bluuebunny/crossref_metadata_2025_split huggingface dataset:
Benefits of Sustained Upregulated Unimolecular GLP-1 and CCK Receptor Signalling in Obesity-Diabetes
Authors: Tanday Neil , English Andrew , Lafferty Ryan A. , Flatt Peter R. , Irwin Nigel 
Published: May 2021

Combined activation of GLP-1 and CCK1 receptors has potential to synergistically augment the appetite-suppressive and glucose homeostatic actions of the individual parent peptides. In the current study, pancreatic beta-cell benefits of combined GLP-1 and CCK1 receptor upregulation were established, before characterising bioactivity and antidiabetic efficacy of an acylated dual-acting GLP-1/CCK hybrid peptide, namely [Lys12Pal]Ex-4/CCK. Both exendin-4 and CCK exhibited (p&lt;0.001) proliferative and anti-apoptotic effects in BRIN BD11 beta-cells. Proliferative benefits were significantly (p&lt;0.01) augmented by combined peptide treatment when compared to either parent peptide alone. These effects were linked to increases (p&lt;0.001) in GLUT2 and glucokinase beta-cell gene expression, with decreased (p&lt;0.05-p&lt;0.001) expression of NFκB and BAX. [Lys12Pal]Ex-4/CCK exhibited prominent insulinotropic actions in vitro, coupled with beneficial (p&lt;0.001) satiety and glucose homeostatic effects in the mice, with bioactivity evident 24 h after administration. Following twice daily injection of [Lys12Pal]Ex-4/CCK for 28 days in diabetic high fat fed (HFF) mice with streptozotocin (STZ)-induced compromised beta-cells, there were clear reductions (p&lt;0.05-p&lt;0.001) in energy intake and body weight. Circulating glucose was returned to lean control concentrations, with associated increases (p&lt;0.001) in plasma and pancreatic insulin levels. Glucose tolerance and insulin secretory responsiveness were significantly (p&lt;0.05-p&lt;0.001) improved by hybrid peptide therapy. In keeping with this, evaluation of pancreatic histology revealed restoration of normal islet alpha- to beta-cell ratios and reduction (p&lt;0.01) in centralised islet glucagon staining. Improvements in pancreatic islet morphology were associated with increased (p&lt;0.05) proliferation and reduced (p&lt;0.001) apoptosis of beta-cells. Together, these data highlight the effectiveness of sustained dual GLP-1 and CCK1 receptor activation by [Lys12Pal]Ex-4/CCK for the treatment of obesity-related diabetes.
Trends in Childhood Thyroid Cancer incidence in Korea and Its Potential Risk Factors
Authors: Park Jun , Park Hyunju , Kim Tae Hyuk , Kim Sun Wook , Jang Hye Won , Chung Jae Hoon 
Published: May 2021

BackgroundAlthough the incidence of thyroid cancer had been increasing until a few years ago, a decrease has been observed in the last years, probably due to the reduction of the screening tests in Korea. Childhood thyroid cancer has been increasing in the past with the same trend as in adults, but there have been few reports on recent trends. We analyzed the trends of thyroid cancer in Korean children and related factors.MethodsFrom national statistics and cancer register database, the data of age-specific incidence rate in Korean childhood thyroid cancer from 1999 to 2017 was obtained, and levels of seaweed intake, the number of computed tomography (CT) and neck ultrasonography (US), obesity prevalence rate, and smoking and alcohol consumption rates in children were analyzed.ResultsThe age-specific incidence of thyroid cancer in Korean children has increased in both genders between 1999 and 2017 (2.0 in 1999 vs. 7.2 in 2017, per population of 100,000), especially in the age group of 14-18 years (1.5 in 1999 vs. 5.5 in 2017, per population of 100,000). During the same period, levels of seaweed intake, number of CT scans and neck US, and prevalence of obesity in children increased significantly, while childhood smoking and alcohol consumption rates decreased.ConclusionUnlike the adult thyroid cancer in Korea, childhood thyroid cancer continues to increase, and the cause might be accompanied by actual increases due to the environmental factors such as excessive iodine intake, exposure to medical radiation, and increased obesity prevalence as well as the screening effect.
What Are the Contextual Enablers and Impacts of Using Digital Technology to Extend Maternal and Child Health Services to Rural Areas? Findings of a Qualitative Study From Nigeria
Authors: Ebenso Bassey , Okusanya Babasola , Okunade Kehinde , Akeju David , Ajepe Adegbenga , Akaba Godwin O. , Yalma Ramsey M. , Dirisu Osasuyi , Tukur Jamilu , Abdullahi Manir K. , Okuzu Okey , Allsop Matthew J. 
Published: May 2021

