bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myocardial Scar Characterization and Future Ventricular Arrhythmia in Patients With Ischemic Cardiomyopathy and an Implantable Cardioverter-Defibrillator
Authors: Noordman Alwin B. P. , Maass Alexander H. , Groenveld Hessel , Mulder Bart A. , Rienstra Michiel , Blaauw Yuri 
Published: August 2021

Background: Implantable cardioverter-defibrillator (ICD) therapy is associated with several deleterious effects, which can be reduced by antiarrhythmic drugs or catheter ablation. However, it is largely unknown which patients might benefit from these therapies. Therefore, this study aimed to investigate whether myocardial scar characterization improves risk stratification for ventricular arrhythmia (VA) occurrence in patients with ischemic cardiomyopathy and an ICD.Methods: In this study, 82 patients with ischemic cardiomyopathy who received an ICD were enrolled retrospectively. Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) images were analyzed using an investigational software tool to obtain quantitative data regarding the total scar, core, and border zone (BZ). Data regarding the QRS complex was obtained from electrocardiography (ECG). The primary endpoint was appropriate ICD therapy.Results: During a median follow-up duration of 3.98 years [interquartile range (IQR) 2.89–5.14 years], appropriate therapy occurred in 24 (29.3%) patients. Patients with appropriate ICD therapy had a significantly larger total scar mass [60.0 (IQR 41.2–73.4) vs. 43.3 (IQR 31.2–61.2) g; P = 0.009] and BZ mass [32.9 (IQR 26.9–42.4) vs. 24.5 (IQR 18.8–32.5) g; P = 0.001] than those without appropriate therapy. In multivariable Cox regression analyses, total scar mass [hazard ratio (HR) 1.02 [95% confidence interval (CI) 1.00–1.04]; P = 0.014] and BZ mass (HR 1.04 [95% CI 1.01–1.07]; P = 0.009) independently predicted appropriate ICD therapy. Core mass and the QRS complex, however, were not significantly associated with the primary endpoint.Conclusion: LGE-CMR-based, but not ECG-based myocardial scar characterization improves risk stratification for VA occurrence in patients with ischemic cardiomyopathy who received an ICD.
The Role of Mitochondrial DNA Variation in Drug Response: A Systematic Review
Authors: Jones Samantha W. , Ball Amy L. , Chadwick Amy E. , Alfirevic Ana 
Published: August 2021

Background: The triad of drug efficacy, toxicity and resistance underpins the risk-benefit balance of all therapeutics. The application of pharmacogenomics has the potential to improve the risk-benefit balance of a given therapeutic via the stratification of patient populations based on DNA variants. A growth in the understanding of the particulars of the mitochondrial genome, alongside the availability of techniques for its interrogation has resulted in a growing body of literature examining the impact of mitochondrial DNA (mtDNA) variation upon drug response.Objective: To critically evaluate and summarize the available literature, across a defined period, in a systematic fashion in order to map out the current landscape of the subject area and identify how the field may continue to advance.Methods: A systematic review of the literature published between January 2009 and December 2020 was conducted using the PubMed database with the following key inclusion criteria: reference to specific mtDNA polymorphisms or haplogroups, a core objective to examine associations between mtDNA variants and drug response, and research performed using human subjects or human in vitro models.Results: Review of the literature identified 24 articles reporting an investigation of the association between mtDNA variant(s) and drug efficacy, toxicity or resistance that met the key inclusion criteria. This included 10 articles examining mtDNA variations associated with antiretroviral therapy response, 4 articles examining mtDNA variants associated with anticancer agent response and 4 articles examining mtDNA variants associated with antimicrobial agent response. The remaining articles covered a wide breadth of medications and were therefore grouped together and referred to as “other.”Conclusions: Investigation of the impact of mtDNA variation upon drug response has been sporadic to-date. Collective assessment of the associations identified in the articles was inconclusive due to heterogeneous methods and outcomes, limited racial/ethnic groups, lack of replication and inadequate statistical power. There remains a high degree of idiosyncrasy in drug response and this area has the potential to explain variation in drug response in a clinical setting, therefore further research is likely to be of clinical benefit.
Probing Electronic Properties of CVD Monolayer Hexagonal Boron Nitride by an Atomic Force Microscope
Authors: Deng Shiyu , Gu Yanyun , Wan Xi , Gao Mingliang , Xu Shijia , Chen Kun , Chen Huanjun 
Published: August 2021

