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2. Efficacy and safety of carbamide peroxide tooth-whitening gels

Author

Yasmin M. Asaad, Sultan T. Alshammari, Ahlam M. S. Faloudah, Taghreed M. Alwabel, Maryam S. Alhazmi, Nadiyah H. Almalki, Hussam E. Almalki, Moayad W. Alturki, Faten A. Alnasser, and Abdulaziz K. Subayt

Subjects
Automotive Engineering
Abstract

Carbamide and hydrogen peroxide are the most frequently utilized compounds for various whitening techniques, that differ as per peroxide level, method of administration, and exposure period, when it comes to the active solutions accessible for important tooth whitening. The 10±1% carbamide peroxide dosage was the only level to date to acquire the American Dental Association's stamp of approval, ensuring its safety and effectiveness for at-home tooth whitening with customized trays. There has been a noticeable growth in the range of in-office tooth whitening compounds commercially available, which typically use elevated carbamide peroxide levels (30 to 37%) with or without an additional illumination. Even though tooth sensitivity appears to be the most frequent side effect of carbamide peroxide bleaching, discomfort goes away when the plan of care is finished. Sensitivity is typically linked to a background of sensitive teeth, greater administration rate, or use of greater carbamide peroxide levels. Additionally, studies have showed that using 10% carbamide peroxide at home to lighten teeth had comparable effectiveness to other methods (over the counter or in-office whitening). Patients generally prefer home vital bleaching with 10% carbamide peroxide to office procedures with 35% hydrogen peroxide. When comparing the safety utilizing 16% carbamide peroxide for nightguard vital bleaching to a placebo or 10% carbamide peroxide, patients receiving 16% reported higher gingival soreness than those administered a 10% carbamide peroxide or a placebo.

Published
2023

4. Scrophularia peyronii Post. from Jordan: Chemical Composition of Essential Oil and Phytochemical Profiling of Crude Extracts and Their In Vitro Antioxidant Activity

Author

Al-Qudah, Yousef Al-Dalahmeh, Sondos Abdullah J. Almahmoud, Nezar Al-Bataineh, Taqwa A. Alghzawi, Abdulrahman G. Alhamzani, Aamal A. Al-Mutairi, Hala I. Al-Jaber, Sultan T. Abu Orabi, Tareq T. Bataineh, Mohammed S. Al-Sheraideh, and Mahmoud A.

Subjects
Scrophularia peyronii, antioxidant activity, essential oil, Z,Z-farnesyl acetone
Abstract

The genus Scrophularia is one of the largest genera belonging to the Scrophulariaceae family. Different members of the genus exhibit an interesting, wide spectrum of bioactivities. Accordingly, the current study aimed to investigate, for the first time, the chemical composition of the essential oil of Scrophularia peyronii Post. from Jordan. Additionally, extracts obtained from the aerial parts with solvents of different polarities were assayed for their phytochemical constituents and in vitro antioxidant activities. The major constituents detected in the essential oil, as revealed by GC/MS analysis, contained mainly Z,Z-farnesyl acetone (11.04%), β-elemene (6.36%), n-octanal (5.98%), and spathulenol (4.58%). Each of the aqueous methanol (Sp-M) and butanol (Sp-B) extracts contained flavonoids, saponins, anthraquinone, and glycosides. Both extracts were evaluated for their total phenolic content (TPC), total flavonoid content (TFC), and their in vitro antioxidant activity, which were assayed using the DPPH radical scavenging activity and ABTS radical scavenging methods. Additionally, the two extracts were then subjected to LC-ESI-MS/MS for the qualitative determination of their secondary metabolite content, especially in flavonoids and phenolic compounds. The results showed that the Sp-B extract of S. peyronii had the highest contents of both phenolic compounds and flavonoids and showed high radical scavenging activity, as determined by the two assay methods, when compared with the Sp-M extract. The LC-ESI-MS/MS analysis resulted in the detection of 21 compounds, including 8 flavonoids, 6 phenolic acids, 6 iridoids, and 2 acids. Although the majority of compounds were detected in both extracts, it was noticed that scropolioside B, 6′-O-cinnamoylharpagide, isoferulic acid, and 6-O-methylcatapol were only detected in the Sp-M fraction.

