bluuebunny/crossref_metadata_2025 huggingface dataset:
Glycyrrhizin improves the pathogenesis of psoriasis through IL-17A and the SIRT1-STAT3 axis
Authors: Qiong Huang , Han Ling , Zhang Nan , Chen Hu , Yan Ke , Zhang Zheng , Ma Ying , Xu Jin
Published: December 2020

Background: The anti-inflammatory effect of glycyrrhizin has been widely recognized, while the specific mechanism of glycyrrhizin in psoriasis remains poorly understood. Results: Here, in an imiquimd-induced mouse model of psoriasis (IMD), we found that glycyrrhizin can substantially improve the adverse symptoms in mice. The hematoxylin-eosin staining results showed that glycyrrhizin can also improve the pathological state of skin cells in IMD mice. Using enzyme-linked immunosorbent assay (ELISA), we found that glycyrrhizin substantially inhibited the expression of IL-17A and IFN-γ in the serum of IMD mice. In order to simulate the effect of IL-17A on keratinocytes in psoriasis, we treated HaCaT cells with 100 ng/mL IL-17A (IL-17A-HaCaT cells) for 48 h. Then, using cell-counting kit-8 (CCK-8) and ELISA assays, we found that glycyrrhizin inhibited the proliferation of IL-17A-HaCaT cells and reversed the promotion of IL-6, CCL20, and TNF-α induced by IL-17A. Further, western blotting (WB) results indicated that glycyrrhizin promoted the expression of SIRT1 and inhibited the expression of STAT3 and phosphorylated STAT3 (p-STAT3). By treating IL-17A-HaCaT cells with EX-527 (a potent and selective inhibitor of SIRT1), combined with CCK-8 and WB experiments, we initially found that EX-527 inhibited the proliferation of IL-17A-HaCaT cells and promoted the expression of STAT3, p-STAT3, and acetylated STAT3 (a-STAT3). However, when glycyrrhizin was added at the same time, the proliferation of IL-17A-HaCaT cells increased, and the expression of STAT3, p-STAT3, and a-STAT3 reduced. We then knocked down the expression of SIRT1 via small interfering RNA in IL-17A-HaCaT cells, and the results were consistent with those of EX-527. Conclusions: Together, these results indicated that glycyrrhizin improved psoriasis by inhibiting the expression of IL-17A and IFN-γ in vivo and suppressed the proliferation of IL-17A-HaCaT cells and the expression of STAT3, p-STAT3, and a-STAT3 by upregulating SIRT1 in vitro.
Quantitative assessment of the effectiveness of joint measures led by the Fangcang shelter hospitals in the response of COVID-19 epidemic in Wuhan, China
Authors: Jiang Hui , Song Pengfei , Wang Siyi , Yin Shuangshuang , Yin Jinfeng , Zhu Chendi , Cai Chao , Xu Wangli , Li Weimin
Published: December 2020

Objective

To quantitatively evaluate the effectiveness of Fangcang shelter hospitals, designated hospitals, and time interval from illness onset to diagnosis in the prevention and control of COVID-19 epidemic.
Methods

We use SEIAR and SEIA-CQFH warehouse models to simulate the two-stage epidemic in Wuhan and calculate the time dependent basic reproduction number (BRN) of symptomatic infected individuals, asymptomatic infected individuals, exposed individuals and community isolated infected individuals. Scenarios that varied in the maximum numbers of open beds in Fangcang shelter hospitals and designated hospitals, the intervals from onset to visit hospitals and diagnosis, are considered to quantitatively assess the optimal measures.
Findings:

The BRN is decreased from 4.50 on Jan 22 to 0.18 on March 18. Without Fangcang shelter hospitals, the case number of cumulative and death will increase by 18.58% and 51.73%. If the number of beds in the designated hospitals decrease by 1/2 or 1/4, the number of cumulative cases will increase by 178.04% and 92.1%. If the time interval from illness onset to hospital visit is 4 days, the number of cumulative cases and deaths will increase by 2.79% and 6.19%. If Fangcang shelter hospitals are not established, the number of beds in designated hospitals reduce 1/4 and the time interval from visiting hospitals to diagnosis is 4 days, the cumulative number of cases will increase 268.97%.
Mi-2β-targeted inhibition induces immunotherapy response in melanoma
Authors: Zhu Bo , Wang Zhengyu , Yao Licheng , Lin Xingyu , Zhang Jie , Li Xin , Hagman James , Shao Jingwei , Tran Phuc , Cao Meng , Zhang Jianming , Goding Colin , Liao Xuebin , Li Hong-yu , Cao Peng , Miao Xiao , Cui Rutao
Published: December 2020

Recent development of some new immune checkpoint inhibitors has been particularly successfully in melanoma, but the majority of melanoma patients exhibit resistance. Understanding and targeting the potential underlying mechanism/targets, especially the tumor-intrinsic modulators to convert resistant melanomas to immunotherapy sensitivity will potentially provide a significant improvement in patient outcome. Here, Mi-2β, a chromatin remodeling enzyme was identified as a key melanoma-intrinsic effector regulating the adaptive anti-tumor immune response. Loss of Mi-2β rescued the immune response to immunotherapy in vivo. Mechanistically, targeting Mi-2β induced the adaptive immune response by transcriptionally enhancing expression of a set of IFN-γ-responsive genes including CXCL9, CXCL10 and IRF1. Finally, we developed a Mi-2β-targeted inhibitor Z36-MP5, which specifically and effectively induced a response to immune checkpoint blockades in otherwise resistant melanomas. Our work provides a new insight into the epigenetic regulation in adaptive immune response, and highlights a viable strategy to improve immunotherapies in melanoma.
Use of Benzodiazepines in Patients With Bipolar Disorder
Authors: Martin Marta Zubia , Mesa Susana Alberich , Peña Maria Purificación López , Martínez Iñaki Zorrilla , Pascual Juan Pablo Chart , Pinto Ana Maria González
Published: December 2020