Ultrathin hexagonal boron nitride (h-BN) has recently attracted a lot of attention due to its excellent properties. With the rapid development of chemical vapor deposition (CVD) technology to synthesize wafer-scale single-crystal h-BN, the properties of h-BN have been widely investigated with a variety of material characterization techniques. However, the electronic properties of monolayer h-BN have rarely been quantitatively determined due to its atomically thin thickness and high sensitivity to the surrounding environment. In this work, by the combined use of AFM (atomic force microscope) PeakForce Tunneling (PF-TUNA) mode and Kevin probe force microscopy (KPFM) model, both the electrical resistivity (529 MΩ cm) and the inherent Fermi level (∼4.95 eV) of the as-grown monolayer h-BN flakes on the copper substrate have been quantitatively analyzed. Moreover, direct visualization of the high-temperature oxidation-resistance effect of h-BN nanoflakes has been presented. Our work demonstrates a direct estimation of the electronic properties for 2D materials on the initial growth substrate without transfer, avoiding any unwanted contaminations introduced during the transfer process. The quantitative analysis by state-of-the-art atomic force microscope techniques implies that monolayer h-BN can be employed as an atomically thin and high-quality insulator for 2D electronics, as well as a high-temperature antioxidation layer for electronic device applications.
Elevated Pancreatic Enzymes in ICU Patients With COVID-19 in Wuhan, China: A Retrospective Study
Authors: Ding Peili , Song Bin , Liu Xuelin , Fang Xing , Cai Hongliu , Zhang Dingyu , Zheng Xia 
Published: August 2021

Background: Pancreatic enzyme elevation has been reported in patients with COVID-19 during the pandemic. However, with the shortage of medical resources and information, several challenges are faced in the examination and treatment of this condition in COVID-19 patients. There is little information on whether such condition is caused by pancreatic injury, and if this is a warning sign of life threatening complications like multiple organ failure in patients. The objective of this study is to explore the relationship between elevated pancreatic enzymes and the underlying risk factors during the management of COVID-19 patients.Method: A total of 55 COVID-19 patients admitted to the intensive care unit (ICU) of Wuhan Jinyintan hospital from January 1 to March 30, 2020 were enrolled in this study. All participants underwent transabdominal ultrasound imaging to assess their pancreas.Results: Out of the 55 patients, three patients had pancreatitis, 29 (52.7%) with elevated pancreatic enzymes, and 23 (41.8%) without. The most common symptoms of patients with COVID-19 were fever and cough. There was no statistical difference in most baseline characteristics except myalgia on admission. Compared with those having normal enzyme levels, patients with elevated pancreatic enzymes had higher rates of mortality (79.3 vs. 52.2%; P = 0.038), and lower rates of discharge (20.7 vs. 47.8%; P = 0.038). Patients with elevated enzymes had higher incidence of mechanical ventilation (P = 0.004) and kidney injury (P = 0.042) than patients without elevated pancreatic enzymes. The results of multivariable logistic analysis showed that the odds ratio were 10.202 (P = 0.002) for mechanical ventilation and 7.673 (P = 0.014) for kidney injury with the elevated enzymes vs. the normal conditions.Conclusions: The findings show that the incidences of pancreatic enzymes elevation are not low in critical COVID-19 patients and only a few of them progressed to acute pancreatitis (AP). Increased pancreatic enzymes levels is associated with poor prognosis in COVID-19 patients. In addition, the kidney injury and oxygenation degradation are associated with the pancreatic enzymes elevation in COVID-19 patients.
Sanhuang Decoction Controls Tumor Microenvironment by Ameliorating Chronic Stress in Breast Cancer: A Report of Ninety Cases
Authors: Feng Ming , Wang Huanhuan , Zhu Zhiyuan , Yao Bowen , Li Yongfei , Xue Jingxian , Cao Sihan , Shao Xinyi , Xu Yanlei , Sohn Ki Cheul , Shin Im Hee , Yao Chang 
Published: August 2021