Background: Strengthening health systems to improve access to maternity services remains challenging for Nigeria due partly to weak and irregular in-service training and deficient data management. This paper reports the implementation of digital health tools for video training (VTR) of health workers and digitization of health data at scale, supported by satellite communications (SatCom) technology and existing 3G mobile networks.Objective: To understand whether, and under what circumstances using digital interventions to extend maternal, newborn and child health (MNCH) services to remote areas of Nigeria improved standards of healthcare delivery.Methods: From March 2017 to March 2019, VTR and data digitization interventions were delivered in 126 facilities across three states of Nigeria. Data collection combined documents review with 294 semi-structured interviews of stakeholders across four phases (baseline, midline, endline, and 12-months post-project closedown) to assess acceptability and impacts of digital interventions. Data was analyzed using a framework approach, drawing on a modified Technology Acceptance Model to identify factors that shaped technology adoption and use.Results: Analysis of documents and interview transcripts revealed that a supportive policy environment, and track record of private-public partnerships facilitated adoption of technology. The determinants of technology acceptance among health workers included ease of use, perceived usefulness, and prior familiarity with technology. Perceptions of impact suggested that at the micro (individual) level, repeated engagement with clinical videos increased staff knowledge, motivation and confidence to perform healthcare roles. At meso (organizational) level, better-trained staff felt supported and empowered to provide respectful healthcare and improved management of obstetric complications, triggering increased use of MNCH services. The macro level saw greater use of reliable and accurate data for policymaking.Conclusions: Simultaneous and sustained implementation of VTR and data digitization at scale enabled through SatCom and 3G mobile networks are feasible approaches for supporting improvements in staff confidence and motivation and reported MNCH practices. By identifying mechanisms of impact of digital interventions on micro, meso, and macro levels of the health system, the study extends the evidence base for effectiveness of digital health and theoretical underpinnings to guide further technology use for improving MNCH services in low resource settings.Trial Registration: ISRCTN32105372.
Comparing COVID-19 and Influenza Presentation and Trajectory
Authors: Reiner Benaim Anat , Sobel Jonathan A. , Almog Ronit , Lugassy Snir , Ben Shabbat Tsviel , Johnson Alistair , Eytan Danny , Behar Joachim A. 
Published: May 2021

Background: COVID-19 is a newly recognized illness with a predominantly respiratory presentation. It is important to characterize the differences in disease presentation and trajectory between COVID-19 patients and other patients with common respiratory illnesses. These differences can enhance knowledge of pathogenesis and help in guiding treatment.Methods: Data from electronic medical records were obtained from individuals admitted with respiratory illnesses to Rambam Health Care Campus, Haifa, Israel, between October 1st, 2014 and October 1st, 2020. Four groups of patients were defined: COVID-19 (693), influenza (1,612), severe acute respiratory infection (SARI) (2,292), and Others (4,054). The variable analyzed include demographics (7), vital signs (8), lab tests (38), and comorbidities (15) from a total of 8,651 hospitalized adult patients. Statistical analysis was performed on biomarkers measured at admission and for their disease trajectory in the first 48 h of hospitalization, and on comorobidity prevalence.Results: COVID-19 patients were overall younger in age and had higher body mass index, compared to influenza and SARI. Comorbidity burden was lower in the COVID-19 group compared to influenza and SARI. Severely- and moderately-ill COVID-19 patients older than 65 years of age suffered higher rate of in-hospital mortality compared to hospitalized influenza patients. At admission, white blood cells and neutrophils were lower among COVID-19 patients compared to influenza and SARI patients, while pulse rate and lymphoctye percentage were higher. Trajectories of variables during the first 2 days of hospitalization revealed that white blood count, neutrophils percentage and glucose in blood increased among COVID-19 patients, while decreasing among other patients.Conclusions: The intrinsic virulence of COVID-19 appeared higher than influenza. In addition, several critical functions, such as immune response, coagulation, heart and respiratory function, and metabolism were uniquely affected by COVID-19.
Motor Symptom Lateralization Influences Cortico-Striatal Functional Connectivity in Parkinson's Disease
Authors: Su Wen , Li Kai , Li Chun-Mei , Ma Xin-Xin , Zhao Hong , Chen Min , Li Shu-Hua , Wang Rui , Lou Bao-Hui , Chen Hai-Bo , Yan Chuan-Zhu 
Published: May 2021

