Gastric cancer, MicroRNA-596, Methylation, Peroxiredoxin 1
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In the present study, we investigated a suppressive role of microRNA-596 (miR-596) in gastric cancer (GC). Moreover, the downregulation of miR-596 in GC cell lines was associated with an increase of miR-596 promoter methylation. We also established that miR-596 controls the expression of peroxiredoxin 1 (PRDX1), which has never been reported before, suggesting that this interaction could play an important role in GC progression.
To study the potential role and possible regulatory mechanism of miR-596 in GC.
The expression levels of miR-596 and PRDX1 in gastric cancer tissues and cell lines were detected by quantitative real-time PCR (qRT-PCR). Western blot and luciferase reporter assay were used to detect the effect of miR-596 on PRDX1 expression. Then, the proliferation, metastasis, and invasion of GC cell lines transfected with miR-596 mimics were analyzed, respectively, by Cell Counting Kit-8 proliferation assay, wound healing assay, and transwell invasion assay. Meanwhile, the methylation status of the promoter CpG islands of miR-596 in GC cell lines was detected by methylation-specific PCR (MSP).
Expression of miR-596 was decreased and PRDX1 was upregulated in GC tissues and cell lines. Overexpression of miR-596 decreased the expression of PRDX1 and luciferase reporter assays detected the direct binding of miR-596 to the 3′-untranslated region (UTR) of PRDX1 transcripts. Furthermore, we found that overexpression of miR-596 remarkably suppressed cell proliferation, migration, and invasion in GC cells. We further analyzed miR-596 promoter methylation by MSP and qRT-PCR, and found the downregulation of miR-596 was associated with promoter methylation status in GC cell lines. Moreover, DNA demethylation and reactivation of miR-596 after treatment with 5-Aza-2’-deoxycytidine inhibited the proliferative ability of GC cells.
MiR-596 has a tumor suppressive role in GC and is downregulated partly due to promoter hypermethylation. Furthermore, PRDX1 is one of the putative target genes of miR-596.
Gastric cancer, MicroRNA-596, Methylation, Peroxiredoxin 1
MicroRNA-596 acts as a tumor suppressor in gastric cancer and is upregulated by promotor demethylation
Zhen Zhang and Dong-Qiu Dai
2019 Mar 14;
Osteosarcoma (OSA), the most common primary bone malignancy, is characterized by a wide spectrum of complicated pathologies and frequent distal metastasis and causes death in adolescents and young adults worldwide. Antitumor drug treatment strategies include various cytotoxic chemotherapy drugs, while molecular targeted therapy for OSA is currently less used. The present work revealed the role played by the miR-596/Survivin axis in affecting the sensitivity of OSA cells to anlotinib, a novel molecular targeting agent.
By virtual screening, we found that miR-596 might target Survivin by using an online tool (miRDB). RNA levels of miR-596 and Survivin in clinical specimens were examined with qPCR. The effect of miR-596 on anlotinib’s antitumor effect was examined with MTT experiments, the subcutaneous tumor model, or the intramuscular tumor model.
Overexpression of miR-596 via lentiviral particles repressed the protein level of Survivin in U2OS cells. Transfection of miR-596 enhanced the antitumor effect of anlotinib on U2OS cells or five cell lines derived from OSA patients.
miR-596 targets Survivin and enhances the antitumor effect of anlotinib on OSA cells.
osteosarcoma cell, microRNAs, Survivin, molecular targeting agents, anlotinib
miR-596 suppresses the expression of Survivin and enhances the sensitivity of osteosarcoma cells to the molecular targeting agent anlotinib
Leisheng Wang,#1 He En,#2 Lei Yang,3 Yanbing Zhang,2 Baisheng Sun,4 and Jianjiang Gao5
Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data.
To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning.
We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence.
In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs).
Conclusions and Relevance
The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.
