bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mining of Subtype Markers for the Prognosis of Ovarian Cancer based on Methylation Data
Authors: Yin Lili , Zhang Ningning , Yang Qing 
Published: March 2020

Abstract
Background: Ovarian cancer is one of three major malignancies involving the female reproductive system, and its morbidity and mortality are ranked number 3 and number 1 among gynecological tumors, respectively. DNA methylation (MET), as one of the main epigenetic modes, is closely related to the occurrence and development of ovarian cancer. To guide individualized treatment and improve the prognosis in ovarian cancer patients, it is of great significance to elucidate effective MET subtype markers.Methods: A total of 571 ovarian cancer MET samples were downloaded from the Cancer Genome Atlas (TCGA), and a COX proportional hazards model was established using the MET spectrum and clinically pathological parameters. Subsequently, the consensus clustering of CpG loci with a significant difference in both univariate and multivariate analyses was performed to screen the molecular subtypes, and these CpG loci were subjected to gene function annotation. Finally, CpG MET loci associated with poor prognosis in ovarian cancer patients were further screened by constructing a weighted gene co-expression network analysis (WGCNA).Results: A total of 250 prognosis-related MET loci were obtained by COX regression and 6 molecular subtypes were screened by clustering. There was a remarkable MET difference between most subtypes, of which Cluster 2 had the highest MET level and demonstrated the best prognosis in patients, while Cluster 4 and Cluster 5 had a MET level significantly lower than that of the other subtypes and demonstrated a very poor prognosis. All Cluster 5 samples were at a high grade, while the percentage of Stage IV samples in Cluster 4 was evidently greater than that in the other subtypes. Using the co-expression network, 5 CpG loci were eventually obtained: cg27625732, cg00431050, cg22197830, cg03152385, and cg22809047. The clustering analysis shows that the prognosis in patients with hypomethylation was significantly worse than that in patients with hypermethylation. Conclusions: These MET molecular subtypes can be used not only to evaluate the prognosis in ovarian cancer patients but also to fully distinguish the tumor stage and histological grade in these patients. Prognosis-related CpG loci can be applied as biomarkers for individualized treatment in ovarian cancer patients.
Computed Tomography Evaluation Of Normal Canine Abdominal Lymph Nodes: Retrospective Study Of Size And Morphology According To Body Weight And Age In 45 Dogs
Authors: Teodori Simone , Aste Giovanni , Tamburro Roberto , Labate Antonio Morselli , Simeoni Francesco , Vignoli Massimo 
Published: March 2020

Abstract
BackgroundThe morphological characteristics of the largest lymphatic vessels and lymph nodes of the body have been described through ultrasonography, although food and gas in the gastrointestinal tract can often have negative effects on the response of small abdominal structures. The aim of the study was to describe the size of normal abdominal lymph nodes (ALs) in dogs affected by disease, not including lymphadenomegaly or lymphadenopathy, and divided according to body weight and age. The ALs studied included the jejunal, medial iliac, portal, gastric, splenic, and pancreaticoduodenal lymph nodes.ResultsMultiple statistical analyses among the three groups showed that all measurements of the ALs increased according to body weight changes (P <0.05). The most reliable values were the volume measurements (P <0.001) compared to the length, thickness and width. A single analysis between just two groups showed different values (P>0.1). Mixed results emerged from a comparison of weight categories and age; only the jejunal lymph nodes showed a possible correlation (P<0.1). Other characteristics (shape, attenuation and enhancement) are subsequently reported.Conclusions and Clinical RelevanceThe resulting data can be used to categorize CT measurements of normal ALs displayed based on the body weight and age of the subjects. This study was able to detect an objective parameter of normalcy that can serve as a reference for the evaluation of infectious or neoplastic events.
Investigation on Urinary and Serum Alpha Klotho in Dogs with Chronic Kidney Disease
Authors: Yi Hong jae , Lee Jong bok , Lee Kyu pil , Song Kun ho , Seo Kyoung won 
Published: March 2020