Objective: The striatum is unevenly impaired bilaterally in Parkinson's disease (PD). Because the striatum plays a key role in cortico-striatal circuits, we assume that lateralization affects cortico-striatal functional connectivity in PD. The present study sought to evaluate the effect of lateralization on various cortico-striatal circuits through resting-state functional magnetic resonance imaging (fMRI).Methods: Thirty left-onset Parkinson's disease (LPD) patients, 27 right-onset Parkinson's disease (RPD) patients, and 32 normal controls with satisfactory data were recruited. Their demographic, clinical, and neuropsychological information was collected. Resting-state fMRI was performed, and functional connectivity changes of seven subdivisions of the striatum were explored in the two PD groups. In addition, the associations between altered functional connectivity and various clinical and neuropsychological characteristics were analyzed by Pearson's or Spearman's correlation.Results: Directly comparing the LPD and RPD patients demonstrated that the LPD patients had lower FC between the left dorsal rostral putamen and the left orbitofrontal cortex than the RPD patients. In addition, the LPD patients showed aberrant functional connectivity involving several striatal subdivisions in the right hemisphere. The right dorsal caudate, ventral rostral putamen, and superior ventral striatum had decreased functional connectivity with the cerebellum and parietal and occipital lobes relative to the normal control group. The comparison between RPD patients and the controls did not obtain significant difference in functional connectivity. The functional connectivity between the left dorsal rostral putamen and the left orbitofrontal cortex was associated with contralateral motor symptom severity in PD patients.Conclusions: Our findings provide new insights into the distinct characteristics of cortico-striatal circuits in LPD and RPD patients. Lateralization of motor symptoms is associated with lateralized striatal functional connectivity.
Deep Genomic Sequencing of Bladder Urothelial Carcinoma in Southern Chinese Patients: A Single-Center Study
Authors: Li Dong-Yang , Yang Fei , Liao Wei-Qiang , Zhou Xiang-Fu , Li Wen-Biao , Cai Jia-Rong , Liu Bo-Long , Luo Yun , Zhan Hai-Lun 
Published: May 2021

ObjectiveBladder urothelial carcinoma (BUC) is a common urological malignancy with molecular heterogeneity. However, the genetic feature of Chinese BUC patients is still not well-identified.MethodsWe performed deep sequencing by a large panel (450 genes) on 22 BUC samples and using matched normal bladder tissue as control. Genomic alterations (GAs), pathways and Tumor Mutation Burden (TMB) were investigated.ResultsThe frequencies of GAs (TERT, 54.5%; CREBBP, 27.3%; GATA3, 22.7%; BRAF, 18.2%; TEK, 18.2% and GLI1, 18.2%) were significantly higher in Chinese than Western BUC patients. Other GAs’ frequencies were in accordance with previous study (TP53, 50.0%; KDM6A, 31.8%; KMT2D, 22.7%; etc.). Besides, we detected gene amplification in ERBB2, FRS2, FAS, etc. The gene fusion/rearrangement took place in the chromosome 11, 12, 14, 17, 19, 22, and Y. Other than cell cycle and PI3K-AKT-mTOR, mutated genes were more associated with the transcription factor, chromatin modification signaling pathways. Interestingly, the TMB value was significantly higher in the BUC patients at stages T1–T2 than T3–T4 (P = 0.025).ConclusionDeep genomic sequencing of BUC can provide new clues on the unique GAs of Chinese patients and assist in therapeutic decision.
Cardiac Surveillance for Early Detection of Late Subclinical Cardiac Dysfunction in Childhood Cancer Survivors After Anthracycline Therapy
Authors: Sofia Rosaria , Melita Veronica , De Vita Antonio , Ruggiero Antonio , Romano Alberto , Attinà Giorgio , Birritella Lisa , Lamendola Priscilla , Lombardo Antonella , Lanza Gaetano Antonio , Delogu Angelica Bibiana 
Published: May 2021