Long-term endocrine treatment which results in estrogen deprivation causes chronic stress associated with a series of uncomfortable symptoms leading not only to a decrease in quality of life but also to cancer recurrence, which may be mediated primarily through the enhanced expression of angiogenic factors, as well as a series of inflammatory microenvironmental changes that favor tumor progression. In this study, we designed a clinical trial and aimed to explore the effects of Sanhuang Decoction (SHD) treatment on chronic stress, inflammatory factors, and breast cancer recovery. A total of 90 patients with breast cancer who met the inclusion/exclusion criteria were randomly allocated to a treatment or control group. The treatment group received the standard endocrine treatment and the traditional Chinese medicine decoction known as SHD. The control group received the standard endocrine treatment only. The treatment period was 6 months. The modified Kupperman Menopausal Index, the self-rating anxiety scale, and the self-rating depression scale were evaluated once per month. The body microenvironment plasma indices related to chronic stress, such as oxidative and antioxidative stress markers, inflammatory factors, hemorheology, coagulation, lipid and D-dimer, immunologic functions, tumor biomarkers, and angiogenic factors of the vascular endothelial growth factor (VEGF) were measured before and after 6 months of treatment. After treatment for 5 months, the scores in the treatment group decreased to nearly normal levels and the control group showed no significant improvement. After treatment for 6 months, all indices related to the body microenvironment, as well as the tumor biomarkers and carcinoembryonic antigen, carbohydrate antigen 153, and angiogenic factor VEGF levels improved significantly to normal levels in the treatment group. Our primary research showed that treatment with SHD effectively improved the quality of life of breast cancer patients by facilitating a change in the body microenvironment that controlled tumor growth and prevented drug resistance.Clinical Trial RegistrationChinese Clinical Trial Registry, identifier ChiCTR-IIR-2000041413. Date of registration: 2017-06-07 (retrospective registration).
Cooperation Between Cancer and Fibroblasts in Vascular Mimicry and N2-Type Neutrophil Recruitment via Notch2–Jagged1 Interaction in Lung Cancer
Authors: Tsai Ying-Ming , Wu Kuan-Li , Liu Yu-Wei , Chang Wei-An , Huang Yung-Chi , Chang Chao-Yuan , Tsai Pei-Hsun , Liao Szi-Hui , Hung Jen-Yu , Hsu Ya-Ling 
Published: August 2021

BackgroundAngiogenesis is required for tumor development and metastasis, which is a major part in a pro-tumor microenvironment. Vascular mimicry (VM) is a process in which cancer cells, rather than endothelia, create an alternative perfusion system to support the tumor progression.ObjectivesTo validate the role of VM and to develop a strategy to inhibit angiogenesis in lung cancer.MethodsIn this study, we utilized lung cancer samples to verify the existence of VM and conducted several experimental methods to elucidate the molecular pathways.ResultsH1299 and CL1-0 lung cancer cells were unable to form capillary-like structures. VM formation was induced by cancer-associated fibroblast (CAFs) in both in vitro and in vivo experiments. Notch2–Jagged1 cell–cell contact between cancer cells and CAFs contributes to the formation of VM networks, supported by Notch intracellular domain (NICD) 2 nuclear translocation and N2ICD target gene upregulated in lung cancer cells mixed with CAFs. The polarization of tumor-promoting N2-type neutrophil was increased by VM networks consisting of CAF and cancer cells. The intravasation of cancer cells and N2-type neutrophils were increased because of the loose junctions of VM. Disruption of cancer cell–CAF connections by a γ‐secretase inhibitor enforced the anticancer effect of anti‐vascular endothelial growth factor antibodies in a mouse model.ConclusionThis study provides the first evidence that CAFs induce lung cancer to create vascular-like networks. These findings suggest a therapeutic opportunity for improving antiangiogenesis therapy in lung cancer.
A Pyroptosis-Related Gene Signature for Predicting Survival in Glioblastoma
Authors: Li Xin-Yu , Zhang Lu-Yu , Li Xue-Yuan , Yang Xi-Tao , Su Li-Xin 
Published: August 2021