BackgroundBenzodiazepines (BZDs) are widely used in patients with bipolar disorder. The aim of this study was to determine chronic use of BZDs in patients with a first bipolar episode and the association between its use and cognition.MethodsA prospective longitudinal study was conducted in a cohort of 63 patients under 40 years old with a first manic or mixed episode. The percentage of patients taking BZDs in the baseline sample was evaluated at 6 months and for the next 3 years. Cognitive functioning was compared between patients with chronic BDZ use and those who did not use them. A linear regression model adjusted for potential confounding variables such as age and education level were used.ResultsJust over half the sample (55.6%; n = 35) took BZD at the start of the study. At 6 months, this percentage decreased to 34.9% (n = 22) and to 14.3% (n = 9) at 3 years of follow-up. Patients who took BZD chronically had worse outcomes in overall attention. These differences remained significant when controlled for the variables age and education level (B -0.462, p = 0.046, 95% CI: - 0.914 - 0.009).ConclusionsChronic administration of BZD occurs in a small percentage of bipolar patients at disease onset, and is associated with decreased attention. These side effects should be followed up.
Two-Dimensional Frank-Kasper Z Phase with One Unit-Cell Thickness
Authors: Hongbo Xie , Bai Junyuan , Ren Haiyan , Li Shanshan , Pan Hucheng , Ren Yuping , Qin Gaowu
Published: December 2020

Z phase is one of the three basic units by which the Frank-Kasper phases are generally assembled. Compared to the other two basic units, i.e., A15 and C15 structures, the Z phase structure is rarely experimentally observed because of a relatively large volume ratio among the constituents to inhibit its formation. Moreover, the discovered Z structures are generally the three-dimensional (3D) ordered Gibbs bulk phases to conform to their thermodynamic stability. Herein, we confirmed the existence of a metastable two-dimensional (2D) Frank-Kasper Z phase with one unit-cell height in the crystallography in a model Mg-Sm-Zn system, by using aberration-corrected high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) combined with density functional theory (DFT) calculations. This finding is important for understanding the relationship between the traditional crystal structures and the quasicrystals, and it is also expected to provide a new insight to understand the clustering and stacking behavior of atoms in condensed matters.
Conserved and None-Conserved Functions of the Rice Homologs of the Arabidopsis Trichome Initiation-Regulating MBW Complex Proteins
Authors: Zheng Kaijie , Wang Xutong , Wang Yating , Wang Shucai
Published: December 2020

Background: Trichome initiation in Arabidopsis is regulated by a MYB-bHLH-WD40 (MBW) transcriptional activator complex formed by the R2R3 MYB transcription factor GLABRA1 (GL1), MYB23 or MYB82, the bHLH transcription factor GLABRA3 (GL3), ENHANCER OF GLABRA3 (EGL3) or TRANSPARENT TESTA8 (TT8), and the WD40-repeat protein TRANSPARENT TESTA GLABRA1 (TTG1). However, the functions of the rice homologs of the MBW complex proteins remained uncharacterized. Results: Based on amino acid sequence identity and similarity, and protein interaction prediction, we identified OsGL1s, OsGL3s and OsTTG1s as rice homologs of the MBW complex proteins. By using protoplast transfection, we show that OsGL1D, OsGL1E, OsGL3B and OsTTG1A were predominantly localized in the nucleus, OsGL3B functions as a transcriptional activator and is able to interact with GL1 and TTG1. By using yeast two hybridization and protoplast transfection assays, we show that OsGL3B is able to interact with OsGL1E and OsTTG1A, and OsGL1E and OsTTG1A are also able to interact with GL3. On the other hand, we found that OsGL1D functions as a transcription activator, and it can interact with GL3 but not OsGL3B. These results suggest that rice homologs of the Arabidopsis MBW complex proteins are able to form MBW complexes, but may have conserved and none-conserved functions. Furthermore, we found that expression of OsTTG1A in the ttg1 mutant restored the phenotypes including alternations in trichome and root hair formation, seed color, mucilage production and anthocyanin biosynthesis, indicating that OsTTG1A and TTG1 may have similar functions. Conclusion: These results aid in our understanding of the mechanism of trichome initiation in rice.
WITHDRAWN: Transcriptome and targeted metabolome reveal the regulation network of Lilium davidii var. unicolor during dormancy release
Authors: Fan Xinyue , Yang Yue , Li Min , Fu Linlan , Zang Yuqing , Wang Chunxia , Hao Tianyou , Sun Hongmei
Published: December 2020