BackgroundIn childhood cancer survivors (CCSs) anthracycline-related cardiotoxicity is an important cause of morbidity and late mortality, but the optimal modality of cardiac surveillance still remains to be defined. The aim of this study was to assess whether non-invasive echocardiography-based functional cardiac measures can detect early subclinical myocardial changes in long-term pediatric cancer survivors who received anthracycline therapy.MethodsTwenty anthracycline-treated long-term CCSs and 20 age, sex, and body surface area matched healthy controls were enrolled in this study. Among cancer survivors, mean age at diagnosis was 6.5 ± 4.4 years, and the mean cumulative anthracycline dose was 234.5 ± 87.4 mg/m2. All subjects underwent a comprehensive functional echocardiographic protocol study including two-dimensional echocardiography (2D Echo), tissue Doppler imaging (TDI), speckle tracking (STE) and three-dimensional echocardiography (3D Echo). Patients were studied at a mean follow-up time of 6.5 ± 2.8 years from the end of therapy.ResultsNo significant differences in two-dimensional left ventricle ejection fraction (LVEF), diastolic parameters and speckle tracking (STE)-derived myocardial strain were observed between patients treated with anthracyclines and controls. Myocardial performance index was significantly prolonged (p = 0.005) and three-dimensional LVEF was significantly reduced (p = 0.002) in CCSs compared to controls, even though most values were within the normal range. There were no significant correlations between 2D, STE, and 3D echocardiographic parameters and age at diagnosis or duration of follow-up. No significant differences in echocardiographic parameters were found when stratifying cancer patients according to established risk factors for anthracycline cardiomyopathy.ConclusionsThis study found significantly reduced three-dimensional LVEF in CCSs compared with controls, despite no significant differences in two-dimensional LVEF and longitudinal strain values. These findings suggest that long-term CCSs who had received anthracycline therapy may be found to have subclinical features of myocardial dysfunction. However, further studies are needed to demonstrate the validity of new imaging techniques, including STE and 3D Echo, to identify patients at risk for cardiomyopathy in the long-term follow-up of CCSs.
Contrast-Enhanced CT-Based Radiomics Analysis in Predicting Lymphovascular Invasion in Esophageal Squamous Cell Carcinoma
Authors: Li Yang , Yu Meng , Wang Guangda , Yang Li , Ma Chongfei , Wang Mingbo , Yue Meng , Cong Mengdi , Ren Jialiang , Shi Gaofeng 
Published: May 2021

ObjectivesTo develop a radiomics model based on contrast-enhanced CT (CECT) to predict the lymphovascular invasion (LVI) in esophageal squamous cell carcinoma (ESCC) and provide decision-making support for clinicians.Patients and MethodsThis retrospective study enrolled 334 patients with surgically resected and pathologically confirmed ESCC, including 96 patients with LVI and 238 patients without LVI. All enrolled patients were randomly divided into a training cohort and a testing cohort at a ratio of 7:3, with the training cohort containing 234 patients (68 patients with LVI and 166 without LVI) and the testing cohort containing 100 patients (28 patients with LVI and 72 without LVI). All patients underwent preoperative CECT scans within 2 weeks before operation. Quantitative radiomics features were extracted from CECT images, and the least absolute shrinkage and selection operator (LASSO) method was applied to select radiomics features. Logistic regression (Logistic), support vector machine (SVM), and decision tree (Tree) methods were separately used to establish radiomics models to predict the LVI status in ESCC, and the best model was selected to calculate Radscore, which combined with two clinical CT predictors to build a combined model. The clinical model was also developed by using logistic regression. The receiver characteristic curve (ROC) and decision curve (DCA) analysis were used to evaluate the model performance in predicting the LVI status in ESCC.ResultsIn the radiomics model, Sphericity and gray-level non-uniformity (GLNU) were the most significant radiomics features for predicting LVI. In the clinical model, the maximum tumor thickness based on CECT (cThick) in patients with LVI was significantly greater than that in patients without LVI (P&lt;0.001). Patients with LVI had higher clinical N stage based on CECT (cN stage) than patients without LVI (P&lt;0.001). The ROC analysis showed that both the radiomics model (AUC values were 0.847 and 0.826 in the training and testing cohort, respectively) and the combined model (0.876 and 0.867, respectively) performed better than the clinical model (0.775 and 0.798, respectively), with the combined model exhibiting the best performance.ConclusionsThe combined model incorporating radiomics features and clinical CT predictors may potentially predict the LVI status in ESCC and provide support for clinical treatment decisions.
The Orphan Nuclear Receptor Gene NR0B2 Is a Favorite Prognosis Factor Modulated by Multiple Cellular Signal Pathways in Human Liver Cancers
Authors: Zhu Runzhi , Tu Yanjie , Chang Jingxia , Xu Haixia , Li Jean C. , Liu Wang , Do Ahn-Dao , Zhang Yuxia , Wang Jinhu , Li Benyi 
Published: May 2021

