bluuebunny/crossref_metadata_2025_split huggingface dataset:
HIST1H1B Promotes Basal-Like Breast Cancer Progression by Modulating CSF2 Expression
Authors: Liao Ruocen , Chen Xingyu , Cao Qianhua , Wang Yifan , Miao Zhaorui , Lei Xingyu , Jiang Qianjin , Chen Jie , Wu Xuebiao , Li Xiaoli , Li Jun , Dong Chenfang 
Published: October 2021

BackgroundBasal-like breast cancer (BLBC) is associated with a poor clinical outcome; however, the mechanism of BLBC aggressiveness is still unclear. It has been shown that a linker histone functions as either a positive or negative regulator of gene expression in tumors. Here, we aimed to investigate the possible involvement and mechanism of HIST1H1B in BLBC progression.Experimental designWe analyzed multiple gene expression datasets to determine the relevance of HIST1H1B expression with BLBC. We employed quantitative real-time PCR, transwell assay, colony formation assay, and mammosphere assay to dissect the molecular events associated with the expression of HIST1H1B in human breast cancer. We studied the association of HIST1H1B with CSF2 by ChIP assay. Using tumorigenesis assays, we determine the effect of HIST1H1B expression on tumorigenicity of BLBC cells.ResultsHere, we show that the linker histone HIST1H1B is dramatically elevated in BLBC due to HIST1H1B copy number amplification and promoter hypomethylation. HIST1H1B upregulates colony-stimulating factor 2 (CSF2) expression by binding the CSF2 promoter. HIST1H1B expression promotes, whereas knockdown of HIST1H1B expression suppresses tumorigenicity. In breast cancer patients, HIST1H1B expression is positively correlated with large tumor size, high grade, metastasis and poor survival.ConclusionHIST1H1B contributes to basal-like breast cancer progression by modulating CSF2 expression, indicating a potential prognostic marker and therapeutic target for this disease.
Tetrathiomolybdate Treatment Attenuates Bleomycin-Induced Angiogenesis and Lung Pathology in a Sheep Model of Pulmonary Fibrosis
Authors: Derseh Habtamu B. , Perera Kopiyawaththage U. E. , Dewage Sasika N. Vithana , Stent Andrew , Koumoundouros Emmanuel , Organ Louise , Pagel Charles N. , Snibson Ken J. 
Published: October 2021

Idiopathic pulmonary fibrosis (IPF) is a progressive chronic lung disease characterized by excessive extracellular matrix (ECM) deposition in the parenchyma of the lung. Accompanying the fibrotic remodeling, dysregulated angiogenesis has been observed and implicated in the development and progression of pulmonary fibrosis. Copper is known to be required for key processes involved in fibrosis and angiogenesis. We therefore hypothesized that lowering bioavailable serum copper with tetrathiomolybdate could be of therapeutic value for treating pulmonary fibrosis. This study aimed to investigate the effect of tetrathiomolybdate on angiogenesis and fibrosis induced in sheep lung segments infused with bleomycin. Twenty sheep received two fortnightly infusions of either bleomycin (3U), or saline (control) into two spatially separate lung segments. A week after the final bleomycin/saline infusions, sheep were randomly assigned into two groups (n= 10 per group) and received twice-weekly intravenous administrations of either 50 mg tetrathiomolybdate, or sterile saline (vehicle control), for 6 weeks. Vascular density, expressed as the percentage of capillary area to the total area of parenchyma, was determined in lung tissue sections immuno-stained with antibodies against CD34 and collagen type IV. The degree of fibrosis was assessed by histopathology scoring of H&amp;E stained sections and collagen content using Masson’s trichrome staining. Lung compliance was measured via a wedged bronchoscope procedure prior to and 7 weeks following final bleomycin infusion. In this large animal model, we show that copper lowering by tetrathiomolybdate chelation attenuates both bleomycin-induced angiogenesis and pulmonary fibrosis. Moreover, tetrathiomolybdate treatment downregulates vascular endothelial growth factor (VEGF) expression, and improved lung function in bleomycin-induced pulmonary fibrosis. Tetrathiomolybdate also suppressed the accumulation of inflammatory cells in bronchoalveolar lavage fluid 2 weeks after bleomycin injury. The molecular mechanism(s) underpinning copper modulation of fibrotic pathways is an important area for future investigation, and it represents a potential therapeutic target for pulmonary fibrosis.
C1q/TNF-Related Protein 9 Attenuates Atherosclerosis by Inhibiting Hyperglycemia-Induced Endothelial Cell Senescence Through the AMPKα/KLF4 Signaling Pathway
Authors: Wang Gang , Han Baihe , Zhang Ruoxi , Liu Qi , Wang Xuedong , Huang Xingtao , Liu Dandan , Qiao Weishen , Yang Mengyue , Luo Xing , Hou Jingbo , Yu Bo 
Published: October 2021

