bluuebunny/crossref_metadata_2025 huggingface dataset:
LncRNA FAM83H-AS1 promotes aerobic glycolysis and tumor progression by regulating miR-4684-5p/ZBTB38 axis in esophageal squamous cell carcinoma
Authors: Qian Cuijuan , Xu Zhurong , Chen Luyan , Wang Yichao , Yao Jun
Published: October 2020

Background: Dysregulation of lncRNAs is implicated in esophageal squamous cell carcinoma (ESCC) progression; However, the precise function of lncRNA FAM83H-AS1 in ESCC remains unknown.

Methods: FAM83H-AS1, miR-4684-5p and ZBTB38 mRNA expressions were detected via qRT-PCR. ZBTB38, GLUT1 and LDH-A protein expressions were tested via Western blot. Cell proliferation, migration and invasion were evaluated via CCK-8 and transwell assay, respectively. A nude mouse xenograft model was used to investigate the role of FAM83H-AS1 in xenograft ESCC growth. The metabolic shift in ESCC cells was examined via glycolysis analysis. The interaction between FAM83H-AS1, miR-4684-5p and ZBTB38 was analyzed via computational algorithms, RNA pull-down, RIP and dual luciferase reporter assay.

Results: We found that FAM83H-AS1 was upmodulated in ESCC cell lines. FAM83H-AS1 knockdown hampered ESCC cell proliferation, migration, invasion and aerobic glycolysis, while FAM83H-AS1 overexpression demonstrated the opposite effects. FAM83H-AS1 knockdown also delayed the tumor growth in vivo. Moreover, FAM83H-AS1 interacted with miR-4684-5p/ZBTB38 axis in ESCC cells. ZBTB38 overexpression or miR-4684-5p inhibition partially reversed the inhibitory effect of FAM83H-AS1 knockdown on cell migration, invasion and aerobic glycolysis in ESCC cells.

Conclusion: Our present results indicate FAM83H-AS1 accelerated aerobic glycolysis and tumorigenesis of ESCC by sponging miR-4684-5p and triggering the expression of ZBTB38, providing new insights into mechanism of ESCC progression and therapeutic strategy.
Genome-Wide Association Studies and Whole-Genome Prediction Reveal the Genetic Architecture of KRN in Maize
Authors: An Yixin , Chen Lin , Li Yongxiang , Li Chunhui , Shi Yunsu , Zhang Dengfeng , Li Yu , Wang Tianyu
Published: October 2020

Background: Kernel row number (KRN) is an important trait for the domestication and improvement of maize. Exploring the genetic basis of KRN has great research significance and can provide valuable information for molecular assisted selection.Results: In this study, one single-locus method (MLM) and six multilocus methods (mrMLM, FASTmrMLM, FASTmrEMMA, pLARmEB, pKWmEB and ISIS EM-BLASSO) of genome-wide association studies (GWASs) were used to identify significant quantitative trait nucleotides (QTNs) for KRN in an association panel including 639 maize inbred lines that were genotyped by the MaizeSNP50 BeadChip. In three phenotyping environments and with best linear unbiased prediction (BLUP) values, the seven GWAS methods revealed different numbers of KRN-associated QTNs, ranging from 11 to 177. Based on these results, seven important regions for KRN located on chromosomes 1, 2, 3, 5, 9, and 10 were identified by at least three methods and in at least two environments. Moreover, 49 genes from the seven regions were expressed in different maize tissues. Among the 49 genes, ARF29 (Zm00001d026540, encoding auxin response factor 29) and CKO4 (Zm00001d043293, encoding cytokinin oxidase protein) were significantly related to KRN, based on expression analysis and candidate gene association mapping. Whole-genome prediction (WGP) of KRN was also performed, and we found that the KRN-associated tagSNPs achieved a high prediction accuracy. The best strategy was to integrate all of the KRN-associated tagSNPs identified by all GWAS models.Conclusions: These results aid in our understanding of the genetic architecture of KRN and provide useful information for genomic selection for KRN in maize breeding.
Evaluation of Preventive, Supportive and Awareness Building Measures among International Students in China in Response to COVID-19: A Structural Equation Modeling Approach
Authors: Sarker Tanwne , Sarkar Apurbo , Rabbany Md. Ghulam , Barmon Milon , Roy Rana , Rahman Md. Ashfikur , Hossain Kh Zulfikar , Hoque Fazlul , Asaduzzaman Muhammad
Published: October 2020

Background: Public awareness campaigns and behavioral change campaigns are a necessary basis to facilitate and motivate the use of preventive measures. During this COVID-19 pandemic, how the Chinese government handled this vulnerable situation through enhancing behavior change communication among international students is a research interest. The objective of this current study is to evaluate the preventive, supportive and awareness building measures adopted among international students in China in response to this deadly pandemic. Method and methodology: In this study, we have evaluated how the level of awareness, satisfaction, and trust in authorities (i.e., government, local authorities, and institutions) shapes the behavior and close interconnection each other. Simple bivariate statistics was used to describe the background characteristics of the respondents along with adoption of the partial least squares-structural equation modeling (PLS-SEM) as the final model to show the association between the variables. Results: Our study findings showed the great impact of preventive and supportive measures in the development of students’ satisfaction. The satisfied students possessed a strong influence which eventually helped in building sufficient trust on their institutions. Moreover, present study provides insight views of the selected latent variables by counteracting the interaction among them. Conclusions: The worldwide student group is one of the most affected and vulnerable communities in this situation. So there is a profound ground of research on how different states or authorities handle such situation. In this study we have depicted the types and magnitude of care taken by Chinese government and educational institutions towards international students to relieve the panic of pandemic situation. Further research and such initiatives should be taken in to consideration for future emerging conditions.
Loss of skeletal muscle mass affects the incidence of minimal hepatic encephalopathy: A case control study
Authors: Tateyama Masakuni , Naoe Hideaki , Tanaka Motohiko , Tanaka Kentaro , Narahara Satoshi , Tokunaga Takayuki , Kawasaki Takeshi , Yoshimaru Yoko , Nagaoka Katsuya , Watanabe Takehisa , Setoyama Hiroko , Sasaki Yutaka , Tanaka Yasuhito
Published: October 2020

