Yang Heng , Xu Ping , Zhang Minxia , Hou Zhenguo
Published: August 2021

In the process of underground resource exploitation, the induced surface subsidence easily leads to the deformation and failure of buried pipeline. And in the process of soil subsidence, the complex interaction between buried pipeline and surrounding soil occurs, which leads to deformation and additional stress in buried pipeline. In this paper, a laboratory test system is designed and developed to analyze the influence of buried depth, cohesion of soil, and angle of internal friction on stress, in order to obtain the deformation mechanism of pipe-soil and the pressure around the pipe and the distribution of additional axial stress along the pipeline. The research results show that in the process of subsidence, the synergistic deformation between the pipe and soil at both ends of the subsidence area is maintained, while there is a compressive nonsynergistic deformation zone in the soil at the top of the pipe, and the deformation zone in the cohesion-less soil and the cohesive soil presents a spire shape and an arch shape, respectively. Areas of maximum additional tensile and compressive stresses occur in the area of maximum curvature and the central position. In addition, the smaller the burial depth, the earlier the unloading phenomenon occurs; and the additional stress in buried pipe in cohesion-less soil is significantly less than that in cohesive soil, and the unloading phenomenon occurs earlier. The research results provide the basis for disaster prevention of buried petroleum transmission pipeline in subsidence process.
Is Electroacupuncture an Effective and Safe Treatment for Poststroke Depression? An Updated Systematic Review and Meta‐Analysis
Authors: Wang Xiafei , Cai Wa , Wang Yongpeng , Huang Song , Zhang Quanbin , Wang Feng
Published: August 2021

Objective. To observe and compare the efficacy and safety of electroacupuncture and antidepressants in the treatment of poststroke depression (PSD) using a meta‐analysis method. Methods. The VIP, CNKI, Wanfang, CMB, Embase, PubMed, and Cochrane databases were searched. All randomized controlled trials (RCT) on electroacupuncture treatment of PSD were searched and further screened. Meta‐analysis was performed on electroacupuncture and western medicine for PSD to explore the difference in efficacy between electroacupuncture and western medicine for PSD. Results. Nineteen RCTs were included in the meta‐analysis. Compared with the Western medicine group, the meta‐analysis showed no significant changes in Hamilton Depression Scale (HAMD) scores between the electroacupuncture group and the antidepressant group (P > 0.05). The number of adverse events in the electroacupuncture group was less than that in the antidepressant group. Conclusion. Compared with antidepressants, electroacupuncture is not less effective in improving depression symptoms in PSD patients with greater safety.
The Potential Antioxidant Activity and Characterization of Bioactive Compounds of Stahlianthus involucratus
Authors: Li Wengkun , Wu BingMin , Wang Yange , Lin Ying , An Lin , Zhang Guifang
Published: August 2021

Stahlianthus involucratus (S. involucratus) has anti‐inflammatory, antinociceptive, and antipyretic activities; however, there are no literature reports on its antioxidant capacity. This study presents a comparative assessment of the polyphenols contents, flavonoids contents, and antioxidant activity of the aqueous and methanol extracts of S. involucratus (ASI and MSI). Moreover, the expression of oxidative stress‐related genes in H2O2‐induced H9c2 cells pretreated with the MSI was measured by RT‐qPCR, and furthermore, MSI were characterized by UHPLC‐Q‐Orbitrap‐MS/MS. The results indicated that the MSI had higher antioxidant contents and antioxidant capacity, and MSI could inhibit H2O2‐induced oxidative stress in H9c2 cells by activating the Nrf2/HO‐1 pathway. UHPLC‐Q‐Orbitrap‐MS/MS characterized 15 phenolic compounds from the MSI. In conclusion, S. involucratus has the potential antioxidant capacity.
Exploring the Biological Mechanism of Huang Yam in Treating Tumors and Preventing Antitumor Drug-Induced Cardiotoxicity Using Network Pharmacology and Molecular Docking Technology
Authors: Zhang Hui , Dan Wenchao , He Qingyong , Guo Jianbo , Dai Shuang , Hui Xiaoshan , Meng Peipei , Cao Qianqian , Yun Wingyan , Guo Xinyuan
Published: August 2021

