bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Foreign Aid on Economic Growth in Ethiopia
Authors: Gebresilassie Belay Asfaw , Gebre Girma Gezmu
Published: September 2020

This study analyzes the impact of foreign aid on economic growth in Ethiopia based on time series annual data for the period of 1974 to 2017. Autoregressive distributed lag Approach to Co-integration and Error Correction Model was applied in order to investigate the long-run and short-run relationship between dependent and the independent variables. The empirical results from econometrics model reveal that foreign aid has negative impact on economic growth in both long run and short run and statistically significant at 1 percent significant level. The negative and significant error correction term shows that the short run disequilibrium adjusts to its long run equilibrium by 84.6 percent each year. The important policy implication of this study suggests that more effort has to be made to improve the negative impact of foreign aid, mainly because of existence of poor institutional arrangement that contributes the fund to unproductive sectors. The government has to ensure, a close monitoring and consistent management strategies, which is used to avoid misallocation and mismanagement problems and has to ensure that foreign aid is linked to the productive sectors to optimize the benefits.
Wavelets for Long Waves: Was Kondratieff’s Intuition Right?
Authors: Focacci Antonio
Published: September 2020

The validity of the Kondratieff’s theory of long-waves is still a controversial issue among historians, economic, social and political science scholars. In this work, both original Kondratieff’s data (never processed by wavelet analysis in their whole dataset) jointly with additional among the longest and most representative economic indicators are investigated. By the application of this statistical technique, the main purpose of the paper is to furnish an additional information to the literature. We trace evidence on the presence of coherent periodicities in the case of original Kondratieff time series and for other relevant and up-dated economic indicators as well.(JEL C22, E32, E37)
Lung adenocarcinoma isolated metastasizing to pancreas a case report and review
Authors: Wang Shupeng , Liu Kaimeng , Gu Yue , Tan Ludong , Jia Feng , Liu Yahui
Published: September 2020

BACKGROUND: Lung cancers are prone to metastasis. It is commonly associated with metastases in the brain, bone, and liver.However, isolated pancreatic metastasis are extremely rare in lung cancer patients。CASE SUMMARY: A Chinese man underwent pulmonary lobectomy for adenocarcinrcinoma 6 years ago. He was referred to our department because that postoperative reexamination revealed space occupying lesions in the neck of the pancreas.Abdomen CT showed a space occupying lesions in the neck of the pan-creas.,and no abnormality was found in any other organ. Therefore, it was considered to pancreatic carcinoma. Pancreatectomy of the pancreatic body and tail, as well as splenectomy, were performed,and he was given four courses of pemetrexed and Carboplatin chemotherapy after one month of operation. Then the gefitinib was given. A year after surgery, the patient survived without tumor.CONCLUSION: Secondary pancreatic tumors are rare in clinical practice.To our knowledge, this is the first report of isolated pancreatic metastasis of lung cancer in China and it is the longer tumor-free survival in patients with isolated pancreatic metastasis of lung cancer.However,the value of surgical treatment for isolated metastasis of lung cancer needs further discussion.
ELOVL2: a novel tumor suppressor attenuating tamoxifen resistance in breast cancer
Authors: Jeong Dawoon , Ham Juyeon , Kim Hyeon Woo , Kim Heejoo , Ji Hwee Won , Yun Sung Hwan , Park Jae Eun , Lee Keun Seok , Jo Heein , Han Jai Hong , Jung So-Youn , Lee Seeyoun , Lee Eun Sook , Kang Han-Sung , Kim Sun Jung
Published: September 2020

Background

To comprehensively understand the molecular mechanism of tamoxifen resistance (TamR) acquisition by epigenetically regulated genes, it is essential to identify pivotal genes by genome-wide methylation analysis and verify their function in xenograft animal model and cancer patients.
Methods

The MCF-7/TamR breast cancer cell line was developed and a genome-wide methylation array was performed. The methylation and expression of ELOVL2 was validated in cultured cells, xenografted tumor tissue, and breast cancer patients by methylation-specific PCR, qRT-PCR, Western blot analysis, and immunohistochemistry. Deregulation of ELOVL2 and THEM4 was achieved using siRNA or generating stable transfectants. Tam sensitivity, cell growth, and apoptosis were monitored by colorimetric and colony formation assay and flow cytometric analysis. Pathway analysis was performed to generate networks for the differentially methylated genes in the MCF-7/TamR cells and for the differentially expressed genes in the ELOVL2-overexpressing cells.
Results

Genome-wide methylation analysis in the MCF-7/TamR cells identified elongation of very-long chain fatty acid protein 2 (ELOVL2) to be significantly hypermethylated and downregulated, which was further verified in the tumor tissues from TamR breast cancer patients (n = 28) compared with those from Tam-sensitive (TamS) patients (n = 33) (P < 0.001). Immunohistochemical analysis of tissues from cancer patients showed lower expression of ELOVL2 in the TamR than TamS tissues. Growth of the MCF-7/TamR cells overexpressing ELOVL2 was retarded in cell culture and also in xenograft tumor tissue. Strikingly, ELOVL2 attenuated resistance to Tam up to 70% judged by the colorimetric and colony formation assay and xenograft mouse model. ELOVL2 contributed to the recovery of Tam sensitivity by regulating a group of genes in the AKT and ERα signaling pathways, e.g., THEM4, which plays crucial roles in drug resistance.
Conclusions