Background: Sarcopenia is a syndrome characterized by progressive and systemic decreases in skeletal muscle mass and muscle strength. The influence or prognosis of various liver diseases in this condition have been widely investigated, but little is known about whether sarcopenia and/or muscle mass loss are related to minimal hepatic encephalopathy (MHE). Methods: To clarify the relationship between MHE and sarcopenia and/or muscle mass loss in patients with liver cirrhosis. Methods: Ninety-nine patients with liver cirrhosis were enrolled. MHE was diagnosed by a neuropsychiatric test. Skeletal mass index (SMI) and Psoas muscle index (PMI) were calculated by dividing skeletal muscle area and psoas muscle area at the third lumbar vertebra by the square of height in meters, respectively, to evaluate muscle volume. Results: This study enrolled 99 patients (61 males, 38 females). MHE was detected in 48 cases (48.5%) and sarcopenia in 6 cases (6.1%). Patients were divided into two groups, with or without MHE. Comparing groups, no significant differences were seen in serum ammonia concentration or rate of sarcopenia. SMI was smaller in patients with MHE (46.4 cm 2 /m 2 ) than in those without (51.2 cm 2 /m 2 , P = 0.027). Similarly, PMI was smaller in patients with MHE (4.24 cm 2 /m 2 ) than in those without (5.53 cm 2 /m 2 , P = 0.003). Skeletal muscle volume, which is represented by SMI or PMI was a predictive factor related to MHE (SMI ≥ 50 cm 2 /m 2 ; odds ratio 0.300, P = 0.002, PMI ≥ 4.3 cm 2 /m 2 ; odds ratio 0.192, P = 0.001).Conclusions: Muscle mass loss was related to minimal hepatic encephalopathy, although sarcopenia was not. Measurement of muscle mass loss might be useful to predict MHE.
Prospective GERiatric Observational (ProGERO) Study: cohort design and preliminary results
Authors: Saraiva Marcos Daniel , Rangel Luís Fernando , Cunha Julia Lusis Lassance , Rotta Thereza Cristina Ariza , Douradinho Christian , Khazaal Eugênia Jatene Bou , Aliberti Márlon Juliano Romero , Avelino-Silva Thiago Junqueira , Apolinario Daniel , Suemoto Claudia Kimie , Jacob-Filho Wilson
Published: October 2020

Background: The demographic changes in Brazil as a result of population aging is one of the fastest in the world. The far-reaching new challenges that come with a large older population are particularly disquieting in low- and middle-income countries (LMICs). Longitudinal studies must be completed in LMICs to investigate the social and biological determinants of aging and the consequences of such demographic changes in their context. Therefore, we designed the Prospective GERiatric Observational (ProGERO) study, a longitudinal study of outpatient older adults in São Paulo, Brazil, to collect data both on aging and chronic diseases, and investigate characteristics associated with adverse outcomes in this population. Methods: The ProGERO study takes place in a geriatric outpatient clinic in the largest academic medical center in Latin America. We performed baseline health examinations in 2017 and will complete subsequent in-person visits every three years when new participants will also be recruited. We will use periodic telephone interviews to collect information on the outcomes of interest between in-person visits. The baseline evaluation included data on demographics, medical history, physical examination, and comprehensive geriatric assessment (CGA; including multimorbidity, medications, social support, functional status, cognition, depressive symptoms, nutritional status, pain assessment, frailty, gait speed, handgrip strength, and chair-stands test). We used a previously validated CGA-based model to rank participants according to mortality risk (low, medium, high). Our selected outcomes were falls, disability, health services utilization (emergency room visits and hospital admissions), institutionalization, and death. We will follow participants for at least ten years.Results: We included 1,336 participants with a mean age of 82±8 years old. Overall, 70% were women, 31% were frail, and 43% had a Charlson comorbidity index score ≥3. According to our CGA-based model, the incidence of death in one year varied significantly across categories (low-risk=0.6%; medium-risk=7.4%; high-risk=17.5%; P<0.001).Conclusion: The ProGERO study will provide detailed clinical data and explore the late-life trajectories of outpatient older patients during a follow-up period of at least 10 years. Moreover, the study will substantially contribute to new information on the predictors of aging, senescence, and senility, particularly in frail and pre-frail outpatients from an LMIC city.
Thyroid-stimulating hormone decreases the risk of osteoporosis by regulating osteoblast proliferation and differentiation
Authors: Deng Tuo , Zhang Wenwen , Zhang Yanling , Zhang Mengqi , Huan Zhikun , Yu Chunxiao , Zhang Xiujuan , Wang Yan , xu jin
Published: October 2020