Drugs for the treatment of tumors could result in cardiotoxicity and cardiovascular diseases. We aimed to explore the anticancer properties of Huang yam as well as its cardioprotective properties using network pharmacology and molecular docking technology. The cardiovascular targets of the major chemical components of Huang yam were obtained from the following databases: TCMSP, ETCM, and BATMAN-TCM. The active ingredients of Huang yam were obtained from SwissADME. The cardiovascular targets of antitumor drugs were obtained using GeneCards, OMIM, DrugBank, DisGeNET, and SwissTargetPrediction databases. The drug-disease intersection genes were used to construct a drug-compound-target network using Cytoscape 3.7.1. A protein-protein interaction network was constructed using Cytoscape’s BisoGenet, and the core targets of Huang yam were screened to determine their antitumor properties and identify the cardiovascular targets based on topological parameters. Potential targets were imported into the Metascape platform for GO and KEGG analysis. The results were saved and visualized using R software. The components with higher median values in the network were molecularly docked with the core targets. The network contained 10 compounds, including daucosterol, delusive, dioxin, panthogenin-B, and 124 targets, such as TP53, RPS27A, and UBC. The GO function enrichment analysis showed that there were 478 items in total. KEGG enrichment analysis showed a total of 140 main pathways associated with abnormal transcription of cancer, PI3K-Akt signaling pathway, cell cycle, cancer pathway, ubiquitination-mediated proteolysis, and other pathways. Molecular docking results showed that daucosterol, delusive, dioxin, and panthogenin-B had the highest affinity for TP53, RPS27A, and UBC. The treatment of diseases using traditional Chinese medicine encompasses multiple active ingredients, targets, and pathways. Huang yam has the potential to treat cardiotoxicity caused by antitumor drugs.
Intratumoral Delivery of STING Agonist Results in Clinical Responses in Canine Glioblastoma
Authors: Boudreau C. Elizabeth , Najem Hinda , Ott Martina , Horbinski Craig , Fang Dexing , DeRay Chase M. , Levine Jonathan M. , Curran Michael A. , Heimberger Amy B.
Published: August 2021

Purpose:

Activation of STING (stimulator of interferon genes) can trigger a robust, innate antitumor immune response in immunologically “cold” tumors such as glioblastoma.

Patients and Methods:

A small-molecule STING agonist, IACS-8779, was stereotactically administered using intraoperative navigation intratumorally in dogs with spontaneously arising glioblastoma. The phase I trial used an escalating dose design, ascending through four dose levels (5–20 μg). Treatment was repeated every 4–6 weeks for a minimum of two cycles. Radiographic response to treatment was determined by response assessment in neuro-oncology (RANO) criteria applied to isovoxel postcontrast T1-weighted MR images obtained on a single 3T magnet.

Results:

Six dogs were enrolled and completed ≥1 cycle of treatment. One dog was determined to have an abscess and was removed from further analysis. One procedure-related fatality was observed. Radiographic responses were dose dependent after the first cycle. The first subject had progressive disease, whereas there was 25% volumetric reduction in one subject and greater than 50% in the remaining surviving subjects. The median progression-free survival time was 14 weeks (range: 0–22 weeks), and the median overall survival time was 32 weeks (range: 11–39 weeks).

Conclusions:

Intratumoral STING agonist (IACS-8779) administration was well tolerated in dogs with glioblastoma to a dose of 15 μg. Higher doses of IACS-8779 were associated with radiographic responses.
Phase I/II Trial of Vemurafenib in Dogs with Naturally Occurring, BRAF-mutated Urothelial Carcinoma
Authors: Rossman Paul , Zabka Tanja S. , Ruple Audrey , Tuerck Dietrich , Ramos-Vara José A. , Liu Liling , Mohallem Rodrigo , Merchant Mark , Franco Jackeline , Fulkerson Christopher M. , Bhide Ketaki P. , Breen Matthew , Aryal Uma K. , Murray Elaine , Dybdal Noel , Utturkar Sagar M. , Fourez Lindsey M. , Enstrom Alexander W. , Dhawan Deepika , Knapp Deborah W.
Published: August 2021