BackgroundIn this study, a prognostic model based on pyroptosis-related genes was established to predict overall survival (OS) in patients with glioblastoma (GBM).MethodsThe gene expression data and clinical information of GBM patients were obtained from The Cancer Genome Atlas (TCGA), and bioinformatics analysis of differentially expressed genes was performed. LASSO Cox regression model was used to construct a three-pyroptosis-related gene signature, and validation was performed using an experimental cohort.ResultsA total of three pyroptosis-related genes (CASP4, CASP9, and NOD2) were used to construct a survival prognostic model, and experimental validation was performed using an experimental cohort. Receiver operating characteristic (ROC) analysis was performed, and the area under the ROC curves (AUC) was 0.921, 0.840, and 0.905 at 1, 3, and 5 years, respectively. Functional analysis revealed that T-cell activation, regulation of T-cell activation, leukocyte cell-cell adhesion, and positive regulation of cell adhesion among other immune-related functions were enriched, and immune-related processes were different between the two risk groups.ConclusionIn this study, a novel prognostic model based on three pyroptosis-related genes is constructed and used to predict the prognosis of GBM patients. The model can accurately and conveniently predict the 1-, 3-, and 5-year OS of GBM patients.
Risk Stratification of Cytogenetically Normal Acute Myeloid Leukemia With Biallelic CEBPA Mutations Based on a Multi-Gene Panel and Nomogram Model
Authors: Wu Li-Xin , Jiang Hao , Chang Ying-Jun , Zhou Ya-Lan , Wang Jing , Wang Zi-Long , Cao Lei-Ming , Li Jin-Lan , Sun Qiu-Yu , Cao Shan-Bo , Lou Feng , Zhou Tao , Liu Li-Xia , Wang Cheng-Cheng , Wang Yu , Jiang Qian , Xu Lan-Ping , Zhang Xiao-Hui , Liu Kai-Yan , Huang Xiao-Jun , Ruan Guo-Rui 
Published: August 2021