ELOVL2 was hypermethylated and downregulated in TamR breast cancer patients compared with TamS patients. ELOVL2 is responsible for the recovery of Tam sensitivity. AKT- and ERα-hubbed networks are pivotal in ELOVL2 signaling, where THEM4 contributes to the relaying ELOVL2 signaling. This study implies that deregulation of a gene in fatty acid metabolism can lead to drug resistance, giving insight into the development of a new therapeutic strategy for drug-resistant breast cancer.
INPP5D Expression is Associated with Risk for Alzheimer’s Disease and Induced by Plaque-Associated Microglia
Authors: Tsai Andy P , Lin Peter Bor-Chian , Dong Chuanpeng , Moutinho Miguel , Casali Brad , Liu Yunlong , Lamb Bruce T , Landreth Gary E , Oblak Adrian L , Nho Kwangsik
Published: September 2020

Background Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, robust microgliosis, neuroinflammation, and neuronal loss. Genome-wide association studies recently highlighted a prominent role for microglia in late-onset AD (LOAD). Specifically, inositol polyphosphate-5-phosphatase (INPP5D), also known as SHIP1, is selectively expressed in brain microglia and has been reported to be associated with LOAD. Although INPP5D is likely a crucial player in AD pathophysiology, its role in disease onset and progression remains unclear. Methods We performed differential gene expression analysis to investigate INPP5D expression in LOAD and its association with plaque density and microglial markers using transcriptomic (RNA-Seq) data from the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD) cohort. We also performed quantitative real-time PCR, immunoblotting, and immunofluorescence assays to assess INPP5D expression in the 5xFAD amyloid mouse model. Results Differential gene expression analysis found that INPP5D expression was upregulated in LOAD and positively correlated with amyloid plaque density. In addition, in 5xFAD mice, Inpp5d expression increased as the disease progressed, and selectively in plaque-associated microglia. Increased Inpp5d expression levels in 5xFAD mice were abolished entirely by depleting microglia with the colony-stimulating factor receptor-1 antagonist PLX5622. Conclusions Our findings show that INPP5D expression increases as AD progresses, predominantly in plaque-associated microglia. Importantly, we provide the first evidence that increased INPP5D expression might be a risk factor in AD, highlighting INPP5D as a potential therapeutic target. Moreover, we have shown that the 5xFAD mouse model is appropriate for studying INPP5D in AD.
Cholesterol Alters Mitophagy by Impairing Optineurin Recruitment and Lysosomal Clearance in Alzheimer’s Disease
Authors: Roca-Agujetas Vicente , Barbero-Camps Elisabet , de Dios Cristina , Podlesniy Petar , Morales Albert , Marí Montserrat , Trullàs Ramon , Riera Anna Colell
Published: September 2020

Background: Emerging evidence indicates that impaired mitophagy-mediated clearance of defective mitochondria is a critical event in Alzheimer’s disease (AD) pathogenesis. Amyloid-beta (A) metabolism and the microtubule-associated protein tau have been reported to regulate key components of the mitophagy machinery. However, the mechanisms that lead to mitophagy dysfunction in AD are not fully deciphered. We have previously shown that intraneuronal cholesterol accumulation can disrupt the autophagy flux, resulting in low A clearance. In this study, we examine the impact of neuronal cholesterol changes on mitochondrial removal by autophagy.Methods: Regulation of PINK1-parkin-mediated mitophagy was investigated in conditions of acute (in vitro) and chronic (in vivo) high cholesterol loading using cholesterol-enriched SH-SY5Y cells, cultured primary neurons from transgenic mice overexpressing active SREBF2 (sterol regulatory element binding factor 2), and mice of increasing age that express the amyloid precursor protein with the familial Alzheimer Swedish mutation (Mo/HuAPP695swe) and mutant presenilin 1 (PS1-dE9) together with active SREBF2.Results: In cholesterol-enriched SH-SY5Y cells and cultured primary neurons, high intracellular cholesterol levels stimulated mitochondrial PINK1 accumulation and mitophagosomes formation triggered by A while impairing lysosomal-mediated clearance. Antioxidant recovery of cholesterol-induced mitochondrial glutathione (GSH) depletion prevented mitophagosomes formation indicating mitochondrial ROS involvement. Interestingly, when brain cholesterol accumulated chronically in aged APP-PSEN1-SREBF2 mice the mitophagy flux was affected at the early steps of the pathway, with defective recruitment of the key autophagy receptor optineurin (OPTN). Sustained cholesterol-induced alterations in APP-PSEN1-SREBF2 mice promoted an age-dependent accumulation of OPTN into HDAC6-positive aggresomes, which disappeared after in vivo treatment with GSH ethyl ester (GSHee). The analyses in post-mortem brain tissues from individuals with AD confirmed these findings, showing OPTN in aggresome-like structures that correlated with high mitochondrial cholesterol levels in late AD stages. Conclusions: Our data demonstrate that accumulation of intracellular cholesterol reduces the clearance of defective mitochondria and suggest recovery of the cholesterol homeostasis and the mitochondrial scavenging of ROS as potential therapeutic targets for AD.
Building low intensity psychosocial support for Syrian refuge families in Istanbul
Authors: Weine Stevan Merrill , Arenliu Aliriza , Görmez Vahdet , Langenecker Scott , Demirtas Hakan
Published: September 2020