Background：Regulation and control of bulb dormancy are critical for ensuring annual production and high-level cultivation of lily. Application of low temperatures is the most effective method for breaking lily bulb dormancy, but the molecular regulatory mechanism underlying this response is unclear. Results：Herein, targeted metabolome and transcriptome analyses were performed with buds of Lilium davidii var. unicolor bulbs stored for 0, 50 and 100 days at 4°C. Dormancy release mainly depended on the accumulation of GA4 and GA7, which are synthesized by the "non13-hydroxylation" pathway, rather than GA3, and ABA was degraded in the process. The contents of nonbioactive GA9, GA15 and GA24, the precursors of GA4 synthesis, increased with bulb dormancy release. Altogether, 113,252 unique transcripts were de novo assembled through high-throughput transcriptome sequences, and 639 genes were continuously differentially expressed. Enrichment analysis showed that the carbohydrate metabolism and hormone metabolism pathways play major roles in dormancy release. Energy sources during carbohydrate metabolism mainly depend on glycolysis and the PPP pathway rather than on the TCA cycle. Association analysis of the transcriptome and target metabolome showed that genes related to ABA, GA, starch and sucrose metabolism and some TF families, such as MYB, WRKY, NAC and TCP, involved in dormancy release were highly correlated with the target metabolome. Coexpression analysis further confirmed that ABI5, PYL8, PYL4 and PP2C, vital ABA signaling elements, regulated GA3ox and GA20ox in the GA4 biosynthesis pathway. The TFs WRKY32, WRKY71, MYB, DAM14, NAC8, ICE1, bHLH93 and TCP15 also participated in the ABA/GA4 regulatory network, and ICE1 may be the key factor linking temperature signals and hormone metabolism. Conclusions：These results will help to reveal the bulb dormancy molecular mechanism and to develop new strategies for high-quality bulb production.
USF2 Knockdown Downregulates THBS1 to Inhibit the TGF-β Signaling Pathway and Reduce Pyroptosis in Sepsis-Induced Acute Kidney Injury
Authors: Sun Jian , Wang Yang , Niu Lei , Tang Lujia , Pan Shuming
Published: December 2020

BackgroundAcute kidney injury (AKI) is a serious complication of sepsis. This study was performed to explore the mechanism that THBS1 mediated pyroptosis by regulating TGF-β signaling pathway in sepsis-induced AKI.MethodsGene expression microarray related to sepsis-induced AKI was obtained from the GEO database, and the mechanism in sepsis-induced AKI was predicted by bioinformatics analysis. qRT-PCR and ELISA were performed to detect expressions of THBS1, TNF-α, IL-1β, and IL-18 in sepsis-induced AKI patients and healthy volunteers. Mouse model of sepsis-induced AKI was established, with serum creatinine, urea nitrogen, 24-h urine output measured, and renal tissue lesions observed by HE staining. Cell model of sepsis-induced AKI was cultured in vitro, with expressions of TNF-α, IL-1β, and IL-18, pyroptosis, Caspase-1 and GSDMD-N, and activation of TGF-β pathway detected. The upstream transcription factor USF2 was knocked down in cells to explore it effect on sepsis-induced AKI.ResultsTHBS1 was highly expressed in patients with sepsis-induced AKI. Silencing THBS1 protected mice against sepsis-induced AKI, and significantly decreased the expressions of NLRP3, Caspase-1, GSDMD-N, IL-1β, and IL-18, increased cell viability, and decreased LDH activity, partially reversing changes in cell morphology. Mechanistically, USF2 promoted oxidative stress response by transcriptionally activating THBS1 to activate TGF-β/NLRP3/Caspase-1 signaling pathway and stimulate pyroptosis, and finally exacerbated sepsis-induced AKI.ConclusionsUSF2 knockdown downregulates THBS1 to inhibit TGF-β signaling pathway and reduce pyroptosis and further to ameliorate sepsis-induced AKI.
Community Health Worker Knowledge , Attitudes, and Practices Towards Epilepsy in Mozambique
Authors: Cumbe Vasco Francisco Japissane , Greene M. Claire , Fumo Afonso Mazine Tiago , Fumo Hélder , Mabunda Dirceu , Gouveia Maria Lídia Chaúque , Oquendo Maria A. , Duarte Cristiane S. , Sidat Mohsin , Mari Jair de Jesus , Wainberg Milton L.
Published: December 2020

Background: Epilepsy is the most common neurological disease in the world, affecting 50 million people, with the majority living in low- and middle-income countries (LMICs). A major focus of epilepsy treatment in LMICs has focused on task-sharing identification and epilepsy care by community health workers (CHWs). The present study aimed to assess the KAPs of CHWs towards epilepsy in Sofala province, Mozambique. Methods: One hundred and thirty five CHWs completed a questionnaire that included socio-demographic characteristics and 44-items divided in six subscales pertaining to KAPs towards epilepsy (QKAP-EPI) in nine districts of Sofala Province, Mozambique. The internal consistency and factor structure were examined to evaluate the reliability and construct validity of the QKAP-EPI, respectively. To examine correlates of KAPs toward epilepsy we evaluated the association between sociodemographic variables and QKAP-EPI subscales using linear regression models. Results: CHWs demonstrated adequate knowledge regarding epilepsy for medical treatment details (Mean=1.63, SD=0.28) and epilepsy safety/risks (Mean=1.62, SD=0.59). However, CHWs reported low levels of knowledge related to the causes of epilepsy, espousing stigmatizing attitudes, as well as cultural treatment, which is the perception in different cultures of how epilepsy should be treated. Knowledge about how to manage epilepsy during crisis varied across the different types of emergency care practices. Heterogeneity in the level of knowledge regarding epilepsy was observed among CHWs in the different districts of Sofala Province and when using different local names of epilepsy (Dzumba, Nzwiti).Conclusion: CHWs knowledge of medical treatment and epilepsy safety/risks were adequate. However, information on the causes of epilepsy, stigmatizing attitudes, cultural treatment, and some aspects of epileptic crisis response were low. These areas of poor knowledge should be the focus of educating CHWs in increasing their ability to provide quality care for patients with epilepsy in LMICs.
Antimicrobial Usage in Cattle and Poultry Production in Dar Es Salaam, Tanzania: Pattern and Quantity
Authors: Azabo Rogers , Mshana Stephen , Matee Mecky , Kimera Sharadhuli I
Published: December 2020