Question What is the cancer burden over time at the global and national levels, measured in incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs), and how does it compare with other diseases? Findings Results of this systematic analysis show that in 2017 there were 24.5 million incident cases (16.8 million without nonmelanoma skin cancer), 9.6 million deaths, and 233.5 million DALYs due to cancer; between 2007 and 2017, incident cases increased by 33%, with the lowest increase in the most developed countries, and between 1990 and 2017 neoplasms increased among the top causes of DALYs from the sixth to the second place. Fifty-one percent of cancer cases occurred in countries of high Socio-demographic Index, but only 30% of cancer deaths and 24% of cancer DALYs. Meaning To ensure sustainable global development, increased efforts are needed in cancer prevention and in ensuring universal access to cancer care.
Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017 A Systematic Analysis for the Global Burden of Disease Study Global Burden of Disease Cancer Collaboration
Christina Fitzmaurice, MD,corresponding author1,2 Degu Abate, MSc,3 Naghmeh Abbasi, MSc,4 Hedayat Abbastabar, PhD,5 Foad Abd-Allah, MD,6 Omar Abdel-Rahman, MD,7,8 Ahmed Abdelalim, MD,6 Amir Abdoli, PhD,9,10 Ibrahim Abdollahpour, PhD,11,12 Abdishakur S. M. Abdulle, PhD,13 Nebiyu Dereje Abebe, MPH,14,15 Haftom Niguse Abraha, MSc,16 Laith Jamal Abu-Raddad, PhD,17 Ahmed Abualhasan, MD,6 Isaac Akinkunmi Adedeji, PhD,18 Shailesh M. Advani, PhD,19,20 Mohsen Afarideh, MD,21 Mahdi Afshari, MD,22 Mohammad Aghaali, PhD,23 Dominic Agius, MD,24 Sutapa Agrawal, PhD,25,26 Ayat Ahmadi, PhD,27 Elham Ahmadian, PhD,28 Ehsan Ahmadpour, PhD,29 Muktar Beshir Ahmed, MPH,30 Mohammad Esmaeil Akbari, MD,31 Tomi Akinyemiju, PhD,32,33 Ziyad Al-Aly, MD,34,35 Assim M. AlAbdulKader, MD,36,37 Fares Alahdab, MD,38 Tahiya Alam, MPH,1 Genet Melak Alamene, BS,39 Birhan Tamene T. Alemnew, MSc,40,41 Kefyalew Addis Alene, MPH,42,43 Cyrus Alinia, PhD,44 Vahid Alipour, PhD,45,46 Syed Mohamed Aljunid, PhD,47,48 Fatemeh Allah Bakeshei, MPH,49 Majid Abdulrahman Hamad Almadi, FRCPC,50,51 Amir Almasi-Hashiani, PhD,11 Ubai Alsharif, MD,52 Shirina Alsowaidi, FRCPS,53 Nelson Alvis-Guzman, PhD,54,55 Erfan Amini, MD,56 Saeed Amini, PhD,57 Yaw Ampem Amoako, MD,58 Zohreh Anbari, PhD,57 Nahla Hamed Anber, PhD,59 Catalina Liliana Andrei, PhD,60 Mina Anjomshoa, PhD,61 Fereshteh Ansari, PhD,62 Ansariadi Ansariadi, PhD,63 Seth Christopher Yaw Appiah, MPhil,64,65 Morteza Arab-Zozani, PhD,66 Jalal Arabloo, PhD,45 Zohreh Arefi, PhD,67 Olatunde Aremu, PhD,68 Habtamu Abera Areri, MSc,69 