bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Clinical, Histological and Molecular Features of Primary Operable Breast Cancer in Patients from Kosovar and Croatian University Hospitals
Authors: Sermaxhaj Faton , Plavetić Natalija Dedić , Kulić Ana , Gozalan Ugur , Varga Ljubica Radmilović , Popović Marina , Sović Slavica , Mijatović Davor , Kurshumliu Fisnik , Bahtiri Elton , Sermaxhaj Besim 
Published: February 2021

Abstract
Background

The aim of this study was to explore the clinical, patohistological and molecular characteristics of primary operable breast cancer in patients from Croatia and Kosovo, in order to compare disease stage at the time of diagnosis, in country with implemented mammography screening and early diagnostic methods with country without it.
Methods

The study prospectively included 213 female patients with breast cancer (BC) ranging from 28 to 87 years of age, from which 100 from Kosovo and 113 from Croatia. Age and menopausal status of the patients were recorded before surgery. Subsequent to surgery, histopathology and immunohistochemistry analysis was carried out and data were statistically analysed. Categorical variables were compared using chi-square analysis and presented as frequencies and percentages. For non-parametric data, Mann-Whitney U test was used in order to compare means of two independent groups. A value of P < 0.05 was considered statistically significant.
Results

There were larger tumors, more patients with metastatic axillary lymph nodes and more stage III patients in Kosovo cohort. In addition, the rate of lympho-vascular invasion (LVI) and the expression of progesteron receptor (PR) were significantly higher in Kosovar patients. The other histological and immunohistochemical features were not found to be any different in the two cohorts.
Conclusions

The results of this study from two university hospitals from Croatia and Kosovo demonstrate that the BC patients in Kosovo have more advanced stage of disease at the time of diagnosis compared to Croatia.
Dysfunction of EAAT3 Enhances LPS-induced Postoperative Cognitive Dysfunction
Authors: Wang Xiaoyan , Ma Yulong , Hou Aisheng , Song Yuxiang , Sui Xin , Liu Wengang , Liu Min , Wang Yongan , Cao Jiangbei , Mi Weidong 
Published: February 2021

Abstract
Background: Studies have shown that excitatory amino acid transporter 3 (EAAT3) function inhibition is related to several neurodegenerative diseases. Our previous studies also found that the EAAT3 function is intimately linked to learning and memory. In this study, we examined the role of EAAT3 in postoperative cognitive dysfunction (POCD) and explored the potential benefit of riluzole against POCD. Methods: We measured EAAT3 protein expression in hippocampus of male mice at different ages. Next, we established a recombinant adeno-associated viral (rAAV)-mediated shRNA to knockdown EAAT3 expression in the hippocampus of adult male mice. And then the mice received 2μg of lipopolysaccharide (LPS) intracerebroventricular microinjection to construct the POCD model. In addition, we intraperitoneally injected 4mg/kg of riluzole 2 days before LPS microinjection for consecutive 3 days in elderly male mice. Cognitive function was assessed using a Morris water maze 24h after LPS microinjection. Animal behavioral tests, as well as pathological and biochemical assays, were performed to clarify the role of EAAT3 function in POCD and evaluate the effect of activation of EAAT3 function by riluzole. Results: We found that the expression of EAAT3 was significantly decreased in old mice and EAAT3 knockdown in hippocampus aggravated LPS-induced learning and memory deficits in adult male mice. LPS significantly inhibited hippocampal EAAT3 membrane protein expression and GluA1 protein phosphorylation level in adult male mice. Moreover, riluzole pretreatment significantly increased hippocampal EAAT3 membrane protein expression and ameliorated LPS-induced cognitive impairment in old male mice. Conclusions: Our results demonstrated that the dysfunction of EAAT3 is an important risk factor for POCD susceptibility and riluzole may be a promising strategy for prevention and treating of POCD in the elderly people.
HPMSCs Inhibit the Expression of PD-1 in CD4+IL-10+ T Cells and Mitigate liver Damage in a GVHD Mouse Model by Regulating the Cross-talk Between Nrf2 and NF-κB Signaling Pathway
Authors: Zhang Aiping , Zhang Jiashen , Li Xiaohua , Zhang Hengchao , Xiong Yanlian , Wang Zhuoya , Zhao Nannan , Wang Feifei , Luan Xiying 
Published: February 2021