Hyperglycemia-induced endothelial cell senescence has been widely reported to be involved in the pathogenesis of type 2 diabetes mellitus‒accelerated atherosclerosis. Thus, understanding the underlying mechanisms and identifying potential therapeutic targets for endothelial cell senescence are valuable for attenuating atherosclerosis progression. C1q/tumor necrosis factor-related protein 9 (CTRP9), an emerging potential cardiokine, exerts a significant protective effect with respect to atherosclerosis, particularly in endothelial cells. However, the exact mechanism by which CTRP9 prevents endothelial cells from hyperglycemia-induced senescence remains unclear. This study aimed to investigate the effects of CTRP9 on hyperglycemia-induced endothelial cell senescence and atherosclerotic plaque formation in diabetic apolipoprotein E knockout (ApoE KO) mice. Human umbilical vein endothelial cells (HUVECs) were cultured in normal glucose (5.5 mM) and high glucose (40 mM) with or without recombinant human CTRP9 protein (3 μg/ml) for 48 h. Purified lentiviruses overexpressing CTRP9 (Lv-CTRP9) and control vectors containing green fluorescent protein (Lv-GFP) were injected via the tail vein into streptozotocin-induced diabetic ApoE KO mice. Results revealed that exposure of HUVECs to HG significantly increased the expression of Krüppel-like factor 4 (KLF4) and cyclin-dependent kinase inhibitor p21 (p21) and decreased that of telomerase reverse transcriptase (TERT). Treatment with recombinant human CTRP9 protein protected HUVECs from HG-induced premature senescence and dysfunction. CTRP9 promoted the phosphorylation of AMP-activated kinase (AMPK), attenuated the expression of KLF4 and p21 induced by HG, and increased the expression of TERT in HUVECs. Furthermore, in the background of AMPKα knockdown or KLF4 activation, the protective effects of CTRP9 were abolished. In-vivo experiments showed that the overexpression of CTRP9 inhibited vascular senescence and reduced atherosclerotic plaque formation in ApoE KO mice with diabetes. In conclusion, we demonstrate that KLF4 upregulation plays a crucial role in HG-induced endothelial senescence. This anti-atherosclerotic effect of CTRP9 may be partly attributed to the inhibition of HG-induced endothelial senescence through an AMPKα/KLF4-dependent mechanism, suggesting that CTRP9 could benefit further therapeutic approaches for type 2 diabetes mellitus‒accelerated atherosclerosis.
Ex vivo Validation of Noninvasive Epicardial and Endocardial Repolarization Mapping
Authors: van der Waal Jeanne G. , Meijborg Veronique M. F. , Belterman Charly N. W. , Streekstra Geert J. , Oostendorp Thom F. , Coronel Ruben 
Published: October 2021

Background: The detection and localization of electrophysiological substrates currently involve invasive cardiac mapping. Electrocardiographic imaging (ECGI) using the equivalent dipole layer (EDL) method allows the noninvasive estimation of endocardial and epicardial activation and repolarization times (AT and RT), but the RT validation is limited to in silico studies. We aimed to assess the temporal and spatial accuracy of the EDL method in reconstructing the RTs from the surface ECG under physiological circumstances and situations with artificially induced increased repolarization heterogeneity.Methods: In four Langendorff-perfused pig hearts, we simultaneously recorded unipolar electrograms from plunge needles and pseudo-ECGs from a volume-conducting container equipped with 61 electrodes. The RTs were computed from the ECGs during atrial and ventricular pacing and compared with those measured from the local unipolar electrograms. Regional RT prolongation (cooling) or shortening (pinacidil) was achieved by selective perfusion of the left anterior descending artery (LAD) region.Results: The differences between the computed and measured RTs were 19.0 ± 17.8 and 18.6 ± 13.7 ms for atrial and ventricular paced beats, respectively. The region of artificially delayed or shortened repolarization was correctly identified, with minimum/maximum RT roughly in the center of the region in three hearts. In one heart, the reconstructed region was shifted by ~2.5 cm. The total absolute difference between the measured and calculated RTs for all analyzed patterns in selectively perfused hearts (n = 5) was 39.6 ± 27.1 ms.Conclusion: The noninvasive ECG repolarization imaging using the EDL method of atrial and ventricular paced beats allows adequate quantitative reconstruction of regions of altered repolarization.
Childhood Maltreatment Predicts Specific Types of Dysfunctional Attitudes in Participants With and Without Depression
Authors: Jugessur Raj , Zhang Yan , Qin Xuemei , Wang Mi , Lu Xiaowen , Sun Jinrong , Dong Qiangli , Zhang Liang , Liu Jin , Ju Yumeng , Liao Mei , Wan Ping , Guo Hua , Zhao Futao , Liu Bangshan , Li Lingjiang 
Published: October 2021

