bluuebunny/crossref_metadata_2025 huggingface dataset:
HLF is a Potential Prognostic Biomarker in Head and Neck Squamous Cell Carcinoma Based on Bioinformatic Analysis and Experimental Validation
Authors: Fang Wei , Wan Di , Chen Jun , Ma Weiqun , Luo Zhen , Yang XiaoQin
Published: January 2021

BackgroundHead and neck squamous cell carcinoma (HNSCC) is one of the most frequent cancers worldwide, with an increasing incidence. However, the underlying molecular mechanisms of HNSCC are poorly understood.MethodIn this work, 5 original datasets (GSE23558, GSE13601, GSE30784, GSE9844, GSE78060) of Head and neck squamous cell carcinoma (HNSCC) were selected from Gene Expression Omnibus (GEO) database. To identify differentially expressed genes (DEGs) in HNSCC and adjacent tissues. The common DEGs were acquired by Venn diagram. The sensitivity and specificity of HLF were determined by Receiver operating characteristic curves (ROC). Then, In order to further confirm the relationship between HLF and HNSCC patient’s prognosis, the expression and survival analysis of HLF was performed by Gene Expression Profiling Interactive Analysis (GEPIA), Cell culture, reverse transcription polymerase chain reaction (RT-PCR), western blotting and immunohistochemical staining.ResultsSeventeen DEGs were screened from five sets of HNSCC functional gene expression series in GEO datasets. The low expression of HLF was indicated might be correlated with poor prognosis of HNSCC patients based on the bioinformatics analysis. According to the results of Cell culture, RT-PCR, western blotting, immunohistochemical staining, it was confirmed that the low level of HLF expression correlated with poor prognosis of HNSCC patients.ConclusionThe study effectively revealed useful information about the relationship of the low level of HLF expression and HNSCC. In summary, we identified HLF as a potential prognostic biomarker and therapeutic target for HNSCC.
Diffuse peritonitis caused by spontaneous perforation of pyometra: A case report and literature review
Authors: Xu Hao , Zhuang Yifan , Wang Caiming , Zhou Yongjie , Chen Haofei , Li Xin , Zhou Wence
Published: January 2021

BackgroundUterine perforation is commonly caused by iatrogenic injuries, tumours, and traumas. Uterine perforation resulting from infection is less common, and such perforation rarely causes abdominal empyema and diffuse peritonitis. Infectious complications such as shock and multiple organ dysfunction are extremely dangerous and even life threatening. Correct early diagnosis and appropriate treatment can reduce the mortality of pyometra.Case presentationA 62-year-old woman presented to our hospital with persistent abdominal pain for 5 hours. The patient had undergone hysteroscopy six months ago, and a cystic space-occupying lesion of the uterus was found one month ago. Perfect the various examinations, consider the patient as acute diffuse peritonitis Perforation of the digestive tract? Uterine cavity infection. In the emergency department, laparoscopic exploration was performed. During the operation, it was diagnosed as pyometra and perforation of the right uterine fundus. Then, combined with a gynecologist, a hysterectomy with double appendages was performed. The operation went smoothly. The patient had paralytic intestinal obstruction after the operation. After active symptomatic treatment The patient recovered well and was discharged. Postoperative pathology results were as follows: 1. Moderately differentiated squamous cell carcinoma of the cervix (non-keratinizing type); 2. Metastatic squamous cell carcinoma of the right ovary; 3. Perforation of the fundus of the uterus, pyometra, and extensive purulent inflammation of the muscle wall .ConclusionsUterine perforation is a rare cause of acute abdomen. Clinicians often don't know enough about this, and they are prone to misdiagnosis and missed diagnosis. For elderly women with abdominal pain and peritonitis, the possibility of empyema perforation should be considered during diagnosis and treatment, and the examination should be improved to avoid misdiagnosis, because correct early diagnosis and appropriate treatment can reduce the mortality of empyema.
The correlation between gross domestic product per capita and the success rate of assisted reproductive technologies worldwide
Authors: Dong Jie , Yan Song , Qian Chenxi , Wang Xiaohong
Published: January 2021

Background
Although there has been increased utilization of assisted reproductive technologies (ART) in the world, there is no conclusive definition of the relationship between the success rate of ART and national wealth.
Methods
In this study, using the data from the International Committee for Monitoring Assisted Reproductive Technologies (ICMART), we sought to determine whether there is a correlation between the success rate of ART (represented by pregnancy/delivery rates) and national wealth (represented by gross domestic product per capita (GDP)). Moreover, to further understand the effect of GDP on ART effectiveness, we analyzed the association between ART success rate and GDP in 50 US states.
Results
Our data showed that the number of ART treatment cycles increased with an increase in GDP. However, we found a negative correlation between ART success rate and GDP in ICMART countries, but no correlation was seen in the US states. Using rough estimation, we derived that the success rate of ART was not related to GDP in the ICMART countries with GDP per capita more than thirteen thousand dollars.
Conclusions
In this study, for the first time, we show that when the GDP of an economic body reaches (or exceeds) thirteen thousand dollars, its ART pregnancy and delivery rates cannot be associated with GDP, and the ART success rate remains stable.
Is Double-Strut Fibula Ankle Arthrodesis a Reliable Reconstruction for Bone Defect after Distal Tibia Tumor Resection? -A Finite Element Study Based on Promising Clinical Outcomes
Authors: Zhao Zhiqing , Yan Taiqiang , Guo Wei , Yang Rongli , Tang Xiaodong
Published: January 2021

