bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Liver Enzymes in Patients with Blunt Abdominal Trauma to Diagnose Liver Injury
Authors: Shrestha Anup , Neupane Harish Chandra , Tamrakar Kishor Kumar , Bhattarai Abhishek , Katwal Gaurav 
Published: July 2020

Abstract
Background:The liver is the second most injured organ following blunt abdominal trauma (BAT) after spleen. Although the computed tomography (CT) scan is considered as the gold standard for diagnosing liver injury in BAT, it is not readily available in the hospital. This study was performed to evaluate the role of aspartate transaminase (AST) and alanine transaminase (ALT) in patients with BAT and its significance in predicting the diagnosis and severity of the liver injury.Method:The study was conducted in Chitwan Medical College Teaching Hospital (CMCTH) study from February 2019 to May 2020. During that period 96 patients with BAT presented to the emergency department(ED) of CMCTH.Results:Among the 96 patients admitted with BAT, 38 patients had liver injury and 58 patients had no liver injury. The median length of the intensive care unit (ICU) stay of patients with liver injury was higher than without liver injury. There was a significant difference in the median level of AST and ALT (<0.001) between patients with liver injury and no liver injury. The area under the ROC curve of AST was 0.89(95% Confidence Interval 0.86-0.98) and of ALT was 0.92(95% Confidence Interval 0.83-0.97). The area under the curve demonstrated that the test was a good predictor for the identification of liver injury and also the severity of liver enzymes. The cut-off values for the liver injury were 106 U/l and 80 U/l for AST and ALT respectively. Based on these values, AST ≥ 106 U/l had a sensitivity of 71.7 %, a specificity of 90 %, a positive predictive value of 86.8 %, and a negative predictive value of 77.6 %. The corresponding values for ALT ≥ 80 U/l were 77.8 %, 94.1%, 92.1% and 82.8 %, respectively.ConclusionIn conclusion, we report the optimal cut-off value of AST and ALT for liver injury in BAT as ≥ 106 U/l and 80 U/l respectively. The elevated level of AST and ALT might assist the surgeons to timely refer the suspected patients with the liver to a tertiary center and it might help the surgeons to go for conservative management for minor liver injuries in BAT preventing the exposure hazards of the CT scan.
PD-L1 Polymorphism Can Predict Clinical Outcome of Brazilian Non-Small Cell Lung Cancer Patients After Postoperative Adjuvant Treatment
Authors: Machado-Rugolo Juliana , Prieto Tabatha Gutierrez , Fabro Alexandre Todorovic , Cuentas Edwin Roger Parras , Sá Vanessa Karen , Baldavira Camila Machado , Rainho Claudia Aparecida , Castelli Erick C. , Farhat Cecilia , Takagaki Teresa Yae , Nagai Maria Aparecida , Capelozzi Vera Luiza 
Published: July 2020