Background
As the incidence of secretory osteoporosis increases, bone loss and osteoporosis and their relationships with thyroid-stimulating hormone (TSH) have received increased attention. In this study, the role of TSH in bone metabolism and the underlying possible mechanisms were investigated.
Methods
We analyzed serum triiodothyronine (FT3), tetraiodothyronine (FT4), TSH and bone mineral density (BMD) levels of 114 men with normal thyroid function. In addition, osteoblasts from rat calvarial samples were treated with different doses of TSH for different times at each time point. The related gene and protein expression levels were investigated.
Results
Comparing the BMD between the high-level and low-level serum TSH group showed that TSH serum concentrations were positively correlated with BMD. TSH at concentrations of 10 mU/mL and 100 mU/mL significantly increased the mRNA levels of ALP, COI1 and Runx2 compared with those of the control (P < 0.05, P < 0.01). BMP2 activity was enhanced both with increased TSH concentration and with increased time. The protein levels of Runx2 and osterix were increased in a dose-dependent manner.
Conclusions
The circulating concentrations of TSH and BMD were positively correlated with normal thyroid function in males. TSH promoted osteoblast proliferation and differentiation in rat primary osteoblasts.
Glycaemia and hand grip strength in aging people: Guangzhou Biobank Cohort Study
Authors: Liang Xue , Jiang Chao Qiang , Zhang Wei Sen , Zhu Feng , Jin Ya Li , Cheng Kar Keung , Lam Tai Hing , Xu Lin
Published: October 2020

Background
There is a link between hyperglycemia and mechanical functions of muscle. However, existing evidence of the association between hyperglycemia and weaker muscle strength is limited and inconsistent. We examined whether glycemic status was associated with relative grip strength (RGS) in older Chinese.
Methods
In 2008-2012, 9180 participants (2516 men and 6664 women) from the Guangzhou Biobank Cohort Study had fasting and 2-hour post-load glucose measured. Glycemic status was categorized as normoglycaemia, prediabetes (i.e., impaired fasting glucose and/or impaired glucose tolerance) and diabetes. RGS was assessed using a Jamar Hydraulic Hand Dynamometer divided by body mass index. General linear model was used to assess the association of glycemic status with RGS.
Results
After adjusting for age, smoking status, alcohol use, physical activity, health status, body fat percentage and waist circumference, in men, hyperglycemia was associated with a lower RGS, with the RGS being 1.38 (95% confidence interval (CI)=1.34, 1.42) in normoglycaemia, 1.35 (95% CI=1.30, 1.39) in prediabetes, 1.33 (95% CI=1.29, 1.38) in newly diagnosed diabetes and 1.32 (95% CI=1.27, 1.37) in known diabetes (P for trend <0.001). The association of glycemic status with RGS was non-significant in women. Among the normoglycaemic group, no association was found between fasting glucose and RGS in men, whereas a significantly inverse association was found in women, with adjusted β for RGS per mmol/l increase in fasting glucose being -0.05 to -0.04 (P values from 0.002 to 0.03).
Conclusions
Higher fasting glucose was associated with reduced grip strength in a dose-response manner, and the association was significant even in women with normoglycaemia. Our findings suggest that lowering glucose across the whole range might be important in preserving muscle strength, especially in aging women.
Etiologic spectrum and clinical characteristics of pediatric diabetes among 276 children and adolescents with diabetes in a single academic center
Authors: Kim Ja Hye , Lee Yena , Choi Yunha , Kim Gu-Hwan , Yoo Han-Wook , Choi Jin-Ho
Published: October 2020

Background
The prevalence of monogenic diabetes is estimated to be 1–5% of patients with diabetes mellitus (DM). The overlapping clinical features of various forms of diabetes make differential diagnosis challenging. Therefore, this study investigated the etiologic distribution and clinical characteristics of pediatric diabetes, including monogenic diabetes, in a single tertiary center over the last 20 years.
Methods
This study included 276 consecutive patients with DM diagnosed before 18 years of age from January 2000 to December 2019. Clinical features, biochemical findings, β-cell autoantibodies, and molecular characteristics were reviewed retrospectively.
Results
Of the 276 patients, 206 patients (74.6%), 49 patients (17.8%), and 21 patients (7.6%) were diagnosed with type 1 DM, type 2 DM, and clinically suspected monogenic diabetes, respectively. Among 21 patients with suspected monogenic diabetes, 8 patients had clinical maturity-onset diabetes of the young (MODY), and the remaining 13 patients had other types of monogenic diabetes. Among them, genetic etiologies were identified in 14 patients (5.1%) from 13 families, which included MODY 5, transient neonatal DM, developmental delay, epilepsy, and neonatal diabetes (DEND) syndrome, Wolfram syndrome, Donohue syndrome, IPEX syndrome, Fanconi-Bickel syndrome, Wolcott-Rallison syndrome, cystic fibrosis-related diabetes, and maternally inherited diabetes and deafness.
Conclusions
Genetically confirmed monogenic diabetes accounts for 5.1% of patients referred to pediatric endocrinology clinics. The frequency of mutations in the major genes of MODY is low among pediatric patients in Korea. Identification of the genetic cause of DM is critical to provide appropriate therapeutic options and genetic counseling.
COVID-19 outbreak, social distancing and mass testing in Kenya - Insights from a mathematical model 
Authors: Mbogo Rachel Waema , Odhiambo John W.
Published: October 2020