Abstract
Background: As a co-receptor for fibroblast growth factor 23, klotho plays a pivotal role in phos-phate metabolism. The kidney is known to be not only the main source of soluble alpha-klotho but also functions as the principal regulator maintaining its concentration. Previous studies in human par-ticipants showed that the concentration of soluble alpha-klotho in serum and urine decreased in chronic kidney disease (CKD) patients. However, no previous study has assessed soluble alpha-klotho levels in dogs. This study aimed to measure serum and urinary alpha-klotho levels in CKD dogs and identify their associations with International Renal Interest Society (IRIS) CKD stages and other parameters known to be associated with CKD.Methods: Serum and urinary alpha klotho concentrations were measured by a commercially avail-able canine-specific sandwich enzyme-linked immunosorbent assay kit and compared between groups by a nonparametric Kruskal–Wallis test. Spearman’s correlation coefficient was used to eval-uate the relationships between variables. A stepwise multiple regression analysis was performed to estimate the effects of independent predictors on klotho concentrations.Results: The urine klotho-to-creatinine ratio (UrKl/Cr) was significantly lower in stage 3 dogs than the control group and was significantly lower in dogs with stage 3 and 4 CKD than in those with stage 1 and 2 disease. UrKl/Cr was negatively correlated with serum symmetric dimethylarginine (sSDMA), blood urea nitrogen (BUN), creatinine, and phosphorus concentration. Serum alpha-klotho concentration in dogs with stages 2 and 3 CKD were significantly lower than those in the control group. There was no significant correlation between serum alpha-klotho and BUN, creatinine, and phosphorus concentrations. No statistically significant differences were observed in UrKl/Cr and se-rum alpha-klotho concentration between groups based on sex, age, urine protein-to-creatinine ratio (UPC), or blood pressure.Conclusions: UrKl/Cr decreased in dogs with advanced CKD, and it was negatively correlated with sSDMA, BUN, creatinine, and phosphorus concentrations. Thus, klotho may play a role in the path-ogenesis of CKD and its clinical consequences, including CKD-mineral bone disorder, in dogs. Alt-hough serum klotho concentration was negatively correlated with sSDMA levels, it was not appar-ently related to IRIS CKD stage or other parameters known to be associated with CKD.
Two-stage revision total knee arthroplasty with antibiotic-impregnated hydroxyapatite
Authors: Hasegawa Masahiro , Tone Shine , Naito Yohei , Wakabayashi Hiroki , Sudo Akihiro 
Published: March 2020

Abstract
Background: Antibiotic-impregnated hydroxyapatite (HA) has been used as a new drug delivery system for the treatment of periprosthetic joint infection (PJI) of the knee. The aim of this study was to evaluate the clinical results of this treatment in patients with PJI. Methods: Fourteen consecutive cases of PJI of the knee who were scheduled to undergo two-stage knee revision were enrolled. In the first stage, all components were removed with thorough debridement, and antibiotic-impregnated HA was inserted in the bone and joint space. In the second stage, revision total knee arthroplasty (TKA) was performed after eradication of infection. The mean period from removal of all components and treatment with antibiotic-impregnated HA to revision TKA was 3.4 months. Clinical and radiographic evaluations were performed after a mean follow-up of 5.1 years following revision TKA. Predictors of reinfection were evaluated. Results: Eleven patients had no recurrent infection, whereas 3 patients showed recurrent infection. No knees had osteolysis or loosening after revision TKA. The present study demonstrated no predictors for reinfection. Conclusion: Antibiotic-impregnated HA could be effective for the treatment of infected knee arthroplasty.
Added value of Contrast Enhanced Mammography (CEM) in staging of malignant breast lesions – a feasibility study
Authors: Åhsberg Kristina , Gardfjell Anna , Nimeus Emma , Rasmussen Rogvi , Behmer Catharina , Zackrisson Sophia , Ryden Lisa 
Published: March 2020

Abstract
Objectives: The aim of this feasibility study was to evaluate the added value of contrast enhanced mammography (CEM) in preoperative staging of malignant breast lesions, beyond standard assessment with digital mammography and ultrasound, as a base for a future prospective randomized trial. Materials and methods: Fifty patients, with confirmed or strongly suspected malignant breast lesions after standard assessment (digital mammography (DM) and ultrasound (US)), scheduled for primary surgery, were invited to undergo CEM as an additional preoperative procedure. The primary endpoint was change in treatment plan defined as mastectomy instead of partial mastectomy or contrariwise, bilateral surgery instead of unilateral or neoadjuvant treatment instead of primary surgery. Accuracy in tumour extent estimation compared to histopathology was evaluated by Bland Altman statistics. Number of extra biopsies and adverse events were recorded. Results: The study cohort consisted of 47 patients. In 10/47 (21%), findings from CEM affected the treatment plan. Agreement with histopathology regarding extent estimation was better for CEM (mean difference -1.36, SD +/- 18.45) in comparison with DM (-4.18, SD +/- 26.20) and US (-8.36, SD +/- 24.30). Additional biopsies were taken from 19 lesions in 13 patients. Nine biopsies showed malignant outcome. No major adverse events occurred.Conclusion: Feasibility of preoperative additional CEM was found to be excellent without any serious negative effects. Results imply an added value of CEM in preoperative staging of breast cancer. Further evaluation in larger prospective randomized trials is needed.
FDNC5/Irisin improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction
Authors: Deng Jingyu , Zhang Ning , Wang Yong , Yang Chao , Xin Chao , Zhao Jinming , Jin Zhitao , Cao Feng , Zhang Zheng 
Published: March 2020

