bluuebunny/crossref_metadata_2025_split huggingface dataset:
Title Does Definitive Local Therapy Offer Cure in Select HER2+ De Novo Metastatic Breast Cancer Patients Treated with Dual Anti-HER2 Blockade?
Authors: Rosier Luderve , Wang Youth , Lee Jihyun , Daily Karen 
Published: June 2021

Abstract
Purpose: The role of surgery with curative intent in HER2+ de novo metastatic breast cancer (dnMBC) is uncertain in the era of dual antibody therapy. We sought to determine from existing retrospective data current practice patterns and if an association exists between surgery to the primary tumor and improved survival in HER2+ dnMBC patients treated with dual anti-HER2 blockade, accounting for selection bias.Methods: This study employed data from the National Cancer Database (NCDB) from the years 2013 to 2015. Study inclusion was limited to adult women with HER2+ dnMBC, who received immunotherapy/biologic response modifier drugs (BRM) as a first line treatment. Patients who received both systemic therapy and surgery to the primary breast tumor and patients who received systemic therapy alone were analyzed in two groups. Chi-square test for discrete variables and Wilcox on Rank-Sum test for numeric variables was used to compare the two groups based on patient, tumor, and treatment characteristics. The primary endpoint was overall survival from the time of diagnosis to the time of death.Results: 928 women with HER2+ dnMBC treated with BRM were identified with 43.5% (n= 404) receiving surgery and 56.5% (n= 524) receiving systemic therapy alone. The 3-year overall survival was superior for the surgery group (74.1%, 95% CI 67.9-79.2%) compared to the no surgery group (53.3%; 95% CI 47.6-58.6%). The no surgery group had median overall survival of 39.8 months (95% CI 34.1-44.9), while the surgery group had not yet reached median overall survival.Conclusion: In a group of HER2+ dnMBC patients receiving systemic treatment in the era of dual antibody therapy, patients who underwent surgery had a superior 3-year survival rate than those who did not. There may be a role for HER2+ dnMBC patients with an excellent response to dual HER2 blockade to undergo curative intent local therapy to the primary tumor.
The Potential Oncogenic and MLN4924-Resistant Effects of CSN5 on Cervical Cancer Cells
Authors: Zhang Huilin , He Ping , Zhou Qing , Lu Yan , Lu Bingjian 
Published: June 2021

Abstract
BackgroundsCSN5, a member of Cop9 signalosome, is essential for protein neddylation. It has been supposed to serve as an oncogene in some cancers. However, the role of CSN5 has not been investigated in cervical cancer yet.MethodsData from TCGA cohorts and GEO dataset was analyzed to examine the expression profile of CSN5 in cervical cancers. The role of CSN5 on cervical cancer cell proliferation was investigated in cervical cancer cell lines, Siha and Hela, through CSN5 knockdown via CRISPR-CAS9. Western blot was used to detect the effect of CSN5 knockdown and overexpression. CCK8, clone formation assay and cell cycle assay were also employed. Besides, the role CSN5 knockdown in vivo was evaluated by xenograft tumor model. Moreover, MLN4924 was applied in Siha and Hela with CSN5 overexpression.ResultsWe found that downregulation of CSN5 in Siha and Hela cells inhibited cell proliferation in vitro and in vivo, and the inhibitory effects were largely rescued by CSN5 overexpression. Moreover, deletion of CSN5 caused cell cycle arrest rather than inducing apoptosis. Importantly, CSN5 overexpression confers resistance to the anti-cancer effects of MLN4924 (pevonedistat) in cervical cancer cells.ConclusionsOur findings demonstrated that CSN5 functions as an oncogene in cervical cancers and may serve as a potential indicator for predicting the effects of MLN4924 treatment in the future.
Chinese Medical Paraphrase Generation: Based on Neural Machine Translation
Authors: Sun Bo , Zhang Fei , Yuan Jing , Wei Zhao , Ting Shu 
Published: June 2021