Published
2023
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8. What are the predictors and costs of nurse absenteeism at select multicenter government hospitals? A cross-sectional study

Author

Hashem Al Ismail, Nawal H. Herzallah, and Sultan T. Al-Otaibi

Subjects
Public Health, Environmental and Occupational Health
Abstract

ObjectivesThe purposes of this study were to determine the prevalence and cost of absenteeism in nurses as well as the factors that affect absenteeism.MethodsThis is a cross sectional study where a self-administered questionnaire response were obtained from 442 nurses for the previous working in 4 hospitals and 3 primary health care centers in Saudi Arabia. Analyses compared those with zero absences with those with one or more absences per month. Attributable risk was calculated as the difference in the absence percentages among nurses with high-risk exposure and low risk exposure.ResultsThe average absence of nurses is 0.62 days per month. This results in an annual loss of around $4 million. The greatest absence frequency was significantly associated with work psychosocial factors. The modifiable factors included the clarity of work responsibilities, rating of managers, work facilities, work environment, transportation difficulties, and work satisfaction. Cost-effectiveness modules for absence intervention programs were built for these factors.ConclusionsThis study demonstrated that nurse absenteeism is a costly issue related to work and psychosocial factors. Preventive programs to improve the quality of work life are likely to be cost effective.

Published
2023

9. Ballota saxatilis from Jordan: Evaluation of Essential Oil Composition and Phytochemical Profiling of Crude Extracts and Their In-Vitro Antioxidant Activity

Author

Nezar Al-Bataineh, Faisal K. Algethami, Hala I. Al-Jaber, Abdulrahman G. Alhamzani, Rand M. Bataineh, Yousef Al-Dalahmeh, Tareq T. Bataineh, Sultan T. Abu-Orabi, and Mahmoud A. Al-Qudah

Subjects
Ballota saxatilis, antioxidants, 7,4′-dimethoxy-3-hydroxyflavone, kaempferol-3-O-rutinoside, chemical composition, Filtration and Separation, essential oil, Analytical Chemistry, LC-MS
Abstract

The chemical composition of essential oil extracted from the aerial parts of Ballota saxatilis Sieber ex C.Presl from Jordan has been elucidated by gas chromatography–mass spectrometry (GC-MS). Additionally, aqueous methanol (BsA), Butanol (BsB) and water (BsW) extracts were screened for their total phenol content (TPC), total flavonoid content (TFC), and antioxidant activities using the 2,2 Diphenyl-1-picrylhydrazyl (DPPH) and 2,2-Azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) diammonium salt (ABTS) methods. The most potent extracts were screened for their phenolic acids and flavonoid content using liquid the chromatography–mass spectrometry (LC-MS) technique. The results indicated that the essential oil predominantly contained cis-pinane (14.76%), β-caryophyllene (8.91%) and allo-aromadendrene epoxide (6.39%). Among the different extracts investigated, the BsB fraction had the most TPC and TFC (455.79 ± 1.03 µg gallic acid/g dry extract; 272.62 ± 8.28 µg quercetin/g dry extract, respectively) and had the best radical and radical cation scavenging activities, as determined using the DPPH and ABTS methods. Quantitative and qualitative LC-MS analyses of BsA and BsB using LC-MS revealed each of the kaempferol-3-O-rutinoside (30.29%), chrysoeriol-7-glucoside (7.93%) and luteolin 7-o-glucoside (7.76%) as the main constituents of the BsA fraction. The BsB fraction was rich in 7,4′-dimethoxy-3-hydroxyflavone (34.68%), kaempferol-3,7,4′-trimethyl ether (29.17%) and corymbosin (9.66%) and lower concentration levels of kaempferol-3-O-rutinoside (1.63%) and chrysoeriol-7-glucoside (0.51%).