Abstract
Background The beneficial functions of bone marrow mesenchymal stem cells (BM-MSCs) decline with decreased cells survival, limiting their therapeutic efficacy for myocardial infarction (MI). Irisin, a novel myokine which is cleaved from its precursor fibronectin type III domain-containing protein 5 (FNDC5), is believed involved in a cardioprotective effect but little was known on injured BM-MSCs and MI repair yet. Here, we investigated whether FNDC5 or irisin could improve the low viability of transplanted BM-MSCs and increase their therapeutic efficacy after MI. Methods BM-MSCs, isolated from dual-reporter firefly luciferase and enhanced green fluorescent protein positive (Fluc + –eGFP + ) transgenic mice, were exposed to normoxic condition and hypoxic stress for 12 h, 24 h, and 48 h, respectively. In addition, BM-MSCs were treated with irisin (20 nmol/L) and FNDC5 +/+ in serum deprivation (H/SD) injury. Furthermore, BM-MSCs were engrafted into infarcted hearts with or without FNDC5 +/+ . Results Hypoxic stress contributed to increased apoptosis, decreased cells viability and paracrine effects of BM-MSCs while irisin or FNDC5 +/+ alleviated these injuries. Longitudinal in vivo bioluminescence imaging illustrated that MSCs FNDC5+/+ treatment improved the survival of transplanted MSCs, which ameliorated the increased apoptosis and decreased angiogenesis of BM-MSCs in vivo . Furthermore, MSCs FNDC5+/+ therapy significantly reduced fibrosis and alleviated injured heart function. Conclusions The present study indicated that irisin or FNDC5 improved BM-MSCs engraftment and paracrine effects in infarcted hearts, which might provide a potential therapeutic target for MI.
Less Pathological Axillary Involvement is Observed in Breast Cancer Patients with Autoimmune Thyroid Disease
Authors: YALÇIN SELİM , Cosar Ramazan , Güngünes Askın , Cifci Aydın , Durmaz Senay Arikan 
Published: March 2020

Abstract
Background: Autoimmune thyroid disease is more frequently observed in breast cancer patients. There are not enough studies showing the prognostic significance of this association in terms of breast cancer. The aim of this study was to determine the breast cancer molecular subgroup frequency and to examine the relationship between autoimmune thyroid disease and the breast cancer in terms of prognosis and predictive factors. Methods: One hundred and one patients have been included to study. They have been divided into subgroups according to molecular classification. The patients with high serum anti-thyroid peroxidase levels were considered positive for autoimmune thyroid disease. Prognostic and predictive parameters [tumor stage, tumor size, axillary lymph node involvement, histologic grade, lymphovascular , perineural invasion, hormone receptor status, HER2 (Human Epidermal Growth Receptor 2) over expression] were compared between breast cancer patients with autoimmune thyroid disease and those patients without autoimmune thyroid disease. Results: The prevalence of thyroid autoimmunity was 23.8% (n = 24) in breast cancer patients. The axillary lymph node involvement in autoimmune thyroid disease positive breast cancer patients was lower than autoimmune thyroid disease negative patients (37.5% versus 61% respectively, p = 0.043). There were no significant differences between the two groups in terms of other prognostic parameters. More importantly, there was a significantly negative correlation between anti thyroid peroxidase levels and axillary lymph node involvement in patients (r= -0.245, p=0.014). Conclusion: Positive axillary lymph nodes, have been found to be lower in breast cancer patients accompanied by autoimmune thyroid disease. This result supports the view that thyroid autoimmunity is a positive prognostic factor in terms of breast cancer. The mechanism through which it is effective should be examined in new studies. Trial registration: A written approval was granted by the Kirikkale University, Faculty of Medicine, Clinical Research Ethics Committee through the 01/09 Numbered and 19.01.2016 Dated Decision in order to conduct this study. Keywords: Thyroid autoimmune, breast cancer, prognostic factors
EBV-positive intravascular large B-cell lymphoma of the liver: a case report and literature review
Authors: Li Qingjiao , Li Jinghe , Yang Keda , Peng Ying , Xiang Yao , Sun Shuyuan , Zeng Jian , Zhang Xin , Wang Junpu 
Published: March 2020

