bluuebunny/crossref_metadata_2025_split huggingface dataset:
The relationship between survival gastric cancer patients and neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio diagnosed before surgery
Authors: Mohammadi Sareh , Veisi Zeinab , Moazeni Mohammad , Kheiri Soleiman , Lorigooini Zahra , masomi Rohollah 
Published: November 2020

Abstract
Aim: This study aims to investigate the relationship of two prognostic factors NLR and PLR to patient survival in gastric cancer patients diagnosed before surgery.Background: Due to the high prevalence of gastric cancer and the lack of appropriate prognostic factors, most patients are diagnosed at advanced stages of the disease. Therefore, this study aimed to determine the appropriate prognostic factor investigated investigate the relationship of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in gastric cancer patients.Methods: This retrospective study was performed on all gastric cancer patients referred to Kashani Hospital of Shahrekord (Chaharmahal and Bakhtiari province) in 2011-2016. Demographic and biological variables such as NLR and PLR were evaluated. Patient survival was calculated by subtracting the date at disease diagnosis (using endoscopy) from the date at death and expressed in month. Data was analyzed by SPSS software.Results: The mean age of patients was 63.79 ± 15.03 (range: 10-92) years. 76% of patients were male and the rest were female. Only NLR had significant effect on survival (P < 0.05) and PLR had no significant effect on survival (P > 0.05).Conclusion: With the increase in NLR by one point, the risk of death in gastric cancer patients increased by 18%. In other words, with increase in NLR, survival rate of gastric cancer after surgery significantly decreased. It is suggested that further studies be conducted with a more statistical population to ensure the reproducibility of the results of the present study.
U-IMD: The First Unified European Registry for Inherited Metabolic Diseases
Authors: Opladen Thomas , Gleich Florian , Kozich Viktor , Scarpa Maurizio , Martinelli Diego , Schaefer Franz , Jeltsch Kathrin , Palacios Natalia Julia , Cazorla Angels Garcia , Vici Carlo Dionisi , Kölker Stefan 
Published: November 2020

Abstract
Background: Following the broad application of new analytical methods, more and more pathophysiological processes in previously unknown diseases have been elucidated. The spectrum of clinical presentation of rare inherited metabolic diseases (IMDs) is broad and ranges from single organ involvement to multisystemic diseases. With the aim of overcoming the limited knowledge about the natural course, current diagnostic and therapeutic approaches, the project has established the first unified patient registry for IMDs that fully meets the requirements of the European Infrastructure for Rare Diseases (ERDRI). Results: In collaboration with the European Reference Network for Rare Hereditary Metabolic Disorders (MetabERN), the Unified European registry for Inherited Metabolic Diseases (U-IMD) was established to collect patient data as an observational, non-interventional natural history study. Following the recommendations of the ERDRI the U-IMD registry uses common data elements to define the IMDs, report the clinical phenotype, describe the biochemical markers and to capture the drug treatment. Until today, more than 1100 IMD patients have been registered.Conclusion: The U-IMD registry is the first observational, non-interventional patient registry that encompasses all known IMDs. Full semantic interoperability for other registries has been achieved, as demonstrated by the use of a minimum common core data set for equivalent description of metabolic patients in U-IMD and in the patient registry of the European Rare Kidney Disease Reference Network (ERKNet). In conclusion, the U-IMD registry will contribute to a better understanding of the long-term course of IMDs and improved patients care by understanding the natural disease course and by enabling an optimization of diagnostic and therapeutic strategies.
Exome Sequencing in Paediatric Patients with Movement Disorders with Treatment Possibilities
Authors: Kwong Anna Ka-Yee , Tsang Mandy Ho-Yin , Fung Jasmine Lee-Fong , Mak Christopher Chun-Yu , Chan Kate Lok-San , Rodenburg Richard J.T. , Lek Monkol , Huang Shushu , Pajusalu Sander , Yau Man-Mut , Tsoi Cheung , Fung Sharon , Liu Kam-Tim , Ma Che-Kwan , Wong Sheila , Yau Eric Kin-Cheong , Tai Shuk-Mui , Fung Eva Lai-Wah , Wu Nick Shun-Ping , Tsung Li-Yan , Smeitink Jan , Chung Brian Hon-Yin , Fung Cheuk-Wing 
Published: November 2020