Al Artaman, PhD,70 Hamid Asayesh, MSc,71 Ephrem Tsegay Asfaw, MSc,72 Alebachew Fasil Ashagre, MSc,73 Reza Assadi, PhD,74 Bahar Ataeinia, MD,75 Hagos Tasew Atalay, MSc,76 Zerihun Ataro, MSc,77 Suleman Atique, PhD,78,79 Marcel Ausloos, PhD,80 Leticia Avila-Burgos, PhD,81 Euripide F. G. A. Avokpaho, MD,82,83 Ashish Awasthi, PhD,25,84 Nefsu Awoke, MSc,85 Beatriz Paulina Ayala Quintanilla, PhD,86,87 Martin Amogre Ayanore, PhD,88 Henok Tadesse Ayele, PhD,89,90 Ebrahim Babaee, PhD,91 Umar Bacha, MPhil,92 Alaa Badawi, PhD,93,94 Mojtaba Bagherzadeh, PhD,95 Eleni Bagli, PhD,96,97 Senthilkuimar Balakrishnan, PhD,98 Abbas Balouchi, MSc,99 Till Winfried Barnighausen, MD,100,101 Robert J. Battista, MBA,102 Masoud Behzadifar, PhD,45,103 Meysam Behzadifar, MS,104 Bayu Begashaw Bekele, MPH,42,105 Yared Belete Belay, MSc,106,107 Yaschilal Muche Belayneh, MSc,108 Kathleen Kim Sachiko Berfield, MD,109 Adugnaw Berhane, PhD,14 Eduardo Bernabe, PhD,110 Mircea Beuran, PhD,111 Nickhill Bhakta, MD,112 Krittika Bhattacharyya, MSc,113 Belete Biadgo, MSc,73 Ali Bijani, PhD,114 Muhammad Shahdaat Bin Sayeed, MSPS,115,116 Charles Birungi, MSc,117,118 Catherine Bisignano, MPH,1 Helen Bitew, MSc,119 Tone Bjørge, PhD,120,121 Archie Bleyer, MD,122,123 Kassawmar Angaw Bogale, MPH,124 Hunduma Amensisa Bojia, BPharm,125 Antonio M. Borz?, MD,126 Cristina Bosetti, PhD,127 Ibrahim R. Bou-Orm, MD,128 Hermann Brenner, MD,129 Jerry D. Brewer, MD,130 Andrey Nikolaevich Briko, MSc,131 Nikolay Ivanovich Briko, DSc,132 Maria Teresa Bustamante-Teixeira, PhD,133 Zahid A. Butt, PhD,134,135 Giulia Carreras, PhD,136 Juan J. Carrero, PhD,137 Felix Carvalho, PhD,138,139 Clara Castro, PhD,140,141 Franz Castro, MD,142 Ferran Catala-Lopez, PhD,143,144 Ester Cerin, PhD,145,146 Yazan Chaiah,147 Wagaye Fentahun Chanie, MPH,148 Vijay Kumar Chattu, MD,149,150 Pankaj Chaturvedi, MD,151 Neelima Singh Chauhan, MD,152 Mohammad Chehrazi, PhD,153,154 Peggy Pei-Chia Chiang, PhD,155 Tesfaye Yitna Chichiabellu, MSc,85 Onyema Greg Chido-Amajuoyi, MD,156 Odgerel Chimed-Ochir, PhD,157 Jee-Young J. Choi, PhD,158 Devasahayam J. Christopher, MD,159 Dinh-Toi Chu, PhD,160,161 Maria-Magdalena Constantin, MD,162,163 Vera M. Costa, PharmD,164 Emanuele Crocetti, MD,165 Christopher Stephen Crowe, MD,166 Maria Paula Curado, PhD,167 Saad M. A. Dahlawi, PhD,168 Giovanni Damiani, MD,169 Amira Hamed Darwish, MD,170 Ahmad Daryani, PhD,171 Jose das Neves, PhD,172,173 Feleke Mekonnen Demeke, MSc,174 Asmamaw Bizuneh Demis, MSc,175,176 Birhanu Wondimeneh Demissie, MSc,85 Gebre Teklemariam Demoz, MPharm,177,178 Edgar Denova-Gutierrez, DSc,179 Afshin Derakhshani, MSc,180 Kalkidan Solomon