BRAF-targeted therapies including vemurafenib (Zelboraf) induce dramatic cancer remission; however, drug resistance commonly emerges. The purpose was to characterize a naturally occurring canine cancer model harboring complex features of human cancer, to complement experimental models to improve BRAF-targeted therapy. A phase I/II clinical trial of vemurafenib was performed in pet dogs with naturally occurring invasive urothelial carcinoma (InvUC) harboring the canine homologue of human BRAFV600E. The safety, MTD, pharmacokinetics, and antitumor activity were determined. Changes in signaling and immune gene expression were assessed by RNA sequencing and phosphoproteomic analyses of cystoscopic biopsies obtained before and during treatment, and at progression. The vemurafenib MTD was 37.5 mg/kg twice daily. Anorexia was the most common adverse event. At the MTD, partial remission occurred in 9 of 24 dogs (38%), with a median progression-free interval of 181 days (range, 53–608 days). In 18% of the dogs, new cutaneous squamous cell carcinoma and papillomas occurred, a known pharmacodynamic effect of vemurafenib in humans. Upregulation of genes in the classical and alternative MAPK-related pathways occurred in subsets of dogs at cancer progression. The most consistent transcriptomic changes were the increase in patterns of T lymphocyte infiltration during the first month of vemurafenib, and of immune failure accompanying cancer progression. In conclusion, the safety, antitumor activity, and cutaneous pharmacodynamic effects of vemurafenib, and the development of drug resistance in dogs closely mimic those reported in humans. This suggests BRAF-mutated canine InvUC offers an important complementary animal model to improve BRAF-targeted therapies in humans.
CD8+ T–cell Immune Surveillance against a Tumor Antigen Encoded by the Oncogenic Long Noncoding RNA PVT1
Authors: Kikuchi Yasuhiro , Tokita Serina , Hirama Tomomi , Kochin Vitaly , Nakatsugawa Munehide , Shinkawa Tomoyo , Hirohashi Yoshihiko , Tsukahara Tomohide , Hata Fumitake , Takemasa Ichiro , Sato Noriyuki , Kanaseki Takayuki , Torigoe Toshihiko
Published: August 2021

CD8+ T cells recognize peptides displayed by HLA class I molecules on cell surfaces, monitoring pathologic conditions such as cancer. Advances in proteogenomic analysis of HLA ligandomes have demonstrated that cells present a subset of cryptic peptides derived from noncoding regions of the genome; however, the roles of cryptic HLA ligands in tumor immunity remain unknown. In the current study, we comprehensively and quantitatively investigated the HLA class I ligandome of a set of human colorectal cancer and matched normal tissues, showing that cryptic translation products accounted for approximately 5% of the HLA class I ligandome. We also found that a peptide encoded by the long noncoding RNA (lncRNA) PVT1 was predominantly enriched in multiple colorectal cancer tissues. The PVT1 gene is located downstream of the MYC gene in the genome and is aberrantly overexpressed across a variety of cancers, reflecting its oncogenic property. The PVT1 peptide was recognized by patient CD8+ tumor-infiltrating lymphocytes, as well as peripheral blood mononuclear cells, suggesting the presence of patient immune surveillance. Our findings show that peptides can be translated from lncRNAs and presented by HLA class I and that cancer patient T cells are capable of sensing aberrations in noncoding regions of the genome.
Epigenetic Regulation and Environmental Sex Determination in Cichlid Fishes
Authors: Renn Suzy C.P. , Hurd Peter L.
Published: August 2021