Abstract
Background: Movement disorders are a group of heterogeneous neurological diseases including hyperkinetic disorders with unwanted excess movements and hypokinetic disorders with reduction in the degree of movements. The objective of our study is to investigate the genetic etiology of a cohort of paediatric patients with movement disorders by whole exome sequencing and to review the potential treatment implications after a genetic diagnosis. Results: We studied a cohort of 31 patients who have paediatric-onset movement disorders with unrevealing etiologies. Whole exome sequencing was performed and rare variants were interrogated for pathogenicity. Genetic diagnoses have been confirmed in 10 patients with disease-causing variants in CTNNB1, SPAST, ATP1A3, PURA, SLC2A1, KMT2B, ACTB, GNAO1 and SPG11. 80% (8/10) of patients with genetic diagnosis have potential targeted treatment implications and treatments have been offered to them. One patient with KMT2B dystonia showed clinical improvement with decrease in dystonia after receiving globus pallidus interna deep brain stimulation. Conclusion: A diagnostic yield of 32% (10/31) was reported in our cohort and this allows a better prediction of prognosis and contributes to a more effective clinical management using targeted therapies. The study highlights the potential of implementing precision medicine in the patients.
A Novel Two-phase Cycle Algorithm for Effective Cyber Intrusion Detection in Edge Computing
Authors: Gong Yiguang , Liu Yunping , Yin Chuanyang 
Published: November 2020

Abstract
Edge computing extends traditional cloud services to the edge of the network, closer to users, and is suitable for network services with low latency requirements. With the rise of edge computing, its security issues have also received more and more attention. In this paper, a novel two-phase cycle algorithm is proposed for effective cyber intrusion detection in edge computing based on multi-objective genetic algorithm (MOGA) and modified back propagation neural network (MBPNN), namely TPC-MOGA-MBPNN. In the first phase, the MOGA is employed to build multi-objective optimization model that tries to find Pareto optimal parameter set for MBPNN. The Pareto optimal parameter set is applied for simultaneous minimization of average false positive rate (Avg FPR), mean squared error (MSE), and negative average true positive rate (Avg TPR) in the dataset. In the second phase some MBPNNs are created based on the parameter set obtained by MOGA and are trained to search for more optimal parameter set locally. The parameter set obtained in the second phase is used as the input of the first phase, and the training process is repeated until the termination criteria are reached. Benchmark dataset namely KDD cup 1999 is used to demonstrate and validate the performance of the proposed approach for intrusion detection. The proposed approach can discover a pool of MBPNN based solutions. Combining these MBPNN can significantly improve prediction performance, and a GA is used to find the optimal MBPNN combination. The result shows that the proposed approach could reach an accuracy of 98.81% and a detection rate of 98.23%, which outperform most systems of previous works found in the literature. In addition, the proposed approach is a generalized classification approach that is applicable to the problem of any field having multiple conflicting objectives.
Chimeric Antigen Receptor T Cells Engineered to Secrete CD40 Agonist Antibodies Enhance Antitumor Efficacy
Authors: Zhang Yajun , Wang Pei , wang tengjiao , Fang Yuan , Ding Yongmei , Qian Qijun 
Published: November 2020

Abstract
BackgroundAlthough chimeric antigen receptor (CAR) T-cell therapy has made remarkable achievements against hematological malignancies, the efficacy of it against solid tumors has been limited. By being combined with immune checkpoint inhibitors, such as PD-1, PD-L1, or CTLA-4 antibodies, this therapy has been shown to be a promising strategy to enhance the antitumor efficacy of CAR-T cells. However, due to the fact that acquired resistance to checkpoint inhibitors will occur in most patients, it is vital to investigate other strategies to further improve the antitumor efficacy of CAR-T cell therapy in solid tumors. Recently, CD40 agonist antibodies have been shown to possess potential antitumor efficacy by activating the CD40 pathway.ResultsBased on the piggyBac transposon system, rather than the widely used viral vector, we constructed a meso3-CD40 CAR-T targeting region III of mesothelin (MSLN) that possesses the ability to secrete anti-CD40 antibodies. The results show that compared with meso3 CAR-T, which does not secrete the anti-CD40 antibody, meso3-CD40 CAR-T secreted more cytokines and had a relatively higher proportion of central memory T (TCM) cells after being stimulated by the target antigen. In addition, compared with meso3 CAR-T, we found that meso3-CD40 CAR-T had a more powerful cytotoxicity effect on target cells at a relatively low effector to target ratio. More importantly, we demonstrated that meso3-CD40 CAR-T also had enhanced antitumor activity in a human ovarian cancer xenograft in vivo.ConclusionsIn conclusion, these results showed that anti-CD40-secreting CAR-T cells generated by non-viral vectors could be a potential clinical strategy for improving the efficacy of CAR-T cell therapies.
Higher-Order Kinematics Modeling of 3-RRS Parallel Mechanism Based on CGA
Authors: Wang Chang , Zhao Tieshi , Li Erwei , Zhao Yanzhi , Bian Hui , Geng Mingchao 
Published: November 2020