Background: The study is located in Istanbul, Turkey, where more than 750,000 Syrian refugees reside, largely in urban settings. It develops and pilot tests a novel model for helping urban refugee families in settings with limited to no access to evidence-based mental health services for refugees, by delivering a transdiagnostic family intervention for common mental disorders in health and non-health sector settings using a task-sharing approach. This case study addresses the following question: How can we address the common mental disorders of both children and parents, and support protective family resilience processes, through a low intensity trans-diagnostic family support intervention? Discussion: The rapidly growing scale of humanitarian crises requires new response capabilities geared towards addressing populations with prolonged high vulnerability to mental health consequences and limited to no access to mental health, health, and social resources. We faced multiple challenges in conducting this research including: 1) identifying local academic partners with research capacity, including in implementation science; 2) lack of culture of partnership between academics and humanitarian organizations; 3) getting local clinicians to embrace on a task-sharing model; 4) cultural competency of local and U.S. partners for refugee population; 5) getting local academics to focus on humanitarian emergency; 6) planning for a family intervention that would work with families with rigid gender role perspectives; 7) multiple social and economic problems that could not be solved, such as children working; 8) engagement challenges due to high demands on families. Through the research process, the research team learned lessons concerning: 1) building a coalition of academic and humanitarian organization partners; 2) investing in research capacity building of local partners; 3) working in a community-collaborative and multi-disciplinary approach to best understand and address socio-cultural, contextual, practical and scientific challenges needed to develop and implement the new family support model. Conclusion: Conducting research in humanitarian emergency settings calls for significant attention to building a coalition of academic and humanitarian organization partners, investing in research capacity building of local partners, and working in a community-collaborative and multi-disciplinary approach.
Clinical Outcomes of Extensive Stage Small Cell Lung Cancer Patients Treated With Thoracic Radiotherapy at Different Timing and Fractionation
Authors: Han Jinmin , Fu Chengrui , Li Baosheng
Published: September 2020

Objective: The purpose of this study was to assess whether combined thoracic radiotherapy (TRT) on the basis of chemotherapy (ChT) showed promising anti-tumor activity in extensive-stage small cell lung cancer (ES-SCLC), then to explore practice patterns for radiation time and dose/ fractionation and to identify prognostic factors for patients who would benefit from ChT/TRT.Methods: A total of 492 ES-SCLC patients were included from January 2010 to March 2019, of which 244 patients experienced ChT/TRT. Propensity score matching (PSM) was performed to minimize bias between the ChT/TRT and ChT-alone groups. Patients in ChT/TRT group were categorized into four groups based on the number of induction chemotherapy cycles. For effective dose fractionation calculation, we introduced the time-adjusted biological effective dose(tBED). Categorical variables were analyzed with Chi-square tests and Fisher’s exact tests. Survival rates were computed by the Kaplan-Meier method. Multivariate prognostic analysis was performed with Cox proportional hazard models. Results: Patients who received ChT/TRT were associated with improved OS (18.2 vs 10.8 months), PFS (9.0 vs 6.0 months) and LRFS (12.0 vs 6.0 months) before matching, with similar results after matching. In the ChT/TRT group, the median LRFS times for groups based on radiation time were 12.7, 12.0, 12.7, and 9.0 months, respectively. Earlier TRT had a tendency to prolong PFS (median 10.6 vs 9.8 vs 9.1 vs 7.7 months, respectively, p = 0.1095), as was not seen in OS (median 17.6 vs 19.5 vs 17.2 vs 19.1 months, respectively, p = 0.7224). To note, patients within 6 cycles had better LRFS (p = 0.0006). For radiation dose, patients in high-dose group (tBED>50Gy) had worse OS (median 25.9 vs 22.9, p = 0.0484) and PFS (median 12.1 vs 11.2, p=0.0042) in patients with complete response and partial response (CR and PR) to systemic therapy, but the above-mentioned results were not drawn when the population was confined to those receiving standard fractionation with CR and PR. Conclusion: ChT/TRT could improve survival for ES-SCLC patients. We cautiously recommend that TRT should be performed within 6 cycles and receiving hyperfractionated 45Gy in 30 fractions may be a feasible treatment scheme for ES-SCLC patients.
Health Related Quality of Life in Patients with Chronic Disease in Lebanese Community Setting
Authors: Dimassi Hani , Nasser Soumana C , Issa Aline , Adrian Sandrine Sarine , Hazimeh Bassima
Published: September 2020

Background: The impact of chronic diseases on patient quality of life are becoming of high priority in healthcare system. There is an increased need of such data in Middle Eastern countries. Objective: To measure health related quality of life (HRQOL) in patients with chronic disease to associate this information with demographic data, socioeconomic status, and health satisfaction.Setting: Six community pharmacies in Beirut region.Method: A prospective cross-sectional study was conducted to gather information on socioeconomic status, health condition and quality of life of participants during their visit to their local pharmacy. Main outcome measure: Health related quality of life using the EQ5D instrumentResults: Participants (n=103) gave an average of 6.8, and 7.4 over ten for their current health and for their satisfaction with their treatment, respectively. The mean utility score was 0.762 (SD 0.202). The number of prescribed medications per respondent indicated a significant impact on HRQOL (p = 0.002); with diuretic agents having a significant difference in utility scores (p<0.001). On average, participants 75 years or older, hospitalized in the past 12 months, diagnosed with hypertension, had a lower utility score of 0.15 (p<0.001), 0.111 (p=0.001), and 0.065 (p=0.035), respectively. For every unit increase in treatment satisfaction, the quality of life score increased by 0.036 unit (p= 0.001)Conclusion: HRQOL as measured by the EQ5D in this study was affected in patients with cardiac disease or diabetes. Male gender, advanced age, low socioeconomic status, frequent hospital and doctor visits were important risk factors for a poor HRQOL.
Genome-Wide Identification of Histone Acetyltransferases and Deacetylases in Epiphytic Orchid Plant Dendrobium Catenatum
Authors: Jiang Wei-Wei , Qu Dong-Hai , Tian Ji-Li , Si Jin-Ping , Chen Dong-Hong
Published: September 2020