Studying environmental sex determination (ESD) in cichlids provides a phylogenetic and comparative approach to understand the evolution of the underlying mechanisms, their impact on the evolution of the overlying systems, and the neuroethology of life history strategies. Natural selection normally favors parents who invest equally in the development of male and female offspring, but evolution may favor deviations from this 50:50 ratio when environmental conditions produce an advantage for doing so. Many species of cichlids demonstrate ESD in response to water chemistry (temperature, pH, and oxygen concentration). The relative strengths of and the exact interactions between these factors vary between congeners, demonstrating genetic variation in sensitivity. The presence of sizable proportions of the less common sex towards the environmental extremes in most species strongly suggests the presence of some genetic sex-determining loci acting in parallel with the ESD factors. Sex determination and differentiation in these species does not seem to result in the organization of a final and irreversible sexual fate, so much as a life-long ongoing battle between competing male- and female-determining genetic and hormonal networks governed by epigenetic factors. We discuss what is and is not known about the epigenetic mechanism behind the differentiation of both gonads and sex differences in the brain. Beyond the well-studied tilapia species, the 2 best-studied dwarf cichlid systems showing ESD are the South American genus Apistogramma and the West African genus Pelvicachromis. Both species demonstrate male morphs with alternative reproductive tactics. We discuss the further neuroethology opportunities such systems provide to the study of epigenetics of alternative life history strategies and other behavioral variation.
Survival Outcomes of Gemcitabine Plus S-1 Adjuvant Chemotherapy after Surgical Resection for Advanced Biliary Tract Cancer
Authors: Hosoda Kiyotaka , Fukushima Kentaro , Shimizu Akira , Motoyama Hiroaki , Kubota Koji , Notake Tsuyoshi , Sugenoya Shinsuke , Hayashi Hikaru , Yasukawa Koya , Kobayashi Ryoichiro , Soejima Yuji
Published: August 2021

Introduction: The usefulness of adjuvant chemotherapy in biliary tract cancer (BTC) is poorly reported. This study aimed to evaluate the effectiveness and safety of adjuvant gemcitabine plus S-1 (GS) chemotherapy after curative surgical resection for BTC. Methods: 225 BTC patients who underwent surgical resection between January 2006 and May 2019 were enrolled in this study. Twenty-seven patients received adjuvant chemotherapy with GS (GS group), whereas 67 patients underwent surgery alone (S group). Twenty-three matching pairs were derived through propensity score (PS) matching analysis. Patients received 12 cycles of adjuvant chemotherapy (70 mg/m2 oral S-1 for 7 consecutive days plus intravenous gemcitabine 1,000 mg/m2 on day 7). The primary end point was recurrence-free survival (RFS). The secondary end points were the 1-, 2-, and 3-year RFS and overall survival (OS) rates, tolerability, and frequency of grade 3/4 toxicity. Results: The completion rate was 81.5%; no treatment-related deaths were observed. Grade 3/4 adverse events were seen in 40.7% of the patients. RFS (3-year RFS rate: 59.3% vs. 39.1%, p = 0.049) and OS (3-year OS rate: 71.7% vs. 53.4%, p = 0.008) were significantly better in the GS group than in the S group among PS-matched pairs. Discussion/Conclusion: GS chemotherapy after curative surgery was well tolerated, showed better clinical benefit in the adjuvant setting, and can effectively reduce BTC recurrence.
Cytology of Undifferentiated Round-Cell Sarcomas of Bone and Soft Tissue: Ewing Sarcoma or Not Ewing Sarcoma, That Is the Question
Authors: Gajdzis Pawel , Pierron Gaëlle , Klijanienko Jerzy
Published: August 2021

Background: Undifferentiated round-cell sarcomas (URCSs) of soft tissue and bone are a group of clinically heterogeneous tumors. Diagnosis of these malignancies is based mainly on recurrent genetic alterations. The most common and the best known representative of this group is Ewing sarcoma (ES) which is characterized by gene fusions including EWSR1 or FUS and ETS transcription factors family. Other newly described entities are CIC-rearranged sarcoma, sarcoma with BCOR genetic alterations, and round-cell sarcoma with EWSR1-non-ETS fusions. All these novel tumors are known as Ewing-like sarcomas. Summary: It is believed that morphologic features of ES and Ewing-like sarcomas vary only slightly or even that cytomorphology is not relevant. But differences are usually obvious, and some cytologic findings, such as spindle cells, connective tissue fragments, or myxoid stroma, are typical for Ewing-like sarcomas but not for ES. Each of these entities is also characterized by different immunoprofiles. The aim of this review was to summarize cytomorphologic and immunohistochemical features of URCS and compare them with other small round-cell tumors. Key Messages: Cytology can be successfully used in URCS diagnosis as a complementary tool for core-needle biopsy or even alone in selected cases, especially in recurrent and metastatic tumors. Knowing the morphologic and immunohistochemical differences between URCS is essential to provide appropriate ancillary studies and make a definitive diagnosis.
Physical Activity and Long-Term Mortality Risk in Older Adults with and without Cardiovascular Disease: A Nationwide Cohort Study
Authors: Shaked Or , Cohen Gali , Goshen Abigail , Shimony Tal , Shohat Tamar , Gerber Yariv
Published: August 2021