Abstract
BackgroundAlthough the incidence and mortality of non-small cell lung cancer (NSCLC) remains high with poor prognosis, programmed death‐1 (PD‐1) and programmed death‐ligand 1 (PD‐L1) pathway are promising prognostic and predictive biomarker of NSCLC. The polymorphisms on PD‐L1 gene may be associated with their protein expressions and affect the adjuvant treatment and outcome of NSCLC patients. The goal of this study was to evaluate the clinicopathologic values of PD-L1 expression and single-nucleotide polymorphisms (SNPs) in the PD-L1 gene in lung adenocarcinoma (ADC), squamous cell carcinoma (SqCC), and large cell carcinoma (LCC). MethodsThe 70 NSCLC samples consisted of 33 samples of ADC, 24 of SqCC and 13 of LCC. All tissue microarray paraffin blocks were used for PD-L1 multiplex immunofluorescence assays with Cell Signaling E1L3N clone. Fifteen polymorphisms in the PD-L1 gene were investigated by deep targeted sequencing.ResultsThe PD-L1 expression was higher in ADC than in SqCC and LCC. Three polymorphisms rs4742098, rs4143815, and rs7041009 were significantly associated with tumor recurrence (P=0.01; P=0.05; P=0.02, respectively). According to the recurrence of the disease, carriers of the G allele were less likely to relapse (P=0.01) compared to the homozygous AA genotype for rs4742098. As in rs4143815, individuals with the C allele were also less likely to relapse (P=0.05). As for rs7041009, individuals with AG or GG genotypes were more likely to relapse. The G allele of rs7041009 also showed a significant correlation with age, younger patients, 16 (41.0%) and status, among 11 (39.3%) compared to carriers of the A allele (P=0.02 and P<0.01, respectively). The rs7041009 AG genotype was inversely associated with E1L3N clone PD-L1 labeling in NSCLCs but did not reach statistical significance. Kaplan-Meier survival curves showed that the prognosis of patients with NSCLC was strongly dependent on the alternative allele G (genotype AG or GG) of rs4742098, alternative allele C (genotype CG or CC) of rs4143815 and individuals with GG genotype of rs7041009 (P=0.02; P=0.05 and P<0.01, respectively). Multivariate analysis by the Cox Regression model showed genotype GG of rs7041009 independently associated with cancer recurrence and patients without adjuvant radiotherapy (hazard ratio [HR] = 7.59, 95% confidence interval [CI] = 1.06-54.03, and HR = 9.24, CI = 1.13-75.16).ConclusionsPD-L1 rs7041009 GG polymorphisms may be useful for the prediction of clinical outcome of radiotherapy in NSCLC. Further studies are needed to confirm our findings and to understand the role of PD-L1 in the radiotherapy outcome of NSCLC patients.
FOXM1D Potentiates PKM2-Mediated Tumor Glycolysis and Angiogenesis
Authors: Zhang Wei , Zhang Xin , Huang Sheng , Chen Jianfeng , Ding Peipei , Wang Qi , Li Luying , Lv Xinyue , Li Ling , Zhang Pingzhao , Zhou Danlei , Wen Wenyu , Wang Yiping , Lei Qunying , Wu Jiong , Hu Weiguo 
Published: July 2020

Abstract
Background: Tumor growth, especially in the late stage, requires adequate nutrients and rich vasculature, in which PKM2 plays a convergent role. It has been reported that PKM2, together with FOXM1D, is upregulated in late stage colorectal cancer and associated with metastasis; however, their underlying mechanism for promoting tumor progression remains elusive. Methods: Western blot, coimmunoprecipitation (Co-IP), glutathione S-transferase (GST)-pull down and Immunofluorescence (IF) were performed to investigate the interaction between FOXM1D with PKM2 and other proteins. Extracellular acidification (ECAR) and oxygen consumption rate (OCR) assays, Protein Cross-linking, Gel chromatography, Pyruvate Kinase (PK) activity assay were used to examine the effect of FOXM1D on glycolysis. The angiogenesis effect was verified by Human umbilical vein endothelial cell (HUVEC) tube formation assay, tumor tissue microangiography, VEGFA Elisa assay and ChIP assay.Results: FOXM1D potentiates PKM2-mediated glycolysis and angiogenesis through multiple protein-protein interactions. In the presence of FBP, FOXM1D binds to tetrameric PKM2 and assembles a heterooctamer, restraining PKM2 metabolic activity by about a half and thereby promoting aerobic glycolysis. Furthermore, FOXM1D interacts with PKM2 and NF-κB and induces their nuclear translocation with the assistance of the nuclear transporter importin 4, which subsequently augments VEGFA transcription that is regulated by the PKM2 and NF-κB complex. The increased VEGFA is secreted extracellularly via exosome, which is potentiated by the interaction of FOXM1 with VPS11, eventually promoting tumor angiogenesis. Conclusion: Our study indicates that FOXM1D plays a crucial role in promoting glycolysis and angiogenesis through its protein-protein interaction. The above findings provide another insight into the role of PKM2 in the regulation of glycolysis and angiogenesis.
EFFECT OF N-ACETYLCYSTEINE ON APOPTOSIS OF P19 CANCER CELLS DURING HYPOXIA
Authors: Nosareva O. L. , Orlov D. S. , Shakhristova E. V. , Stepovaya E. A. , Sadykova A. A. 
Published: July 2020