Background: Dendrobium catenatum is a kind of precious Traditional Chinese Medicine, and possesses unique developmental programs and epiphytic lifestyle. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) are responsible for maintenance of histone acetylation homeostasis, and they are widely involved in developmental regulation and stress responses via remodeling chromatin structure, but their biological functions in orchid plants remain largely unknown.Results: Here we identified 8 HAT genes and 14 HDAC genes from D. catenatum genome. We carried out phylogenetic construction, gene structure and domain architecture analysis of these D. catenatum HAT/HDAC (DcHAT/DcHDAC) proteins using the well-defined homologs from the model plants Arabidopsis thaliana and Oryza sativa as references. DcHAT proteins can be classified into four families: GNAT family (3 members), MYST family (2), CBP family (2), and TAFII250 family (1), and DcHDAC proteins can be grouped into three families: RPD3/HDA1 family (10), SIR2 family (2), and HD2 family (2), in accordance with previously described classification. Cis-acting element analysis indicated that the promoter regions of DcHAT/DcHDAC genes contain diverse stress-responsive elements. Subcellular localization predictions suggested that DcHAT/DcHDAC proteins might be localized in nucleus or/and cytoplasm. Spatiotemporal expression profiling showed that DcHAT/DcHDAC genes generally exhibit either universal or specific expression pattern in different tissues and organs. Finally, stress response assay suggested drought treatment significantly represses the expression of DcHAG1 and DcHDA14, cold exposure evidently influences the expression of DcHAG1 and DcHDT1, and heat shock has a broad impact on the expression of DcHAT/DcHDAC genes.Conclusions: In this study, we reveal the identification and expression profiles of DcHATs and DcHDACs in epiphytic orchid plant D. catenatum, indicating their roles in the regulation of both long-term developmental programs and short-term stress responses. This study provides a foundation for in-depth functional excavation of HATs/HDACs associated with dynamic histone acetylation levels in orchids.
Parasitic Contamination of Fresh Vegetables in Open Air Markets of Aksum, Ethiopia
Authors: Gebremariam Gebrehiwot kiros , Girmay Tsgab Gebrecherkos
Published: September 2020

Background: Intestinal parasitic diseases are the foremost causes of illness in humans, responsible for significant morbidity and mortality. Recently, there have been so many reports related to a foodborne illness linked to consuming fresh vegetables, especially in developing countries. The study was aimed to assess the parasitic contamination level of fresh vegetables collected from open air markets in Aksum town, Tigray region, Ethiopia.Method: A total of 384 samples belonging to six vegetable types were collected randomly from local markets in Aksum town. Samples were washed in saline solution followed by sedimentation for 24 hours.After that the supernatant was decanted leaving the sediment. The sediment was then transferred to a centrifuge tube and centrifuged at 3000 revolution per minute for 5minutes. Finally, the supernatant was decanted and the sediment was examined under light microscope for protozoan cyst, helminthes ova, and larvaeResults: The overall prevalence of parasitic contamination was 57.3%. The Cabbage was the most frequently contaminated (79.7%) vegetable succeeded by Spinach (75%), Lettuce (73.4%), Potato (46.9%), Green pepper (37.5%), and tomato (31.2%). Among the parasites detected, Taenia spp. proglottides/egg was the most frequent contaminant with 41.1% prevalence rate followed by Enetrobius vermicularis egg (20.3%), Hookworm spp.(19.5%), Fasciola spp. egg (17.2%), Giardia lamblia cyst (18.5%), Entamoeba spp. cyst(15.9%), Strongyloides stercoralis larva (12.5%),Ascarislumbricoidese gg (9.4%), and Cryptosporidium spp.Chai-square analysis showed that the type of fertilizer used, educational status of the vendors, status of wash before display, and type of vegetable they produce was statistically and significantly associated with the prevalent parasite forms detected (P < 0.001).Conclusion: This study identified a high prevalence of fresh vegetables contaminated with medically important parasites, thus effective prevention measures such as standard washing before consuming fresh vegetables, and avoiding raw manure as a fertilizer should be implemented to avoid infection from contaminated vegetables.
Correlation of Age and Bone Marrow Derived CD 34+ Cells and Leucocytes in 873 Patients.
Authors: Pabinger Christof , Dammerer Dietmar , Lothaller Harald , Gieringer Sandra , Krall Marcel , Kobinia Georg Stefan
Published: September 2020