Background: Antimicrobials are extensively used in cattle and poultry production in Tanzania. However, there is dearth of information on its quantitative use. A questionnaire-based cross-sectional study was conducted from August to September 2019 in randomly selected poultry and small-scale dairy farms, in three districts of Dar es Salaam City eastern, Tanzania, to assess the practice and quantify antimicrobial use. Descriptive and statistical analyses were performed at a confidence interval of 95%. The ratio of Used Daily Dose (UDD) and Defined Daily Dose (DDD) were used to determine whether the antimicrobial was overdosed or under dosed. Results: A total of 51 poultry and 65 small-scale dairy farms were involved in the study. The route of antimicrobial administration was 98% orally via drinking water and 2% in feeds for poultry and for small-scale dairy farms, all through parenteral route. Seventeen types of antimicrobials comprising seven classes were recorded in poultry farms while nine belonging to six classes in the small dairy farms. Majority of the farms (poultry, 87.7% and small-scale dairy, 84.3%) used antimicrobials for therapeutic purposes. About 41% of the poultry and one third (34%) of the dairy farmers’ were not compliant to the drug withdrawal periods. Beta-lactams, fluoroquinolones, sulphonamides, tetracyclines and macrolides were the commonly used antimicrobials on these farms. Trimethoprim and tylosin were under dosed whereas colistin, sulfadiazine, sulfamerazine, flumequin and sulfadimidine were over dosed in the poultry farms and only tylosin over dosed in small dairy farms. The majority (58.6%) of farmers had adequate level of practices regarding antimicrobial use in cattle and poultry production. This was associated with the age and level of education of the cattle and poultry farmers. Conclusion: The study revealed a high and widespread misuse of antimicrobials of different types and classes in both poultry and small-scale dairy farming in Dar es Salaam, Tanzania. This result gives insight into the antimicrobial use practices and its quantification. The information obtained can guide and promote prudent use of antimicrobials among the farmers by developing mitigate strategies that reduce antimicrobial resistance risk potentials.
Volatile Constituents Analysis and Antimicrobial Activity of Two Subspecies Ballota nigra L. From Iran
Authors: Bidgoli Reza Dehghani
Published: December 2020

Background Ballota nigra L. is a perennial herb of the Lamiaceae family and it's native to the Mediterranean region and central Asia, also it can found throughout Europe. during this research, the volatile oil composition and antimicrobial activity of the methanol extract from flowering aerial parts of two subspecies of B. nigra (B. nigra ssp. foetida and B. nigra ssp. anatolica) were evaluated. Plant extraction was prepared by the maceration method and the antibacterial activity of methanolic extracts against 12 microorganisms was investigated by disc diffusion and minimal inhibitory concentration (MIC) methods.Results: GC/MS analysis of the volatile oil confirms the presence of 25 constituents in B. nigra ssp. foetida and 27 constituents in B. nigra ssp. anatolica. the most constituents in these two subspecies were α- Terpineol, Eicosane, Hexadecanoic acid, Longipinene epoxide, and Ethyl linoleate, which had slight differences within the amount of total volatile oil. within the antibacterial and MIC tests, indicated that methanolic extract of two subspecies Ballota nigra L. had acceptable antibacterial activity and therefore the B. nigra ssp. anatolica had more antibacterial activity in compression to B. nigra ssp. foetida.Conclusion: Today the tendency of natural products due to antioxidant and antimicrobial properties is increasing, and plants are the main source of these safe materials. During this respect, our study is often considered because of the first report on the volatile oil composition and antimicrobial activity of methanol extract of various subspecies of .B. nigra.
Rickettsiae in Red Fox (Vulpes Vulpes), Marbled Polecat (Vormela Peregusna) and Their Ticks in Northwestern China
Authors: Liu Gang , Zhao Shanshan , Tan Wenbo , Hornok Sándor , Yuan Wumei , Mi Ligu , Wang Suwen , Liu Zhiqiang , Zhang Yanyan , Hazihan Wurelihazi , Gu Xinli , Wang Yuanzhi
Published: December 2020

BackgroundPreviously, twelve Rickettsia species were found in ticks, fleas, sheep keds (Melophagus ovinus), bats (common pipistrelle: Pipistrellus pipistrellus) and a tick-bitten patient in Xinjiang Uygur Autonomous Region (XUAR), northwestern China. Here we aimed to molecularly detect rickettsial agents in red fox (Vulpes vulpes), marbled polecat (Vormela peregusna) and their ticks.MethodsDuring 2018-2019, 12 red foxes, 1 marbled polecat and their ticks were sampled in two counties and a city of Xinjiang Uygur Autonomous Region (northwestern China). The heart, liver, spleen, lung and kidney of these 13 carnivores were dissected, followed by DNA extraction. Hard ticks were identified both morphologically and molecularly. All samples were examined for the presence of rickettsiae by amplifying four genetic markers.ResultsA total of 26 adult ticks and 28 nymphs (38 Ixodes canisuga, nine Ixodes kaiseri, six Haemaphysalis erinacei and one Dermacentor marginatus) were collected from red foxes, and four H. erinacei ticks were removed from a marbled polecat. Analysis of cytochrome c oxidase subunit I (COI) gene sequences indicated that 2-32 nucleotides differed between I. canisuga, I. kaiseri and H. erinacei from northwestern China and Europe. Rickettsia raoultii was detected in three red foxes, Candidatus Rickettsia barbariae in a red fox, Rickettsia sibirica in a red fox and a marbled polecat, and R. raoultii in two tick species (I. canisuga and D. marginatus).Conclusions﻿To the best of our knowledge, I. canisuga and I. kaiseri have not been previously reported from red foxes in China. The DNA of R. sibirica and R. raoultii was detected for the first time in organs of red foxes, and R. sibirica in organs of marbled polecat. This is also the first molecular evidence for the presence of R. raoultii in I. canisuga. Our findings add to the range of tick-borne pathogens in wildlife species and associated ticks in China.
Evaluation and Selection of Suitable qRT-PCR Reference Genes for Light Responses in Tea Plant (Camellia Sinensis)
Authors: Wang Jiaxin , Tang Qianhui , Sun Kang , Zeng Liang , Wu Zhijun
Published: December 2020