Introduction. Hypoxia in tumor growth contributes to mitochondrial dysfunction and exacerbates oxidative stress in the immortalized cell. The objective of the study was to investigate the molecular mechanisms of the effects of N-acetylcysteine on redox regulation of tumor cell apoptosis under hypoxia.Material and Methods. P19 cells (mouse teratocarcinoma) cultured under hypoxia served as the material for the study. The redox status was modulated with N-acetylcysteine in the final concentration of 5 mM. The level of reactive oxygen species, concentration of calcium ions, transmembrane potential and the number of CD95-, CD120- and Annexin V-positive cells were determined by flow cytometry. The concentration of glutathione system components as well as the levels of protein SH groups and protein carbonyl derivatives were measured by spectrophotometry.Results. The use of N-acetylcysteine under hypoxic conditions was accompanied by the increased total glutathione concentration and protein SH groups levels, decreased levels of Са2+ ions, proteinbound glutathione and protein carbonyl derivatives, as well as the production of reactive oxygen species and more appropriate functioning of P19 cells mitochondria. N-acetylcysteine contributed to the development of additional resistance of P19 cells to apoptosis under hypoxia.Conclusion. The alteration in the state of the glutathione system under hypoxia influences the changes in tumor cell metabolism on the whole and promotes formation of additional mechanisms to escape apoptosis.
THE CHOICE OF THE METHOD OF ENDOSCOPIC STENTING IN PATIENTS WITH UNRESECTABLE ADENOCARCINOMA OF THE PANCREATIC HEAD
Authors: Shabunin A. V. , Tavobilov M. M. , Lebedev S. S. , Korzheva I. Yu. , Karpov A. A. , Lantsynova A. V. 
Published: July 2020

The purpose of the study was to comparatively assess the endoscopic plastic or nitinol stenting in patients with unresectable adenocarcinoma of the pancreatic head, who subsequently received systemic chemotherapy.Material and Methods. Between 2014 and 2018, 64 patients underwent retrograde stenting followed by chemotherapy. All patients were divided into 2 groups. Group I consisted of 21 patients, who underwent nitinol stent implantation. Group II comprised 43 patients, who underwent plastic stent implantation.Results. The technical success was 91.3 % in group I and 93.5 % in group II (р=0.324); clinical success was 95.2 % in group I and 90.6 % in group II (р=0.218). Complications according to the Clavien–Dindo classification in group I patients: Grade II in 2 (9.5 %), Grade III in 1 (4.5 %), and Grade IV 2 in (9.5 %). In group II patients, these complications were as follows: Grade II in 4 (9.3 %), Grade III in 4 (9.3 %), and Grade IV in 1 (2.3 %). The median duration of chemotherapy was 127.3 days. Stent dysfunction was observed in 5 (23.8 %) patients of group I and in 24 (55.8 %) patients of group II (р=0.026). The median time of stent patency was 108 ± 5.2 days in group I and 64 ± 4.3 days in group II (р=0.034). In group I patients, the median survival time was 100 days in 5 patients, 120 days in 9 patients, and 150 days in 5 patients. Two patients are alive. In group II patients, the median survival time was 100 days in 10, 120 days in 16, and 150 days in 13. Five patients are alive.Conclusion. Based on the results obtained, it is advisable to recommend the use of nitinol stents for resolving obstructive jaundice in patients with unresectable ductal adenocarcinoma of the pancreatic head, who are scheduled to undergo chemotherapy.
THE ROLE OF GATA3, FOXA1, ELF5 TRANSCRIPTION FACTORS IN THE PATHOGENESIS AND PROGNOSIS OF BREAST CANCER
Authors: Vasilchenko D. V. , Krakhmal N. V. , Vtorushin S. V. , Zavyalova M. V. 
Published: July 2020