Deribe, MPH,181 Rupak Desai, MBBS,182 Beruk Berhanu Desalegn, MSc,183 Melaku Desta, MSc,184,185 Subhojit Dey, PhD,186 Samath Dhamminda Dharmaratne, MD,1,187 Meghnath Dhimal, PhD,188 Daniel Diaz, PhD,185,189 Mesfin Tadese Tadese Dinberu, MA,184 Shirin Djalalinia, PhD,190 David Teye Doku, PhD,191,192 Thomas M. Drake, MD,193 Manisha Dubey, PhD,194 Eleonora Dubljanin, PhD,195 Eyasu Ejeta Duken, MSc,196,197 Hedyeh Ebrahimi, MD,75,198 Andem Effiong, MB,199 Aziz Eftekhari, PhD,28,200 Iman El Sayed, PhD,201 Maysaa El Sayed Zaki, MD, PhD,202 Shaimaa I. El-Jaafary, MD,6 Ziad El-Khatib, PhD,203 Demelash Abewa Elemineh, MSc,204 Hajer Elkout, PhD,205,206 Richard G. Ellenbogen, MD,207,208 Aisha Elsharkawy, MD,209 Mohammad Hassan Emamian, PhD,210 Daniel Adane Endalew, MSc,211 Aman Yesuf Endries, MPH,212 Babak Eshrati, PhD,213,214 Ibtihal Fadhil, PhD,215 Vahid Fallah, PhD,216 Mahbobeh Faramarzi, PhD,217 Mahdieh Abbasalizad Farhangi, PhD,218 Andrea Farioli, PhD,219 Farshad Farzadfar, MD,75 Netsanet Fentahun, PhD,220 Eduarda Fernandes, PhD,221 Garumma Tolu Feyissa, PhD,222,223 Irina Filip, MD,224,225 Florian Fischer, PhD,226 James L. Fisher, PhD,227 Lisa M. Force, MD,1,228 Masoud Foroutan, PhD,229 Marisa Freitas, PhD,230 Takeshi Fukumoto, PhD,231,232 Neal D. Futran, MD,233 Silvano Gallus, DSc,234 Fortune Gbetoho Gankpe, MD,235,236 Reta Tsegaye Gayesa, MSc,237 Tsegaye Tewelde Gebrehiwot, MPH,30 Gebreamlak Gebremedhn Gebremeskel, MSc,76,238 Getnet Azeze Gedefaw, MSc,239,240 Belayneh K. Gelaw, MSc,241 Birhanu Geta, MSc,108 Sefonias Getachew, MPH,181,242 Kebede Embaye Gezae, MSc,243 Mansour Ghafourifard, PhD,244 Alireza Ghajar, MD,21,245 Ahmad Ghashghaee, BSc,246 Asadollah Gholamian, MSc,247,248 Paramjit Singh Gill, DM,249 Themba T. G. Ginindza, PhD,250,251 Alem Girmay, MSc,252 Muluken Gizaw, MPH,14 Ricardo Santiago Gomez, PhD,253 Sameer Vali Gopalani, MPH,254,255 Giuseppe Gorini, MD,256 Barbara Niegia Garcia Goulart, DSc,257 Ayman Grada, MD,258 Maximiliano Ribeiro Guerra, PhD,259 Andre Luiz Sena Guimaraes, PhD,260 Prakash C. Gupta, DSc,101,261 Rahul Gupta, MD,262,263 Kishor Hadkhale, MPH,264 Arvin Haj-Mirzaian, MD,265,266 Arya Haj-Mirzaian, MD,265,267 Randah R. Hamadeh, DPhil,268 Samer Hamidi, DrPH,269 Lolemo Kelbiso Hanfore, MSc,85 Josep Maria Haro, MD,270,271 Milad Hasankhani, MSc,272 Amir Hasanzadeh, PhD,273,274 Hamid Yimam Hassen, MPH,105,275 Roderick J. Hay, MD,276,277 Simon I. Hay, FMedSci,1,278 Andualem Henok, MPH,279 Nathaniel J. Henry, BS,1 Claudiu Herteliu, PhD,280 Hagos D. Hidru, MPH,281 Chi Linh Hoang, BMedSc,282 Michael K. Hole, MD,283 Praveen Hoogar, PhD,284 Nobuyuki Horita, PhD,285,286 H. Dean