Abstract
Higher-order kinematics of mechanisms has been applied in servo motor control, human-robot interaction and machinery life design fields, etc. The representations of acceleration and jerk by screws have been fully developed by researchers with the methods of the differential of the matrix representation of SE(3) group. Clifford algebra, which is tighter and with higher computational efficiency than the matrix method, is another representation of the motions of rigid bodies. It has been used in position kinematics, grub task motion planning, and robot vision for its convenience of geometric representations and calculations. As far as we know, the work of higher-order kinematics of mechanisms based on Clifford algebra is rare. First, after recalling the based theory of motion representation in conformal geometric algebra (CGA), the mathematical relationships between flag and motor are built. Second, a method for the higher-order kinematics modeling of serial chain mechanisms is proposed. Finally, the higher-order kinematics of the 3-RRS parallel mechanism is built to prove the correctness of the algorithm. This work further enriches the application of CGA for the higher-order kinematics modeling of parallel mechanisms.
The Efficacy and Safety of Niraparib for Advanced Ovarian Cancer: A Single-center Observational Study From China
Authors: Ni Jing , Cheng Xianzhong , Zhao Qian , Dai Zhiqin , Xu Xia , Guo Wenwen , Gu Hongyuan , Zhou Rui , chen xiaoxiang 
Published: November 2020

Abstract
BackgroundNiraparib, a poly (ADP-ribose) polymerase (PARP) inhibitor, is approved for first/second-line maintenance treatment of ovarian cancer patients with complete or partial response to platinum-based chemotherapy, and multi-line monotherapy in BRCAmt patients or platinum-sensitive recurrence patients with homologous recombination deficiency (HRD) positive. We present real-world experience from China. MethodsPatients with niraparib in Jiangsu Cancer Hospital between June 2019 to July 2020 were recruited. The initial dose was given according to individualization. Response and adverse events (AEs) were analyzed by Response Evaluation Criteria in Solid Tumors v1.1. and National Cancer Institute Common Terminology Criteria for Adverse Events v5.0, respectively. HRD testing (AmoyDx®) was detected in most patients. Treatment was given until unequivocal progression or intolerable toxicity. ResultsTwenty-two patients all received niraparib at an bolus of 200mg/d. 50% of patients with high-grade serous ovarian cancer are HRD-positive. Six patients underwent first-line maintenance therapy. Sixteen patients received exploratory therapy. Ultimately image evaluation revealed that two patients achieved partial response (PR) and one patient achieved stable disease (SD), yielding objective response rate (ORR) of 33.3% (95%CI=0.060-0.759) and DCR of 50% (95%CI=0.140-0.861) in the exploratory multi-line monotherapy group. Commonly AEs were nausea, thrombocytopenia, and anemia. Grade 3-4 thrombocytopenia were managed by dose reduction and interruption. Leg swelling was observed as a new adverse event. Conclusion﻿It is feasible for patients received a bolus of 200mg/d in Chinese population with promising efficacy and well tolerated. This is first real world data about niraparib in ovarian cancer patients with HRD status from China.
DegSampler: Gibbs sampling strategy for predicting E3-binding sites with position-specific prior information
Authors: Maruyama Osamu , Matsuzaki Fumiko 
Published: November 2020