Abstract
Background: The activation of T cells and imbalanced redox metabolism enhances the development of graft-versus-host disease (GVHD). Human placenta-derived mesenchymal stromal cells (hPMSCs) can improve GVHD through regulating T cell responses. However, whether hPMSCs balance the redox metabolism of CD4+IL-10+ T cells and liver tissue and alleviate GVHD remains unclear. This study aimed to investigate the effect of hPMSC-mediated treatment of GVHD associated with CD4+IL-10+ T cell generation via control of redox metabolism and PD-1 expression and whether the Nrf2 and NF-κB signaling pathways were both involved in the process.Methods: A GVHD mouse model was induced using 6-8-week-old C57BL/6 and Balb/c mice, which were treated with hPMSCs. In order to observe whether hPMSCs affect the generation of CD4+IL-10+ T cells via control of redox metabolism and PD-1 expression, a CD4+IL-10+ T cell culture system was induced using human naive CD4+ T cells. The percentage of CD4+IL-10+ T cells and their PD-1 expression levels were determined in vivo and in vitro using flow cytometry, and Nrf2, HO-1, NQO1, GCLC, GCLM, and NF-κB levels were determined by western blotting, qRT-PCR, and immunofluorescence, respectively. Hematoxylin-eosin, Masson’s trichrome and periodic acid-Schiff staining methods were employed to analyze the changes in hepatic tissue. Results: A decreased activity of superoxide dismutase (SOD) and a proportion of CD4+IL-10+ T cells with increased PD-1 expression were observed in GVHD patients and the mouse model. Treatment with hPMSCs increased SOD activity and GCL and GSH levels in the GVHD mouse model. The percentage of CD4+IL-10+ T cells with decreased PD-1 expression, as well as Nrf2, HO-1, NQO1, GCLC, and GCLM levels, both in the GVHD mouse model and in the process of CD4+IL-10+ T cell generation, were also increased, but NF-κB phosphorylation and nuclear translocation were inhibited after treatment with hPMSCs, which was accompanied by improvement of hepatic histopathological changes.Conclusions: The findings suggested that hPMSC-mediated redox metabolism balance and decreased PD-1 expression in CD4+IL-10+ T cells were achieved by controlling the crosstalk between Nrf2 and NF-κB, which further provided evidence for application of hPMSC-mediated treatment of GVHD.
Pressure-Volume Relationship By Pharmacological Stress Cardiovascular Magnetic Resonance
Authors: Meloni Antonella , De Luca Antonio , Nugara Cinzia , Vaccaro Maria , Cavallaro Camilla , Cappelletto Chiara , Barison Andrea , Todiere Giancarlo , Grigoratos Chrysanthos , Calvi Valeria , Novo Giuseppina , Grigioni Francesco , Emdin Michele , Sinagra Gianfranco , Pepe Alessia 
Published: February 2021

Abstract
Background. The variation between rest and peak stress end-systolic pressure-volume relation (ΔESPVR) is an index of myocardial contractility, easily obtained during routine stress echocardiography and never tested during dipyridamole stress-cardiac magnetic resonance (CMR). We assessed the ΔESPVR index in patients with known/suspected coronary artery disease (CAD) who underwent dipyridamole stress-CMR.Methods. One-hundred consecutive patients (24 females, 63.76±10.17 years) were considered. ESPVR index was evaluated at rest and stress from raw measurement of systolic arterial pressure and end-systolic volume by biplane Simpson’s method. Results. The ΔESPVR index showed a good inter-operator reproducibility. Mean ΔESPVR index was 0.48±1.45 mmHg/mL/m2. ΔESPVR index was significantly lower in males than in females. ΔESPVR index was not correlated to rest left ventricular end-diastolic volume index or ejection fraction. Forty-six of 85 patients had myocardial fibrosis detected by the late gadolinium enhancement technique and they showed significantly lower ΔESPVR values. An abnormal stress CMR was found in 25 patients and they showed significantly lower ΔESPVR values. During a mean follow-up of 56.34±30.04 months, 24 cardiovascular events occurred. At receiver-operating characteristic curve analysis, a ΔESPVR<0.02 mmHg/mL/m2 predicted the presence of future cardiac events with a sensitivity of 0.79 and a specificity of 0.68. Conclusions. The noninvasive assessment of the ΔESPVR index during a dipyridamole stress-CMR exam is feasible and reproducible. The ΔESPVR index was independent from rest LV dimensions and function and can be used for a comparative assessment of patients with different diseases. ΔESPVR by CMR can be a useful and simple marker for additional prognostic stratification.
Umbilical Cord Mesenchymal Stem Cells for the Treatment of Atherosclerosis in a Mouse Model: A Randomized Controlled Trial
Authors: Song Yijia , Liu Gaomiyang , Shi Fei , Jiang Xiaochun , Liu Jufen , Zhang Xuejuan , Lin Qingkeng , He Falian , Li Zian , He Jie , Ruan Guangping , Pang Rongqing , Pan Xinghua , Zhu Xiangqing 
Published: February 2021