Hosgood, PhD,287 Mostafa Hosseini, PhD,288 Mehdi Hosseinzadeh, PhD,289,290 Mihaela Hostiuc, PhD,291,292 Sorin Hostiuc, PhD,293,294 Mowafa Househ, PhD,295,296 Mohammedaman Mama Hussen, MA,297 Bogdan Ileanu, PhD,280,298 Milena D. Ilic, PhD,299 Kaire Innos, PhD,300 Seyed Sina Naghibi Irvani, MD,75,301 Kufre Robert Iseh, MD,302 Sheikh Mohammed Shariful Islam, PhD,303,304 Farhad Islami, PhD,305 Nader Jafari Balalami, PhD,306 Morteza Jafarinia, MSc,307 Leila Jahangiry, PhD,308 Mohammad Ali Jahani, PhD,309 Nader Jahanmehr, PhD,310,311 Mihajlo Jakovljevic, PhD,312 Spencer L. James, MD,1 Mehdi Javanbakht, PhD,313 Sudha Jayaraman, MD,314 Sun Ha Jee, PhD,315,316 Ensiyeh Jenabi, PhD,317 Ravi Prakash Jha, MSc,318 Jost B. Jonas, MD,319,320 Jitendra Jonnagaddala, PhD,321,322 Tamas Joo, MSc,323 Suresh Banayya Jungari, MA,324 Mikk Jurisson, PhD,325 Ali Kabir, MD,326 Farin Kamangar, MD,327 Andre Karch, MD,328 Narges Karimi, MD,329,330 Ansar Karimian, DipLangStud,331,332 Amir Kasaeian, PhD,333,334 Gebremicheal Gebreslassie Kasahun, MSc,177 Belete Kassa, MSc,335 Tesfaye Dessale Kassa, MSc,16 Mesfin Wudu Kassaw, MSc,175,336 Anil Kaul, MD,337,338 Peter Njenga Keiyoro, PhD,339 Abraham Getachew Kelbore, MSc,340 Amene Abebe Kerbo, MPH,341,342 Yousef Saleh Khader, PhD,343 Maryam Khalilarjmandi, MSc,4 Ejaz Ahmad Khan, MPH,344 Gulfaraz Khan, PhD,345 Young-Ho Khang, MD,346 Khaled Khatab, PhD,347,348 Amir Khater, MD,349 Maryam Khayamzadeh, MD,31,350 Maryam Khazaee-Pool, PhD,351,352 Salman Khazaei, PhD,353 Abdullah T. Khoja, MD,354,355 Mohammad Hossein Khosravi, MD,356,357 Jagdish Khubchandani, PhD,358 Neda Kianipour, MA,359 Daniel Kim, DrPH,360 Yun Jin Kim, PhD,361 Adnan Kisa, PhD,362,363 Sezer Kisa, PhD,364 Katarzyna Kissimova-Skarbek, PhD,365 Hamidreza Komaki, MD,366,367 Ai Koyanagi, MD,368,369 Kristopher J. Krohn, MPH,1 Burcu Kucuk Bicer, BEP,370,371 Nuworza Kugbey, MSc,88,372 Vivek Kumar, MD,373 Desmond Kuupiel, MPH,250,374 Carlo La Vecchia, MD,375 Deepesh P. Lad, DM,376 Eyasu Alem Lake, BSc,85 Ayenew Molla Lakew, MPH,377 Dharmesh Kumar Lal, MD,25 Faris Hasan Lami, PhD,378 Qing Lan, PhD,379 Savita Lasrado, MS,380 Paolo Lauriola, MD,381 Jeffrey V. Lazarus, PhD,382 James Leigh, MD,383 Cheru Tesema Leshargie, MPH,384 Yu Liao, PhD,385,386 Miteku Andualem Limenih, MSc,42 Stefan Listl, PhD,387,388 Alan D. Lopez, PhD,1,389 Platon D. Lopukhov, PhD,132 Raimundas Lunevicius, PhD,390,391 Mohammed Madadin, MD,392 Sameh Magdeldin, PhD,393,394 Hassan Magdy Abd El Razek, MD,395 Azeem Majeed, MD,396 Afshin Maleki, PhD,397,398 Reza Malekzadeh, MD,399,400 Ali Manafi, MD,401 Navid Manafi, MD,402,403 Wondimu Ayele Manamo, MS,14 Morteza