Purpose of the study: to review available data on the role and significance of GATA3, FOXA1 and ELF5 transcription factors in the pathogenesis, progression and therapy resistance of breast cancer.Material and Methods. The Medline and PubMed databases were used to identify all studies that evaluated the structure, functional parameters and participation of the studied transcription factors in the pathogenesis of breast cancer. More than 180 publications were analyzed, of which 76 were included into the review.Results. The review shows that molecular genetic studies in relation to transcription factors and subsequent comparison of the obtained results with various clinical and morphological characteristics of breast cancer are of great importance. The review also demonstrates the inconsistency of the available data regarding clinical significance in assessing the prognosis of the disease and the sensitivity of the tumor to hormone therapy.Conclusion. The study of the expression parameters of GATA3, FOXA1, and ELF5 transcription factors, as well as their relationship with tumor progression mechanisms will increase the reliability of immunomorphological studies, most likely suggesting the efficiency of hormone therapy. Therefore, the results of this study can help to plan adequate treatment tactics and predict outcomes in patients with breast cancer.
PATHOLOGICAL COMPLETE RESPONSE TO NEOADJUVANT CHEMORADIOTHERAPY IN PATIENTS WITH LOCALLY ADVANCED GASTRIC CANCER
Authors: Skoropad V. Yu. , Kudriavtsev D. D. , Titova L. N. , Moserov S. A. , Agababyan T. A. , Ivanov S. A. , Kaprin A. D. 
Published: July 2020

The impact of pathological complete response (pCR) on long-term treatment outcomes was analyzed in patients with locally advanced gastric cancer, who received prolonged neoadjuvant chemoradiotherapy.Material and Methods. The study included 45 patients with locally advanced gastric cancer. Neoadjuvant hyperfractionated accelerated radiotherapy at a total dose of 45 Gy was given concurrently with capecitabine and oxaliplatin chemotherapy. There were more men than women. The median age of the patients was 62 years. Tumors were most commonly located in the upper (46 %) and middle (38 %) thirds of the stomach. Low-grade adenocarcinoma and signet-ring cell carcinoma were the most common (65 %). According to a comprehensive examination, including CT and laparoscopy, tumors which invaded the subserous layer of the stomach wall were diagnosed in 17 (37.8 %) patients, and tumors which penetrated the serous layer or surrounding structures were found in 28 (62.2 %) patients. Regional lymph node metastases were detected in 38 (84.4 %) cases.Results. The absolute majority of patients underwent gastrectomy (43 patients, 96 %). Grade IaIb pathological response occurred in almost half of the patients (45.4 % of cases). Peritoneal metastases were found to be the most common mode of cancer dissemination; they were mostly observed in patients with poorly differentiated gastric cancer. Multivariate analysis revealed no effect of any of the factors characterizing the patient, tumor and completeness of treatment on the pathological response grade. However, a correlation between the clinical and morphological assessments of tumor regression was observed. In cases with complete or partial responses of the primary tumor and regional lymph nodes to chemoradiotherapy, 1aIb grades of pathological response were more frequently observed. It was also demonstrated a direct correlation between the pathological response grade and pathomorphological stage of the tumor (yp), as well as ypT and ypN categories. Analysis of long-term treatment outcomes showed that the overall and relapse-free 5-year survival rates were significantly higher in patients with 1a and Ib grades of pathological response. The overall 3-year survival rates were 70 ± 10 % and 41 ± 11 %, respectively (p=0.003). Multivariate analysis using the Cox regression model confirmed a statistically significant independent effect of the pathological response grade on the overall survival (p=0.015).Conclusion. Grade IaIb pathological response was observed in almost half of the patients, who received neoadjuvant chemoradiotherapy for locally advanced gastric cancer. No clinical and morphological factors influencing the pathological response grade were found. A correlation between the clinical and morphological assessments of tumor regression was observed. Patients with Ia-Ib pathological response had significantly higher overall and disease-free survival rates.
THE INFLAMMATORY STATUS AND LYMPH NODE METASTASES IN NON-SMALL CELL LUNG CANCER
Authors: Pismenny D. S. , Savelieva O. E. , Zavyalova M. V. , Rodionov E. O. , Tashireva L. A. , Tuzikov S. A. , Pankova O. V. , Perelmuter V. M. 
Published: July 2020