Background: There are different surgical methods for primary malignant tumor located at distal tibia. Previous studies have reported that double-strut fibula ankle arthrodesis is an alternative reconstruction. The purpose of this study was to investigate the biomechanical effect of double-strut fibula ankle arthrodesis by finite element analysis (FEA). Methods: Computer aided design software was used to established three-dimension models. Three different models were construct: normal tibia-fibula-talus complex (Model A), double-strut fibula ankle arthrodesis (Model B), and reconstruction by ipsilateral fibula (Model C). We used FEA to evaluate and compared the biomechanical characteristics of these constructs. Simulated loads of 600 N was applied to the tibial plateau to simulate balanced single-foot standing. Output results representing the model von Mises stress, and displacement of the components were analyzed.Results: Construct stiffness was significantly increased when the internal plate fixation was used. For axial loads, Model B (963.79 N/mm) was significantly stiffer than the construct of Model A (430.76 N/mm), and Model C (616.06 N/mm), indication Model B was more stable. Maximum stress on the fibular graft occurred on the proximal end. There were no significant differences in von Mises stress and stress distribution of fibular graft in Model B (22.73 MPa) and Model C (23.69 MPa). In Model B, the ipsilateral fibula in Model B has a higher value of stress (12.07 MPa) than that in Model A (0.67 MPa), indicating the ipsilateral fibula shared load after fusion with talus. For axial load, displacement at the fibular graft in Model B (0.37 mm) was significantly less than that in Model C (0.82 mm).Conclusions: Our computational findings suggest that double-strut fibula ankle arthrodesis is an acceptable construct for distal tibia defect and the ipsilateral fibula shared load after fusion with talus.
Angiotensin-(1-7) Oral Formulation Improves Physical Performance in Mountain Bike Athletes: a Double-blinded Crossover Study
Authors: Moura Samara Silva de , Mendes Adália Táci Pereira , Júnior Francisco de Assis Dias Martins , Totou Nádia Lúcia , Coelho Daniel Barbosa , Oliveira Emerson Cruz , Motta-Santos Daisy , Santos Robson Augusto Souza dos , Becker Lenice Kappes
Published: January 2021

Background: The ECA2/Ang-(1-7)/Mas axis is shown to be involved in effects mediated by physical exercise, as it can induce the release of nitric oxide (ON) and bradykinin (BK), which are potent vasodilators. The vasodilating action the NO/BK can contribute to increased metabolic efficiency in muscle tissue and central nervous system. The formulation HPβ-CD-Ang-(1-7) through its mechanisms of action can be a promising supplement to aid in the maintenance and improvement of performance and may also favor recovery during competitions. The premise of this study was to investigate the effects of acute oral supplementation HPβ-CD-Ang-(1-7) on the performance of mountain bike (MTB) practitioners. Methods: Fourteen recreational athletes, involved in training programs for at least one year, participated in this crossover design study. Subjects underwent two days of testing with a seven-day interval. HPβ-CD-Ang-(1-7) (1.75 mg) and HPβCD-Placebo were provided in capsules three hours prior to tests. To determine the safety of the HPβ-CD-Ang-(1-7) formulation associated with physical effort, cardiovascular parameters heart rate (HR) and blood pressure (BP) were analyzed. Physical performance was measured using maximal oxygen uptake (VO2), total exercise time (TET), mechanical work (MW), mechanical efficiency (ME), and rating of perceived exertion (RPE). Respiratory exchange coefficient (REC), lactate and non-esterified fatty acids (NEFAs) were measured. Maximal incremental tests were performed on a progressively loaded leg cycle ergometer. Results: There were no significant differences in terms of HR or BP at rest and maximum effort between the HPβ-CD-Ang-(1-7) and placebo groups. The VO2max showed significant differences (p = 0.04). It was higher in the Ang-(1-7)condition (66.15 mlO2.kg-1.min-1) compared to the placebo (60.72 mlO2.kg-1.min-1). This was also observed for TET (Ang-(1-7) 39.10 min vs. placebo 38.14 min; p = 0.04), MW (Ang-(1-7) 156.7 vs. placebo 148.2; p = 0.04), and at the lowest RPE (Ang-(1-7) vs. placebo; p = 0.009). No significant differences were observed for REC, NEFAs, or Lactate.Conclusion: These results suggest that HPβ-CD-Ang-(1-7) improves the physical performance of MTB recreational athletes and could be a promising supplement.Trial registration: RBR-2x56pw8, registered January 15th, 2021.
Relationship between Suicidal Ideation and Stigma, Disclosure, and Perceived Social Support in HIV /AIDS Patients
Authors: Yu Yong
Published: January 2021

Objective: To explore the relationship between suicidal ideation and stigma, disclosure and social support in HIV /AIDS patients.Methods: A total of 1146 HIV-infected /AIDS patients were investigated by a general situation questionnaire, Perceived Social Support Scale (PSSS), Beck Suicidal Ideation Scale (Chinese version) (BSI-CV), disclosure questionnaire and Stigma Scale (SSS-S) on a WeChat platform. Results: 54.01% (619/1146) of the sample reported having suicidal ideation in the past week or at the height of depression; The results of multivariate logistic regression analysis showed that In SS-S, the affective dimension [OR value (95%CI) was 1.63(1.17-2.26)], the cognitive dimension [OR value (95%CI) was 2.06 (1.48-2.87)], the behavioral dimension [OR value (95%CI) was 2.05 (1.53-2.76)], and the family support [OR value (95%CI) was 0.64 (0.47 ~ 0.87)], which were associated with suicidal ideation in HIV /AIDS patients; Social support mediated between AIDS-related stigma and suicidal ideation (19.80% of the total effect). Conclusion: Suicidal ideation in HIV /AIDS patients is strongly associated with stigma, awareness, and perceived social support. So, stigma, awareness, and perceived social support should be incorporated into the suicide intervention system for HIV /AIDS patients.
Prevalenceof Intestinal Parasites and Associated Factors Among Food Handlers Working in Food and Drink Establishments at Mizan-aman Town, Southwest Ethiopia, 2018, Community Based Study
Authors: Dachew Aklilu Mamo , Zegene Girma Mamo , Shanab Esrael Derekiab , Endalew Mesenbet Muluken , Kebede Samuel Sahle
Published: January 2021