Abstract
BackgroundThe purpose of this study was to determine the efficacy of umbilical cord mesenchymal stem cell (UCMSC) transplantation in a mouse atherosclerosis (AS) model and explore its potential antioxidative stress and lipid metabolism regulatory effects.MethodsA mouse AS model was established by feeding ApoE-/- mice a high-fat diet, after which UCMSCs were administered by intraperitoneal injection. The treatment effect was evaluated by measuring heart size and carrying out aortic arch histological staining and blood biochemical detection of blood lipids; RT-PCR was utilized to detect the levels of autophagy-related genes, and Q-TOF was used to detect free fatty acids.ResultsAfter UCMSC treatment in a mouse model of AS: the number of aortic arch plaques, length of the heart and heart-to-weight ratio were significantly reduced. Aortic arch staining showed that UCMSC treatment reduced the degree of aortic arch intima lesions. Furthermore, serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels were decreased, while the serum high-density lipoprotein cholesterol (HDL-C) level was increased The transcript levels of autophagy-related genes in the heart and liver were significantly higher in AS model mice than in control mice. Finally, the levels of phosphatidylinositol (PI) and ceramide (Cer) in the mouse plasma decreased to the level of the metabolite PI in the liver.Conclusions﻿UCMSCs increased the overall autophagy level in AS model mice, improved liver metabolic dysfunction, inhibited the formation of atherosclerotic plaques and improved the clinical symptoms of AS in the mouse model.
Lack of Changes in Preterm Delivery and Stillbirths During COVID-19 Lockdown in a European Region
Authors: Arnaez Juan , Ochoa-Sangrador Carlos , Caserío Sonia , Gutiérrez Elena Pilar , Jiménez Maria del Pilar , Castañón Leticia , Benito Marta , Peña Ana , Hernández Natalio , Hortelano Myriam , Schuffelmann Susana , Prada Maria Teresa , Gayte Pablo Diego , Villagómez Francisco Joaquín , Garcia-Alix Alfredo 
Published: February 2021

Abstract
Preliminary data in Europe have suggested a reduction in prematurity rates during the COVID-19 pandemic, implying that contingency measures could have an impact on prematurity rates. We designed a population-based prevalence proportion study to explore the potential link between national lockdown measures and a change in preterm births and stillbirths. Adjusted multivariate analyses did not show any decrease in preterm proportions during the lockdown period with respect to the whole pre-lockdown period or to the pre-lockdown comparison periods (2015-2019): 6.5% (95%CI 5.6-7.4), 6.6% (95%CI 6.5-6.8), and 6.2% (95%CI 5.7-6.7), respectively. Proportions of preterm live births did not change during lockdown when different gestational age categories were analyzed, nor when birthweight categories were considered. No differences in stillbirth rates among the different study periods were found: 0.33% (95%CI 0.04-0.61) during the lockdown period vs 0.34% (95%CI 0.22-0.46) during the pre-lockdown comparison period (2015-2019).ConclusionWe did not find any link between prematurity and lockdown, nor between stillbirths and lockdown. Collaborative efforts are desirable to gather more data and additional evidence on this global health issue.
Is Function-Based Resection Using Intraoperative Awake Brain Mapping Feasible and Safe for Solitary Brain Metastases Within Eloquent Areas?
Authors: Pelletier Jean-Baptiste , Moiraghi Alessandro , Zanello Marc , Roux Alexandre , Peeters Sophie , Trancart Bénédicte , Edjlali Myriam , Lechapt Emmanuele , Tauziede-Espariat Arnault , Zah-Bi Gilles , Parraga Eduardo , Chrétien Fabrice , Dezamis Edouard , Dhermain Frédéric , Pallud Johan 
Published: February 2021