Background: Studies have shown a strong association between childhood maltreatment (CM) and major depressive disorder (MDD). Dysfunctional attitudes (DAs) play a crucial role in the development of MDD. In this study, we aimed to investigate whether (1) DAs are associated with CM, (2) specific CM types predict specific types of DAs, and (3) higher childhood trauma counts (CTCs) predict more DAs.Methods: One hundred seventy-one MDD participants and 156 healthy controls (HCs) were enrolled for the study. CM was assessed retrospectively with the Childhood Trauma Questionnaire. DAs were evaluated using the Chinese version of the Dysfunctional Attitude Scale–Form A (C-DAS-A). A series of analyses, including multiple analyses of covariance and hierarchical regression analyses, were used in this study to examine the hypotheses.Results: The proportion of CM was 60.2% in the MDD group and 44.2% in the HC group. The 2 × 2 analysis of covariance results showed no interaction effect between CM and MDD on C-DAS-A total score. When the factor scores replaced the C-DAS-A total score, a similar trend was observed. Within the MDD group, emotional abuse (EA) predicted two forms of DAs: self-determination type and overall DAs; physical neglect (PN) was predictive of attraction and repulsion-type DAs. Higher childhood trauma counts significantly predicted more types of DAs in the MDD group.Conclusion: DAs are a trait feature of CM. EA and PN predict specific types of DAs in MDD patients. Higher CTCs predict more DAs in MDD patients.
Relating Global Cognition With Upper-Extremity Motor Skill Retention in Individuals With Mild-to-Moderate Parkinson's Disease
Authors: Lingo VanGilder Jennapher , Lopez-Lennon Cielita , Paul Serene S. , Dibble Leland E. , Duff Kevin , Schaefer Sydney Y. 
Published: October 2021

Background and Purpose:Cognition has been linked to rehabilitation outcomes in stroke populations, but this remains unexplored in individuals with Parkinson's disease (PD). The purpose of this secondary data analysis from a recent clinical trial (NCT02600858) was to determine if global cognition was related to skill performance after motor training in individuals with PD.Methods:Twenty-three participants with idiopathic PD completed 3 days of training on an upper-extremity task. For the purposes of the original clinical trial, participants trained either “on” or “off” their dopamine replacement medication. Baseline, training, and 48-h retention data have been previously published. Global cognition was evaluated using the Montreal Cognitive Assessment (MoCA). Linear regression examined whether MoCA score predicted longer-term retention at nine-day follow-up; baseline motor task performance, age, PD severity, depressive symptoms, and group (medication “on”/“off”) were included as covariates. Baseline and follow-up motor task performance were assessed for all participants while “on” their medication.Results:MoCA score was positively related to follow-up motor task performance, such that individuals with better cognition were faster than those with poorer cognition. Baseline task performance, age, PD severity, depressive symptoms, and medication status were unrelated to follow-up performance.Discussion and Conclusions:Results of this secondary analysis align with previous work that suggest cognitive impairment may interfere with motor learning in PD and support the premise that cognitive training prior to or concurrent with motor training may enhance rehabilitative outcomes for individuals with PD. Findings also suggest that assessing cognition in individuals with PD could provide prognostic information about their responsiveness to motor rehabilitation.
Management of Severe Traumatic Brain Injury: A Single Institution Experience in a Middle-Income Country
Authors: Basha Ahmed Kamel , Mahmoud Mohamed Ashraf , Al Ashwal Mohamed Ismail , Aglan Osama , ElShawady Sherif Bahaa , Abdel-Latif Assem Mounir , Elsayed Ahmed M. , AbdelGhany Walid 
Published: October 2021