Background: Food borne diseases has remained a major global public health issue with substantial morbidity and mortality associated with the consumption of contaminated food staffs. Parasitic infection is among the major disease especially in developing countries and sub-Saharan countries.Objective:-This study was to determine the prevalence of intestinal parasites and associated factors among food handlers working in food and drink establishments at Mizan Aman town southwest Ethiopia.Method:- A community based cross sectional study was conducted in Mizan Aman town. A total of 418 food handlers from randomly selected 209 foods and drink establishments were interviewed and finally stool samples were taken. Parasitological assessment was performed by qualified laboratory technologists using the physiological saline for wet mount and zinc sulphate and formol ether concentration techniques were used. Data were analyzed using statistical SPSS version 21. P ≤0.05 was taken as statistically significantResult: The overall prevalence of intestinal parasites in Mizan Aman town was 26.1% .work experience >10 years (AOR=0.52,95% CI ;2.430,5.012),the food handlers who did not trimmed their finger,(AOR =1.89,95% CI :1.01,3.960) and using common knife for cutting raw meat and other foods (AOR=0.57, 95% CI : 3.61,5.54) were factors associated with parasitic infections. Conclusion: The magnitude of intestinal parasite in mizan aman town is high and work experience, finger trimming status, and using common knife for cutting raw meat and other foods were factors associated with the parasitic infections
Free Leptin Index is Elevated in Preeclamptic but not Healthy Women throughout Gestation. A Prospective Cohort Study
Authors: Leal María Carolina Páez - , Garces Maria Fernanda , Bermudez María Alejandra Cano – , Acosta Luis Miguel Maldonado - , Franco Jhon Jairo Peralta - , Cardenas Álvaro Javier Burgos - , Müller Edith Ángel - , Baños Arturo José Parada – , Schmalbach Javier Eslava – , Navarro Haiver Antonio Rodríguez - , Acosta Julieth Daniela Buell - , Castaño Justo , Nogueiras Rubén , Dieguez Carlos , Sanchez Elizabeth , Parra Ariel Iván Ruiz – , Caminos Jorge Eduardo
Published: January 2021

The ratio leptin/soluble leptin receptor (sOB-r), free leptin index (FLI), is used as a marker of leptin sensitivity/resistance in different pathologies. The aim of this study was to evaluate FLI in healthy non-pregnant, healthy pregnant and mild preeclamptic women during pregnancy. We conducted a nested case-control study within a longitudinal observational prospective cohort study. Serum leptin (p=0.0001) and sOB-r (p=0.0000) levels rose significantly throughout pregnancy in healthy pregnant and preeclamptic women [leptin (p=0.0000); sOB-r (p=0.0380)]. Serum leptin levels were significantly higher in preeclamptic compared to healthy pregnant women at 2nd (p=0.0245) and 3rd trimesters of pregnancy (p=0.0016). Additionally, serum sOB-r levels were significantly lower in preeclamptic women during the 2nd (p=0.0236) and 3rd trimester (p=0.0024) of pregnancy compared to healthy pregnant women. Moreover, we found that FLI did not vary significantly during any of the three periods studied in healthy pregnant women (p=0.7640), whereas, increased throughout preeclamptic pregnancy (p=0.0037). Indeed, FLI was significantly higher at 2nd (p=0.0053) and 3rd (p=0.0003) trimesters of pregnancy in preeclamptic compared to healthy pregnant women. Additionally, FLI was significantly higher during luteal phase compared to the follicular phase (p=0.0039). These results demonstrate that FLI increases significantly in preeclamptic pregnant women towards the end of pregnancy.
Reverse glycerol catabolism pathway for dihydroxyacetone and glycerol production by Klebsiella pneumoniae
Authors: Sun Shaoqi , Wang Yike , Shu Lin , Lu Xiyang , Wang Qinghui , Zhu Chengang , Shi Jiping , Lye Gary J. , Baganz Frank , Hao Jian
Published: January 2021

Background: Klebsiella pneumoniae is a bacterium that can be used as producer for numerous chemicals. Glycerol can be catabolised by K. pneumoniae and dihydroxyacetone is an intermediate of this catabolism pathway. Here dihydroxyacetone and glycerol were produced from glucose by this bacterium based on a reverse glycerol catabolism pathway. Results: tpiA, encoding triosephosphate isomerase, was knocked out to block the further catabolism of dihydroxyacetone phosphate in the glycolysis. After overexpression of a Corynebacterium glutamicum dihydroxyacetone phosphate dephosphorylase (hdpA), the engineering strain produced remarkable levels of dihydroxyacetone and glycerol from glucose. Further increase in product formation were obtained by knocking out gapA encoding an iosenzyme of glyceraldehyde 3-phosphate dehydrogenase. There are two dihydroxyacetone kinases in K. pneumoniae. They were both disrupted to prevent an inefficient reaction cycle between dihydroxyacetone phosphate and dihydroxyacetone, and the resulting strains had a distinct improvement in dihydroxyacetone and glycerol production. pH 6.0 and low air supplement were identified as the optimal conditions for dihydroxyacetone and glycerol production by K, pneumoniae ΔtpiA-ΔDHAK-hdpA. In fed batch fermentation 23.9 g/L of dihydroxyacetone and 10.8 g/L of glycerol were produced after 91 hours of cultivation, with the total conversion ratio of 0.97 mol/mol glucose.﻿Conclusions: This study provides a novel and highly efficient way of dihydroxyacetone and glycerol production from glucose.
A Qualitative Study Exploring Barriers, Facilitators and Solutions to Equitable Coverage of Preventive Chemotherapy Towards the Control and Elimination of Neglected Tropical Diseases in South Omo Zone, Nomadic Setting of Southern Ethiopia: Stakeholders’ Perspectives and Experiences
Authors: Asfaw Mekuria Asnakew , Hailu Chernet , Beyene Tariku J.
Published: January 2021