Background:The use of regenerative medicine, such as autologous chondrocyte implantation (ACI), matrix associated stem cell therapy (MAST) and bone marrow derived stem cell therapy against arthritis is the gold standard for certain indications. However, the clinical improvement of patients using these novel therapies remains heterogeneous and the reasons for this are not fully understood. The impact of age is always a concern for patients and doctors and elderly patients can only be mobilized with lower total collected CD34+ cells, older age correlates with inferior results, fatty degeneration of the bone marrow, delayed fracture-healing and osteoporosis, but solid data are missing. Purpose:This is the first study to determine the average quantity of leukocytes and CD 34+ cells and their relationship in human bone marrow. Study design: Descriptive Laboratory Study Methods:We evaluated the laboratory results of 873 patients (aged 1-90 years), who underwent stem cell transplantation for non malignant diseases. Results:We found no age-related decrease regarding the number and the vitality of leukocytes and CD 34+ stem cells. The number of bone marrow derived leucocytes and CD 34+ cells showed a strong and significant correlation.Conclusion:The amount of bone marrow derived stem cells can be predicted by leukocytes. This study makes further research possible in order to link clinical outcome to the absolute number of stem cells and leukocytes.An upper age-limit for stem cell therapy can therefore not be defined from the donor-site perspective.Clinical Relevance:The number of leucocytes might be used to predict the amount of stem cells in order to select the ideal patient.
Differential Production and Secretion of Potentially Toxigenic Extracellular Proteins From A Hypervirulent Strain of Aeromonas Hydrophila
Authors: Barger Priscilla Carmen , Liles Mark R , Beck Benjamin H , Newton Joseph C
Published: September 2020

Background: Hypervirulent Aeromonas hydrophila (vAh) is a pathogen in freshwater aquaculture that results in the loss of over 3 million pounds of marketable channel catfish, Ictalurus punctatus, and catfish hybrids (I. punctatus, ♀ x blue catfish, I. furcatus, ♂) each year from freshwater catfish production systems in Alabama, U.S.A. vAh isolates are clonal in nature and are genetically unique from, and significantly more virulent than, traditional A. hydrophila isolates from fish. Even with the increased virulence, natural infections cannot be reproduced in aquaria challenges making it difficult to determine modes of infection and the pathophysiology behind the devastating mortalities that are commonly observed. Despite the intimate connection between environmental adaptation and plastic response, the role of environmental adaption on vAh pathogenicity and virulence has not been previously explored. In this study, secreted proteins of vAh cultured as free-living planktonic cells and within a biofilm were compared to elucidate the role of biofilm growth on virulence. Results: Functional proteolytic assays found significantly increased degradative activity in biofilm secretomes; in contrast, planktonic secretomes had significantly increased hemolytic activity, suggesting higher toxigenic potential. Intramuscular injection challenges in a channel catfish model showed that in vitro degradative activity translated into in vivo tissue destruction. Identification of secreted proteins by HPLC-MS/MS revealed the presence of many putative virulence proteins under both growth conditions. Biofilm grown vAh produced higher levels of proteolytic enzymes and adhesins, whereas planktonically grown cells secreted higher levels of toxins, porins, and fimbrial proteins. Conclusions: This study is the first comparison of the secreted proteomes of vAh when grown in two distinct ecological niches. These data on the adaptive physiological response of vAh based on growth condition increase our understanding of how environmental niche partitioning could affect vAh pathogenicity and virulence. Increased secretion of colonization factors and degradative enzymes during biofilm growth and residency may increase bacterial attachment and host invasiveness, while increased secretion of hemolysins, porins, and other potential toxins under planktonic growth (or after host invasion) could result in increased host mortality. The results of this research underscore the need to use culture methods that more closely mimic natural ecological habitat growth to improve our understanding of vAh pathogenesis.
Neutrophil-to-lymphocyte ratio has limited predictive value for determining outcomes in perforated colon cancer: a retrospective study.
Authors: Wu Chunyi , Chiang Jy-Ming , You Jeng-Fu , Tang Reiping , Chen Jinn-Shiun , Yeh Chien-Yuh , Hsieh Pao-Shiu , Tsai Wen-Sy , Hung Hsin-Yuan , Chiang Sum-Fu , Lai Cheng-Chou
Published: September 2020

Background: The neutrophil-to-lymphocyte ratio (NLR) is a significant prognostic marker in resectable colorectal cancer; however, there are no equivalent findings for perforated colon cancer. Using our colorectal cancer database, we retrospectively analyzed the data from 1995 to 2015 to determine if preoperative NLR was associated with survival outcomes in patients with perforated colon cancer. Methods: One-to-one propensity score matching (PSM) was applied to minimize the difference between the higher- (>5) and lower- (≤5) NLR groups. Clinicopathological factors, long-term overall survival (OS), and disease-free survival (DFS) were analyzed and compared between the two groups. The main outcome measures were OS and DFS. Results: Before PSM, the higher-NLR group had significantly higher prevalence of leukocytosis (lower- vs. higher-NLR groups: 12 [12.9%] vs. 46 [59.7%], p<0.001), lower serum albumin levels (lower- vs. higher-NLR groups: 30 [32.3%] vs. 42 [54.5%], p=0.003), and higher emergent operation rate (lower- vs. higher-NLR groups: 5 [5.4%] vs. 20 [26.0%], p<0.001). After one-to-one PSM, the groups comprised 41 patients each; none of the parameters were significantly different. The mean follow-up period was 76.3 months. Five-year OS and DFS were not significantly different (OS: p=0.637; DFS: p=0.827) between the higher- and lower-NLR groups. Conclusion: NLR have limited predictive value for outcomes in patients with perforated colon cancer.
A New Risk Score Model Based on Lactate Dehydrogenase Predicting Prognosis in Esophageal Squamous Cell Carcinoma Treated With Chemoradiotherapy
Authors: Han Jinmin , Zhou Tao , Liu Chengxin , Li Baosheng
Published: September 2020