As reported by the World Health Organization (WHO), the world is currently facing a devastating pandemic of a novel coronavirus ( COVID -19), which started as an outbreak of pneumonia of unknown cause in the Wuhan city of China in December 2019. Within days and weeks, the COVID -19 pandemic had spread to over 210 countries. By the end of April, COVID -19 had caused over three million confirmed cases of infections and 230,000 fatalities globally. The trend poses a huge threat to global public health. Understanding the early transmission dynamics of the infection and evaluating the effectiveness of control measures is crucial for assessing the potential for sustained transmission to occur in new areas.We employed a SEIHCRD delay differential mathematical transmission model with reported Kenyan data on cases of COVID -19 to estimate how transmission varies over time and which population to target for mass testing. The model is concise in structure, and successfully captures the course of the COVID -19 outbreak, and thus sheds light on understanding the trends of the outbreak and the vulnerable populations. The results from the model gives insights to the government on the population to target for mass testing. The government should target population in the informal settlement for mass testing. People with pre-existing medical and non-medical conditions should be identified and given special medical care. With aggressive effective mass testing and adhering to the government directives and guidelines, we can get rid of COVID -19 epidemic.
The Effect of Sevoflurane Anesthesia for Dental Procedure on Neurodevelopment in Children: A Prospective, Equivalence, Controlled Trial
Authors: Zhou Pinping , Zhang Chao , Huang Guijin , Hu Yuan , Ma Wenzhu , Yu Cong
Published: October 2020

Background: Dental procedures under general anesthesia (DGA) was found to improve the oral health-related quality of children's life. However, some parents and pediatricians expressed concern about the neurotoxicity of general anesthesia. The purpose of this trial was to investigate whether DGA in children has an adverse effect on neurodevelopment.Methods: In this prospective, assessor-masked, controlled, equivalence trial, we recruited 340 children younger than 7 years who were undergoing caries treatment between Feb 1, 2019, and Aug 31, 2019, without factors affecting neurodevelopment. They received either sevoflurane-based general anesthesia or awake-local anesthesia. The Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition was used to evaluate the neurodevelopment of children at six months after surgery, and the Full-Scale IQ (FSIQ) was selected as the primary outcome. Predefine the 95% CI of a difference in means within five (1/3 SD) as the equivalence margin.Results: The outcome data were obtained from 129 children in the general anesthesia group and 144 in the local anesthesia group. The median length of general anesthesia was 130 min (IQR 110 – 160). There was equivalence in means of FSIQ score between the general anesthesia group and the local anesthesia group (local minus general anesthesia 0.46, 95% CI -2.35 to 1.61). There was no significant difference in FSIQ scores between different age groups and different anesthesia durations. Only the mother's education could affect the primary outcome.Conclusions: In this trial, prolonged DGA with a sevoflurane-only anesthetic in preschool children, does not adversely affect neurodevelopment at six months after surgery compared with awake-local anesthesia. Trial registration: Chinese Clinical Trial Registry, ChiCTR1800015216. Registered Mar 15 2018, http://www.chictr.org.cn/showproj.aspx?proj=24830.
Genetic Aetiology of Primary Adrenal Insufficiency in Chinese Children
Authors: Chang Zhuo , Lu Wei , Zhao Zhu-Hui , Xi Li , Li Xiao-Jing , Ye Rong , Ni Jin-Wen , Pei Zhou , Zhang Miao-Ying , Cheng Ruo-Qian , Zheng Zhang-Qian , Sun Cheng-Jun , Wu Jing , Luo Feihong
Published: October 2020

Background: Primary adrenal insufficiency (PAI) is a life-threatening condition, and a definitive aetiological diagnosis is essential for management and prognostication. We conducted this study to investigate the genetic aetiologies of PAI in South China and explore their clinical features.Methods: Seventy children were enrolled. Clinical information was collected, and combined genetic tests were performed according to the children’s manifestations. Statistical analysis was performed among the different groups. In silico or in vitro experiments were applied to determine the pathogenicity of novel variants.Results: Among the 70 children, 84.29% (59/70) were diagnosed with congenital adrenal hyperplasia (CAH), and a diagnosis of 21-hydroxylase deficiency (21-OHD) was subsequently genetically confirmed in 91.53% of the cases. Salt wasting (SW), simple virilization (SV), and non-classic (NC) CAH accounted for 66.10% (39/59), 30.51% (18/59), and 3.39% (2/59) of the cases, respectively. Interestingly, 17-hydroxyprogesterone (17-OHP) and testosterone levels in females were significantly higher than those in males among both SW and SV CAH patients. Additionally, 15.71% (11/70) of the patients were diagnosed with PAI, 72.73% (8/11) of whom had positive genetic findings. Among all the cases, two novel variants in CYP21A2, c.833dupT (p.279GfsX17) and c.651+2T>G, were harboured by CAH patients. A microdeletion (Xp21.2-21.3) and five novel variants, including 2 in the NR0B1 gene (p.108S>X, p.L411Vfs*6, c.1231_1234delCTCA, p.L411Vfs*6), 2 in the AAAS gene (c.399+1G>A, p.V103Afs*8, c.250delT, p.W84Gfs*10) and 1 in the NNT gene (p.I758Mfs*10), were detected. The novel variant c.399+1G>A in the AAAS gene was further confirmed to lead to exon 4 deletion in mRNA transcription and produce a truncated ALADIN protein.Conclusions: We found ethnic differences in the CYP21A2 gene variant spectrum among different study populations. Female 21-OHD patients tended to have higher 17-OHP and testosterone levels, which warrants caution in relation to the virilization effect both physically and psychologically. Novel gene variants detected in the CYP21A2, NR0B1, AAAS and NNT genes expanded the genetic spectrum of paediatric PAI; however, further improvement of genetic testing tools beyond our protocol is still needed to uncover the complete aetiology of PAI in children.
Clinical Features and Survival Outcome of Patients with Malignant Transformation Arising in Mature Cystic Teratoma: A 20-Year Experience at Multicenter Institution and Literature Review on 342 Cases
Authors: Wang Tian , Yang Runfeng , Wang Shixuan , Wu Mingfu
Published: October 2020