BackgroundDespite substantial progress made towards the control and elimination neglected tropical diseases (NTDs) in Ethiopia using preventive chemotherapy (PC) for lymphatic filariasis, onchocerciasis, schistosomiasis, trachoma, and soil-transmitted helminths, its implementation is facing challenges to achieve equitable coverage especially under mobile populations. This study, therefore, aimed at exploring multiple stakeholders’ perspectives and experiences on barriers, facilitators, and potential solutions to equitable coverage of PC in a mobile nomadic setting of Southern Ethiopia.MethodsThis study was conducted in the South Omo zone in August 2019. Qualitative data collection methods involving key informant interviews (KIIs) and focus group discussions (FGDs) were used to collect data from a total of 27 KIIs and 16 FGDs in a nomadic community of Southern Ethiopia using a semi-structured tool. Data were analyzed using a thematic approach, supported by NVivo 11 software.ResultsThis study revealed multiple barriers affecting equitable access and use of PC, and its facilitators and possible solutions were revealed by taking four dimensions (availability, accessibility, acceptability, and effective coverage) into consideration. The emerged barriers were lack of resource and infrastructure; inadequate information, mobilization and community engagement, lack of awareness, inappropriate scheduling of MDA, distribution of drugs at central point, mobile nature of nomadic communities, security challenges, low school attendance, misconception, misbelief, distrust of government, rumor and drugs’ side-effects, lack of community drug distributors’ (CDDs’) motivation, weak leadership and supportive system. On the other hand, the emerged facilitators were the provision of drugs at no-cost, partners' support, the presence of the religious and cultural organization, and decentralization of services. The possible suggested solutions were increasing partnership, improve supervision, engaging parents in mass drug administration (MDA), arrange a visiting schedule out of working hours, involve the village chief in training, intensify awareness creation, home-to-home visit, and plan mop-up activities.ConclusionsThere is a need of addressing barriers that affect efforts in equitable implementation of MDA to ensure no one is left behind from PC in nomadic settings of Southern Ethiopia. Most importantly, information, mobilization and community engagement, mobile nature of the nomadic community, and high level of low school attendance should take special consideration when MDA is planned in these settings.
An Observational Study on HIV and Syphilis Rates and Associated Risk Factors Among Elderly Men in Wuxi, China
Authors: Chen Ying , Bao Yining , Wu Zunyou , Robbins Sarah , Chu Minjie , Gu Jing , Meng Xiaojun , Zhuang Xun
Published: January 2021

Background: Human immunodeficiency virus (HIV) remains a nationwide health problem in China, there were a reported 1,045,000 people living with HIV/Acquired Immune Deficiency Syndrome (AIDS) by the end of October 2020, and the number of individuals aged 50 years and older living with HIV has also increased over the past two decades.Methods: A cross-sectional and 1:2 matched case-control studies were conducted from July to August 2016, in three community of Wuxi city, eastern China. A total of 1000 men aged 50 and over completed a face-to-face interview regarding their HIV-related knowledge and attitudes, as well as risk behaviors. All participants also provided a five-milliliter blood sample for syphilis and HIV testing.Results: Among the 1,000 participants, the mean age was 64.7±8.1 years. Less than half of the participants answered all HIV and sexually transmitted diseases (STDs)-related questions correctly (range 40.7%-63.9%). Younger men (χ2=23.175, P<0.05) with more education (χ2=52.054, P<0.05) were more knowledgeable about HIV compared to others. Less than 10% men knew where to get test for HIV, while only 2.1% had ever been tested. Serological testing showed that 20 participants were currently infected with syphilis and one person was tested positive for HIV antibody, however, none of them admitted having risky behaviors related to HIV/STDs. The 1꞉2 matched case-control indicated that only the AIDS-related attitudes were different between two groups (χ2=8.726, P=0.013), the conditional logistic regression analysis indicated that scores of AIDS health knowledge was the only significant prognostic factor for the infection (HR=0.754 (0.569-0.999), P=0.049).Conclusions: The overall HIV/STDs-related knowledge among elderly men in Wuxi, China was low. Further research aimed at identifying how these factors impact their sexual decision making can shed valuable insight into further prevention program in this population.
The Isoflavone Puerarin Exerts Anti-Tumor Activitiy in Pancreatic Ductal Adenocarcinoma by Suppressing Akt/mTOR Activity
Authors: Zhu Hengyue , Lu Hong , Xiao Yanyi , Guo Hangcheng , Guo Yangyang , Huang Youze , Liu Xiaodong , Shan Yunfeng , Bai Yongheng , Lin Xiangyang
Published: January 2021

Background: Puerarin (7,4’-dihydroxyisoflavone-8-β-glucopyranoside) is a natural flavonoid compound isolated from the traditional Chinese herb Radix puerariae. Recent studies have demonstrated that puerarin has potential anti-tumor effects via induction of apoptosis and inhibition of proliferation. However, the effect and molecular mechanism of puerarin in pancreatic ductal adenocarcinoma (PDAC) remains unknown.Methods: The effects of puerarin on the proliferation, apoptosis, migration and invasion of pancreatic cancer cells (PCCs), and tumor growth and metastasis in PDAC xenograft mouse model were performed. In addition, Akt/mTOR signaling activity was evaluated both in vivo and in vitro.Results: Puerarin treatment significantly repressed PCC proliferation in concentration- and time-dependent manners. Puerarin induced the mitochondrial-dependent apoptosis of PCCs by causing a Bcl-2/Bax imbalance. Moreover, puerarin inhibited PCC migration and invasion by antagonizing epithelial-mesenchymal transition (EMT). In nude mouse model, PDAC growth and metastasis were reduced by puerarin administration. Mechanistically, puerarin exerted its therapeutic effects on PDAC by suppressing Akt/mTOR signaling. Importantly, puerarin bound to the kinase domain of mTOR protein, affecting the activity of the surrounding amino acid residues associated with the binding of the ATP-Mg2+ complex. Further studies showed that the inhibitory effects of puerarin on PCCs were abolished by a mTOR activator MHY1485, indicating a crucial role of mTOR in anti-tumor effects of puerarin in PDAC. As a result, puerarin hindered glucose uptake and metabolism by downregulating the oxygen consumption rate (OCR) and the extracellular acidification rate (ECAR) dependent upon HIF-1α and glucose transporter GLUT1.Conclusion: Puerarin has therapeutic potential for the treatment of PDAC by suppressing Akt/mTOR activity.
Targeting SLC3A2 Subunit of System XC- is Essential for m6A Reader YTHDC2 to be an Endogenous Ferroptosis Inducer in Lung Adenocarcinoma
Authors: Ma Lifang , Zhang Xiao , Yu Keke , Xu Xin , Chen Tianxiang , Shi Yi , Wang Yikun , Qiu Shiyu , Guo Susu , Cui Jiangtao , Miao Yayou , Tian Xiaoting , Du Lutao , Yu Yongchun , Xia Jinjing , Wang Jiayi
Published: January 2021