Abstract
Background: As people prefer to obtain medical knowledge online, medical intelligence question-answer systems based on question matching have attracted more and more attention, especially in China. However, due to the lack of paraphrase corpus of medical question, the development of this field is limited.Objective: We propose a method for paraphrase generation which suitable for the Chinese medical field and use deep learning models instead of artificial evaluation for the first time. The method is designed to be able to automatically construct high quality Chinese medical paraphrase.Methods: Validation experiments were carried out on two Chinese paraphrase data (one is general data, the other is medical data). Neural machine translation is used to generated paraphrase, that is, translate a sentence into other languages, and then reverse-translate it back to the original language to get the corresponding paraphrase. BLUE, ROUGEs, are used as quantitative evaluation metrics. Three deep text matching models are used to evaluate the generated paraphrase, instead of manual. Precision, Recall, F1 and AUC are used as qualitative evaluation metrics.Results: 49908 and 4062 paraphrases were generated on the two datasets, and the generated efficiency was 97.03% and 98.38%, respectively. For the data in the two fields, the generated and original paraphrase pairs are very similar at the quantitative and qualitative evaluation metrics, especially the medical field. Take medical data as example, BLUE of generated and original paraphrase pairs are 0.556 and 0.626, respectively; the mean difference of AUC between the two groups was 0.015. Conclusions: We first propose a paraphrase generation method based on neural machine translation and use deep text matching model instead of manual evaluation to evaluate the generated paraphrase. By analyzing the evaluation metrics, it can be concluded that：the paraphrase generated method has reached or even exceeded the level of artificial construction at the semantic level, especially in medical field; the deep text matching model can replace manual evaluation and realize automated paraphrase generation. This is of great significance to the development of Chinese medical paraphrase generation.
Precise tuning of bacterial translation initiation by non-equilibrium 5’-UTR unfolding observed in single mRNAs
Authors: Ray Sujay , Dandpat Shiba , Chatterjee Surajit , Walter Nils 
Published: June 2021

Abstract
Noncoding, structured 5’- untranslated regions (5’-UTRs) of messenger RNAs (mRNAs) control translation efficiency by forming structures that can either recruit or repel the ribosome. Here we exploit a bacterial, preQ1-sensing translational riboswitch to probe how binding of a small ligand controls binding of the bacterial ribosome to the Shine-Dalgarno (SD) sequence. Combining single-molecule fluorescence microscopy with mutational analyses, we find that the stability of 30S ribosomal subunit binding is inversely correlated with the free energy needed to unfold the 5’-UTR during mRNA accommodation from the standby site to the binding cleft. Ligand binding stabilizes 5’-UTR structure to both antagonize 30S recruitment and accelerate 30S dissociation. Depletion of small ribosomal subunit protein S1, known to resolve structured 5’-UTRs, further increases the energetic penalty for mRNA accommodation. The resulting model of rapid standby site exploration followed by gated non-equilibrium unfolding of the 5’-UTR during accommodation provides a mechanistic understanding of translation efficiency.
Inhibition of TRIM32 Attenuates the Apoptosis, Oxidative Stress and Inflammatory Injury of Podocytes Induced by High Glucose by Affecting the Akt/GSK-3β/Nrf2 Pathway
Authors: Chen Zhao , Tian Lifang , Wang Li , Ma Xiaotao , Lei Fuqian , Chen Xianghui , Fu Rongguo 
Published: June 2021

Abstract
Hyperglycemia-induced oxidative stress of podocytes exerts a major role in the pathological process of diabetic nephropathy. Tripartite motif-containing protein 32 (TRIM32) has been reported as a key protein in the modulation of cellular apoptosis and oxidative stress under various pathological processes. However, whether TRIM32 participates in the regulation of high glucose (HG)-induced injury in podocytes has not been investigated. The aims of this work were to assess the possible role of TRIM32 in mediating HG-induced apoptosis, oxidative stress and inflammatory response in podocytes in vitro. Herein, our results showed a marked increase in TRIM32 expression in HG-exposed podocytes. Loss-of-function experiments showed that the knockdown of TRIM32 improved the viability of HG-stimulated podocytes, and suppressed HG-induced apoptosis, oxidative stress and inflammatory response in podocytes. Further investigation revealed that the inhibition of TRIM32 enhanced the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling associated with modulation of the Akt/glycogen synthase kinase-3β (GSK-3β) axis in podocytes following HG exposure. However, the suppression of Akt abrogated the TRIM32-knockdown-mediated activation of Nrf2 in HG-exposed podocytes. In addition, the knockdown of Nrf2 markedly abolished the TRIM32-inhibition-induced protective effects in HG-exposed podocytes. In summary, the results of this work show that the inhibition of TRIM32 protects podocytes from HG-induced injury by potentiating Nrf2 signaling via the modulation of Akt/GSK-3β signaling. This study indicates a potential role of TRIM32 in mediating podocyte injury during the progression of diabetic nephropathy.
Genome Sequencing-based Coverage Analyses Facilitate High-resolution Detection of Causal Deletions in Gamma-Irradiated Wheat Mutants
Authors: Komura Shoya , Jinno Hironobu , Sonoda Tatsuya , Oono Yoko , Handa Hirokazu , Takumi Shigeo , Yoshida Kentaro , Kobayashi Fuminori 
Published: June 2021