Background: Tea plant (Camellia sinensis) is an important woody economic crop used for processing leaf-type beverages. Tea has been proved to be beneficial to human health because it is rich in tea polyphenols and other active ingredients. Numerous studies have shown that light is a necessary environmental condition to control the growth and metabolism of C. sinensis. Gene expression experiments are always performed to explore the transcriptional regulation mechanism of plants widely based on the technique of quantitative real time polymerase chain reaction (qRT-PCR). The screening and application of reference genes are necessary for the normalization of gene expression under specific conditions. However, the reference genes for systematic analysis of light-induced transcription mechanisms are still not available in C. sinensis.Results: In this research, we identified actin family genes that are always used as reference genes with high frequency and without distinction for various expression experiments in C. sinensis. Six pairs of distinctive primers (corresponding to CsACT1, CsACT2, CsACT(3-4), CsACT(5-6), CsACT(7-8), and CsACT(9-10) genes) were designed to evaluate their expression stability in response to light quality (LQ), light intensity (LI), and photoperiod (PD). Simultaneously, six other family members (CsUBC1, CsCLATHRIN1, CsGAPDH, CsTBP, CsTIP41, and CseIF-4α) of C. sinensis commonly used as reference genes were also investigated. The stability rankings of gene expression were calculated by the statistical algorithms of geNorm, BestKeeper, NormFinder, and RefFinder softwares. Conclusions: CsACT(5-6), CsTIP41, and CsACT(3-4) were the most stable genes for light quality (LQ), light intensity (LI), and photoperiod (PD) treatments, respectively. This study provides a basis for the selection of reference genes for future research on the transcription mechanism of light response in C. sinensis. Moreover, the analysis of actin family members of C. sinensis will help to understand the individual transcription mechanism of housekeeping family.
Gender-specific Predictive Ability for the Risk of Hypertension Incidence Related to Baseline Level or Trajectories of Adiposity Indices: Cohort Study of Functional Community in Beijing Urban from 2015 to 2019 year
Authors: LU Ya-ke , DONG Jing , SUN Yue , HU Li-kun , LIU Yu-hong , Chu Xi , Yan Yu-xiang
Published: December 2020

Background: Early prevention of hypertension is important for global cardiovascular disease morbidity and mortality. The current study aims to exploit better predictor for hypertension incidence related to baseline level or trajectories of adiposity indices, as well as the gender-specific effect.Methods: 6085 subjects from a functional community cohort in urban Beijing participated in our study. Restricted cubic splines were used to estimated nonlinear associations of BMI and WHtR as continuous variable with risk of hypertension. Stepwise logistic regression model was performed to estimate the RRs of adiposity indices and metabolic status, adjusted for covariates. Nomogram models and receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive power of BMI trajectory groups and WHtR trajectory groups. Further, all analysis were performed by gender.Results: The risk of hypertension incidence was significant related to BMI trajectory groups (persistent overweight: RR=1.99, 95%CI: 1.57-2.52; persistent obese: RR=3.07, 95%CI: 2.40-3.93; persistent the highest: RR=4.55, 95%CI: 3.37-6.14) and WHtR trajectory groups (persistent medium: RR=2.90, 95%CI: 2.23-3.77; persistent high: RR=4.48, 95%CI: 3.41-5.89; increasing to higher: RR=7.77, 95%CI:5.48-11.0). In total population, BMI trajectories and WHtR trajectories showed similar ability to predict the risk of hypertension incidence with AUC 0.713 and 0.720, respectively. After stratified by gender, BMI trajectories showed higher power in female than male butsimilar in WHtR trajectories (BMI trajectories: 0.762 vs. 0.662; WHtR trajectories: 0.769 vs. 0.663). Conclusions: BMI and WHtR trajectories have higher predictive power for hypertension incidence compared to baseline data. Women are more vulnerable to obese and abnormal MS than man.
S100A8/A9 Acts as Prognostic Indicators and Promotes Migration and Invasion via p38 MAPK Pathway in Nasopharyngeal Carcinoma
Authors: Xu Ning , Zhang Beibei , Yan Xuemin , Cai Yan , He Qin , Han Zijian , Yi Xiang , Huang Yuanjiao
Published: December 2020