Background: The m6A reader YT521-B homology containing 2 (YTHDC2) inhibits lung adenocarcinoma (LUAD) tumorigenesis by suppressing solute carrier 7A11 (SLC7A11)-dependent antioxidant function. SLC7A11 is a major functional subunit of system XC-. Inhibition of system XC- can induce ferroptosis. However, whether suppressing SLC7A11 is sufficient for YTHDC2 to be an endogenous ferroptosis inducer in LUAD is unknown.Methods: Bioinformatics were used to predict overall survival (OS) and possible correlations. Gene expressions were examined by immunoblotting (IB), reverse transcription-quantitative PCR (RT-qPCR), immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA). The doxycycline (Dox)-inducible YTHDC2 cell model, spontaneous LUAD and xenograft mouse models were used to study the function of YTHDC2. SYTOX green and C11-BODIPY581/591 staining following flow cytometry were used to evaluate cell death and lipid reactive oxygen species (ROS) generation. Luciferase reporter assay, electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) were performed to study promoter. RNA immunoprecipitation (RIP), RNA pull down and photoactivatable ribonucleotide crosslinking and immunoprecipitation (PAR-CLIP) were used to determine protein-RNA interactions. Actinomycin D chase experiments were used for RNA stability and four independent LUAD cohorts with a total volume of 384 were recruited to evaluate clinical significance.Results: Induction of YTHDC2 to a high level can induce ferroptosis in LUAD cells but not in lung and bronchus epithelial cells. In addition to SLC7A11, solute carrier 3A2 (SLC3A2), another subunit of system XC- was equally important for YTHDC2-induced ferroptosis. YTHDC2 m6A-dependently destabilized Homeo box A13 (HOXA13) mRNA because a potential m6A recognition site was identified within its 3’ untranslated region (3’UTR). Interestingly, HOXA13 acted as a transcription factor to stimulate SLC3A2 expression. Thereby, YTHDC2 suppressed SLC3A2 via inhibiting HOXA13 in an m6A-indirect manner. Mouse experiments further confirmed the associations among YTHDC2, SLC3A2 and HOXA13, and demonstrated that SLC3A2 and SLC7A11 were both important for YTHDC2-impaired tumor growth and –induced lipid peroxidation in vivo. Moreover, higher expression of SLC7A11, SLC3A2 and HOXA13 indicate poorer clinical outcome in YTHDC2-suppressed LUAD patients.Conclusion: YTHDC2 is a powerful endogenous ferroptosis inducer and targeting SLC3A2 subunit of system XC- is essential for this process. Increasing YTHDC2 is an alternative ferroptosis-based therapy to treat LUAD.
WITHDRAWN: Unbalanced YAP-autophagy Circuit Promotes the Malignant Progression of Pancreatic Cancer
Authors: Sun Ting , Mao Wenhao , Peng Hui , Ma Liwei , Liu Hongyang , Mai Jia , Jiao Lin
Published: January 2021

Background: Pancreatic ductal adenocarcinoma (PDAC) is the most lethal malignancy in humans, and new therapeutic targets are urgently needed. Yes-associated protein (YAP) plays a significant role in tissue homeostasis and cancer progression. Autophagy is also closely associated with various human cancers. However, the interplay between YAP and autophagy in pancreatic cancer remains poorly understood. Methods: The expression of YAP in PDAC was evaluated by immunohistochemistry (IHC). The effects of YAP on pancreatic cancer cells ware evaluated by CCK-8, EdU, wound healing and Transwell invasion assays. Subsequent mechanistic studies were performed in PDAC cell lines by western blotting, qRT-PCR, chromatin immunoprecipitation (ChIP) assay, luciferase reporter assay and immunofluorescence assay. The consequence of the dual inhibition of YAP and autophagy on tumor growth was evaluated in AsPC-1 xenograft mice.Results: YAP was upregulated and activated in PDAC tissues. Functional assays showed that YAP promoted PDAC cell proliferation, migration and invasion. Further analysis revealed a YAP-autophagy feedback loop in pancreatic cancer. Mechanistically, YAP activated autophagy by promoting Atg5 transcription via TEAD1-mediated binding, while autophagy negatively regulated YAP by controlling its degradation. The hyperactivation of YAP in PDAC unbalanced the YAP-autophagy circuit and promoted cancer progression. The dual inhibition of YAP and autophagy suppressed the malignant progression of pancreatic cancer. Conclusions: Our study elucidates a novel mechanism involving a YAP-autophagy feedback loop and suggests that the YAP-autophagy circuit may represent a potential therapeutic target for PDAC.
Why Patients Do Not Comply With Headache Diaries?
Authors: Borbinha Cláudia , Martins Isabel Pavão
Published: January 2021