Abstract
BackgroundGamma-irradiated mutants of hexaploid wheat, Triticum aestivum L., have been providing novel and agriculturally important traits and are used for breeding materials. However, identification of causative genomic regions of mutant phenotypes was challenging due to the large and complicated genome of hexaploid wheat. Recently, the combined use of high-quality reference genome sequences of common wheat and cost-effective resequencing technologies has made it possible to evaluate genome-wide polymorphisms even in hexaploid wheat.ResultsTo investigate whether genome sequencing approach can effectively detect structural variations such as deletions that are frequently caused by gamma irradiation, we selected a grain-hardness mutant from gamma-irradiated population of Japanese elite wheat cultivar “Kitahonami”. It is known that a Hardness (Ha) locus including puroindoline protein-encoding genes Pina-D1 and Pinb-D1 on the short arm of chromosome 5D mainly regulates the grain hardness variation in common wheat. We performed short-read genome sequencings of the wild-type and the grain-hardness mutant, and then aligned their short reads to the reference genome of wheat cultivar “Chinese Spring.” The genome-wide comparisons of depth-of-coverage between wild-type and the mutant detected a ~130 Mbp deletion on the short arm of chromosome 5D in the mutant genome. Molecular markers for this deletion were applied to the progeny populations generated by a crosse between wild-type and the mutant. The large deletion in the region including the Ha locus was exactly associated with the mutant phenotype, indicating that genome sequencing approach is powerful and efficient to detect a causal deletion of a gamma-irradiated mutant. We also investigated a pre-harvest sprouting tolerance mutant and identified a 67.8 Mbp deletion on chromosome 3B where Viviparous-B1 and GRAS family transcription factor are located. Co-dominant markers designed to detect the deletion-polymorphism clearly confirmed an association with the low germination rate led to pre-harvest sprouting tolerance. ConclusionsShort-read-based genome sequencings of gamma-irradiated mutants facilitate the identification of large deletions responsible for mutant phenotypes when combined with segregation analyses in progeny populations. The method we adopted in this study allows the effective application of mutants with agriculturally important traits to breeding with marker-assisted selection.
Detecting Dengue Fever in Children Using A Combined Scheme Compared with Individual Algorithms: An APP Development and Usability Study
Authors: Chow Julie Chi , WEI CHIEN TSAI , Chou Willy 
Published: June 2021

Abstract
BackgroundDengue fever (DF) is an important public health issue in Asia. However, the disease is extremely hard to detect using traditional dichotomous (i.e., absent vs. present) evaluations of symptoms. Convolution neural network (CNN) and artificial neural networks(ANN) can improve prediction accuracy on account of its usage of a large number of parameters for modeling. A hypothesis using a combined scheme of algorithms, including convolutional neural networks(CNN), artificial neural networks(ANN), K-nearest Neighbors Algorithm(KNN), and logis-tical regression(LR), was made to improve the prediction DF accuracy for children. MethodsWe extracted 19 feature variables of DF-related symptoms from 177 pediatric patients (69 diagnosed with DF). A 11-variables were eligible by observing the statistical significance in predicting DF risk. The prediction accuracy was based on two training (80%) and testing (20%) sets on model accuracy of the area under the receiver operating characteristic curve (AUC) greater than 0.80 and 0.70, respectively, for discriminating DF+ and DF− in the two sets. Two scenarios of the combined scheme and individual algorithms were compared using the training set to predict the testing set. ResultsWe observed that (i) k-nearest neighbors algorithm has poorer AUC(<0.50), (ii)LR has relatively higher AUC(=0.70), and (ii) the three alternatives have almost equal AUC(=0.68), but smaller than the individual algorithms of NaiveBayes, Logistic regression in raw data and NaiveBayes in normalized data. Conclusion﻿An LR-based APP was designed to detect DF in children. The 11-item model is suggested to develop the APP for helping patients, family members, and clinicians discriminate DF from other febrile illnesses at an early stage.
Risk and Prognostic Factors of Replantation Failure in Patients With Severe Traumatic Major Limb Mutilation: a Retrospective Cohort Study
Authors: Gao Chang , Yang Ling , Ju Jihui , Zhang Keran , Wu Mingming , Yang Lijuan , Lu Xiaoting , Hou Ruixing , Guo Qiang 
Published: June 2021