Introduction. The development of inflammation is characterized by changes in blood hematology parameters and indices. Various inflammatory parameters are used to assess the inflammatory status (IS) during cancer treatment. Recent studies have revealed a relationship between tumor progression and the presence of chronic inflammation. Consequently, there have been many attempts to predict the risk of tumor recurrence and distant metastases, as well as patient’s survival assessing the various inflammatory markers. The relationship between IS parameters and lymph node metastasis remains poorly understood in non-small cell lung cancer (NSCLC).Material and Methods. The prospective study included 35 patients with NSCLC (T1–4N0–2M0). Seventeen patients received 2–3 cycles of neoadjuvant chemotherapy (NAC). A leukocyte formula was determined in the peripheral blood and inflammatory indices, such as neutrophils to lymphocytes ratio (NLR), platelets to lymphocytes ratio (PLR), lymphocytes to monocytes ratio (LMR) and systemic immuno-inflammatory index (SII) were calculated. In addition, the concentrations of fibrinogen, C-reactive protein (CRP) and cortisol were evaluated.Results. NAC alone did not significantly change the parameters of patients’ IS. Lymph node metastases were associated with changes in parameters indicating the enhanced IS. In the group of patients who did not receive NAC, lymph node metastasis was associated with fibrinogen blood levels (cut-off value 5.35 g/L), PLR index value (cut-off value 7.18) and cortisol blood concentration (cut-off value 414 nmol/mL). The confidence level was χ2 =10.118; р=0.018. In the group of patients who received NAC, lymph node metastasis was associated with the leukocyte count (cut-off value 7.1×109 /L), PLR index value (cut-off value is 7.18) and CRP blood concentration (cut-off value is 8.5 mg/L). The confidence level was χ2 =8.193; р=0.042.Conclusion. Risk of lymph node metastasis in NSCLC is associated with IS. Parameters of IS can be used to predict the risk of lymph node metastases.
ASSOCIATION OF THE COMBINATION OF STEMNESS GENE AMPLIFICATIONS AND COPY NUMBER ABERRATIONS OF WNT-SIGNALING GENES IN BREAST TUMORS WITH METASTASIS
Authors: Litviakov N. V. , Ibragimova M. K. , Tsyganov M. M. , Deriusheva I. V. , Pevsner A. M. , Garbukov E. Yu. , Doroshenko A. V. , Slonimskaya E. M. 
Published: July 2020