Mansourian, PhD,404 Mohammad Ali Mansournia, PhD,288 Lorenzo Giovanni Mantovani, DSc,405 Saman Maroufizadeh, PhD,406 Santi Martini S. Martini, DrPH,407,408 Tivani Phosa Mashamba-Thompson, PhD,250 Benjamin Ballard Massenburg, MD,166 Motswadi Titus Maswabi, PhD,409 Manu Raj Mathur, PhD,25,410 Colm McAlinden, PhD,411 Martin McKee, DSc,412 Hailemariam Abiy Alemu Meheretu, MPH,413,414 Ravi Mehrotra, PhD,415 Varshil Mehta, MD,416 Toni Meier, PhD,417,418 Yohannes A. Melaku, MPH,42,419 Gebrekiros Gebremichael Meles, MPH,420 Hagazi Gebre Meles, MPH,421 Addisu Melese, MSc,422 Mulugeta Melku, MSc,42 Peter T. N. Memiah, DrPH,423 Walter Mendoza, MD,424 Ritesh G. Menezes, MD,425 Shahin Merat, MD,399 Tuomo J. Meretoja, MD,426,427 Tomislav Mestrovic, PhD,428,429 Bartosz Miazgowski, MD,430,431 Tomasz Miazgowski, MD,432 Kebadnew Mulatu M. Mihretie, MPH,433 Ted R. Miller, PhD,434,435 Edward J. Mills, PhD,436 Seyed Mostafa Mir, MSc,4,437 Hamed Mirzaei, PhD,438 Hamid Reza Mirzaei, PhD,439 Rashmi Mishra, BDS,440 Babak Moazen, MSc,441,442 Dara K. Mohammad, PhD,443,444 Karzan Abdulmuhsin Mohammad, PhD,443,445 Yousef Mohammad, MD,446 Aso Mohammad Darwesh, PhD,447 Abolfazl Mohammadbeigi, PhD,23 Hiwa Mohammadi, PhD,448 Moslem Mohammadi, PhD,449 Mahdi Mohammadian, BA,450 Abdollah Mohammadian-Hafshejani, PhD,451 Milad Mohammadoo-Khorasani, PhD,452 Reza Mohammadpourhodki, MSc,453 Ammas Siraj Mohammed, BA,125 Jemal Abdu Mohammed, MPH,454 Shafiu Mohammed, PhD,441,455 Farnam Mohebi, MD,75,456 Ali H. Mokdad, PhD,1,278 Lorenzo Monasta, DSc,457 Yoshan Moodley, PhD,250 Mahmood Moosazadeh, PhD,352 Maryam Moossavi, PhD,458 Ghobad Moradi, PhD,459,460 Mohammad Moradi-Joo, MSc,461 Maziar Moradi-Lakeh, MD,91 Farhad Moradpour, PhD,459 Lidia Morawska, PhD,462 Joana Morgado-da-Costa, MSc,463 Naho Morisaki, MD,464 Shane Douglas Morrison, MD,465 Abbas Mosapour, PhD,4,452 Seyyed Meysam Mousavi, PhD,466 Achenef Asmamaw Muche, MPH,42 Oumer Sada S. Muhammed, MSc,467 Jonah Musa, MD,468,469 Ashraf R. Nabhan, PhD,470,471 Mehdi Naderi, MSc,472 Ahamarshan Jayaraman Nagarajan, MTech,473,474 Gabriele Nagel, PhD,475 Azin Nahvijou, PhD,476 Gurudatta Naik, MPH,477 Farid Najafi, PhD,478 Luigi Naldi, MD,479,480 Hae Sung Nam, PhD,481,482 Naser Nasiri, MSc,483 Javad Nazari, PhD,484,485 Ionut Negoi, PhD,111 Subas Neupane, PhD,486 Polly A. Newcomb, PhD,487,488 Haruna Asura Nggada, MD,489,490 Josephine W. Ngunjiri, DrPH,491 Cuong Tat Nguyen, MPH,492 Leila Nikniaz, PhD,493 Dina Nur Anggraini Ningrum, MPH,494,495 Yirga Legesse Nirayo, MS,16 Molly R. Nixon, PhD,1 Chukwudi A. Nnaji, MPH,496,497 Marzieh Nojomi, MD,91,498 Shirin Nosratnejad, PhD,499 Malihe Nourollahpour