Introduction: Severe traumatic brain injury (TBI) is a major public health problem usually resulting in mortality or severe disabling morbidities of the victims. Intracranial pressure (ICP) monitoring is recently recognized as an imperative modality in the management of severe TBI, whereas growing evidence, based on randomized controlled trials (RCTs), suggests that ICP monitoring does not affect the outcome when compared with clinical and radiological data-based management. Also, ICP monitoring carries a considerable risk of intracranial infection that cannot be overlooked. The aim of this study is to assess the different aspects of our current local institutional management of severe TBI using non-invasive ICP monitoring for a potential need to change our management strategy.Methods: We retrospectively reviewed our data of TBI from June 2019 through January 2020. Patients with severe TBI were identified. Their demographics, Glasgow coma score (GCS) at presentation, treatments received, and imaging data were extracted from the charts. Glasgow outcome scale extended (GOS-E) at 6 months was also assessed for the patients.Results: Twenty patients with severe TBI were identified on chart review. Ten patients received only medical treatment measures to lower the ICP, whereas the other 10 patients had additional surgical interventions. In one patient, a ventriculostomy tube was inserted to monitor ICP and to drain cerebrospinal fluid (CSF). This was complicated by ventriculostomy-associated infection (VAI) and the tube was removed. In our cohort, the total mortality rate was 40%. The average GOS-E for the survivor patients managed without ICP monitoring based on the clinical and radiological data was 6.2 at 6 months follow-up. The 6-month overall good outcome, based on GOS-E, was 33.3%.Conclusion: Although recent guidelines advocate for the use of ICP monitoring in the management of severe TBI, they remain underutilized in our practice due to many factors. External ventricular drains were mainly used to drain CSF; however, the higher rates of VAIs in our institution compared with the literature-reported rates are not in favor of the use of ICP monitoring. We recommend doing a comparative study between our current practice using clinical-and radiological-based management and subdural or intraparenchymal bolts. More structured RCTs are needed to validate these findings in our setting.
Postoperative Systemic Immune-Inflammation Index (SII): A Superior Prognostic Factor of Endometrial Cancer
Authors: Huang Yihong , Chen Yu , Zhu Yan , Wu Qing , Yao Chengyun , Xia Hongping , Li Congzhu 
Published: October 2021

Objective: This study evaluates the preoperative and postoperative systemic immune-inflammation index (SII) capacity to predict the prognosis of patients with endometrial carcinoma after the operation and build a nomogram model to assist clinical practice.Methods: The retrospective study included 362 consecutive patients with surgically resected endometrial cancer between January 2010 and June 2015 at The Affiliated Cancer Hospital of Shantou University Medical College. Blood routine was examined within 1 week before surgery to calculate SII, NLR, PLR, and MLR and 3 days after surgery to measure SII. The Pearson's χ2-test or Fisher's exact test was used to explore their relationship to clinical variables. The univariate and multivariate survival analyses were performed by Cox regression to identify the independent prognostic indicators. The Kaplan–Meier method with the log-rank test was used to generate the overall survival (OS) curves. R software was used to generate the receiver operating characteristic (ROC) curve and then it got the optimum cutoff value through the maximum Youden index. A nomogram model was formed with systemic immune inflammation and clinical factors.Results: The preoperative SII was related to age (p = 0.009), FIGO stage (p = 0.02) and menopause (p = 0.014). The postoperative SII was associated with menopause (p = 0.014). Univariate analysis indicated that FIGO stage, lymphatic invasion, depth of myometrial invasion, postoperative chemotherapy, postoperative radiotherapy, preoperative SII, NLR, PLR, MLR, CRP, CA125, and postoperative SII were predictors of OS (p &lt; 0.05). Multivariate analysis showed that lymphatic invasion and postoperative SII were independent prognostic factors of OS (p &lt; 0.05). The nomogram model was visualized precisely to reflect the prognosis with a C-index value of 0.866 in this model.Conclusion: The postoperative SII is the independent prognostic factor in patients with endometrial carcinoma after the operation and contributes to poor outcomes. However, after surgery, the preoperative SII and preoperative NLR, PLR, and MLR are not associated with OS endometrial carcinoma. Making good use of the nomogram model would contribute to better subsequent therapy.
Case Report: Cutaneous Pleomorphic Lymphangiosarcoma in a Dog Exhibiting Features of Human Composite Hemangioendothelioma
Authors: Cook Matthew R. , Lorbach Joshua N. , White Mary E. , Zann Geoffrey J. , Cianciolo Rachel E. , Selmic Laura E. , Wavreille Vincent , Kisseberth William C. 
Published: October 2021