We studied the association between the presence of 2 or more stemness gene amplifications as well as copy number aberrations (CNAs) of WNT signaling genes in residual breast tumor and metastasis. WNT pathway genes associated with metastasis were identified.Material and Methods. The study included 30 patients with breast cancer, who had 2 or more stemness gene amplifications in the residual tumor after neoadjuvant chemotherapy. Fifteen of the thirty patients developed hematogenous metastases; they constituted a group with metastases, the remaining 15 patients entered the second group without metastases. The tumor DNA was examined using a CytoScanHD Array microarray (Affymetrix, USA).Results. By subtracting amplification and deletion frequencies in 852 cytobands between groups with metastases and without metastases, 21 cytobands were identified with the largest difference in deletion and amplification frequencies. They contain 19/150 of WNT genes (12 activators: SKP1, WNT8A, MAPK9, CCND3, FZD9, WNT8B, CCND1, PLCB2, PRKCB, FZD2, WNT3, WNT9B and 7 negative regulators: GSK3B, APC, CSNK2B, SFRP5, BTRC, TCF7L2, CSNK2A2). A point system was developed: when amplifying WNT-signaling activators or deletion of negative regulators, one point was added to the total score, and vice versa when deleting WNT-signaling activators or amplification of negative regulators, one point was taken from the total amount. It was shown that 93% (14/15) of patients with metastases had a total score higher than 0, while 93% (14/15) of patients without metastases had a total score of zero or less than zero. The differences between the groups were statistically significant according to the two-sided Fisher test with a high level of confidence probability (p=0.000003) and the log-rank test (p=0.00004) when assessing non-metastatic survival by the Kaplan-Mayer method.Conclusion. Nineteen WNT signaling genes were identified. Copy number aberrations of these genes in combination with stemness gene amplifications in residual tumors were associated with metastasis. A new highly effective prognostic factor for breast cancer was identified.
LOSS OF HETEROZYGOSITY IN THE BRCA1 AND BRCA2 LOCUS IN BREAST CANCER
Authors: Tsyganov M. M. , Ibragimova M. K. , Pevzner A. M. , Litviakov N. V. 
Published: July 2020

One of the factors of variability of malignant neoplasms is the loss of heterozygosity (LOH). The biological meaning of LOH, in relation to carcinogenesis, is associated with the inactivation of heterozygous loci of pathogenetically significant genes. Thus, the aim of this work was to study BRCA1/2 LOH in breast tumors.Material and Methods. The study included 122 patients with stage IIAIIIC breast cancer. DNA was isolated from 122 biopsy samples of tumor tissue using the QIAamp DNA mini Kit (Qiagen, Germany). To assess the status of LOH, microarray analysis was performed on high-density DNA chips from Affymetrix CytoScanTM HD Array. To process the results of microchipping, we used the Chromosome Analysis Suite 3.3 program (Affymetrix, USA).Results. The loss of heterozygosity in the BRCA1 gene was found to be associated with response to NAC. It was shown that in 59 patients LOH in the BRCA1gene was associated with an objective response to treatment (p=0.005). The presence of LOH in the studied genes was associated with a favorable prognosis. The 5-year non-metastatic survival rates were 75 % and 100 % in patients with LOH in the BRCA1 and BRCA2 genes, respectively (log-rank test: p=0.003 and p=0.05, respectively).Conclusion. The phenomenon of LOH in the BRCA1/2 genes was shown to be associated with response to NACT. BRCA1/2. Further studies are needed to evaluate the frequency of BRCA1/2 LOH after NAC for choosing and changing treatment tactics.
Framework conditions to design sustainable business models for decentralised water treatment technologies in Viet Nam for international technology providers
Authors: Fritz Mona , Hohmann Claudia , Tettenborn Felix 
Published: July 2020

AbstractThe expansion of water-intensive industrial activities and the impacts of climate change are jeopardising the sufficiency of safe drinking water in several Southeast Asian countries. One is Viet Nam, where geogenic arsenic contamination further limits the availability of freshwater resources with a simultaneous increase in water demand. Innovative and sustainable water treatment technologies are required to meet these challenges. Equally, we assume that the provision of safe drinking water requires tailored business models (BMs). In this study, we focus on the key stakeholders and framework conditions to design tailored BMs providing safe drinking water to the low-income and middle-income population in Viet Nam. We consider decentralised technologies to be suitable due to their lower investment costs for implementation and the avoidance of strong path dependencies. We therefore conducted a literature review and interviews with international experts in the domain of decentralised water treatment technologies. Our results show that relevant aspects include a lack of financial resources, specific characteristics associated with Vietnamese culture, e.g. the importance of relationships and trust in the business domain, lack of education and vocational training, market saturation suggesting co-operation with existing water suppliers, lack of suitable partners, and deficiencies in the institutional environment.