Background Nasopharyngeal carcinoma (NPC) is one type of malignancy associated with migration and invasion through a currently unclear mechanism. We previously discovered S100A8/A9 levels were roughly elevated in the plasma of NPC patients as the promising biomarkers. However, their expressions and underlying functions in NPC tissues are still unknown. Methods In the present study, we analyzed 49 NPC tissues and 20 chronic pharyngitis (CP) tissues. Immunohistochemical staining was performed in different tissues and analyzed by mann-whitney U test statistically. Transwell migration and invasion experiments were further performed to determine S100A8/A9 effects on NPC. Results Our results showed that S100A8/A9 in NPC tissues were significantly higher than those in CP tissues, closely associated with NPC clinical stages. Intriguingly, exogenous S100A8/A9 protein stimulation could dramatically enhance NPC migration and invasion abilities. In addition, p38 MAPK pathway blockade could diminish the migration and invasion of NPC cells stimulated by S100A8/A9 proteins. The downstream tumor invasion and migration associated proteins (e.g. MMP7) were also elevated in NPC tissues, consistent with S100A8/A9 overexpression. Conclusions Taken together, our present findings suggest that the secreted soluble inflammatory factors S100A8/A9 might promote cancer migration and invasion via p38 MAPK signaling pathway along with invasion/migration associated proteins overexpression in the tumor microenvironment of NPC. This may shed light on the mechanism understanding of NPC prognosis and provide more novel clues for NPC diagnosis and therapy.
Enhancing Existing Medical School Curricula with an Innovative Healthcare Disparities Curriculum
Authors: Treacy-Abarca Sean , Aguilar Marisela Nicole , Vassar Stefanie , Hernandez Estebes , Farra Neveen El , Brown Arleen
Published: December 2020

Background: Effective healthcare disparities curricula are essential to improve care of minority patients. Methods: A cost-neutral, evidence-based curriculum was created by enhancing established medical school lectures at the UCLA David Geffen School of Medicine class of 2021 (n=188). Lectures within an 8-week course were evaluated for “teachable moments” or broad topics suitable to introduce specific healthcare disparities content. A lecture-enhancing curriculum based on Society of General Internal Medicine learning objectives was introduced into the DGSOM learning management system via supplemental PDF documents. Results: A total of 92 of 188 students completed curricular assessments and were stratified into intervention group (“utilized materials” n=52) and comparison (“did not utilize the material” n=40) groups based on self-reported use of materials. Minorities were more likely to utilize the material (41% of the intervention group vs 17% of the comparison group, p<.01). Post-course 16-item knowledge composite scores, and confidence in addressing healthcare disparities improved only in the intervention group (p=0.001), and 96% of respondents described the health disparities curriculum as a valuable learning resource. Conclusions: Enhancing pre-existing lectures by identifying and harnessing “teachable moments” is a cost-neutral and effective strategy to integrate a healthcare disparities curriculum.
Definition and prevalence of familial short stature
Authors: Grigoletto Veronica , Occhipinti Alessandro Agostino , Pellegrin Maria Chiara , Sirchia Fabio , Barbi Egidio , Tornese Gianluca
Published: December 2020

Objective
A significant portion of familial short stature (FSS) cases may not be recognized in clinical practice if the parents’ height is not adequately investigated. This study aimed to verify the prevalence of different definition of FSS on a cross-sectional cohort of children referred for short stature (SS) when their height and that of both parents were measured.
Methods
We consecutively enrolled 65 individuals referred for SS when both parents were present. We defined “target height related short stature” (TH-SS) when child height SDS was ≤-2 and included in the range of TH (i.e. TH SDS ± 1.5) and “autosomal dominant short stature” (AD-SS) when child and at least one parent heights were ≤-2 SDS.
Results
On 65 children referred for SS, 48 individuals had a height ≤-2 SDS. Based on measured parents’ heights, 24 children had TH-SS and 16 children AD-SS; 12 children were identified by both TH-SS and AD-SS, while 12 children with TH-SS did not have any of parents with SS. When considering reported parents’ heights, 3 out of 24 children with TH-FSS and 9 out of 16 with AD-FSS would have been missed.
Conclusion
This study underlines that adequate measurement and consideration of both parents’ height should be part of the clinical evaluation of every children with SS and new definitions should be used to detect and adequately approach the cases of FSS, since the identification of a causative gene in AD-SS can support treatment and follow-up decisions.
Research Relationship Between Hemodialysis and Health-Related Quality of Life - A Cross-Sectional Study of Diagnosis and Duration of Hemodialysis
Authors: Noto Shinichi , Miyazaki Masashi , Takeuchi Hidemi , Saito Shinya
Published: December 2020

Background: Hemodialysis is a medical technology implemented for various renal diseases and has a significant budget impact in Japan. Hemodialysis also affects health-related quality of life, as it interferes with daily life, but the effect of diagnosis and duration of hemodialysis is not clear. The purpose of this study was to examine the impact of hemodialysis on health-related quality of life, with a focus on diagnosis and duration of hemodialysis.Methods: We conducted EQ-5D-5L surveys among hemodialysis patients at a single hemodialysis hospital between November 2015 and September 2017 and used a scoring algorithm that was developed in Japan to calculate the scores. Results: A total of 274 subjects without missing data were included in the data analysis. The mean score of the entire group was 0.772 ± 0.215. Compared with other domains, pain/discomfort had the highest percentage of problems (59.1%). There were no differences in the distributions with respect to diagnostic names in any domain. Multiple regression analysis showed that hemodialysis duration was the only explanatory variable that had a significant effect on EQ-5D-5L scores.Conclusions: QOL measured using the EQ-5D-5L survey score was not affected by age, gender, or diagnosis but was affected by hemodialysis duration. A prolonged hemodialysis duration decreased the QOL of Japanese hemodialysis patients.
Beneficial effect of omarigliptin on diabetic patients with non-alcoholic fatty liver disease/non-alcoholic steatohepatitis
Authors: Hattori Sachiko , Nomoto Kazuhiro , Suzuki Tomohiko , Hayashi Seishu
Published: December 2020