Abstract
Background: Traumatic mutilation of major limbs can result in limb loss, motor disability, or even death. Despite advancements in treatment, replantation failure could result in additional financial burden and severe psychosocial pressure on patients. Here, we determine the risk and prognostic factors of replantation failure in patients with traumatic major limb mutilation.Methods: In this retrospective cohort study, severed adult inpatients with traumatic major limb mutilation who underwent replantation from three hospitals in the Suzhou Ruixing Medical Group were included. Data obtained from electronic medical records were used to analyze predictors and risk factors for replantation failure.Results: From the 66 patients included, replantation failure occurred in 48 patients (72.7%). The area under the curve of the joint prediction of lactic acid on admission, 72 h cumulative fluid balance, and albumin level immediately postoperatively was 0.838 (95% CI, 0.722-0.954; P < 0.001) with a sensitivity of 89.7% and a specificity of 69.2%. Lower limb trauma (OR 8.65, 95%CI 1.64-45.56, P = 0.011), mangled extremity severity scores (OR 2.24, 95%CI 1.25-4.01, P = 0.007), and first 72 h cumulative fluid balance > 4885.6 ml (OR 10.25, 95%CI 1.37-76.93, P = 0.024) were independent risk factors for replantation failure.Conclusions: Lower limb trauma, mangled extremity severity scores, and cumulative water balance were associated with replantation failure. This implies that fluid management is necessary for major limb salvage. More studies are needed to explore the predictive power of indicators related to tissue oxygenation and wound healing for replantation failure.
A Comprehensive Nonlinear Dynamic Model for Ball Screw Feed System With Rolling Joint Characteristics
Authors: Xu Mengtao , Li Changyou , Zhang Hongzhuang , Liu Zhendong , Zhang Yimin 
Published: June 2021

Abstract
Modern tendency of machine tools design requires more accurate model to predict the system dynamics, in order to anticipate its interaction with machining process. In this paper, a comprehensive dynamic model of ball screw feed system (BSFS) considering nonlinear kinematic joints is introduced to investigate the varying dynamic characteristics when worktable is subjected to combined load from six directions. The load-deformation relationship of each kinematic joint is dealt with a set of translational and angular spring elements. The nonlinear restoring force function of each joint involving coupling displacement is calculated. Based on the lumped mass method, the analytical 18-DOF dynamic equation is formulated by the analysis of force dependence between joints. Model verification tests are conducted. The worktable response exhibits the abundant and fascinating nonlinear phenomena arising in nonlinear joint and coupling effect. The nonlinear behavior behaves significant difference owing to the variations of excitation, platform position, screw length, preload and damping of joints. Thus, the model is promising for comprehension of machine dynamic behavior and for development of sophisticated control strategy.
(Mis)trusting the Process: How Post-Disaster Home Buyout Processes Can Degrade Public Trust
Authors: Schwaller Nora Louise , Campbell Leah , Nguyen Mai Thi , Smith Gavin 
Published: June 2021