Aims: To evaluate the association between physical activity (PA) levels and mortality among older adults, to determine whether it differs according to cardiovascular disease (CVD) status, and to assess the optimal weekly duration of PA associated with subsequent survival. Methods: Participants (n = 1,799) were drawn from a national survey conducted from 2005 to 2006, constituting Israeli adults aged ≥65 years. Sociodemographic, clinical, behavioral, and psychosocial data were collected via interview at study entry. Based on a detailed PA questionnaire and according to published guidelines, participants were classified as sufficiently active, insufficiently active, and inactive. CVD status was self-reported. Mortality data (last follow-up, December 2016) were obtained from the Israeli Ministry of Health. Using Cox models, inverse probability weighted hazard ratios (HRs) for mortality, based on propensity score, were estimated for PA categories. Results: Among the participants at baseline (mean age, 74.6 years), 559 (31.1%) were sufficiently active, 506 (28.1%) were insufficiently active, and 734 (40.8%) were inactive. During follow-up (mean, 9.0 years), 684 participants (38.0%) died. PA was inversely associated with mortality, with propensity score-adjusted HRs (95% confidence intervals) of 0.84 (0.71–1.01) in insufficiently and 0.73 (0.61–0.88) in sufficiently active participants (ptrend < 0.001). No PA-by-CVD interaction was detected on multiplicative scale (p = 0.36) or additive scale (p = 0.58). A monotonic survival benefit was observed until ∼150 min of PA per week, beyond which no further gain was apparent. Conclusions: In a nationwide cohort of older adults, nearly 70% did not meet the guideline for PA. PA engagement was inversely associated with long-term mortality risk, similarly in individuals with and without CVD. A maximum survival advantage was achieved at around 150 min of exercise per week.
Race Differences in Interventions and Survival After Out‐of‐Hospital Cardiac Arrest in North Carolina, 2010 to 2014
Authors: Moeller Sidsel , Hansen Carolina M. , Kragholm Kristian , Dupre Matt E. , Sasson Comilla , Pearson David A. , Tyson Clark , Jollis James G. , Monk Lisa , Starks Monique A. , McNally Bryan , Thomas Kevin L. , Becker Lance , Torp‐Pedersen Christian , Granger Christopher B.
Published: August 2021

Background

Following the implementation of the HeartRescue project, with interventions in the community, emergency medical services, and hospitals to improve care and outcomes for out‐of‐hospital cardiac arrests (OHCA) in North Carolina, improved bystander and first responder treatments as well as survival were observed. This study aimed to determine whether these improvements were consistent across Black versus White individuals.

Methods and Results

Using the Cardiac Arrest Registry to Enhance Survival (CARES), we identified OHCA from 16 counties in North Carolina (population 3 million) from 2010 to 2014. Temporal changes in interventions and outcomes were assessed using multilevel multivariable logistic regression, adjusted for patient and socioeconomic neighborhood‐level factors. Of 7091 patients with OHCA, 36.5% were Black and 63.5% were White. Black patients were younger, more females, had more unwitnessed arrests and non‐shockable rhythm (Black: 81.0%; White: 75.4%). From 2010 to 2014, the adjusted probabilities of bystander cardiopulmonary resuscitation (CPR) went from 38.5% to 51.2% in White,
P
<0.001; and 36.9% to 45.6% in Black,
P
=0.002, and first‐responder defibrillation went from 13.2% to 17.2% in White,
P
=0.002; and 14.7% to 17.3% in Black,
P
=0.16. From 2010 to 2014, survival to discharge only increased in White (8.0% to 11.4%,
P
=0.004; Black 8.9% to 9.5%,
P
=0.60), though, in shockable patients the probability of survival to discharge went from 24.8% to 34.6% in White,
P
=0.02; and 21.7% to 29.0% in Black,
P
=0. 10.