BackgroundLiver cancer is a leading cause of cancer death worldwide, and novel prognostic factor is needed for early detection and therapeutic responsiveness monitoring. The orphan nuclear receptor NR0B2 was reported to suppress liver cancer development in a mouse model, and its expression levels were reduced in liver cancer tissues and cell lines due to hypermethylation within its promoter region. However, it is not clear if NR0B2 expression is associated with cancer survival or disease progression and how NR0B2 gene expression is regulated at the molecular level.MethodsMultiple cancer databases were utilized to explore NR0B2 gene expression profiles crossing a variety of human cancers, including liver cancers, on several publicly assessable bioinformatics platforms. NR0B2 gene expression with or without kinase inhibitor treatment was analyzed using the qPCR technique, and NR0B2 protein expression was assessed in western blot assays. Two human hepatocellular carcinoma cell lines HepG2 and Huh7, were used in these experiments. NR0B2 gene activation was evaluated using NR0B2 promoter-driven luciferase reporter assays.ResultsNR0B2 gene is predominantly expressed in liver tissue crossing human major organs or tissues, but it is significantly downregulated in liver cancers. NR0B2 expression is mostly downregulated in most common cancers but also upregulated in a few intestinal cancers. NR0B2 gene expression significantly correlated with patient overall survival status in multiple human malignancies, including lung, kidney, breast, urinary bladder, thyroid, colon, and head-neck cancers, as well as liposarcoma and B-cell lymphoma. In liver cancer patients, higher NR0B2 expression is associated with favorite relapse-free and progression-free survival, especially in Asian male patients with viral infection history. In addition, NR0B2 expression negatively correlated with immune infiltration and PIK3CA and PIK3CG gene expression in liver cancer tissues. In HepG2 and Huh7 cells, NR0B2 expression at the transcription level was drastically reduced after MAPK inhibition but was significantly enhanced after PI3K inhibition.ConclusionNR0B2 gene expression is altered mainly in most human malignancies and significantly reduced in liver cancers. NR0B2 is a prognosis factor for patient survival in liver cancers. MAPK and PI3K oppositely modulate NR0B2 expression, and NR0B2 gene upregulation might serve as a therapeutic responsiveness factor in anti-PI3K therapy for liver cancer.
Chronological and Skeletal Age in Relation to Physical Fitness Performance in Preschool Children
Authors: Ke Dandan , Lu Dajiang , Cai Guang , Wang Xiaofei , Zhang Jing , Suzuki Koya 
Published: May 2021

Introduction: Physical fitness is an adaptive state that varies with an individual's growth and maturity status. Considering that the difference in skeletal maturity already existed among preschool children, this study was designed to determine the influence of skeletal age and chronological age on preschoolers' physical fitness performance.Methods: This cross-sectional study was conducted in 945 healthy preschoolers (509 males, 436 females) aged between 3.0 and 6.0 years in Shanghai, China. We used the method of TW3-C RUS to determine skeletal age. Chronological age was measured by subtracting the date of birth from the test date. Sit and reach, 2 × 10 m shuttle run test, standing long jump, tennis ball throw, 5 m jump on both feet, and balance beam walk were considered for physical fitness performance. Correlation coefficients and partial correlations adjusting height and weight were used to determine the relationships among the variables of skeletal age/ relative skeletal age, chronological age/relative chronological age, and physical fitness items.Results: Skill-related physical fitness was weakly to moderately associated with skeletal age (the absolute value of r: 0.225–0.508, p &lt; 0.01) and was moderately to strongly associated with chronological age (the absolute value of r: 0.405–0.659, p &lt; 0.01). Health-related physical fitness items (BMI and sit and reach) showed a fairly weak to no correlation with skeletal age and chronological age. After adjusting the height and weight, an extremely weak to no correlation was observed between skeletal age and both health- and skill-related physical fitness, and weak-moderate correlations were noted between chronological age and skill-related physical fitness (the absolute value of r: 0.220–0.419, p &lt; 0.01). In children in Grade 1, skill-related physical fitness (except for balance beam walk) showed a weak to moderate correlation with relative chronological age (the absolute value of r: 0.227–0.464, p &lt; 0.05).Conclusion: (1) both skeletal age and chronological age are associated with skill-related rather than health-related physical fitness performance, and after adjusting height and weight, chronological age, rather than skeletal age, is associated with skill-related physical fitness performance; (2) for preschool children, skill-related physical fitness performance is influenced by relative chronological age rather than individual differences in skeletal maturation, especially in the lower grades.