Published
2023
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10. Musculoskeletal disorders among sonographers in secondary care hospitals in the city of Al-Ahsa, Saudi Arabia

Author

Norah Abdullah AlMubarek, Sultan T. Al-Otaibi, and Hatem K. Herzallah

Subjects
Adult, Male, Rehabilitation, Saudi Arabia, Public Health, Environmental and Occupational Health, Hospitals, Secondary Care, Occupational Diseases, Cross-Sectional Studies, Risk Factors, Surveys and Questionnaires, parasitic diseases, Prevalence, Humans, Female, Musculoskeletal Diseases
Abstract

BACKGROUND: Work-related musculoskeletal disorders (WMSDs) among sonographers have raised significant concerns in recent years. OBJECTIVES: This study aimed to estimate the prevalence of WMSDs and identify risk factors for WMSDs among sonographers. To date, there is little research on WMSDs among sonographers in Saudi Arabia. Therefore, this study aimed to contribute to the Saudi literature by filling this gap. METHODS: A cross-sectional study was conducted among sonographers (n = 98) working in four major governmental hospitals in the city of Al-Ahsa, Saudi Arabia. The participants completed a validated, self-administered questionnaire that focused on the analysis of musculoskeletal symptoms among sonographers. RESULTS: The mean age of the respondents was 35.5±9 years. The majority of the participants were female (71.4%), non-Saudi (51%), and working as technicians (49%). The prevalence rates of shoulder and neck disorders among the participants were 65.3% and 57.1%, respectively. Gender (female), job title (sonography technicians), and years of experience (seasoned sonographers) were identified as risk factors for WMSDs. CONCLUSIONS: Among the studied sonographers, WMSDs were a significant, common problem. Being female, being a sonography technician, and being a seasoned sonographer were identified as risk factors for these disorders. Preventive measures should be implemented to reduce the risk of WMSDs in this occupational setting.

Published
2022

11. Synthesis, Characterization, Antimicrobial and Antioxidant Activities of 1,2,4-triazolyl-isoxazole Moieties via Dehydration Reactions of Carbohydrazides

Author

Mahmoud A. Al-Qudah, Sultan T. Abu-Orabi, Asma K. Alshamari, Lo’ay Al-Momani, and Fedaa Hamadeh

Subjects
chemistry.chemical_compound, Antioxidant, chemistry, medicine.medical_treatment, Organic Chemistry, medicine, Dehydration, Isoxazole, Antimicrobial, medicine.disease, Biochemistry, Combinatorial chemistry
Abstract

Abstract: For the reason of distinct place in the field of medicinal and pharmaceutical chemistry of 1,2,4-triazole derivatives, a new class of fused 1,2,4-triazolyl-isoxazole moieties was prepared from 3- (2,4,6-trimethoxyphenyl)isoxazolo-4,5-bis[carbonyl-(4̍-phenyl) thiosemicarbazide via dehydration reactions of carbohydrazides by using the appropriate chemical reagents. The structures of the compounds were elucidated by both elemental and spectral (IR, NMR and MS) analyses. The in vitro antioxidant activity of the new compounds was determined by free radical scavenging and metal chelating activity. All the synthesized compounds showed good activity according to free radical scavenging and metal chelating activity compared with standards. The new compounds were screened in vitro antibacterial activity against three gram-positive bacteria and three gram-negative bacteria.

Published
2022

12. Prevalence of Job-Related Injuries among Construction Workers in Eastern Region, Saudi Arabia

Author

Muna Faisal Alnaim, Sultan T. Al Otaibi, Hassan Abugad, Kyle Humphrey, Phillip Harber, Mary Kay O’Rourke, and Abdulrahman Al Naeem