Background: To analyze the clinicopathologic characteristics and prognosis in malignant transformation of mature cystic teratoma (MT-MCT).Methods: We retrospectively reviewed 23 patients (cohort 3) diagnosed with MT-MCT from the medical center (Tongji Hospital and Hubei cancer hospital), between January 1990 to June 2020. Cohort 2 was obtained from the PubMed, CNKI, Web of Science, and MEDLINE database, between January 1990 to June 2020. Cohort 3 was based on the surveillance, epidemiology, and results registry (SEER) database, between January 1975 and December 2016. Results: Among 3865 cases diagnosed with mature cystic teratoma, the incidence of MT-MCT is 23 (0.59%). The mean age of 23 patients was 50.6 years (median 49.0, range 24 to71 years). Patients mainly had abdominal pain (21.7%) or complained about an abdominal mass (30.4%). The mean tumor size was 11.6 cm (median 11.9, range 5.2 to 14.8 cm). According to the FIGO stage, eight patients were in stage I (34.8%), two cases were in stage II (8.6%), III (47.8%), and IV (8.7%), respectively. Most patients were diagnosed with squamous cell carcinoma (91.3%). Most patients received total hysterectomy, salpingo-oophorectomy, and omentectomy. Five patients (21.7%) received lymphadenectomy. Platinum-based chemotherapy and radiotherapy were selectively used for patients after surgical resection. The mean of disease-free survival was 27.3 months (median 22.0, range 3.0 to 67.0 months). According to the published data analysis of 342 cases, the 1-, 3-, and 5-year overall survival rates were 53.2%, 33.1%, and 23.2%, respectively. The young patients (＜55 years) showed better prognosis. Conclusion: MT-MCT has an aggressive clinical course, with poor long-term prognosis. The high incidence in postmenopausal women should not be ignored. The effectiveness of adjuvant chemotherapy or radiotherapy after surgery is needed to elucidate in the future.
Colorectal Cancer Incidence and Mortality Trends by Sex and Population Group in South Africa: 2002-2014.
Authors: Motsuku Lactatia Matsie , Chen Wenlong Carl , Muchengeti Mazvita Molleen , Quene Tamlyn Mac , Kellett Patricia , Mohlala Matshediso Ivy , Chu Kathryn Minghsia , Singh Elvira , Naidoo Megan
Published: October 2020

BackgroundSouth Africa (SA) has experienced a rapid transition in the Human Development Index (HDI) over the past decade, which had an effect on the incidence and mortality rates of colorectal cancer (CRC). This study aims to provide CRC incidence and mortality trends by population group and sex in SA from 2002 to 2014.MethodsIncidence data were extracted from the South African National Cancer Registry and mortality data obtained from Statistics South Africa (STATS SA), for the period 2002 to 2014. Age-standardised incidence rates (ASIR) and age-standardised mortality rates (ASMR) were calculated using the STATS SA mid-year population as the denominator and the Segi world standard population data for standardisation. A Joinpoint regression analysis was computed for the CRC ASIR and ASMR by population group and sex.ResultsA total of 33,232 incident CRC cases and 26,836 CRC deaths were reported during the study period. Of the CRC cases reported, 54% were males and 46% were females, and among deaths reported, 47% were males and 53% were females. Overall, there was a 2.5% annual average percentage change (AAPC) increase in ASIR from 2002 to 2014 (95% CI: 0.6- 4.5, p-value <0.001). For ASMR overall, there was 1.3% increase from 2002 to 2014 (95% CI: 0.1- 2.6, p-value <0.001). The ASIR and ASMR among population groups were stable, with the exception of the Black population group. The ASIR increased consistently at 4.3% for black males (95% CI: 1.9- 6.7, p-value <0.001) and 3.4% for black females (95% CI: 1.5- 5.3, p-value <0.001) from 2002 to 2014, respectively. Similarly, ASMR for black males and females increased by 4.2% (95% CI: 2.0- 6.5, p-value <0.001) and 3.4% (, 95%CI: 2.0- 4.8, p-value <0.01) from 2002 to 2014, respectively.ConclusionsThe disparities in the CRC incidence and mortality trends may reflect socioeconomic inequalities across different population groups in SA. The rapid increase in CRC trends among the Black population group is concerning and requires further investigation and increased efforts for cancer prevention, early screening and diagnosis, as well as better access to cancer treatment.
Pharmacological Treatment After Acute Coronary Syndrome: Baseline Clinical Characteristics and Sex Differences in a Population-Based Cohort Study.
Authors: Sotorra-Figuerola Gerard , Ouchi Dan , García-Sangenís Ana , Giner-Soriano Maria , Morros Rosa
Published: October 2020

Background: Cardiovascular disease remains the most common cause of death worldwide. Some differences between sexes in secondary prevention pharmacological therapies after an acute coronary syndrome (ACS) have been described, being women less likely to be treated. The aim was to to describe baseline socio-demographic and clinical characteristics and drugs prescribed for secondary prevention after a first episode of ACS in a Primary Health Care cohort population in Catalonia (Spain) and to assess differences between sexes.Methods: Population-based observational cohort study of patients with a first episode of ACS during 2009-2016. Data source: Information System for Research in Primary Care (SIDIAP) database. Results: There were 8,071 patients included, 71.3% of them were men and 80.2% had an acute myocardial infarction (AMI). Their mean age was 65.3, being older the women than the men. The most frequent comorbidities were hypertension, dyslipidaemia and diabetes and they were more common in women. Antiplatelets (91.3%) and statins (85.7%) were the study drugs most prescribed. The uses of all comedications were significantly higher in women, except for nitrates. The combination of four study groups was initially prescribed in 47.7% of patients and combination of beta-blockers, statins and antiplatelets was prescribed in 18.4%. More men than women received all recommended pharmacological groups.Conclusion: Women were older, had more comorbidities and received more comedication. Most patients were treated with a combination of four or three study drugs for secondary prevention. Men initiated more treatments for secondary prevention and dual antiplatelet therapy than women.
Spinal reflexive movement follows General Tau Theory
Authors: Bahadori Mehrdad , Cesari Paola , Craig Cathy M , Andani Mehran Emadi
Published: October 2020