BackgroundApproximately 30% of Chinese individuals with cytogenetically normal acute myeloid leukemia (CN-AML) have biallelic CEBPA (biCEBPA) mutations. The prognosis and optimal therapy for these patients are controversial in clinical practice.MethodsIn this study, we performed targeted region sequencing of 236 genes in 158 individuals with this genotype and constructed a nomogram model based on leukemia-free survival (LFS). Patients were randomly assigned to a training cohort (N =111) and a validation cohort (N =47) at a ratio of 7:3. Risk stratification was performed by the prognostic factors to investigate the risk-adapted post-remission therapy by Kaplan–Meier method.ResultsAt least 1 mutated gene other than CEBPA was identified in patients and mutation number was associated with LFS (61.6% vs. 39.0%, P =0.033), survival (85.6% vs. 62.9%, P =0.030) and cumulative incidence of relapse (CIR) (38.4% vs. 59.5%, P =0.0496). White blood cell count, mutations in CFS3R, KMT2A and DNA methylation related genes were weighted to construct a nomogram model and differentiate two risk subgroups. Regarding LFS, low-risk patients were superior to the high-risk (89.3% vs. 33.8%, P &lt;0.001 in training cohort; 87.5% vs. 18.2%, P =0.009 in validation cohort). Compared with chemotherapy, allogenic hematopoietic stem cell transplantation (allo-HSCT) improved 5-year LFS (89.6% vs. 32.6%, P &lt;0.001), survival (96.9% vs. 63.6%, P =0.001) and CIR (7.2% vs. 65.8%, P &lt;0.001) in high-risk patients but not low-risk patients (LFS, 77.4% vs. 88.9%, P =0.424; survival, 83.9% vs. 95.5%, P =0.173; CIR, 11.7% vs. 11.1%, P =0.901).ConclusionsOur study indicated that biCEBPA mutant-positive CN-AML patients could be further classified into two risk subgroups by four factors and allo-HSCT should be recommended for high-risk patients as post-remission therapy. These data will help physicians refine treatment decision-making in biCEBPA mutant-positive CN-AML patients.
Evaluation of the Phytochemical, Antioxidant, Enzyme Inhibition, and Wound Healing Potential of Calotropis gigantea (L.) Dryand: A Source of a Bioactive Medicinal Product
Authors: Alafnan Ahmed , Sridharagatta Swathi , Saleem Hammad , Khurshid Umair , Alamri Abdulwahab , Ansari Shabana Yasmeen , Zainal Abidin Syafiq Asnawi , Ansari Siddique Akber , Alamri Abdulhakeem S. , Ahemad Nafees , Anwar Sirajudheen 
Published: August 2021

Traditionally, plants of the genus Calotropis have been used to cure various common diseases. The present research work explores the chemical and biological characterization of one of the most common species of this genus, i.e., Calotropis gigantea (L.) Dryand (syn. Calotropis gigantea (L.) Dryand.), having multiple folklore applications. The ethanolic extract of leaves of Calotropis gigantea (L.) Dryand was analyzed for the phytochemical composition by determining the total bioactive (total phenolic and total flavonoid) contents and UHPLC-MS secondary metabolites analysis. For phytopharmacological evaluation, in vitro antioxidant (including DPPH, ABTS, FRAP, CUPRAC, phosphomolybdenum, and metal chelation antioxidant assays) activities, enzyme inhibition potential (against AChE, BChE, α-amylase, and tyrosinase enzymes), and in vivo wound healing potential were determined. The tested extract has been shown to contain considerable flavonoid (46.75 mg RE/g extract) and phenolic (33.71 mg GAE/g extract) contents. The plant extract presented considerable antioxidant potential, being the most active for CUPRAC assays. Secondary metabolite UHPLC-MS characterization, in both the positive and negative ionization modes, indicated the tentative presence of 17 different phytocompounds, mostly derivatives of sesquiterpene, alkaloids, and flavonoids. Similarly, the tested extract exhibited considerable inhibitory effects on tyrosinase (81.72 mg KAE/g extract), whereas it showed weak inhibition ability against other tested enzymes. Moreover, in the case of in vivo wound healing assays, significant improvement in wound healing was observed in both the tested models at the doses of 0.5 percent w/w (p &lt; 0.001) and 2.0 percent w/w (p &lt; 0.01) on the 16th day. The outcomes of the present research work suggested that C. gigantea (L.) Dryand plant extract could be appraised as a potential origin of bioactive molecules having multifunctional medicinal uses.
Fatigue Is Associated With Diminished Cardiovascular Response to Anticipatory Stress in Patients With Coronary Artery Disease
Authors: Gecaite-Stonciene Julija , Hughes Brian M. , Burkauskas Julius , Bunevicius Adomas , Kazukauskiene Nijole , van Houtum Lisanne , Brozaitiene Julija , Neverauskas Julius , Mickuviene Narseta 
Published: August 2021