Purpose: The current study was to assess the prognostic value of the lactate dehydrogenase (LDH) in esophageal squamous cell cancer (ESCC) patients and to generate a risk score model to predict prognosis in patients who undergone chemoradiotherapy.
Patients and Methods: 614 ESCC patients who received chemoradiotherapy were performed from 2012 to 2016.The optimal cutoff points for continuous variables were calculated by the X-tile program. We analyzed the association between LDH level and clinicopathological characteristics. And a 1:3 propensity score matching analysis was used to compensate for differences in baseline characteristics. The Kaplan-Meier methods and Cox regression models were used to explore the prognostic factors for overall survival (OS) and progression-free survival (PFS). Based on the results, we developed a corresponding risk score model and assessed its predictive capacity in the subgroups.
Results: The optimal cutoff points of age, CEA, Cyfra21-1, tumor length, total dose and LDH were defined as follows:69 years, 2.4 ng/ml, 6.4 ng/ml, 6.5 cm, 58.8Gy and 134 U/L, respectively. A high level of LDH was associated with advanced M stage (p=0.005) and larger tumor length (p=0.026). Patients in the high-LDH group had shorter PFS and worse OS than those in the low-LDH group. Multivariate survival analysis indicated that pretreatment serum LDH level (p=0.039)，Cyfra21-1 level (p=0.003), tumor length (p=0.013), clinical N stage (p=0.047) and clinical M stage (p=0.011) were independent predictors for OS. Furthermore, a risk score model based on these five prognostic factors was established to divide patients into three groups with obvious prognosis (χ2 = 20.53, p< 0.0001).
Conclusion: Pretreatment serum LDH levels may be a reliable factor in predicting the therapeutic effect of chemoradiotherapy in ESCC. A risk score model combined LDH, Cyfra21-1 and other prognostic factors could help to guide a personalized management. Further validation is needed before widely used in clinical practice.
Hypofractionated Proton Beam Radiotherapy in Patients With Unresectable Liver Tumors: Multi-institutional Prospective Results From the Proton Collaborative Group
Authors: Parzen Jacob S , Hartsell William , Chang John , Apisarnthanarax Smith , Molitoris Jason , Durci Michael , Tsai Henry , Urbanic James , Ashman Jonathan , Vargas Carlos , Stevens Craig , Kabolizadeh Peyman
Published: September 2020

Background: Recent advances in radiotherapy techniques have allowed ablative doses to be safely delivered to inoperable liver tumors. In this setting, proton beam radiotherapy (PBT) provides the means to escalate radiation dose to the target volume while sparing the uninvolved liver. This study evaluated the safety and efficacy of hypofractionated PBT for liver tumors, predominantly hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).Methods: We evaluated the prospective registry of the Proton Collaborative Group for patients undergoing definitive PBT for liver tumors. Demographic, clinicopathologic, toxicity, and dosimetry information were compiled.Results: To date, 63 patients have been treated at 9 institutions between 2013-2019. Thirty (48%) had HCC and 25 (40%) had ICC. The median dose and biological equivalent dose (BED) delivered was 58.05 GyE (range, 32.5-75) and 80.5 GyE (range, 53.6-100), respectively. The median mean liver BED was 13.9 GyE. Three (4.8%) patients experienced at least one grade ³3 toxicity. With median follow-up of 5.1 months (range, 0.1-40.8), the local control (LC) rate at 1 year was 91.2% for HCC and 90.9% for ICC. The 1-year LC was significantly higher (95.7%) for patients receiving BED greater than 75.2 GyE than for patients receiving BED of 75.2 GyE or lower (84.6%, p = 0.029). The overall survival rate at 1 year was 65.6% for HCC and 81.8% for ICC. Conclusions: Hypofractionated PBT results in excellent LC, sparing of the uninvolved liver, and low toxicity, even in the setting of dose-escalation. Higher dose correlates with improved LC, highlighting the importance of PBT especially in patients with recurrent or bulky disease.
Identification of Long Non-Coding RNAs Involved in Fat Deposition in Pigs Using Two High-Throughput Sequencing Methods
Authors: Liu Yibing , Ao Hong , Zhang Fengxia , Zhao Xitong , Liu Huatao , Shi Yong , Xing Kai , Yu Ying , Wang Chuduan
Published: September 2020

Background: Adipose is an important body tissue in pigs, and fatty traits are critical in pig production. The function of long non-coding RNA (lncRNA) in fat deposition and metabolism has been proven in previous studies. In this study, we focused on lncRNAs associated with fattening traits in pigs. The adipose tissue of six Landrace pigs with either extremely-high or -low backfat thickness ( n high = 3, n low = 3) was collected, after which we performed strand-specific RNA sequencing using biological replicates and pooling methods. Results: A total of 19,631 genes and 2,013 lncRNAs were identified using the coding potential calculator, coding-non-coding index, and Pfam database, including 334 known transcripts and 1,679 novel transcripts. Using edgeR, we determined that 220 lncRNAs and 1,512 genes were differentially expressed (|Fold Change| > 2 and false discovery rate < 0.05) between the two groups in biological replicate RNA sequencing (RNA-seq), and 127 lncRNAs and 2,240 genes were differently expressed in pooling RNA-seq. Further Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis of the differentially expressed genes found that some of the genes were involved in several key pathways related to fat development. After targeting gene prediction, we determined that some cis-target genes of the differentially expressed lncRNAs play an important role in fat deposition. For example, ACSL3 is cis-targeted by lncRNA TCONS-00052400, and it can activate the conversion of long-chain fatty acids. In addition, lncRNA TCONS_00041740 was up-regulated in the high backfat thickness group, and its cis-target gene ACACB was also up-regulated in this group. It has been reported that ACACB is the rate-limiting enzyme in fatty acid oxidation. Conclusions: Since these genes have necessary functions in fat metabolism, the results imply that the lncRNAs detected in our study may affect fat deposition in pigs through regulation of their target genes. In summary, our study explored the regulation of lncRNA and their target genes on fat deposition in pigs and provided new insights for further investigation of the biological functions of lncRNA.
Synthesis,Surface Morphology, Optical Properties and Photocatalyst Activities of TiO2/ZnO/Fe2O3 Nanocomposites.
Authors: Parambil Juliya Acha , V.M Abdul Mujeeb , Karazhanov S. Zh. , Peediyekkal Jayaram
Published: September 2020