Abstract
Background: The ubiquitin-proteasome system is a pathway in eukaryotic cells for degrading polyubiquitin-tagged proteins through the proteasomal machinery to control various cellular processes and maintain intracellular homeostasis. In this system, the E3 ubiquitin ligase (hereinafter E3) plays an important role in selectively recognizing and binding to specific regions of its substrate proteins. The relationship between a substrate protein and its sites bound by E3s is not well understood. Thus, it is challenging to computationally identify such sites in substrate proteins. Results: In this study, we proposed a collapsed Gibbs sampling algorithm called DegSampler (Degron Sampler) to identify the binding sites of E3s. DegSampler employs a position-specific prior probability distribution, based on the estimated information of the disorder-to-order region bound by any protein. Conclusions: Our computational experiments show that DegSampler achieved 5 and 3.5 times higher the F-measure values of MEME and GLAM2, respectively. Thus DegSampler is the first model demonstrating an effective way of using estimated information on disorder-to-order binding regions in motif discovery. We expect our results to improve further as higher quality proteome-wide disorder-to-order binding region data become available.
The Impact of Childhood Psychological Maltreatment on Mental Health Outcomes in Adulthood: A Protocol for a Systematic Review and Meta-Analysis
Authors: Xiao Zhuoni , Baldwin Mina Murat , Meinck Franziska , Obsuth Ingrid , Murray Aja Louise 
Published: November 2020

Abstract
Background: Research suggests that childhood psychological maltreatment (i.e., emotional abuse and emotional neglect) is associated with mental and physical health problems that persist into adulthood, for example anxiety, depression, post-traumatic stress disorder (PTSD), suicidal ideation, and aggression; however, a systematic review and meta-analysis of the existing literature would help clarify the magnitude and moderators of these associations, and the extent to which they may be affected by publication bias, as well as the methodological strengths and weakness of studies in this area.Method: Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guideline will be employed to structure the review. Several searches will be carried out via databases including Web of Science, Medline, PubMed, PsycINFO, Applied Social Science Index and Abstract, ERIC and EMBASE. Empirical peer reviewed research articles that fit pre-specified eligibility criteria will be included in the review. This review will include literature written in either English or Chinese. Two independent reviewers will screen and assess studies for inclusion in the review as well as extract the data, with consensus reached through discussion in cases of discrepancy. A third reviewer will be consulted to resolve any discrepancies that cannot be resolved through discussion between the original reviewers. The relevant Newcastle-Ottawa scales will be used for assessing the quality of studies. If a sufficient number of comparable studies are retrieved, a meta-analysis will be conducted using a random effects model. Discussion: This systematic review will provide an understanding of the long-term effects of childhood psychological maltreatment on adult mental health, which adds to previous reviews focusing primarily on the effects of physical and sexual abuse. The results of the review will help inform clinical practice in approaches to treating those with a history of psychological maltreatment in childhood. The gaps and weaknesses in the evidence identified will also inform recommendations for future research.
Circulating Tumor Cells and TWIST Expression in Patients with Metastatic Gastric Cancer
Authors: Jhi Joon Hyung , Kim Gwang Ha , Park Su Jin , Kim Dong Uk , Lee Moon Won , Lee Bong Eun , Kwon Chae Hwa , Cho Yoon-Kyoung 
Published: November 2020

Abstract
Background: The clinical significance of circulating tumor cells (CTCs) and TWIST expression in CTCs remains unelucidated in patients with gastric cancer (GC). Here, we evaluated CTCs and TWIST expression in CTCs and explored their correlation with prognosis in patients with metastatic GC. Methods: Peripheral blood samples were prospectively obtained from 31 patients with metastatic GC between September 2017 and December 2018, prior to treatment. CTCs were detected using a centrifugal microfluidic system and CTCs positive for TWIST immunostaining were defined as TWIST (+) CTCs. CTCs and TWIST (+) Results: CTCs were detected in 25 (80.6%) of the 31 patients. CTC count in patients with first diagnosis of metastatic cancer tended to be higher than that in those with recurrent metastatic cancer, but TWIST (+) CTC count was not different between the two groups. There was no difference in CTC and TWIST (+) CTC counts according to histopathologic type, peritoneal dissemination, hematogenous metastasis, serum tumor makers, or response to first-line chemotherapy. Patients with CTCs >7.5/7.5 mL of blood showed shorter overall survival (OS) than those with CTCs ≤7.5/7.5 mL of blood (P = 0.049). Additionally, patients with TWIST (+) CTCs >2.5/7.5 mL of blood showed shorter OS than those with TWIST (+) CTCs ≤2.5/7.5 mL of blood (P = 0.105). Conclusions: Our study demonstrated that high levels of CTCs and TWIST (+) CTCs were associated with worse OS.
Size, Composition and Distribution of Health Workforce in India: Why, and Where to Invest?
Authors: Karan Anup , Negandhi Himanshu , Hussain Suhaib , Zapata Tomas , Mairembam Dilip , De Graeve Hilde , Buchan James , Zodpey Sanjay 
Published: November 2020