Conclusions

After the HeartRescue program, bystander CPR and first‐responder defibrillation increased in both patient groups; however, survival only increased significantly for White patients.
Disease Expression and Outcomes in Black and White Adults With Hypertrophic Cardiomyopathy
Authors: Arabadjian Milla E. , Yu Gary , Sherrid Mark V. , Dickson Victoria Vaughan
Published: August 2021

Background

There is limited research on hypertrophic cardiomyopathy (HCM), which is the most common inherited cardiac disorder, in diverse populations, including Black individuals. Current literature lacks comprehensive data on HCM disease expression, comorbidities, and outcomes in this historically disadvantaged group. The purpose of this study was to examine structural HCM characteristics, comorbidities, and outcomes in a Black and White cohort with HCM.

Methods and Results

The study was a subgroup analysis from a longitudinal, prospective study on HCM, with supplemental chart review. The sample included adults (≥18 years) with a clinical diagnosis of HCM, who self‐identified as Black/African American or White. The study sample comprised 434 individuals; 57 (13.1%) were Black, and 180 (41.5%) were women. Black patients were younger than White patients, 54.6 (13.4) versus 62.5 (14.8) years,
P
=0.001. Black patients were more likely to have sub‐basal and diffuse hypertrophy, 22 (38.6%) versus 56 (14.9%),
P
<0.001, 6 (10.5%) versus 15 (4%),
P
=0.017, mid‐LV obstruction, 7 (12.3%) versus 21 (5.5%),
P
=0.025, and cardiac fibrosis ≥15%, 10 (22.2%) versus 19 (8.8%),
P
=0.009, than White patients. Black patients were more likely to experience appropriate implantable cardioverter defibrillator interventions, 5 (38.5) versus 5 (6.8),
P
<0.001 and were more likely to have ≥2 sudden death risk factors. Comorbidities were largely similar between groups, though more Black participants had Class II obesity, 12 (21.8) versus 30 (8.1),
P
<0.001. Both groups had similar rates of genetic testing usage.

Conclusions

This study underscores the need for continued research of HCM in Black populations, including tailored approaches to diagnosis and precise evaluation of cardiac anatomy.
Incident Heart Failure Within the First and Fifth Year after Delivery Among Women With Hypertensive Disorders of Pregnancy and Prepregnancy Hypertension in a Diverse Population
Authors: Malek Angela M. , Wilson Dulaney A. , Turan Tanya N. , Mateus Julio , Lackland Daniel T. , Hunt Kelly J.
Published: August 2021

Background

Hypertensive disorders of pregnancy (HDP) and pre‐pregnancy hypertension are associated with increased morbidity and mortality for the mother. Our aim was to investigate the relationships between HDP and pre‐pregnancy hypertension with maternal heart failure (HF) within 1 and 5 years of delivery and to examine racial/ethnic differences.

Methods and Results

We conducted a retrospective cohort study in South Carolina (2004–2016) involving 425 649 women aged 12 to 49 years (58.9% non‐Hispanic White [NHW], 31.5% non‐Hispanic Black [NHB], 9.6% Hispanic) with a live, singleton birth. Incident HF was defined by hospital/emergency department visit and death certificate data. Pre‐pregnancy hypertension and HDP (preeclampsia, eclampsia, or gestational hypertension) were based on hospitalization/emergency department visit and birth certificate data (i.e., gestational hypertension for HDP). The 425 649 women had pre‐pregnancy hypertension without superimposed HDP (pre‐pregnancy hypertension alone; 0.4%), HDP alone (15.7%), pre‐pregnancy hypertension with superimposed HDP (both conditions; 2.2%), or neither condition in any pregnancy (81.7%). Incident HF event rates per 1000 person‐years were higher in NHB than NHW women with HDP (HDP: 2.28 versus 0.96; both conditions: 4.30 versus 1.22, respectively). After adjustment, compared with women with neither condition, incident HF risk within 5 years of delivery was increased for women with pre‐pregnancy hypertension (HR,2.55, 95% CI: 1.31–4.95), HDP (HR,4.20, 95% CI: 3.66–4.81), and both conditions (HR,5.25, 95% CI: 4.24–6.50).