Abstract
ObjectiveTo assess feasibility and safety of function-based resection under awake conditions for solitary brain metastasis patients.MethodsRetrospective, observational, single-institution case-control study (2014-2019). Inclusion criteria: adult patients, solitary brain metastasis, supratentorial location within eloquent areas, function-based awake resection. Case matching (1:1) criteria between metastasis group and control group (high-grade gliomas): sex, tumor location, tumor volume, preoperative Karnofsky Performance Status score, age, educational level.ResultsTwenty patients were included. Intraoperatively, all patients were cooperative, no obstacles precluded procedure from being performed. A positive functional mapping was achieved at both cortical and subcortical levels, allowing for a function-based resection in all patients. The case-matched analysis showed that intraoperative and postoperative events were similar, except for a shorter duration of the surgery (p<0.001) and of the awake phase (p<0.001) in the metastasis group. A total resection was performed in 18 cases (90%, including 10 supramarginal resections), and a partial resection was performed in two cases (10%). At three months postoperative months, none of the patients had worsening of their neurological condition or uncontrolled seizures, three patients had an improvement in their seizure control, and seven patients had a Karnofsky Performance Status score increase ≥10 points.ConclusionsFunction-based resection under awake conditions preserving the brain connectivity is feasible and safe in the specific population of solitary brain metastasis patients and allows for high resection rates within eloquent brain areas while preserving the overall and neurological condition of the patients. Awake craniotomy should be considered to optimize outcomes in brain metastases in eloquent areas.
Anastomotic Leak in Colorectal Cancer Surgery: From Diagnosis to Management or Failure - A Retrospective Cohort Study.
Authors: Rama Nuno , Parente Diana , Silva Cândida , Neves Miguel , Figueiredo Nuno , Alves Paulo , Clara Paulo , Amado Sandra , Lourenço Óscar , Guarino Maria , Rocha Anabela , Castro-Poças Fernando , Pimentel João 
Published: February 2021

Abstract
Background

Anastomotic leakage (AL) after colorectal resections is a common surgical experience and the most frequent major adverse outcome. Early recognition of AL is critical to reduce mortality. We aim to evaluate the incidence, diagnostic criteria, morbidity, and mortality related with AL.
Methods

This is a cohort, descriptive retrospective, single-centred study of consecutive patients who underwent surgery with a colorectal anastomosis due to colorectal cancer, over a 4-year period (2013–2016).
Results

From 2013 to 2016, a total of 480 patients were included. A total of 37 (7.7%) had an anastomotic leakage. AL was diagnosed after 6.8 days in average (range 2–17), but most frequently on day 5. 25 out of the 37 patients were diagnosed based on clinical criteria, and 12 had a CT scan of the abdomen; 3 (25%) did not show unequivocal signs of AL. From all AL patients, 6 were managed non-operatively. 24 out of 31 patients (64.8%) were submitted to anastomotic takedown and Hartmann-type of procedure. The rate of Clavien-Dindo grade III and IV complications was significantly higher in the AL-patient group (70.2 vs. 7.7%, p < 0.0005). Mortality was higher in the leakage group (21.6% vs. 4.7%, p < 0.0005).
Conclusions

In this study, most patients were diagnosed earlier based on clinical criteria and the remaining patients had an abdomen-pelvic CT scan, with 25% of false negatives and a significant delay in diagnosis. The leakage group had higher morbidity and mortality, longer hospital stays and rate of reoperations. Both systematic use of scores in AL diagnosis and early reoperation, may have a positive impact in FTR rate reduction, and for this, additional prospective studies are needed.
RNAi Targeting-STIL Suppresses Cell Growth and Induces Apoptosis of Lung Cancer NCI-H1299 Cells via Inactivation of Akt/SAPK/TAK1 Pathways
Authors: Li Hailong , Niu Rong , Zhang Yi , Song Yanmei , Wang Jing , Yang Yali , Duan Yongqiang , Zhu Xiangdong , Zhang Zhiming , Hu Yonghua 
Published: February 2021

Abstract
Background: Gradually emerged studies demonstrated that SCL/TAL1 interrupting locus (STIL or SIL) is upregulated in multiple kinds of fatal tumors; at present, there is no clean understanding about the role of STIL in lung adenocarcinoma cells. This study aimed to discover the significance of STIL in lung adenocarcinoma, so as to find a potential gene target for diagnosis and therapy. Methods: STIL expression in lung adenocarcinoma tissue and clinical pathological characteristic was analyzed using the online databases, UALCAN and GEPIA. Lentivirus STIL-shRNA was manufactured and transducted into lung adenocarcinoma cells to seek and analyze the effects on tumor phenotype. The cell proliferation was assessed using Cellomics Array Scan imaging assay, and colony-formation assay, respectively. The apoptosis was detected by flow cytometry assay. Moreover, the antibody array of PathScan Cancer Phenotype, PathScan stress and apoptosis pathway was used to explore relevant molecular mechanisms following STIL knockdown in NCI-H1299 cells. Results: The clinical pathological characteristic assay showed that STIL is upregulated in lung adenocarcinoma tissues, and this trend was associated with cancer stage1 and histological subtypes. Silencing experiment showed that downregulation of STIL could inhibit cell growth and colony formation, induce cell apoptosis, and a G2 phase arrest effect significantly, and antibody array detection revealed that p-Bad were upregulated, and p-Akt, p-Bad, p-HSP27, p-SAPK/JNK, p-TAK1, Vimentin, CD45, PCNA and Ki-67 were downregulated significantly after STIL silenced in NCI-H1299 cells.Conclusions: In conclusion, STIL is overexpressed in lung adenocarcinoma tissues compared with normal lung tissue. Knockdown of STIL could inhibit cell growth and colony formation ability, promote apoptosis via Akt/SAPK/TAK1 signal pathways inactivation.
Mining the TCGA Database for Microenvironment‐Related Genes&nbsp;with Prognostic Value in Gastric Cancer
Authors: Liu Ting , Gong Zheng , Zhang Hong , Wan Yi , Ren Ming-Han , Liu Lili , Wang Bin , Tian Zibin 
Published: February 2021