Abstract
Background Intravascular large B-cell lymphoma (IVLBCL) is an extremely rare subtype of diffuse large B-cell lymphoma that most commonly involves the central nervous system, skin, and bone marrow. To our knowledge, Epstein-Barr virus (EBV)-positive IVLBCL in the liver has never been reported in the literature. Case presentation We report a case of a 65-year-old Chinese man with complaint of fever for 18 days. No obvious abnormality was found by physical examination. Laboratory findings were notable for anemia, thrombocytopenia, and elevated level of serum lactate dehydrogenase. Imaging studies showed a slightly lower density lesion in the liver with high fluorodeoxyglucose uptake. Percutaneous liver biopsy revealed clustering of large atypical lymphocytes within the hepatic sinusoids. Immunohistochemically, these lymphoma cells were positive for CD20, PAX-5, MUM-1, BCL-6 and CD5, but negative for CD3 and CD10. Besides, Epstein-Barr virus-encoded RNA was detected in tumor cells by in situ hybridization. BCL-2 , BCL-6 and MYC genes were intact tested by fluorescence in situ hybridization analysis. The patient was diagnosed as IVLBCL and died after 1 month of hospitalization without receiving immunochemotherapy. Conclusions IVLBCL of the liver is a highly rare lymphoma with nonspecific manifestations and dismal prognosis. Full recognition of its clinicopathological features will help to better diagnose this disease.
Why does Mycophenolate use only for kidney complications in Schonlein Henoch Syndrome? Case report
Authors: Gicchino Maria Francesca , Iafusco Dario , Marrapodi Maria Maddalena , Melone Rosa , Cuomo Giovanna , Zanfardino Angela , Giudice Emanuele Miraglia del , Olivieri Alma Nunzia 
Published: March 2020

Abstract
Background : Henoch Schonlein purpura (HSP) is an acute small vessel vasculitis. It is the most common vasculitis in children. Although the cause is unknown, IgA seems to play a central role in the pathogenesis of Henoch Schonlein purpura. The major clinical features include a palpable purpuric rash on the lower extremities, abdominal pain or renal involvement, and arthritis. Cutaneous manifestations are the essential elements in the diagnosis of Henoch Schonlein purpura. The palpable purpura is characteristically 2 to 10mm in diameter and is usually present on the lower extremities. There are no specific diagnostic tests available for diagnosing this condition. Laboratory studies are useful to exclude other conditions that may mimic Henoch Schonlein purpura. In majority of the cases, the disease is self-limited. Relapsing can occur, in particular during the first year of the disease. There is no consensus on a specific treatment. Corticosteroids are effective in rapid resolution of renal and abdominal manifestations. Immunosuppressive drugs, such as Mycophenolate Mofetil may be a better treatment choice in case of renal involvement.Case report : We report a case of a 14 years old girl affected from recurrent Henoch Schonlein Purpura. From the age of nine years patient presented three episodes of purpura with gastrointestinal involvement, in particular hematemesis, abdominal pain and diarrhoea. Each episode was treated with high doses of corticosteroids (methylprednisolone in vein or prednisone per os). Patient came to our Department during the third episode of Purpura. In consideration of the recurrence of the Henoch Schonlein Purpura and the gastrointestinal involvement we decided to start Mycophenolate Mofetil treatment. Patient’s conditions improved thanks to Mycophenolate Mofetil treatment. Conclusion: In our case of recurrent HSP Mycophenolate Mofetil treatment has been very effective, avoiding the adverse events of a prolonged steroid treatment. This experience teaches us that immunosuppressive agents may be very useful to induce and maintain remission not only in renal involvement, but in all cases of persistence, recurrence or complicated forms of Henoch Schonlein purpura in children.
Statistical Joint Modeling of Longitudinal CD4 Cell variation and Time-to-Lost Follow-up from ART Predictors on HIV/AIDS Patients: A case of Mekelle General Hospital
Authors: Gebrerufael Gebru Gebremeskel 
Published: March 2020