BackgroundFatigue and psychophysiological reactions to mental stress are known to be problematic in coronary artery disease (CAD) patients. Currently, studies exploring the relationship between fatigue and cardiovascular reactivity to stress are scarce and inconsistent. The current study aimed to investigate the links between cardiovascular response to mental stress and fatigue in CAD patients after acute coronary syndrome (ACS).MethodsThe cross-sectional study investigated 142 CAD patients (85% males, 52 ± 8 years) within 2–3 weeks after recent myocardial infarction or unstable angina pectoris. Fatigue symptoms were measured using Multidimensional Fatigue Inventory 20-items, while cardiovascular reactivity to stress [i.e., systolic (S) and diastolic (D) blood pressure (ΔBP), and heart rate (ΔHR)] was evaluated during Trier Social Stress Test (TSST). In addition, participants completed psychometric measures, including the Hospital Anxiety and Depression scale and the Type D Scale-14. Multivariable linear regression analyses were completed to evaluate associations between fatigue and cardiovascular response to TSST, while controlling for confounders.ResultsAfter controlling for baseline levels of cardiovascular measures, age, gender, education, heart failure severity, arterial hypertension, smoking history, use of nitrates, anxiety and depressive symptoms, Type D Personality, perceived task difficulty, and perceived task efforts, cardiovascular reactivity to anticipatory stress was inversely associated with both global fatigue (ΔHR: β = –0.238; p = 0.04) and mental fatigue (ΔSBP: β = –0.244; p = 0.04; ΔHR β = –0.303; p = 0.01) as well as total fatigue (ΔSBP: β = –0.331; p = 0.01; ΔHR: β = –0.324; p = 0.01).ConclusionIn CAD patients after ACS, fatigue was linked with diminished cardiovascular function during anticipation of a mental stress challenge, even after inclusion of possible confounders. Further similar studies exploring other psychophysiological stress responses are warranted.
Retrospective Observational Study of Daytime Add-On Administration of Zopiclone to Difficult-to-Treat Psychiatric Inpatients With Unpredictable Aggressive Behavior, With or Without EEG Dysrhythmia
Authors: Ceccherini-Nelli Alfonso , Bucuci Elena , Burback Lisa , Li Daniel , Alikouzehgaran Maryam , Latif Zahid , Morin Kevin , Ganapathy Karthikeyan , Salsali Manhaz , Abdullah Ubaid , Westwood Wanda , Orris Janice , White Patrick J. 
Published: August 2021

Managing violent behavior is a particularly challenging aspect of hospital psychiatric care. Available pharmacological interventions are often unsatisfactory.Aim: To assess the effectiveness and safety of daytime zopiclone add-on administration in violent and difficult-to-treat psychiatric inpatients.Methods: Chart review of inpatients treated with daytime zopiclone, between 2014 and 2018, with up to 12 weeks follow-up. Effectiveness was retrospectively assessed with the Clinical Global Impression rating scale (CGI) and the frequency and severity of aggressive incidents recorded with the Staff Observation Aggression Scale-Revised (SOAS-R).Results: Forty-five (30 male, 15 female) cases, 18–69 years age range, average (SD) baseline CGI-S score of 5.4 (1.0), and a variety of diagnoses. Sixty-nine percent showed CGI-S improvement of any degree. For patients with at least one aggressive incident within 7 days prior to initiation of zopiclone (N = 22), average (SD) SOAS-R-Severity LOCF to baseline change was −3.5 (2.7) P &lt; 0.0001. Most patients reported no side effects; 24% reported one or more side effects, and 11% discontinued zopiclone due to sedation (4), insomnia (1) or slurred speech (1). No SAEs were recorded. Zopiclone maximum daily dose correlated with CGI-S baseline-to-LOCF change (rho = −0.5, P = 0.0003). The ROC AUC of zopiclone maximum daily dose and improvement on CGI-S was 0.84 (95% CI 0.70–0.93, P &lt; 0.0001). The ROC AUC of zopiclone maximum daily dose and SOAS-R-N improvement was 0.80 (95% CI 0.58–0.92; P = 0.0008) and maximum Youden's index value was achieved at a dose of &gt;30 mg.Conclusions: Zopiclone doses &gt;30 mg daily achieved the best anti-aggressive effect.