The photocatalytic degradation of methylene blue in aqueous solutions is enhanced significantly by formulating multiphase TiO2/ZnO/Fe2O3 nanocomposites. The photocatalytic activity of unary TiO2, binary TiO2/ZnO, and ternary TiO2/ZnO/Fe2O3 compounds are compared and reported. Using TiO2/ZnO/Fe2O3, methylene blue degradation became rapid and the reaction followed first-order kinetics. The consequences of the phase transition, surface features, and optical properties are compared and elucidated. The reduced photoluminescence intensity and decreased optical band gap energy in tertiary compounds impose higher degradation of methylene blue under irradiation.
Cell Banking of HEK293T Cell Line for Clinical-Grade Lentiviral Particles Manufacturing
Authors: Perpiña Unai , Herranz Cristina , Martin-Ibañez Raquel , Boronat Anna , Chiappe Felipe , Monforte Verónica , Orpella-Arecet Gemma , González Ester , Olive Myriam , Castella María , Suñe Guillermo , Urbano-Ispizua Alvaro , Delgado Julio , Juan Manel , Canals Josep M.
Published: September 2020

Background: Cell banks have been widely used to preserve cell properties as well as to record and control cell line access in research. However, the generation of cell banks involved in the manufacturing of Advanced therapy medicinal products such as cell or gene therapy products must comply with the current Good Manufacturing Practice regulation. Similarly, the quality of those cell lines used as starting materials in viral-vector manufacturing processes must be also evaluated.Methods: Three batches of both Master Cell Bank and Working Cell Bank of the HEK293T cell line were manufactured under the current Good Manufacturing Practices regulation. Quality control test were performed according to the product specifications. The process validation includes previous qualification of the manufacturing personnel by performing simulation tests as well as the continuous measure of environmental parameters during manufacturing such as air particles and microorganism. Cell number and viability of cryopreserved cells were periodically measured in order to define the stability of these cellular products.Results: All batches of Master Cell Bank and Working Cell Bank fulfilled the acceptance criteria of their specifications showing the robustness and homogeneity of the processes. In addition, both Master and Working cell bank maintain the defined viability and cell number 37 months after cryopreservation. Conclusions: Manufacturing cell banks under Good Manufacturing Practices regulation for its use as raw material or final cellular product is feasible. HEK293T cell banks have been used to manufacture clinical-grade lentiviral particles for Chimeric Antigen Receptor T-cell based clinical trials.
Identification of the Role of GLS2 in the Development and Progression of Clear Cell Renal Cell Carcinoma.
Authors: sun dantong , tian lu , wo yang , zhao han , yan weihua , wei xiaojuan , Li Hong , Hou Helei
Published: September 2020

Background The incidence of RCC has drastically increased in recent years. The large intratumor heterogeneity of RCC, especially ccRCC, usually leads to treatment failure. In addition, single biomarkers have a limited ability to predict prognosis. Therefore, we performed this study to select variables and provided a simple but efficient way to predict prognosis.MethodThree studies from GEO database were involved in the DEGs selection. A total of 840 RCC patients and 524 ccRCC patients from TCGA database were involved in the prognostic analyses. Nomograms based on Cox regression model were used to select variables to predict the prognosis, and GSEA was used to demonstrate the potential pathways altered by gene expression.ResultOur study suggested that DEGs existed between metastatic and primary tumor tissues. Loss of GLS2 was related to poor prognosis in RCC and ccRCC. These results revealed that GLS2 expression, combined with basic characteristics, including age and TNM stage, could efficiently predict prognosis. GLS2 serves as a tumor suppressor in ccRCC, loss of GLS2 function endows cells with oncogenic functions and is related to advanced disease. According to the GSEA results, loss of GLS2 function may alter the cell cycle by activating the E2F pathway.ConclusionGLS2 is a tumor suppressor in RCC. Loss of GLS2 function in ccRCC predicts a poor prognosis via the underlying E2F pathway. Nomograms based on DEGs and clinical features provide physicians with a simple but efficient way to predict prognosis. Further studies are needed to verify the pathway in our study.
Characteristics and outcomes of culture-negative versus culture-positive with fungus in sepsis patients: a retrospective analysis of the MIMIC-III database
Authors: Zou Zhiye , Wu Ming
Published: September 2020