Background
Tau theory explains how both intrinsically and perceptually guided movements are controlled by the brain. According to general tau theory, voluntary, self-paced human movements are controlled by coupling the tau of the movement (i.e. the rate of closure of the movement gap at its current closure rate) onto an intrinsically generated tau-guide (Lee, 1998). To date there are no studies that have looked at involuntary movements, which are directly guided by innate patterns of neural energy generated at the level of the spinal cord or brain, and that can be explained by general tau theory. This study examines the guidance of an involuntary movement generated by the Patellar reflex in presence of a minimized gravitational field.
Results
The results showed that the Patellar reflexive movement is strongly coupled to an intrinsic tau-guide particularly when the limb is not moving in the direction of gravity.
Conclusion
These results suggest that the same principles of control underpin both voluntary and involuntary movements irrespective of whether they are generated in the brain or the spinal cord. Secondly, given that movements like the patellar reflex are visible from infancy, one might conclude that tau-guidance is an innate form of motor control, or neural blueprint, that has evolved over time.
Impact of Central Nervous System International Prognostic Index on the treatment of Diffuse Large B Cell Lymphoma
Authors: Ma'koseh Mohammad , Ma’koseh Mohammad , Tamimi Faris , Abufara Alaa , Abusalem Lana , Salama Osama , Saleh Jacob , Khader Rnad , Faiyoumi Baha A. , Al-Rwashdeh Mohammad , Halahleh Khaled
Published: October 2020

Background
The central nervous system international prognostic index [CNS-IPI]is being usedwidely for the identification of patients with diffuse large B cell lymphoma [DLBCL]with highrisk of CNS relapse. The aim of our study is to confirm the value of the CNS-IPI in predicting CNS relapse in our young study population and to evaluate the impact on selection of patients for CNS prophylaxis.
Methods
We retrospectively reviewed patients with pathological diagnosis of DLBCL who were treated with R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone] regimen from January 2004 till December 2016 with no evidence of CNS involvement on diagnosis. Different demographic, disease characteristics and treatment given including the use of intrathecal chemotherapy prophylaxis were collected. Correlation between CNS-IPI and CNS relapse was examined through chi square test. Median time to CNS relapse and median overall survival [OS] after CNS relapse were estimated using the Kaplan-Meier plots.
Results
354 patients were included. Median age was 46 years. 52 [15%] patients were given intrathecal chemotherapy [ITC] prophylaxis, of whom CNS-IPI was high in 7[13%]. Overall, 5% of the patients [n = 17] developed CNS relapse.The median survival after CNS relapse was 7 months. The rate of CNS relapse in patients with low, intermediate and high risk CNS-IPI was 0.6%, 3% and 22% respectively [p = < 0.001].On multivariate analysis, involvement of bone marrow [p = 0.039]and renal or adrenal glands[p = 0.023]significantly correlated with CNS relapse. Considering theCNS-IPI and high risk anatomical sites [breast, uterus, testis and epidural space], 26% of our patients with DLBCLwould have needed prophylaxis.
Conclusion
Although CNS-IPI helps in better selection of DLBCL patients for CNS prophylaxis, it will significantly and possibly unnecessarily increase the number of patients exposed to prophylaxis. More investigational biomarkers and methods are necessary to better refining high risk patients.
Risk Factors Associated with Ischemic Stroke in a Young Non-Diabetic and Non-Hypertensive Population: A Retrospective Case-Control Study
Authors: Zhang Nan , Zhang Lin , Wang Qiu , Zhao Jingwei , Liu Jia , Wang Guang
Published: October 2020

Background: Globally, rates of ischemic stroke (IS) have been rising among young adults. This study was designed to identify risk factors associated with IS incidence in young adults unaffected by hypertension or diabetes.Methods: This was a retrospective case-control study of early-onset IS patients without diabetes and hypertension. Control patients were matched with healthy individuals based upon sex, age (±2 years), and BMI (±3 kg/m2) at a 1:3 ratio. Sociodemographic, clinical, and risk factor-related data pertaining to these patients was collected. The association between these risk factors and IS incidence was then assessed using conditional logistic regression models.Results: We recruited 60 IS patients and 180 controls with mean ages of 44.37±4.68 and 44.31±4.71 years, respectively, for this study. Relative to controls, IS patients had significantly higher total cholesterol (TG), homocysteine (HCY), white blood cell (WBC), absolute neutrophil count (ANC), systolic blood pressure (SBP), and diastolic blood pressure (DBP) levels, and significantly lower high-density lipoprotein cholesterol (HDL-C) and triglyceride cholesterol (TC), free triiodothyronine (FT3), and free thyroxine (FT4) levels (all P< 0.05). After controlling for potential confounding factors, HCY and ANC were found to be significantly positively associated with IS incidence (OR 1.518, 95%CI 1.165-1.977, P= 0.002 and OR 2.418, 95%CI 1.061-5.511, P=0.036, respectively), whereas HDL-C and FT3 levels were negatively correlated with IS incidence (OR 0.001, 95%CI 0.000-0.083, P=0.003 and OR 0.053, 95%CI 0.008-0.326, P=0.002, respectively).Conclusion: In young non-diabetic and non-hypertensive patients, lower HDL-C and FT3 levels and higher HCY and ANC levels may be associated with an elevated risk of IS. Additional prospective studies of large patient cohorts will be essential to validate these findings.
Flow of Room Air Leads to Rapid Changes in Mucociliary Transport in the Tracheal Epithelium
Authors: Kelly Susyn Joan , Martinsen Paul , Tatkov Stanislav
Published: October 2020