Background: Angiosarcomas are a broad category of vascular origin neoplasms that are poorly characterized in veterinary species. Lymphangiosarcoma (LAS) is an uncommon type of angiosarcoma reported in humans and canines arising from lymphatic endothelium. LAS can be differentiated from other angiosarcomas in dogs based on expression of Prospero-related homeobox gene-1 (PROX-1) or lymphatic vessel endothelial receptor-1 (LYVE-1). Composite hemangioendothelioma (CHE) is a rare angiosarcoma subtype described in people and characterized by a variable biologic behavior and infrequent metastasis. This variant of angiosarcoma histologically combines features of retiform hemangioendothelioma and epithelioid hemangioendothelioma. Information regarding the cytologic and histopathologic appearance and clinical course of dogs with vascular tumors that exhibit features of CHE are unknown. Here, we report a case of pleomorphic LAS with features of CHE arising in a dog and treated with surgery and adjuvant chemotherapy.Case presentation: A 10-year-old intact male Labrador retriever presented with an approximately 6-cm-diameter cutaneous mass caudal to the left elbow that was progressively growing over 1.5 years. On physical examination, palpable extensions were identified coursing proximally over the triceps with concurrent loco-regional peripheral lymphadenopathy. Fine needle aspirates (FNA) and cytologic assessment of the cutaneous mass, left prescapular, and accessory axillary lymph nodes reported that this appeared to be a metastatic epithelial neoplasm, although a mixed carcinoma or collision tumor could not be excluded. An incisional biopsy of the mass was submitted for histopathology and was consistent with a well-differentiated angiosarcoma with features of CHE. The neoplasm expressed vimentin, CD31, von Willebrand factor (vWf), and PROX-1, supporting the diagnosis of LAS. Complete staging was performed, and no additional metastatic lesions were identified. Left forelimb amputation and lymph node removal were performed. Based on the diagnosis of metastatic LAS, doxorubicin chemotherapy was administered. 7 months post-amputation, the tumor recurred at the amputation site without evidence of metastatic disease.Conclusion: This report describes a malignant, locally aggressive lymphatic origin vascular tumor in a dog, with features consistent with descriptions of CHE in humans. Cytologic features in this case were discordant with its true mesenchymal etiology, obfuscating diagnosis. The morphologic features of the mesenchymal neoplastic population and immunohistochemistry (IHC) labeling ultimately supported a diagnosis of pleomorphic LAS with features of CHE.
Challenges to Generating Reliable COVID Statistics: Domestic and International Experience
Authors: Chetverikov V. M. , Pugacheva O. V. , Vorontsova T. D. 
Published: October 2021

The article discusses specifc issues of the reliability of statistics on the spread of the coronavirus pandemic and the comparability of similar statistics across diﬀerent countries. All countries faced challenges, regardless of the level of well-being and social system. However, the examples outlined in the article refer mainly to large economies, each of which for at least one year from 1980 to 2019 produced more than 1% of the global GDP. The organization of the health care system in these countries is diﬀerent, and only the general requirements of WHO could provide information on the spread of the pandemic in comparable formats.The authors formulated the problems of identifying those infected with Covid-19 and mortality statistics, indicating the various impact of the pandemic on deaths. It has been shown that the formal application of the WHO recommendations to the identifcation of infected persons and diﬀerences in the practical use of these recommendations in diﬀerent countries can give poorly comparable results. The example of Russian statistics illustrates that it is possible to compare the operational data on the mortality of those infected with the coronavirus with the data on the total mortality in the country. Attention is drawn to the example of statistics from Germany, demonstrating the possibility of practical overlapping of the excess mortality rate and the operational data on the mortality of those infected with Covid-19.Data on daily increments of infected, dead, and recovered per million people allows one to see the nature and prevalence rate of the pandemic in diﬀerent countries in a comparable format. The largest single-day increase in coronavirus cases in some countries in 2020–2021 reached 2–3 thousand per 1 million population, while in others – it was less than 30. In most countries under review, daily deaths' peaks amounted to less than 40 cases, but there were other countries for which these peaks did not exceed 10 cases or less per 1 million population.In conclusion, the report identifes six all-cause mortality factors associated with the pandemic and social distancing demands formulated by the American Institute for Health Metrics and Evaluation. According to the authors, it would be interesting to learn the experts' assessment of how realistic and benefcial it is to know how to keep track of these factors. It would improve the quality of international comparative analysis of socio-demographic indicators.