BACKGROUND: We compared the characteristics of culture-positive and culture-negative with fungi in septic patients to determine whether fungi culture status is associated with mortality and the relationship between antifungal therapy and sepsis patient mortality.METHODS: The study was based on the Medical Information Mart for Intensive Care (MIMIC) III database, we included all intensive care unit (ICU) admissions between 2001 and 2012 with sepsis, which met the Martin’s criteria. The primary outcome was hospital mortality. Secondary outcomes included the usage of antifungal drugs, duration of mechanical ventilation and hospital stay. Multivariable logistic regression and propensity score matching were used to investigate any association.RESULTS: The study population included 836 fungi-positive patients (16.6%) and 4191 fungi-negative patients (83.4%). Fungi-positive patients had more congestive heart failure and chronic pulmonary, higher sequential organ failure assessment (SOFA), and more need for renal replacement therapy on day one than fungi-negative patients. There was no correlation between antifungal therapy and hospital mortality (adjusted odds ratio = 1.03, 95% CI [0.89, 1.20]; P=0.676）. Hospital mortality was lower in the fungi-negative group (25.5%) than in the fungi-positive group (37.3%, P<0.001). After propensity score matching, 613 cases from each group were matched. The hospital mortality remained significantly higher in the fungi-positive group (167/613 vs. 216/613, p=0.003).CONCLUSIONS: Although residual confounding cannot be excluded, significant differences between fungi-positive and fungi-negative sepsis are identified, with the former group having more comorbidities, worse severity of illness, longer hospitalizations, and higher mortality. Antifungal therapy does not affect the outcome.
An External Pilot Cluster Randomised Controlled Trial of a Theory-based Intervention to Improve Appropriate Polypharmacy in Older People in Primary Care (Polyprime): Study Protocol
Authors: Rankin Audrey , Cadogan Cathal A , Barry Heather E , Gardner Evie , Agus Ashley , Molloy Gerard J , Gorman Ashleigh , Ryan Cristín , Leathem Claire , Maxwell Marina , Gormley Gerard J , Ferrett Alan , McCarthy Pat , Fahey Tom , Hughes Carmel M
Published: September 2020

Background: The use of multiple medications (polypharmacy) is a concern in older people (≥65 years) and is associated with negative health outcomes. For older populations with multimorbidity, polypharmacy is the reality and the key challenge is ensuring appropriate polypharmacy (as opposed to inappropriate polypharmacy). This external pilot cluster randomised controlled trial (cRCT) aims to further test a theory-based intervention to improve appropriate polypharmacy in older people in primary care in two jurisdictions, Northern Ireland (NI) and the Republic of Ireland (ROI).Methods: Twelve GP practices across NI (n=6) and the six counties in the ROI that border NI will be randomised to either the intervention or usual care group. Members of the research team have developed an intervention to improve appropriate polypharmacy in older people in primary care using the Theoretical Domains Framework of behaviour change. The intervention consists of two components: 1) an online video which demonstrates how a GP may prescribe appropriate polypharmacy during a consultation with an older patient; and 2) a patient recall process, whereby patients are invited to scheduled medication review consultations with GPs. Ten older patients receiving polypharmacy (≥4 medications) will be recruited per GP practice (n=120). GP practices allocated to the intervention arm will be asked to watch the online video and schedule medication reviews with patients on two occasions; an initial and a 6-month follow-up appointment. GP practices allocated to the control arm will continue to provide usual care to patients. The study will assess the feasibility of recruitment, retention and study procedures including collecting data on medication appropriateness (from GP records), quality of life and health service use (i.e. hospitalisations). An embedded process evaluation will assess intervention fidelity (i.e. was the intervention delivered as intended), acceptability of the intervention and potential mechanisms of action.Discussion: This pilot cRCT will provide evidence of the feasibility of a range of study parameters such as recruitment and retention, data collection procedures and the acceptability of the intervention. Pre-specified progression criteria will also be used to determine whether or not to proceed to a definitive cRCT.Trial registration: ISRCTN, ISRCTN41009897. Registered 19 November 2019, https://doi.org/10.1186/ISRCTN41009897. Clinicaltrials.gov, NCT04181879. Registered 02 December 2019, https://clinicaltrials.gov/ct2/show/NCT04181879.
Do they really wash their hands? Prevalence estimates for personal hygiene behaviour during the coronavirus crisis based on indirect questions
Authors: Mieth Laura , Mayer Maike , Hoffmann Adrian , Buchner Axel , Bell Raoul
Published: September 2020

Background: During the so-called coronavirus crisis, billions of people have to change their behaviours to slow down the pandemic. Protective measures include self-isolation, social (physical) distancing and compliance with personal hygiene rules, particularly regular and thorough hand washing. To adjust public information campaigns to the level of people’s commitment and to evaluate the effectiveness of these campaigns, valid information about the degree to which people comply with protective measures is desirable.Methods: However, during a health crisis there is strong public pressure to comply with health and safety regulations so that people’s responding in direct questionings may be seriously compromised by social desirability. Here we use an indirect questioning technique to test whether the prevalence of hygiene practices may be lower when confidentiality of responding is guaranteed.Results: In the direct questioning group 94.5 % of the participants claimed to practice proper hand hygiene; in the indirect questioning group a significantly lower estimate of only 78.1 % was observed.Conclusions: These results indicate that estimates of the degree of commitment to measures designed to counter the spread of the disease may be significantly inflated by social desirability in direct questionings. Indirect questioning techniques with higher levels of confidentiality seem helpful in obtaining more realistic estimates of the degree to which people follow the recommended personal hygiene measures.