Abstract
Federally funded housing buyout programs are the dominant method of government-supported retreat in the United States. Done correctly, buyouts can reduce pre-disaster vulnerability and facilitate post-disaster recovery. However, the success of buyout programs hinges on successful coordination and implementation by local administrators, who represent buyout participants, manage the buyout process at the community level, and connect them to state and federal resources. Because of this, trust between local administrators and the members of their communities is crucial for project participation and successful outcomes. While local administrators play a critical role in the buyout program, their role in building trust throughout the process has been an understudied aspect of the buyout literature. To address this gap, our paper looks at the conditions following Hurricane Matthew’s landfall in North Carolina, USA in 2016 through in-depth interviews with 18 local HMGP administrators, and an analysis of over 300 local newspaper articles to analyze how trust is built and lost in the buyout process. Our findings indicate that a lack of program clarity, unclear communication about the program’s guidelines across all levels of governments, and extended timeframes deteriorated public trust in a manner that hindered program success and diminished program results.
Collaboration Challenges of Non-Governmental Organizations in Healthcare System in Iran
Authors: Hooshmand elahe , Pardasi Esmat , jamali Jamshid , Javan-Noughabi Javad , vafaee-Najar Ali 
Published: June 2021

Abstract
Background: Despite the strong emphasize of government on collaboration and application of non-governmental organizations in healthcare, there can be seen a research gap in this area in developing countries. The present study aims to investigate collaboration challenges of non-governmental organizations in healthcare from the viewpoint of healthcare managers and active managers of non-governmental organizations of Iran as an example of low-middle income country. Methods: This study is carried out via 54 semi-structured interviews with the managers of governmental sector and the active managers of non-governmental organizations at the national level from 2019 to 2020. Data framework analysis method in Atlas.T software is used for analysis of the interviews. Results: The results of this study highlight five major concepts in collaboration challenges of non-governmental organizations in healthcare: political issues, operational issues, cultural issues, management issues, and communication issues. Conclusions: This study presents a clear framework for identification of collaboration challenges of non-governmental organizations in healthcare Especially for developing countries. This framework should be taken into consideration by authorities of Ministry of health in their policy makings.
Diagnostic Efficacy of Pelvic Ultrasound in Central Precocious Puberty in Girls: a Retrospective Cohort Study
Authors: Zarei Elham , Rakhshankhah Nima , Khodadost Mahmoud , Abouie Abolfazl , Mohammadnejad Kosar , Vafadar Mehdi 
Published: June 2021

Abstract
Background: Differentiating central precocious puberty (CPP) patients from normal cases and CPP-like patients “isolated premature thelarche (IPA) and isolated premature thelarche (IPT)” is important for beginning of treatment. Although the GnRH stimulation test is considered the gold standard for diagnosis of CPP, Because of its wide limitations, our study targets to evaluate pelvic sonography parameters as a contributory tool for CPP diagnosis.Methods: We consecutively enrolled 183 cases (93 CPP, 16 IPT, 12 IPA and 62 of age-matched normal controls) in our study over four years. All cases are classified by clinical and laboratory findings and are followed up for at least 2 years. Pelvic sonography parameters included uterine fundus, body and cervix anteroposterior diameter, fundus/cervix ratio, uterine length and transverse diameter, uterine volume, endometrial thickness, ovarian volumes and diameter of the largest follicle are evaluated in all classified groups. One-way ANOVA, post hoc and receiver operating characteristic (ROC) analysis was used to compare the study groups.Results: Our study found that all sonography parameters differ significantly between CPP and normal control cases, also a significant difference is found between CPP compared to IPT or IPA cases in all parameters except in cervix anteroposterior diameter, ovarian volumes and diameter of the largest follicle. In order of best parameters for differentiating CPP compared to study groups, uterine volume (a cut-off of 1.40 ml had a sensitivity of 75.27% and a specificity of 75.56%), transverse diameter (a cut-off of 13.5 mm had a sensitivity of 72.04% and a specificity of 71.11%) and F/C ratio (a cut-off of 0.98 had a sensitivity of 78.49% and a specificity of 70%) was selected. Our study also classified sonography parameters as in equal diagnostic value to uterine volume (as the best diagnostic parameter with area under the curve of 0.826) and not equal diagnostic value to uterine volume.Conclusions: Pelvic Sonography parameters may improve the diagnosis of CPP patients and can have a contributory role in distinguishing treatment needed patients from other patients. The best diagnostic parameter and its cut-off value could change according to different ethnicities and studies.