Background: Headache calendars are part of good clinical practice in headache clinics. However, patients’ compliance is rather variable. We aim to identify factors associated with poor compliance. Methods: Consecutive patients observed in follow-up visits of a tertiary headache center were divided into two groups; with a fullfilled calendar (Calendar compliers, CC) and without calendar (Calendar noncompliers, CNC). Incomplete / forgotten records were excluded. Demographic and clinical variables were compared, and CNC were asked the reasons for not filling the calendar. Results: From 93 patients (45.6±13.3 years, on average; 83 females), the majority with migraine (96.8%), 61.3% were CC. CNC were more likely to have medication overuse (34.5% vs. 12.3%, p=0.01) and had a tendency to be paid workers (79.3% vs. 52.6%, p=0.05) compared to CC. Most CC considered calendars useful to improve doctors and patients knowledge about headaches.Conclusions: Although these results need to be evaluated in other contexts, they suggest that patients with medication overuse have a more denial attitute towards headache records and may need additional reinforcement.
Feasibility of lattice radiotherapy using proton and carbon ion pencil beam for sinonasal adenoid cystic carcinoma
Authors: Yang Dong , Wang Wei Wei , Hu Ji Yi , Hu Wei Xu , Zhang Xi Yu , Wu Xiao Dong , Lu Jiade J , Kong Lin
Published: January 2021

Background: Adenoid cystic carcinomas (ACCs) are extremely rare, but they are a treatment challenge because they are highly radioresistant and are surrounded by several organs at risk (OARs). We aimed to investigate the feasibility of lattice radiotherapy (LRT) using pencil beam scanning (PBS) proton or carbon ion beams in the treatment of sinonasal ACC.Patients and methods: Ten patients with nonoperative, bulky, and radioresistant ACCs were enrolled. Spherical vertices with a 1-cm diameter and average centre-to-centre distance of 3.51 cm were delineated within the gross tumour volumes. The prescription was 15 Gy (relative biological effectiveness [RBE]) to vertices and 3–3.5 Gy (RBE) to the periphery as clinical boost target volumes (CTVboosts) in one fraction. Photon, proton, and carbon-ion LRT plans were generated based on this. Peak-to-valley ratios (PVDRs) and dose delivered to the vertices, CTVboost, and OARs were compared among the three plans. The OAR doses were also compared between LRT plans and one fraction of clinical boost plans. Results: The mean for photon, proton, and carbon-ion LRT plans were 4.78 (range: 4.34–5.36), 4.82 (range: 4.15–5.37), and 4.69 (range: 4.31–5.28), respectively. The mean for the same plans were 3.42 (range: 3.15–3.79), 2.93 (range: 2.19–3.74), and 3.58 (range: 3.09–4.68), respectively, with no significant differences in both. The brain stem, chiasm, optic nerve, parotids, spinal cord, and brain were better protected in proton and carbon-ion LRT plans than in photon LRT plans. Further, these plans did not introduce more doses to the OARs compared to the one-fraction clinical boost plan, with a significant difference. Conclusion: Despite the minimal difference in PVDR between proton and carbon-ion LRT plans and photon LRT plans, the former can better protect OARs than photon LRT plans. Therefore, PBS proton and carbon-ion LRT can be used for sinonasal ACC.
Experimental Research on the Nanoindentation of Bovine Compact Bone under Fatigue Loading
Authors: Meng Xianjia , Qin Qinghua , Qu Chuanyong
Published: January 2021

Background

The role of bone fatigue damage at the nanostructural level, and its effect on fatigue properties is an understudied and important subject. An understanding of the subtler aspects of bone’s properties is crucial to understanding bone fragility caused by aging, disease, and fatigue damage. The primary strength of this study was the demonstration of the degradation of bone’s microscopic mechanical properties by nanoindentation following fatigue loading.
Methods

Nanoindentation was used to probe the micro-mechanical properties of bovine tibiae subjected to fatigue loading in four-point bending. Indentation tests were conducted in the same 30×120 µm region before fatigue loading and after loading to fracture. We analysed the effects of residual indentations on bone’s fatigue resistance using an optical microscope and scanning electron microscope. The mechanical properties calculated using nanoindentation were reduced modulus and hardness, the time constant based on creep, long-term creep viscosity and the dissipated work. Differences of each parameter before loading and post fracture were examined using paired t-tests.
Results

The morphology of the initial residual indentation before fatigue loading appeared the same as that after loading to fracture. The results show that the reduced modulus decreased significantly (p = 9.47×10− 3) by 7.62%~15.16% after fracture whereas the time constant of creep increased slightly (p = 0.049) by 2.81%~5.41%. The p-value was significantly lower (p < 0.001) for reduced modulus compared to all other mechanical properties.
Conclusion

Residual indents different from fatigue damage created no crack initiators that would weaken bone’s resistance to fatigue loading. Fatigue loading has the most heavy effect on bone’s reduced modulus compared to all other microscopic mechanical properties.
Cpg Island Methylator Phenotype With Distinctly Different Prognosis And Molecular Features In Pancreatic Cancer Patient
Authors: Ning Gang , Li Yongqiang , Chen Wenji , Tang Wenjuan , Shou Diwen , Luo Qingling , Chen Huiting , Zhou Yongjian
Published: January 2021