BACKGROUND: Inspired air is heated and humidified in the nose before it reaches lower airways. This mechanism is bypassed during tracheostomy, directly exposing the lower airways to colder and drier air from the environment, which is known to have negative effects on mucociliary transport; however, little is known about how quickly mucociliary transport deteriorates. The purpose of this study was to determine the short-term effect of flowing room air on mucociliary transport in the trachea. In an ovine perfused in vitro tracheal model (N=7) the epithelium was exposed to 25 L/min of flow, heated to lamb body temperature (38 °C) and fully saturated with water vapor as the control, followed by room air (22 °C and 50% relative humidity) for a short duration, until mucociliary transport had visually stopped. Mucus transport velocity (MTV) and cilia beat frequency (CBF), as well as the area of the surface with beating cilia, were continuously measured with video-microscopy.RESULTS: Exposing the tracheal epithelium to air heated to body temperature and fully humidified resulted in stable MTV 9.5 ± 1.1 mm/min and CBF 13.4 ± 0.6 Hz. When exposed to the flow of room air, MTV slowed down to 0.1 ± 0.1 mm/min in 2.0 ± 0.4 seconds followed by a decrease in CBF to 6.7 ± 1.9 Hz, after 2.3 ± 0.8 second. Both MTV and CBF recovered to their initial state when heated and humidified air-flow was re-introduced. CONCLUSIONS: This study demonstrates mucociliary transport can deteriorate within seconds of exposing the tracheal epithelium to flowing room air. The reduction in MTV precedes slowing of CBF. Their relationship is non-linear and a minimum CBF of approximately 6 Hz is required for MTV > 0. Clinically these findings indicate a potential rapid detrimental effect of breathing with non-humidified air via bypassed upper airways.
Turn-key super-resolution mapping of cell receptor force orientation and magnitude using a commercial structured illumination microscope
Authors: Blanchard Aaron , Combs J. Dale , Brockman Joshua , Kellner Anna , Glazier Roxanne , Su Hanquan , Bender Rachel , Bazrafshan Alisina , Chen Wenchun , Quach M , Li Renhao , Mattheyses Alexa , Salaita Khalid
Published: October 2020

Many cellular processes, including cell division, development, and cell migration require spatially and temporally coordinated forces transduced by cell surface receptors. Nucleic acid-based molecular tension probes allow one to quantify and visualize the piconewton (pN) forces applied by these receptors. Building on this technology, we recently imaged DNA tension probes using fluorescence polarization imaging to map the magnitude and 3D orientation of receptor forces with diffraction limited resolution (~ 250 nm). Further improvements in spatial resolution are desirable as many force-sensing receptors are organized at the nano-scale in supramolecular complexes such as focal adhesions. Here, we show that structured illumination microscopy (SIM), a super-resolution technique, can be used to perform super-resolution molecular force microscopy (MFM). Using SIM-MFM, we generate the highest resolution maps of both the magnitude and orientation of the pN traction forces applied by cells. We apply SIM-MFM to map platelet and fibroblast integrins forces, as well as T cell receptor forces. The method reveals that platelets dynamically re-arrange the orientation of their integrin forces during activation. Monte Carlo simulations validated the results and provided analysis of the sources of noise. Importantly, we envision that SIM-MFM will be broadly adopted by the cell biology and mechanobiology communities because it can be implemented on any standard SIM microscope without hardware modifications.
A Novel Xanthene Derivative, DS20060511, Attenuates Glucose Intolerance by Inducing Skeletal Muscle-specific GLUT4 Translocation in Diabetic Mice
Authors: Furuzono Shinji , Kubota Tetsuya , Taura Junki , Konishi Masahiro , Naito Asuka , Karasawa Hiroshi , Kubota Naoto , Kadowaki Takashi
Published: October 2020

Reduced glucose uptake into the skeletal muscle is an important pathophysiological abnormality in type 2 diabetes, and is caused by impaired translocation of glucose transporter 4 (GLUT4) to the skeletal muscle cell surface. We found a novel xanthene compound, DS20060511, which induces GLUT4 translocation to the skeletal muscle cell surface, thereby stimulating glucose uptake into the skeletal muscle. DS20060511 induced GLUT4 translocation and glucose uptake into differentiated L6-miytubes and into the skeletal muscles of live mice. These effects were completely abolished in GLUT4 knockout mice. Induction of GLUT4 surface translocation by DS20060511 was independent of the insulin signaling pathways including IRS1-Akt-AS160 phosphorylation and IRS1-Rac1-actin polymerization, eNOS pathway and AMPK pathway. Acute and chronic DS20060511 treatment attenuated the glucose intolerance in obese diabetic mice. Taken together, DS20060511 acts as a skeletal muscle specific-GLUT4 translocation enhancer to facilitate glucose utilization. Further studies with DS20060511 would help to develop a novel antidiabetic medicine.
A Novel Prognostic Model to Predict Prognosis of Patients With Osteosarcoma Based on Clinical Characteristics and Blood Biomarkers
Authors: Tian Liru , Chen Shulin , Li Chuan , Zhong Dongmei , Chen Yuyu , Zhou Taifeng , Yang Xiaoming , Liao Zhiheng , Wang Tingting , Su Peiqiang , Xu Caixia
Published: October 2020