Abstract
BackgroundGastric cancer (GC) is the fifth most common cancer worldwide. Previous studies have suggested that the tumor microenvironment (TME) plays an important role in the development and prognosis of GC. In this study, we aimed to identify genes in tumor-infiltrating immune cells (TICs) that influence the progression and prognosis of GC. MethodsWe used the ESTIMATE algorithm to calculate the scores of the stromal and immune components of the TME in 407 GC samples collected from The Cancer Genome Atlas (TCGA) database.The differentially expressed genes (DEGs) were intersected by a protein-protein interaction (PPI) network and analyzed by univariate Cox regression.Further analysis showed the correlation between MCEMP1 and the clinicopathological characteristics of GC patients (clinical stage, distant metastasis) and survival.Then we used Gene set enrichment analysis (GSEA) and CIBERSORT analysis to examine the relationship between MCEMP1 and the TME.ResultsThe analysis revealed that the expression of MCEMP1 was positively correlated with the clinicopathological characteristics of GC patients (clinical stage, distant metastasis) and negatively correlated with survival. Gene set enrichment analysis (GSEA) indicated that gene sets in the MCEMP1 high expression group were concentrated mainly in immune-related pathways. CIBERSORT analysis of the proportion of TICs revealed that neutrophils and M2 macrophages were positively correlated with MCEMP1 expression, suggesting that MCEMP1 is responsible for preservation of the immune-dominant status of the TME. ConclusionHigh MCEMP1 expression might be a biomarker of a poor prognosis in GC patients and provide a clue regarding the different statuses of the TME, offering additional insight into therapy for GC.
PD-L1 Expression on Circulating Tumor Cells and Platelets in Patients with Metastatic Breast Cancer
Authors: Darga Elizabeth P , Dolce Emily M. , Fang Fang , Kidwell Kelley M. , Gersch Christina L. , Kregel Steven , Thomas Dafydd G. , Gill Anoop , Brown Martha E. , Gross Steven , Connelly Mark , Holinstat Michael , Cobain Erin F. , Rae James M. , Hayes Daniel F. , Paoletti Costanza 
Published: February 2021

Abstract
Background: Immune checkpoint inhibition (ICPi) is effective in several cancers. Expression of programmed death-ligand 1 (PD-L1) on circulating tumor or immune effector cells could provide insights into selection of patients for ICPi. Methods: Whole blood (WB) was collected at serial timepoints from metastatic breast cancer (MBC) patients and healthy donors for circulating tumor cell (CTC) and platelet PD-L1 analysis using the CellSearch® assay. CTC PD-L1 was considered positive if detected on at least 1% of the cells; platelet PD-L1 was considered positive if ≥100 platelets per CellSearch frame expressed PD-L1. Results: A total of 207 specimens from 124 MBC patients were collected. 52/124 (42%) samples at timepoint-1 (at or close to time of progressive disease) had ≥5 CTC/7.5ml WB. Of those, 21 (40%) had positive CTC PD-L1. In addition, platelet PD-L1 expression was observed in 35/124 (28%) at timepoint-1. Platelet PD-L1 was not detected in more than 70 specimens from 12 healthy donors. Platelet PD-L1 was associated with ≥5 CTC/7.5ml WB (p=0.0002), less likely in patients with higher red blood cell counts (OR=0.72, p<0.001) and a history of smoking tobacco (OR=0.76, p<0.001). Platelet PD-L1 staining was not associated with tumor marker status, recent procedures or treatments, platelet-affecting drugs, or CTC PD-L1 expression. Conclusion: PD-L1 expression was found in MBC patients on both CTC and platelets in an independent fashion. Inter-patient platelet PD-L1 expression was highly heterogeneous suggesting that it is a biological event associated with cancer in some but not all patients. Taken together, our data suggest that CTC and platelet PD-L1 expression could play a role in predicting which patients should receive ICPi and as a pharmacodynamics biomarker during treatment.