Background: Dipeptidyl peptidase 4 (DPP4) is a serine exopeptidase able to inactivate various oligopeptides and also a hepatokine. Hepatocyte-specific overexpression of DPP4 is associated with hepatic insulin resistance and liver steatosis. Method: We examined whether weekly DPP4 inhibitor omarigliptin (OMG) improves liver function as well as levels of inflammation and insulin resistance in type 2 diabetic patients with non-alcoholic fatty liver disease (NAFLD). Furthermore, we tried OMG in a diabetic patient with biopsy-confirmed nonalcoholic steatohepatitis (NASH). Results: In NAFLD patients, OMG significantly decreased levels of aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (gGTP), homeostatic model assessment of insulin resistance (HOMA-IR), and high-sensitivity C-reactive protein (hsCRP), while no significant change was seen in hemoglobin A1c (HbA1c) or body mass index (BMI). In a NASH patient, liver function had improved markedly, and the hepatic fibrosis marker FIB-4 decreased in parallel with HOMA-IR and hsCRP. Improvements in intrahepatic fat deposition and fibrosis appeared to be seen on ultrasonography.Conclusion: The effects of OMG in ameliorating hepatic insulin resistance may lead to decreasing intrahepatic fat accumulation and improving intrahepatic adipose inflammation in NAFLD/NASH.Trial registration: UMIN Clinical Registry (UMIN000029288). Registered 22 September, 2017, https://upload.umin.ac.jp/UMIN000029288
Geographically Masking Addresses to Study COVID-19 Clusters
Authors: Houfaf-Khoufaf Walid , Touya Guillaume
Published: December 2020

Background: The spatio-temporal analysis of cases is a good way an epidemic, and the recent COVID-19 pandemic unfortunately generated a huge amount of data. But analysing this raw data, with for instance the address of the people who contracted COVID-19, raises some privacy issues, and geomasking is necessary topreserve both people privacy and the spatial accuracy required for analysis. This paper proposes dierent geomasking techniques adapted to this COVID-19 data.Methods: Different techniques are adapted from the literature, and tested on a synthetic dataset mimicking the COVID-19 spatio-temporal spreading in Paris and a more rural nearby region. Theses techniques are assessed in terms of k-anonymity and cluster preservation.Results: Three adapted geomasking techniques are proposed: aggregation, bimodal gaussian perturbation, and simulated crowding. All three can be useful in different use cases, but the bimodal gaussian perturbation is the overall best techniques, and the simulated crowding is the most promising one, provided some improvements are introduced to avoid points with a low k-anonymity.Conclusions: It is possible to use geomasking techniques on addresses of people who caught COVID-19, while preserving the important spatial patterns.
The Epidemiology of Moebius Syndrome in Italy
Authors: carta arturo , Favilla Stefania , Calzetti Giacomo , Casalini Maria Cristina , Ferrari Pier Francesco , Bianchi Berrnardo , Simonelli Maria Beatrice , Farci Roberta , gandolfi Stefano , Mora Paolo
Published: December 2020

Background: The epidemiology of Moebius Syndrome (MBS) is actually difficult to assess. In the present study we investigated the epidemiology of MBS in a well-defined population over a precise geographical area. Materials and Methods: Our University Hospital is the only national referral Centre for the diagnosis and treatment of MBS. Participants to this cross-sectional study are patients affected by MBS who have been periodically followed by our medical staff since 1998. Most of the patients were referred to our hospital by the Italian Association of Moebius Syndrome (AISMO). Demographic data necessary for our purposes were made available by AISMO database updated to April 2018. Subjects were assigned to the geographical macro- areas which are the ones conventionally used for surveys and epidemiological investigations by the Italian National Institute of Statistics. Rates and prevalence of the MBS cases were calculated referring to the last survey of the Italian population available. Every study parameter was then calculated by reference to the whole country and to macro-area partition. Gender rate and the corresponding prevalence were calculated with respect to the weighted whole population and to the respective gender population. Chi-square analysis was adopted to investigate possible differences among geographical regions and/or gender. A p value <0.05 was considered statistically significant. Results: One-hundred and sixty-four out of 212 MBS patients fulfilled our inclusion criteria. All cases were Caucasian and sporadic. The median age at diagnosis was 3.6 years, ranging from 0-55; this range was significantly reduced to 0-5 years (median age at diagnosis: 2.2 years) for patients included after 2007. The birth prevalence calculated was 0.06 cases per 10000 live births with an overall prevalence of 0.27/100000 without any gender or geographical predisposition. Conclusions: The rate of MBS prevalence herein observed, rounded for possible underestimation, is 0.3/100000 people without any regional difference in the distribution of the cases. Our data confirm on a national basis the rarity of the disease.
Skin cancers in people with albinism in Togo in 2019: results of two rounds of national mobile skin care clinics
Authors: Saka Bayaki , Akakpo Sefako Abla , Teclessou Julienne Noude , Gnossike Piham , Adam Saliou , Kassang Panawe , Elegbede Yvette , Mouhari-Toure Abas , Darre Tchin , Kombate Koussake , Pitche Palokinam
Published: December 2020