Abstract

The aim of the study was to detect the prevalence of work-related Musculoskeletal Injuries among construction workers, to evaluate injury-related sick leave, and identify factors contributing to injury. the study was conducted and distributed to Saudi construction companies in three cities in the eastern region and 201 workers were approached and 149 were enrolled in the study. Jobs were categorized based on level of impact and jobs with similar levels were grouped together. Multiple Regression was used to evaluate stress categories and a cluster analysis was run on scaled and normalized types of stress and pain to identify factors closely associated with sick days taken. The results showed a response rate of 74.1%. A univariate analysis was used, and it demonstrated a 75.2% pain in upper and lower extremities, 61.7% pain was reported in upper extremities (Shoulder and Neck > Wrists and Hands > Elbow) and 12.8% pain reported in lower extremities (Lower back > Hips > Knees). In conclusion, the prevalence of work-related MSI in this large construction company was 75.2%. stratified multiple regression suggests job categories are good predictors of physical stress exposure and sick leave taken, also, the amount of force exerted, and vibration experienced by workers is closely linked to sick leave taken as well. Medium and high pain levels were linked to keyboard work, pushing / pulling, lifting and use of vibrating tools these workers would benefit from training emphasizing ergonomics and an explanation of proper techniques to handle tools. Lastly, applying new engineering controls would be helpful in the prevention of injuries that can minimize sick leave.