Shiadeh, PhD,500 Mohammed Suleiman Obsa, BHlthSci,501 Richard Ofori-Asenso, MSc,502,503 Felix Akpojene Ogbo, PhD,504 In-Hwan Oh, PhD,505 Andrew T. Olagunju, MD,506,507 Tinuke O. Olagunju, MD,508 Mojisola Morenike Oluwasanu, PhD,509 Abidemi E. Omonisi, FWACP,510,511 Obinna E. Onwujekwe, PhD,512 Anu Mary Oommen, MD,513 Eyal Oren, PhD,488,514 Doris D. V. Ortega-Altamirano, DrPH,81 Erika Ota, PhD,515 Stanislav S. Otstavnov, PhD,516 Mayowa Ojo Owolabi, DrM,517 Mahesh P A, DNB,518 Jagadish Rao Padubidri, MD,519 Smita Pakhale, MD,520 Amir H. Pakpour, PhD,521,522 Adrian Pana, MD,280,298 Eun-Kee Park, PhD,523 Hadi Parsian, PhD,4 Tahereh Pashaei, PhD,524 Shanti Patel, MD,525 Snehal T. Patil, MS,526 Alyssa Pennini, MSc,1 David M. Pereira, PhD,221,527 Cristiano Piccinelli, MPH,528 Julian David Pillay, PhD,529 Majid Pirestani, PhD,530 Farhad Pishgar, MD,75,531 Maarten J. Postma, PhD,532,533 Hadi Pourjafar, PhD,534,535 Farshad Pourmalek, PhD,134 Akram Pourshams, MD,399 Swayam Prakash, PhD,536 Narayan Prasad, MD,536 Mostafa Qorbani, PhD,537 Mohammad Rabiee, PhD,538 Navid Rabiee, PhD,95,539 Amir Radfar, MD,540 Alireza Rafiei, PhD,541,542 Fakher Rahim, PhD,21,543 Mahdi Rahimi, PhD,332 Muhammad Aziz Rahman, PhD,544,545 Fatemeh Rajati, PhD,546 Saleem M. Rana, PhD,547,548 Samira Raoofi, MSc,246 Goura Kishor Rath, MD,549 David Laith Rawaf, MD,550,551 Salman Rawaf, MD,396,552 Robert C. Reiner, PhD,1,278 Andre M. N. Renzaho, PhD,553 Nima Rezaei, PhD,554,555 Aziz Rezapour, PhD,556 Ana Isabel Ribeiro, PhD,557 Daniela Ribeiro, PhD,558 Luca Ronfani, PhD,457 Elias Merdassa Roro, MPH,14,559 Gholamreza Roshandel, PhD,399,560 Ali Rostami, PhD,561 Ragy Safwat Saad, MSc,562 Parisa Sabbagh, PhD,561 Siamak Sabour, PhD,563 Basema Saddik, PhD,564 Saeid Safiri, PhD,565 Amirhossein Sahebkar, PhD,566,567 Mohammad Reza Salahshoor, PhD,568 Farkhonde Salehi, MA,569 Hosni Salem, MD,570 Marwa Rashad Salem, MD,571 Hamideh Salimzadeh, PhD,399 Joshua A. Salomon, PhD,572 Abdallah M. Samy, PhD,573 Juan Sanabria, MD,574,575 Milena M. Santric Milicevic, PhD,576 Benn Sartorius, PhD,278,577 Arash Sarveazad, PhD,578 Brijesh Sathian, PhD,579,580 Maheswar Satpathy, PhD,581,582 Miloje Savic, PhD,583 Monika Sawhney, PhD,584 Mehdi Sayyah, MD,585 Ione J. C. Schneider, PhD,586 Ben Sch?ttker, PhD,129 Mario Sekerija, PhD,587,588 Sadaf G. Sepanlou, MD,399,400 Masood Sepehrimanesh, PhD,589 Seyedmojtaba Seyedmousavi, PhD,590,591 Faramarz Shaahmadi, PhD,592 Hosein Shabaninejad, PhD,593 Mohammad Shahbaz, MSc,594 Masood Ali Shaikh, MD,595 Amir Shamshirian, BMedSci,596 Morteza Shamsizadeh, MSc,597 Heidar Sharafi, PhD,598 Zeinab Sharafi, PhD,599 Mehdi