Background: In people with albinism (PWA), the deficiency of melanin increase the risk of skin cancers. The aim of this study was to determine the prevalence of skin cancers and characteristics of these detected skin cancers (histological types, localization) in PWA in 10 cities in Togo in 2019.Methods: This is a cross-sectional study of medical records of PWA systematically examined during two mobile skin care clinics in 2019, as part of a programme for the prevention and management of skin cancers in these subjects. Results: During the study period, 280 (95.2%) of the 294 PWA consulted, had developed skin lesions. Of the 280 PWA, the pathological reports from the medical records of 33 patients (11.8%; (95%CI= [8.2-16.2]) had concluded to non-melanoma skin cancers. The mean age of these 33 patients was 38.6±15.2 years and the sex-ratio was 1. Their occupations were mainly resellers (21.2%), traders (15.2%) and farmers (12.2%). In the 33 patients, 54 cases of non-melanoma skin cancers were identified, with some patients having more than one tumor, and some of them having more than one (histologically confirmed) diagnosis. These 54 non-melanoma skin cancers were divided into 21 cases of invasive squamous cell carcinomas, 2 cases of Bowen’s disease and 31 cases of basal cell carcinomas. These non-melanoma skin cancers mainly occurred in the head and neck (33 cases; 61.1%), the upper limbs (15 cases; 27, 8%) and the trunk (4 cases; 7.4%).Conclusion: The results of this study show a high prevalence of skin cancers among PWAs in Togo in 2019, only non-melanoma skin cancers. In addition, they illustrate the role of ultraviolet rays with regard to the localization of skin cancers and the occupations of patients. Popularization and compliance with photo protection measures, systematic and regular examination of the skin of these PWAs will allow early detection and treatment of these skin cancers.
Design and validation of Brucellosis prevention questionnaire focused on animal vaccination
Authors: Bahadori Farhad , Ghofranipour Fazlollah , Ghaﬀarifar Saeideh , Ziaei Reza
Published: December 2020

Background: The inadequate awareness of livestock breeders on brucellosis transmission, as well as their improper knowledge about preventing brucellosis is considered as one of the important barriers to animal vaccination against brucellosis. The present study aimed to design and validate a brucellosis prevention questionnaire focused on animal vaccination. The valid questionnaire was used to design, implement, and evaluate an interventional training program.Method: A brucellosis prevention questionnaire (BPQ) was developed in the exploratory psychometric study. In addition, face-to-face interviews were conducted to formulate its initial items, the results of which were merged with those obtained from literature review. Further, the face, content, and construct validity of the questionnaire were assessed by co-operating livestock breeders, veterinarians, and health educationists. The impact score (IS), and content validity ratio (CVR) and index (CVI) of the items were calculated, and the construct validity of the questionnaire was evaluated through factor analysis. Furthermore, the reliability of the results related to the questionnaire was measured by using Cronbach’s alpha, intra-class correlation coefficient (ICC), and composite reliability, as well as the standard error of measurement (SEM).Results: The questionnaire was finalized with 53 items and its validity was confirmed by CVI (0.90), CVR (0.74), and IS (4.30). Additionally, the items were loaded into three constructs of awareness, attitude, and practice. Further, the predictive power of awareness, attitude, and practice was determined as 43.43, 15.81, and 15.78%, respectively. Furthermore, the fitness of the proposed model among the constructs was confirmed by the root mean square error of approximation (RMSEA) <0.08, as well as normed chi-square (x 2/ df) < 5.0, comparative fit index (CFI) ≥ 0.90, and Tucker- Lewis index (TLI) ≥ 0.9. Conclusion: The brucellosis prevention questionnaire represented acceptable psychometric properties. The factors influencing the preventive behavior of livestock breeders can be identified by applying the questionnaire, and co-operating veterinarians and educational planners.
The influence of the Municipal Human Development Index and maternal education on infant mortality: an investigation in a retrospective cohort study in the extreme south of Brazil
Authors: Anele Carolina Ribeiro , Hirakata Vânia Naomi , Goldani Marcelo Zubaran , Silva Clécio Homrich da
Published: December 2020

Background: Infant mortality is considered an important and sensitive health indicator in several countries, especially in underdeveloped and developing countries. Most of the factors influencing infant mortality are interrelated and are the result of social issues. Therefore, this study performed an investigation of the influence of the MHDI and maternal education on infant mortality in a capital in the extreme south of Brazil. Methods: It is a retrospective cohort study with data on births and deaths in the first year of life for the period of 2000-2017. The association between the independent variables and the outcome was done by bivariate analysis through simple Poisson regression. The variables that can potentially be considered confounding factors were used in a multiple Poisson regression for robust variances - adjusted model. Results: The study included 317545 children, of whom 3107 died. The medium MHDI showed associated with infant death in the first year of life. Maternal education, individually and jointly analyzed with the MHDI, showed association with the outcome of infant death in the first year of life, particularly for children of mothers with lower maternal education (p<0.001). In relation to other related factors, maternal age; number of Prenatal Care Consultations; gestational age, weight, gender and Apgar Index (5th minute) of the newborn showed association with IM (p<0.001). Conclusions: The HDI is considered a good predictor of infant mortality by some authors and the analyzes of the present study also confirm an association of the medium MHDI and its low MHDIE component with infant mortality. In addition, it was maternal education with less than eight years of study that that demonstrated a higher risk of death, revealing itself to be a social determinant with a relevant impact on infant mortality. Thus, it is possible to conclude that maternal education is available information, and it is superior to the MHDI to assess the infant mortality outcome.