Abstract
BACKGROUND: Investment in human resources for health not only strengthen the health system but also generates employment and contributes to economic growth. India can gain from enhanced investment in health workforce in multiple ways. This study in addition to presenting updated estimates on size and composition of health workforce, identifies areas of investment in health workforce in India. METHODS: We analyzed two sources of data: i) National Health Workforce Account (NHWA) 2018 and ii) Periodic Labour Force Survey 2017-18 of the National Sample Survey Office (NSSO). Using the two sources we collated comparable estimates of different categories of health workers in India, density of health workforce and skill-mix at the all India and state levels. RESULTS: The study estimated (from NHWA 2018) a total stock of 5.76 million health workers which included allopathic doctors (1.16 million), nurses/midwives (2.34 million), pharmacist (1.20 million), dentists (0.27 million), and traditional medical practitioner (AYUSH 0.79 million). However, the active health workforce size estimated (from NSSO2017-18) is much lower (3.12 million) with allopathic doctors and nurses/midwives estimated as 0.80 million and 1.40 million respectively. Stock density of doctor and nurses/mid-wives are 8.8 and 17.7 respectively per 10,000 persons as per NHWA. However, active health workers’ density (estimated from NSSO) of doctor and nurses/mid-wives are estimated to be 6.1 and 10.6 respectively. The numbers further drop to 5.0 and 6.0 respectively after accounting for the adequate qualifications. All these estimates are well below the WHO threshold of 44.5 doctor, nurses and midwives per 10,000 population. The results reflected highly skewed distribution of health workforce across states, rural-urban and public-private sectors. A substantial proportion of active health worker were found not adequately qualified on the one hand and on the other more than 20% of qualified health professionals are not active in labour markets. CONCLUSION: India needs to invest in HRH for increasing the number of active health workers and also improve the skill-mix which requires investment in professional colleges and technical education. India also needs encouraging qualified health professionals to join the labour markets and additional trainings and skill building for already working but inadequately qualified health workers.
Influence of 200 Years of Water Resource Management on a Typical Central European River&nbsp;
Authors: Wolf Stefanie Sabine , Esser Verena , Schüttrumpf Holger , Lehmkuhl Frank 
Published: November 2020

Abstract
Background Over the last 200 years, most European river courses experienced significant irreversible changes. These changes were connected with different kinds of anthropogenic river use and exploitation, which varied from running water mills and rafting to large-scale hydroelectric power plants, industrial water withdrawal and measures for flood protection. Today, in most of the developed countries water quality and ecological river development are stakeholders in water management. The aim of the following study is to evaluate the specific impact of different time periods during the last 200 years on river courses, and its effects on the current river management using the example of the 165 km long German Rur River (North Rhine-Westphalia). The Rur River is a representative central European upland to lowland river, whose catchment has been affected by various phases of industrial development.MethodsIn this study, large-scale morphological changes over the last 200 years are determined based on historic maps and up-to-date orthophotos. The indicators river length, sinuosity, oxbow structures, sidearms and the number of islands are used to investigate human impact. The results are correlated with historic time periods.ResultsThis analysis shows that river straightening does increase especially during the industrial revolution, even without direct hydraulic channelization, which applies not only to the study area but also to further examples worldwide. The period and grade of river straightening has a direct morphodynamic impact on today’s river restorations. Since the Rur River is a typical upland to lowland river, the results show additional impact of geo-factors, like landform configurations.ConclusionsThe morphodynamic development is correlated with five historic periods between 1801 and 2019 of industrial development up to the introduction of the EU - Water Framework Directive (EU-WFD). Each period shows different influence on the watercourse which is connected with human intervention. Even if worldwide comparisons show that the five historical phases differ slightly in time between regions, they are applicable to other study areas.