BackgroundCpG island methylator phenotype (CIMP), featured with concurrent and widespread hypermethylation of a cluster of CpGs, has been reported to play an important role in carcinogenesis. Limited studies have investigated the CIMP in pancreatic cancer (PC). The aim of this study was to explore the CIMP in PC patients and its clinical-pathological and genomic characteristics. Methods:DNA methylation, somatic mutation, mRNA and corresponding clinical data of PC patients were downloaded from TCGA (184 patients) and ICGC (264 patients). Univariate and multivariate regression analysis were used to identify prognosis related CpGs. Consensus clustering analysis was used for identification of the CIMP in PC patients. ESTIMATE and CIBORORT were used for estimation of tumor microenvironment (TME) in PC patients.ResultsIn TCGA PC cohort, 22,450 differential CpGs, including 12,937 hypermethylated CpGs and 9,513 hypomethylated CpGs were identified between185 PC patients and 10 normal controls. Univariate and multivariate Cox analysis further screened out 72 OS related CpGs and three distinct CIMP groups with distinctly different prognosis and molecular features, including CIMP-L subgroup, CIMP-M subgroup and CIMP-H subgroup were identified based on unsupervised consensus clustering analysis of these CpGs. Patients of the CIMP-H subgroup had poorer OS and RFS, while patients of CIMP-L subgroup had better OS and RFS. The CIMP status were also an independent prognostic factors for OS and PFS. In molecular features, significantly higher somatic mutation burdens and tumor mutational burden were found at patients of CIMP-H subgroup compared to that in patients of CIMP-L subgroup. Besides, lower stromal score, immune score and higher cancer stemness indices and tumor purity were also found at patients of CIMP-H subgroup compared to that in patients of CIMP-L subgroup. Correspondingly, significantly total T cells, total B cells, CD8 T cells, memory CD4 T cells and higher regulatory T cells were found at patients of CIMP-H subgroup. Moreover, significantly lower expression of immune checkpoint genes, such as PD-1, CTLA4, CD86, VTCN1 and LAG-3 were also found at patients of CIMP-H subgroup compared to that in patients of CIMP-L subgroup. In the end, we validated the CIMP status in PC patients of ICGC dataset.ConclusionThree distinct CIMP subgroups of PC patients with distinct clinical characteristic, prognosis, gene mutation landscape and TME were identified and validated. The CIMP may help to make an assertion to provide specific and efficient treatment options for patients of different subtypes.
Dispensing errors in hospital pharmacies: A prospective study in Yemen
Authors: Al-Worafi Yaser Mohammed , Elkalmi Ramadan Mohamed , Ming Long Chiau , Othman Gamil , Halboup Abdulsalam M. , Battah Mohammed Mohammed , Dhabali Abdullah Ahmed , Jaber Amamr Ali Saleh , Al-Shami Abdulkareem Mohammed , Alakhali Khaled M. , Alseragi Wafa Mohammed , Alshakhshir Sami Mustafa , Alshahrani Sultan M. , Mani Vasudevan
Published: January 2021

AimsThe aim of this study was to describe the dispensing errors that occurred during the dispensing process in selected hospital pharmacies in Sana’a, Yemen; and to describe their types and causes.MethodologyA prospective study was carried out in selected hospital pharmacies in Yemen over 40 days using a validated tool. ResultsA total of 9000 dispensed prescriptions were evaluated for the dispensing errors and 2.13 % dispensing errors were identified. Wrong dosage form (134/192); wrong strength (24/192); wrong drug (18/192); wrong quantity, wrong instructions written and drug available in the pharmacy but not given were (6/192) and dispense the expired drugs (3/192) were the reported dispensing errors in this study. Poor handwriting, similar drug names, similar drug packaging, fatigue, heavy work, workforce issues, and poor communication were the most common reported causes of dispensing errors. ConclusionThe prevalence of dispensing errors in this study was 2.13%. Pharmacists can play an important role in the improving the safety of medicines. Study of the dispensing errors incidence in national wide, it's types and causes of dispensing errors are very important and highly recommended. Study the impact of different interventions to improve dispensing quality, reducing and preventing dispensing errors are strongly recommended.
The Alcohol Use Disorders Identification Test (AUDIT) in the Russian language - a systematic review of validation efforts and application challenges
Authors: Neufeld Maria , Bunova Anna , Ferreira-Borges Carina , Bryun Evgeniy , Fadeeva Eugenia , Gil Artyom , Gornyi Boris , Khaltourina Daria , Koshkina Evgenia , Nadezhdin Aleksey , Tetenova Elena , Vujnovic Melita , Vyshinsky Konstantin , Yurasova Elena , Rehm Jürgen
Published: January 2021

The Alcohol Use Disorders Identification Test (AUDIT) is one of the most frequently used screening instrument for hazardous and harmful use of alcohol and potential alcohol dependence in primary health care (PHC) and other settings worldwide. It has been translated into many languages and adapted and modified for use in some countries, following formal adaptation procedures and validation studies. In the Russian Federation, the AUDIT has been used in different settings and by different health professionals, including addiction specialists (narcologists). In 2017, it was included as a screening instrument in the national guidelines of routine preventive health checks at the population-level (dispanserization). However, various Russian translations of the AUDIT are known to be in use in different settings and, so far, little is known about the empirical basis and validation of the instrument in Russia—a country, which is known for its distinct drinking patterns and their detrimental impact on health. The present contribution is the summary of two systematic reviews that were carried out to inform a planned national validation study of the AUDIT in Russia.Two systematic searches were carried out to 1) identify all validation efforts of the AUDIT in Russia and to document all reported problems encountered, and 2) identify all globally existing Russian translations of the AUDIT and document their differences and any reported issues in their application. The qualitative narrative synthesis of all studies that met the inclusion criteria of the first search highlighted the absence of any large-scale rigorous validation study of the AUDIT in primary health care in Russia, while a document analysis of all of the 122 Russian translations has revealed 61 unique versions, most of which contained inconsistencies and signaled obvious application challenges of the test.The results clearly signal the need for a validation study of the Russian AUDIT.
Resistance and Representation: The Making of Chinese Identity in the Art of The Yiyanhui and the Equator Art Society in 1950s Singapore
Authors: Ong Emelia Ian Li
Published: January 2021