Abstract
Back ground: Time-to-lost follow-up and CD4 cell variation measures are the outcome variables of infection in HIV/AIDS patients after starting ART in this study. The time-to-lost follow-up from ART was determined by month time interval among dates of ART commencement to drop-out, as documented by the health information data administrator. The main goal of this study was to identify association of CD4 cell variation measurements on time-to-lost follow-up and main predictors of HIV/AIDS positive patients.Methods: Institution based retrospective cohort study design was used among 216 HIV/AIDS patients under ART follow-up from period September 11, 2013 to September 5, 2016 at Mekelle General Hospital, Ethiopia and employed both survival and longitudinal outcome to fit separate and statistical joint modeling approach.Results: A total of 216 HIV/AIDS patients were selected using systematic random sampling technique to analyze the longitudinal and survival outcome using joint model study. The result of this study showed that relationship between CD4 cell variation on hazard of time-to-lost follow-up was negatively statistical significant. Thus, time-to-lost follow-up from ART is less probable to occur in HIV/AIDS patients which have higher CD4 cell evolution. In survival sub-model Baseline CD4, sex of male, living in rural and comorbidity HIV/TB were significant factors of risk to time-to-lost follow-up from ART of HIV/AIDS patients. The longitudinal sub-model shows Baseline CD4 cell and being bedridden were significant factors of variation at 5% significance levels.Conclusions: The author assessed relationship of repeated measured CD4 cell variation on hazard of time-to-lost follow-up was negatively statistical significant and performance of both separate and statistical joint sub-models in terms model parsimony, smaller AIC & smaller standard error in statistical joint model performs. Thus, the author concluded that statistical joint model was preferred for simultaneous analyses of repeated biomarker CD4 cell and survival time-to-lost follow-up data.
Exosome derived from mesenchymal stem cells enhance autophagy and inhibit iNOS/TXNIP/NLRP3 inflammasome axis in injured spinal cord
Authors: Lv Bin , Wang Lei , Huang Anquan , Zou Tianming , Yuan Jishan 
Published: March 2020

Abstract
Background: Neuroinflammation, autophagy, NLRP3 inflammasome, and microglia polarizationhave been implicated in spinal cord injury (SCI).Moreover, exosomes, a classic nanovesicles secreted by MSCs, may have a neuroprotective effect on transformation of microglia from the M1 state to the M2 phenotype. However, the effect of MSCs derived exosomes on neuroinflammation is still unclear. Here, we investigated the mechanisms of MSCs derived exosomes mediated NLRP3 inflammasome signaling cascades and its protective effects in SCI. Methods:The SCI model was performed by weight-drop impact in adult male Sprague-Dawley (SD) rats. Control andexosome rats were randomly subjecttoexosomeadminister (20 mg/kg) or placebo via intraperitoneal route 1 h after SCI.Autophagy inhibitor(3-MA) was administered intraperitoneally 20 min before experiment.Neurological function was measured by Basso-Beattie-Bresnahan (BBB) scoring and an open-field test.Neuronal death was measured by HE stainingandNisslstaining.Inducible nitric oxide synthase (iNOS) levels were determined using fluorescent probes. The autophagy and TXNIP and its downstream signaling pathways-mediated polarization of macrophages/microglia was assessed by immunohistochemistry. Results:Exosome significantly downregulated intracellular iNOS and inhibited TXNIP, pyrin domain-containing 3 (NLRP3) inflammasome pathway activation by activating autophagy. Additionally, Exosomepromoted expression of autophagy markers, such as LC3A/B and beclin1,and abrogated the expression of p62. Autophagy inhibitor, 3-MA, blockage of autophagy flux abolished the inhibition of apoptosis and iNOS/TXNIP/NLRP3 inflammasome axisafterSCI. Here, we demonstrated that exosomeadministration in spinal cord markedly reduced tissue loss, attenuate pathological morphology of the injuredregion, and promoted tissue recovery. Moreover. our resultshowed that exosome administration alleviated neuronal cells apoptosis, and inhibited nitric oxide release in microglia.The activation of inflammatoryresponse in neuronal cells facilitates interactions of iNOS‐NLRP3 andTXNIP‐NLRP3and inhibited NLRP3 inflammasome where neuronal cells apoptosis was induced.Further, we found that exosome could suppress macrophages/microglia polarized to M1 phenotype in vivo and in vitro.Taken together, exosome administration exerts protective effects in neuronal cells through inhibiting iNOS production, and exosome administration could inhibit iNOS/TXNIP/NLRP3 inflammasome axis via enhancing autophagy and both in vitro and in vivo. Conclusions:These resultsreveal that exosometreatment alleviatedneuroinflammation and mitigates neuronal apoptosis via autophagy-mediate inhibition of the iNOS/TXNIP/NLRP3 inflammasome axis. Our findings suggest that exosome may be a novel therapeutic target for treating SCI.