Conclusions

Women with HDP and pre‐pregnancy hypertension were at higher HF risk (highest for superimposed preeclampsia) within 5 years of delivery. NHB women with HDP had higher HF risk than NHW women, regardless of pre‐pregnancy hypertension.
Racial and Sex Disparities in Anticoagulation After Electrical Cardioversion for Atrial Fibrillation and Flutter
Authors: Mentias Amgad , Nakhla Shady , Desai Milind Y. , Wazni Oussama , Menon Venu , Kapadia Samir , Vaughan Sarrazin Mary
Published: August 2021

Background

Anticoagulation is indicated for 4 weeks after cardioversion in patients with atrial fibrillation/flutter. We sought to examine whether there is evidence of sex or racial disparity in anticoagulant prescription following cardioversion, and whether postcardioversion anticoagulation affects outcomes.

Methods and Results

We identified a representative sample of Medicare patients who underwent elective electric cardioversion in an outpatient setting from 2015 to 2017. We identified patients who had an anticoagulant prescription for 3 months after the cardioversion date. Multivariable logistic regression was used to assess factors associated with a prescription of an anticoagulant after cardioversion. Cox regression analysis was used to test association of anticoagulation with a composite end point of 90‐day mortality, ischemic stroke, or arterial embolism. The final study cohort included 7860 patients. Overall, 5510 patients (70.1%) received any anticoagulation following cardioversion, while 2350 (29.9%) did not. Patients who did not receive anticoagulation were younger, with a lower burden of most comorbidities. Patients were less likely to receive anticoagulation if they had dementia or atrial flutter, while patients with valvular heart disease, obesity, heart failure, peripheral vascular or coronary disease, or hypertension were more likely to receive anticoagulation. Female sex (adjusted odds ratio, 0.84; 95% CI, 0.75–0.92;
P
<0.001), Black and Hispanic race (adjusted odds ratio, 0.50; 95% CI, 0.38–0.65; and odds ratio, 0.56; 95% CI, 0.41–0.75, respectively;
P
<0.001) were independently associated with lower probability of anticoagulant prescription. Postcardioversion anticoagulation was associated with lower risk of the composite end point (adjusted hazard ratio, 0.38; 95% CI, 0.27–0.52;
P
<0.001).

Conclusions

Racial and sex disparities exist in anticoagulant prescription after outpatient elective cardioversion for atrial fibrillation.
Hypertension Management in Stroke Prevention
Authors: McCarthy Josephine , Yang Jun , Clissold Ben , Young Morag J. , Fuller Peter J. , Phan Thanh
Published: August 2021