Background: To develop a novel prognostic model based on clinical characteristics and blood biomarkers to estimate overall survival (OS) and progression-free survival (PFS) in osteosarcoma (OSC) patients.Methods: A total of 71 patients with OSC from Sun Yat-sen University Cancer Center were retrospectively included. The novel prognostic model for predicting OS and PFS was established by using Lasso regression analysis based on blood biomarkers. The predictive accuracy and discriminative ability of the novel prognostic model was compared with TNM staging and clinical treatment using concordance index (C-index), time-dependent ROC (tdROC) curve, decision curve analysis (DCA), net reclassification improvement index (NRI), and integrated discrimination improvement index (IDI).Results: Based on the Lasso regression analysis, we identified a 5 prognostic factors module (RBC, Ca2+, CRE, PNI, and LSR) as a novel predictive model for the OSC patients. The C-index of the novel prognostic model for predicting OS and PFS were 0.782 (95% CI = 0.658 - 0.905) and 0.741 (95% CI = 0.632 - 0.851), respectively, which were higher than that of TNM staging and clinical treatment. The tdROC curve and DCA also showed the novel model had good predictive accuracy and discriminatory power than TNM staging and treatment both in predicting OS and PFS. Moreover, the novel prognostic model performed well in all time frames (1, 3 and 5 years) in terms of the IDI and NRI when compared with the TNM staging, and clinical treatment.Conclusions: The novel prognostic model showed favorable performance than TNM staging and clinical treatment for predicting OS and PFS in OSC patients.
Identification of an Immune-related Signature That Indicates the Dedifferentiation of Thyroid Cells
Authors: Wang Xuemin , Li Chunyan , Qin Rujia , Zhong Zhaoming , Sun Chuan-Zheng
Published: October 2020

Background: Patients with well-differentiated thyroid carcinoma can achieve long-term survival after reasonable treatments, but there is no standard treatment mode for poorly or undifferentiated thyroid carcinoma and its prognosis is very poor. Immune cells, especially tumor-associated macrophages, account for a large proportion of the tumor microenvironment of anaplastic thyroid carcinomas (ATCs). However, whether immune-related genes can mediate the dedifferentiation of thyroid cells is unclear.Methods: We initially compared the differences of thyroid differentiation score, infitration of immune cells and enriched pathways between ATCs and papillary thyroid carcionma (PTCs) or normal thyroid tissues in Gene Expression Omnibus database. Then, The Cancer Genome Atlas database was used to screen out the prognosis associated IRGs. A risk score was constructed and we next investigated its predictive value for differentiation by applying receiver operating characteristic (ROC) curves and correlation analyses. Kaplan-Meier curves were used to evaluated its prognostic value. We further explored the associations of the risk score with important immune checkpoint molecules, infiltrating immune cells and response to immunotherapy.Results: Compared with PTCs or normal thyroid tissues, ATCs exhibited lower thyroid differentiation scores, higher infiltration of most immune cells and higher activation of inflammatory response. The risk score composed of MMP9 and SDC2 was significantly increased in ATCs and low differentiated PTCs. Moreover, it showed favorable predictive value for differentiation and survival. Higher risk score displayed dedifferentiation status and a worse prognosis. Additionly, the risk score was positively correlated with immune checkpoint molecules PDL1, CTLA4, IDO1, HAVCR2 and infiltration of multiple immune cells. Importantly, we found that samples with higher risk score tend to have a better response to immune checkpoint agents than lower ones.Conclusion: Our findings indicate that the risk score may not only contribute to the judgement of differentiation and prognosis of thyroid cancer, but also help to the prediction of immune cell infiltration and immune checkpoint inhibitor response.
Analysis of the Early Clinical Outcomes of Arthroscopic Debridement in the Treatment of Shoulder Tuberculosis
Authors: He Yan Wei , Liu Jun-Cai , Wang Zhi , Zhou Peng , Deng Xiang tian , Yang Li , Chen Zan , Li Zhong
Published: October 2020

Background Due to atypical clinical symptoms, it is difficult to diagnose joint tuberculosis infection, which often results in misdiagnosis and missed diagnosis. It is easy to cause joint disability, and there are few reports of using arthroscopy to diagnose and treat shoulder tuberculosis. This case series aims to introduce the clinical outcomes of arthroscopic treatment of shoulder tuberculosis.Methods 29 patients with shoulder tuberculosis from September 2013 to February 2019, 10 males, 19 females. Age range from 22-69, The average age is 37.6 years. All patients underwent arthroscopic lesion debridement, preoperative and postoperative regular use of isoniazid, rifampicin, pyrazinamide, streptomycin quadruple anti-tuberculosis drugs.The erythrocyte sedimentation rate (ESR) and C reactive protein (CRP) were recorded before and at the last follow-up. The shoulder function was evaluated according to the visual analogue scoring method (visual analogue scale,VAS) pain score and Constant score. Results 29 patients were followed up for 12-24 months, the average follow-up time was 15.7 months. The pathological diagnosis of all patients after surgery was shoulder tuberculosis. No serious complications were found at the last follow-up, and the incision healed well. VAS pain score, Constant score, ESR and CRP at the last follow-up were significantly improved compared with those before treatment (p<0.05).Conclusion On the basis of the standard use of anti-tuberculosis drugs before and after surgery, shoulder arthroscopy is used to treat early and mid-term shoulder tuberculosis, which can be diagnosed by direct observation under the arthroscope and postoperative pathological examination. It has the advantages of thorough lesion removal, minimally invasive, rapid recovery, and reliable clinical effect.