This paper examines the social realist paintings of the art groups Yiyanhui and the Equator Art Society which emerged during the 1950s in Malaya and Singapore. Their works centred on the social functions of art and its subject matters featured the working class, the Japanese occupation and anti-British colonial sentiment. Their artworks are viewed here as cultural productions shaped by the negotiation between dominant-subordinate relationships within a postcolonial framework. It is argued that the artistic productions examined here may be viewed not only for its overarching “social realist” endeavours but, also as a struggle to rewrite the narrative of the Chinese in Malaya against of the prevailing static representations forwarded by the colonial campaign. The first part of the paper illustrates how colonial discourse in the local press propagated an image of the Chinese as inherently susceptible to communism, untrustworthy, and opportunistic. The second part of the paper shows how the artists resisted this essentialist image of Chinese identity and offered a more complex picture of a Chinese-Malayan identity. Through a combination of interviews, written artist’s statements, formal and contextual considerations of the artworks, as well as a cultural studies framework, I demonstrate how a different narrative is being offered by these artists through two related processes in identity construction: qualifications for authenticity and belonging, the articulation of ambivalence. Resistance thus, is explored as encompassing a network of strategies employed by these artists as a way to reject colonialist representations of otherness and gain authorial agency against the intellectual and ideological dominance of colonial discourse.
Kent İçi Trafikten Kaynaklanan Stratejik Gürültü Haritalarının Değerlendirilmesi
Authors: TERCAN Şafak , YAMAN Gökhan
Published: January 2021

Kentlerde, trafik, sanayi ve eğlence gibi çeşitli faaliyetlerden oluşan çevresel gürültü önemli çevre sorunlarından birisi olmuştur. Gelişmiş ülkelerdeki sağlık sorunları sıralamasında kara, hava ve demiryollarındaki trafikten kaynaklanan gürültü ikinci sırada yer almaktadır. Trafikten kaynaklanan gürültünün, insan sağlığı üzerinde negatif etkileri bulunmaktadır. Yüksek nüfus yoğunluğu olan yaşam alanları trafikten kaynaklı gürültü maruziyetlerinin oluştuğu bölgelerdir. Kentlerdeki gürültü alanlarını belirlemek ve yaşanabilir kentler oluşturmak için stratejik gürültü haritaları hazırlanmaktadır. Böylece, çevresel gürültü ile ilgili sorunlar belirlenmekte ve gerekli kontrol tedbirleri alınabilmektedir. Bu çalışmada, Gaziantep’te nüfus yoğunluğu yüksek olan bölgelerde karayolu trafiğinden kaynaklanan stratejik gürültü haritaları trafik sayımları ve simülasyon programı ile oluşturulmuştur. Çalışma kapsamında 161 km'si ana karayolu olmak üzere toplam 193 km karayolu modellenmiş ve 33 yol kesitinde araç sayımı yapılmıştır. Elde edilen simülasyon verileri ile gündüz, akşam ve gece için stratejik gürültü haritaları hazırlanmıştır. Daha sonra, karayolu trafiğinden kaynaklanan gürültü sınır değerlerini aşan bölgelerdeki nüfus oranları hesaplanmıştır. Buna göre; Gaziantep nüfusunun % 5,4’ü gündüzleri, % 8,2’si akşamları ve % 7,5’i geceleri belirlenen kritik seviyelerin üzerinde karayolu kaynaklı gürültü seviyelerine maruz kalmaktadır. Hassas bölgeler olan 201 okul ve 95 hastane bu gürültü alanlarında bulunmakta ve karayolu kaynaklı gürültü seviyelerine maruz kalmaktadır.
Şiran (Gümüşhane) İlçe Merkezi Su Kaynaklarının Kalitesi ve Hidrojeokimyasal Özelliklerinin Değerlendirilmesi
Authors: SEMİZ Ümmühan , GÜCER Mehmet Ali , ALEMDAĞ Selçuk
Published: January 2021

İnceleme alanı, Gümüşhane (KD Türkiye) ilinin güneybatısında yer alan Şiran ilçe merkezini kapsamaktadır. Bu çalışmada, ilçe merkezindeki suların hidrojeokimyasal karakteristikleri incelenmiş ve metal element içerikleri belirlenmiştir. İnceleme alanında, temel birimleri kumtaşı, kiltaşı, marn, şeyl ve tüf ardışımından meydana gelen Eosen yaşlı Kelkit Formasyonu oluşturmakta olup Kuvaterner yaşlı alüvyon ile uyumsuz bir şekilde örtülmüştür. Bu birimler hidrojeolojik özelliklerine göre taneli gözenekli serbest akiferleri oluşturmaktadır. Örneklerin pH, özgül elektriksel iletkenlik (ÖEİ) ve toplam sertlik (Fr°) değerleri sırasıyla 5.41-7.48, 106.9-141.3 μS/cm ve 4.72-6.78 (n= 18) arasında değişmektedir. Bu veriler, Kıta İçi Yerüstü Su Kaynakları sınıflamasına göre, suların çoğunlukla I. ve II. sınıf, az oranda ise III. sınıf kalitede olduğunu göstermektedir. İnceleme alanındaki sular genelde Ca-Mg-HCO3 tipli karbonatlı (Ca+Mg>Na+K) olup, zayıf asit kökleri güçlü asit köklerinden (HCO3>SO4+Cl) daha fazladır. İnceleme alanındaki suların (Ca+Mg)/(SO4+HCO3) oranları sularda silikat ayrışmasının etkisini işaret etmekte, Cl/(Cl+HCO3) ve (Na+K)/(Na+K+Ca) oranları ise, bu suların kimyasının kayaç yapıcı minerallerin kimyasal ayrışması tarafından kontrol edildiğini, dolayısıyla su-kayaç etkileşimini göstermektedir. Su örneklerindeki çözünmüş potansiyel toksik element içerikleri, birkaç örnek dışında, kabul edilebilir sınırlar arasında dağılım sergilemektedir. Sonuç olarak, elde edilen hidrojeokimyasal veriler, inceleme alanındaki suların genel olarak içme suyu açısından iyi sınıf sular kategorisinde yer aldığını göstermiştir.