Primary aldosteronism confers a higher risk of stroke, atrial fibrillation, and cardiovascular disease than blood pressure matched essential hypertension. It is the most common endocrine cause of secondary hypertension with prevalence estimates of up to 13% in primary care and 30% in referral centers around the world. Unlike essential hypertension, primary aldosteronism has targeted medical treatment and potentially curative surgical solutions which can ameliorate the associated cardiovascular risks. This narrative review highlights an evidence gap in the optimal diagnosis and targeted treatment of primary aldosteronism in secondary stroke prevention. Over half of the patients suffering a stroke have blood pressure in the hypertensive range and less than a third achieve optimal blood pressure control. There are no guideline recommendations to test for primary aldosteronism in these patients, although up to 30% of patients with resistant hypertension may have this disease. The accurate diagnosis of primary aldosteronism could significantly improve blood pressure, simplify the medication regimen and reduce the overall cardiovascular risk in these patients. The challenges associated with screening for primary aldosteronism following stroke may be overcome by novel blood tests which are less affected by antihypertensive medications routinely used in stroke care. Approximately one-quarter of all strokes occur in patients who have previously had a stroke. Modifying hypertension, the leading modifiable risk factor, would, therefore, have significant public health implications. As clinicians, we must increase our awareness of primary aldosteronism in patients with stroke, particularly in those with resistant hypertension, to enable targeted therapy and reduce the risk of stroke recurrence.
Bone Marrow Mesenchymal Stem Cells (BMSCs)-Derived miR-31 in the Pathogenesis of Recurrent Abortion by Regulating Kisspeptins 1 (KISS1) Expression
Authors: Yu Ruiping , Wu Changfen , Qin Ying , Li Cong , Mo Zhongfu , Zhai Hongwei , Jiang Lei
Published: August 2021

Bone marrow mesenchymal stem cells (BMSCs) are potentially efficacious in treating recurrent pregnancy disorders and endometrial injury. Uterine parenchymal cells interact with BMSCs to promote functional recovery. Our research aimed to explore the effect of BMSCs-derived miR-31 on
recurrent pregnancy loss. A recurrent pregnancy loss mouse model was constructed followed by nanoparticle analysis of BMSC and miR-31 expressing by RT-PCR. The levels of miR-31 in BMSCs (miR-31+BMSCs or BMSCs) and their counterpart exosomes were up- or down-regulated to explore the effects
of aberrant expression of miR-31 on endometrial damage in recurrent pregnancy loss. The analysis of BMSC nanoparticles showed that miR-31 was derived from BMSC. We found increased levels of miR-31 in miR-340 + BMSCs after incubation with endometrial stromal cells (ESCs) compared to controls.
Labeling of exosomes by red fluorescent protein indicated that exosomes were liberated out of BMSCs and translocated into neighboring ESCs, and mice treated with miR-340 + BMSCs had improved functional recovery from recurrent pregnancy loss. BMSC-derived miR-31 mediates functional recovery
induced in recurrent pregnancy miscarriage mice by regulating KISS1 expression and fibrosis gene expression.
Physicochemical and Morphological Characterization of Dentin from Deciduous and Permanent Teeth Processed by Different Methods for Tissue Regeneration
Authors: Maria Estrada-Delgado , Marine Ortiz-Magdaleno , Diana Escobar-García , Amaury Pozos-Guillén , Mariana Gutiérrez-Sánchez , Gabriel Romo-Ramírez
Published: August 2021

The composition of autogenous dentin differs from that of extracted deciduous and permanent teeth, as graft material must undergo procedures prior to implantation. The aim of this study was to characterize the physicochemical and morphological properties of dentin from deciduous (DTs) and permanent teeth (PTs) that had been demineralized (DMA), deproteinized (DPA), and decellularized (DSA). The dentin particles were DMA with ethylenediaminetetraacetic acid (EDTA), DPA with isopropanol, and DSA with sodium dodecyl sulfate (SDS). Sound dentin (SD) was used as the control group. Scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), Fourier transform infrared (FTIR) and X-ray diffraction (XRD) were used to examine the surface and physicochemical properties of the dentin. DMA and DPA dentin had lower concentrations of calcium and protein respectively than SD, showing a significant difference compared with DMA and DPA dentin from DTs and PTs (p< 0.05). In the DSA dentin, it was possible to eliminate the cellular residues of dentin from DTs and PTs, and the gene GAPDH was not expressed. The results of FTIR and XRD revealed a different physicochemical composition according to the dentin processing. EDS demonstrated that DMA dentin obtained the lowest values of calcium and phosphate, and the micrographs obtained by SEM exhibited a porous matrix structure in DMA dentin to a greater degree than in DPA or DSA dentin. The physicochemical properties and morphology of dentin as an autograft material differ depending on whether the teeth are deciduous or permanent; the processing method conditions the characteristics of the dentin substrate as a matrix for tissue regeneration.