Sharif, PhD,600,601 Ali Sharifi, MD,602 Hamid Sharifi, PhD,603 Rajesh Sharma, PhD,604 Aziz Sheikh, MD,605,606 Reza Shirkoohi, PhD,476,607 Sharvari Rahul Shukla, PhD,608 Si Si, PhD,609 Soraya Siabani, PhD,610,611 Diego Augusto Santos Silva, PhD,612 Dayane Gabriele Alves Silveira, MD,613,614 Ambrish Singh, MTech,615,616 Jasvinder A. Singh, MD,617,618 Solomon Sisay, MPH,619 Freddy Sitas, PhD,321,620 Eug?ne Sobngwi, PhD,621,622 Moslem Soofi, PhD,623 Joan B. Soriano, MD,624,625 Vasiliki Stathopoulou, PhD,626 Mu’awiyyah Babale Sufiyan, MD,627 Rafael Tabares-Seisdedos, PhD,628,629 Takahiro Tabuchi, MD,630 Ken Takahashi, PhD,383,631 Omid Reza Tamtaji, MSc,438 Mohammed Rasoul Tarawneh, PhD,632 Segen Gebremeskel Tassew, MSc,421 Parvaneh Taymoori, PhD,633 Arash Tehrani-Banihashemi, PhD,91,634 Mohamad-Hani Temsah, MD,147,635 Omar Temsah,147 Berhe Etsay Tesfay, MPH,636 Fisaha Haile Tesfay, MPH,421,637 Manaye Yihune Teshale, MPH,638 Gizachew Assefa Tessema, MPH,42,639 Subash Thapa, PhD,640 Kenean Getaneh Tlaye, MSc,175 Roman Topor-Madry, PhD,641,642 Marcos Roberto Tovani-Palone, MSc,643 Eugenio Traini, MSc,457 Bach Xuan Tran, PhD,644 Khanh Bao Tran, MD,645,646 Afewerki Gebremeskel Tsadik, MSc,119 Irfan Ullah, PhD,647 Olalekan A. Uthman, PhD,648 Marco Vacante, PhD,649 Maryam Vaezi, MD,650,651 Patricia Varona Perez, PhD,652,653 Yousef Veisani, PhD,654 Simone Vidale, MD,655 Francesco S. Violante, MD,219,656 Vasily Vlassov, MD,657 Stein Emil Vollset, DrPH,1,278 Theo Vos, PhD,1,278 Kia Vosoughi, MD,658 Giang Thu Vu, BA,282 Isidora S. Vujcic, PhD,195 Henry Wabinga, MD,659 Tesfahun Mulatu Wachamo, MPH,660 Fasil Shiferaw Wagnew, MSc,413 Yasir Waheed, PhD,661 Fitsum Weldegebreal, MSc,77 Girmay Teklay Weldesamuel, MSc,76 Tissa Wijeratne, MD,662,663 Dawit Zewdu Wondafrash, MSc,467,664 Tewodros Eshete Wonde, MPH,384 Adam Belay Wondmieneh, MSc,665,666 Hailemariam Mekonnen Workie, MSc,667 Rajaram Yadav, PhD,668 Abbas Yadegar, PhD,669 Ali Yadollahpour, PhD,670 Mehdi Yaseri, PhD,288,671 Vahid Yazdi-Feyzabadi, PhD,672,673 Alex Yeshaneh, BHlthSci,674 Mohammed Ahmed Yimam, MPH,660 Ebrahim M. Yimer, MSc,119 Engida Yisma, MPH,675 Naohiro Yonemoto, MPH,676 Mustafa Z. Younis, PhD,677,678 Bahman Yousefi, PhD,332,679 Mahmoud Yousefifard, PhD,680 Chuanhua Yu, PhD,681,682 Erfan Zabeh, BS,683,684 Vesna Zadnik, PhD,685 Telma Zahirian Moghadam, PhD,556,686 Zoubida Zaidi, PhD,687 Mohammad Zamani, MD,688 Hamed Zandian, PhD,686 Alireza Zangeneh, MD,623 Leila Zaki, PhD,689 Kazem Zendehdel, PhD,476 Zerihun Menlkalew Zenebe, MSc,690 Taye Abuhay Zewale, MSc,691 Arash Ziapour, PhD,692 Sanjay Zodpey, PhD,25 and Christopher J. L. Murray, DPhil1,278