Published
2022

13. A deep learning system accurately classifies primary and metastatic cancers using passenger mutation patterns

Author

Jiao, Wei, Atwal, Gurnit, Polak, Paz, Karlic, Rosa, Cuppen, Edwin, Al-Shahrour, Fatima, Bailey, Peter J, Biankin, Andrew V, Boutros, Paul C, Campbell, Peter J, Chang, David K, Cooke, Susanna L, Deshpande, Vikram, Faltas, Bishoy M, Faquin, William C, Garraway, Levi, Getz, Gad, Grimmond, Sean M, Haider, Syed, Hoadley, Katherine A, Kaiser, Vera B, Kato, Mamoru, Kübler, Kirsten, Lazar, Alexander J, Li, Constance H, Louis, David N, Margolin, Adam, Martin, Sancha, Nahal-Bose, Hardeep K, Nielsen, G Petur, Nik-Zainal, Serena, Omberg, Larsson, P’ng, Christine, Perry, Marc D, Rheinbay, Esther, Rubin, Mark A, Semple, Colin A, Sgroi, Dennis C, Shibata, Tatsuhiro, Siebert, Reiner, Smith, Jaclyn, Stein, Lincoln D, Stobbe, Miranda D, Sun, Ren X, Thai, Kevin, Wright, Derek W, Wu, Chin-Lee, Yuan, Ke, Zhang, Junjun, Danyi, Alexandra, de Ridder, Jeroen, van Herpen, Carla, Lolkema, Martijn P, Steeghs, Neeltje, Morris, Quaid D, Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Amin, Samirkumar B, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Baez-Ortega, Adrian, Bailey, Matthew H, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, Barbi, Stefano, Barbour, Andrew P, Barenboim, Jonathan, Barnholtz-Sloan, Jill, Barr, Hugh, Barrera, Elisabet, Bartlett, John, Bartolome, Javier, Bassi, Claudio, Bathe, Oliver F, Baumhoer, Daniel, Bavi, Prashant, Baylin, Stephen B, Bazant, Wojciech, Beardsmore, Duncan, Beck, Timothy A, Behjati, Sam, Behren, Andreas, Niu, Beifang, Bell, Cindy, Beltran, Sergi, Benz, Christopher, Berchuck, Andrew, Bergmann, Anke K, Bergstrom, Erik N, Berman, Benjamin P, Berney, Daniel M, Bernhart, Stephan H, Beroukhim, Rameen, Berrios, Mario, Bersani, Samantha, Bertl, Johanna, Betancourt, Miguel, Bhandari, Vinayak, Bhosle, Shriram G, Bieg, Matthias, Bigner, Darell, Binder, Hans, Birney, Ewan, Birrer, Michael, Biswas, Nidhan K, Bjerkehagen, Bodil, Bodenheimer, Tom, Boice, Lori, Bonizzato, Giada, De Bono, Johann S, Boot, Arnoud, Bootwalla, Moiz S, Borg, Ake, Borkhardt, Arndt, Boroevich, Keith A, Borozan, Ivan, Borst, Christoph, Bosenberg, Marcus, Bosio, Mattia, Boultwood, Jacqueline, Bourque, Guillaume, Bova, G Steven, Bowen, David T, Bowlby, Reanne, Bowtell, David DL, Boyault, Sandrine, Boyce, Rich, Boyd, Jeffrey, Brazma, Alvis, Brennan, Paul, Brewer, Daniel S, Brinkman, Arie B, Bristow, Robert G, Broaddus, Russell R, Brock, Jane E, Brock, Malcolm, Broeks, Annegien, Brooks, Angela N, Brooks, Denise, Brors, Benedikt, Brunak, Søren, Bruxner, Timothy JC, Bruzos, Alicia L, Buchanan, Alex, Buchhalter, Ivo, Buchholz, Christiane, Bullman, Susan, Burke, Hazel, Burkhardt, Birgit, Burns, Kathleen H, Busanovich, John, Bustamante, Carlos D, Butler, Adam P, Butte, Atul J, Byrne, Niall J, Børresen-Dale, Anne-Lise, Caesar-Johnson, Samantha J, Cafferkey, Andy, Cahill, Declan, Calabrese, Claudia, Caldas, Carlos, Calvo, Fabien, Camacho, Niedzica, Campo, Elias, Cantù, Cinzia, Cao, Shaolong, Carey, Thomas E, Carlevaro-Fita, Joana, Carlsen, Rebecca, Cataldo, Ivana, Cazzola, Mario, Cebon, Jonathan, Cerfolio, Robert, Chadwick, Dianne E, Chakravarty, Dimple, Chalmers, Don, Chan, Calvin Wing Yiu, Chan, Kin, Chan-Seng-Yue, Michelle, Chandan, Vishal S, Chanock, Stephen J, Chantrill, Lorraine A, Chateigner, Aurélien, Chatterjee, Nilanjan, Chayama, Kazuaki, Chen, Hsiao-Wei, Chen, Jieming, Chen, Ken, Chen, Yiwen, Chen, Zhaohong, Cherniack, Andrew D, Chien, Jeremy, Chiew, Yoke-Eng, Chin, Suet-Feung, Cho, Juok, Cho, Sunghoon, Choi, Jung Kyoon, Choi, Wan, Chomienne, Christine, Chong, Zechen, Choo, Su Pin, Chou, Angela, Christ, Angelika N, Christie, Elizabeth L, Chuah, Eric, Cibulskis, Carrie, Cibulskis, Kristian, Cingarlini, Sara, Clapham, Peter, Claviez, Alexander, Cleary, Sean, Cloonan, Nicole, Cmero, Marek, Collins, Colin C, Connor, Ashton A, Cooper, Colin S, Cope, Leslie, Corbo, Vincenzo, Cordes, Matthew G, Cordner, Stephen M, Cortés-Ciriano, Isidro, Covington, Kyle, Cowin, Prue A, Craft, Brian, Craft, David, Creighton, Chad J, Cun, Yupeng, Curley, Erin, Cutcutache, Ioana, Czajka, Karolina, Czerniak, Bogdan, Dagg, Rebecca A, Danilova, Ludmila, Davi, Maria Vittoria, Davidson, Natalie R, Davies, Helen, Davis, Ian J, Davis-Dusenbery, Brandi N, Dawson, Kevin J, De La Vega, Francisco M, De Paoli-Iseppi, Ricardo, Defreitas, Timothy, Dei Tos, Angelo P, Delaneau, Olivier, Demchok, John A, Demeulemeester, Jonas, Demidov, German M, Demircioğlu, Deniz, Dennis, Nening M, Denroche, Robert E, Dentro, Stefan C, Desai, Nikita, Deshwar, Amit G, Desmedt, Christine, Deu-Pons, Jordi, Dhalla, Noreen, Dhani, Neesha C, Dhingra, Priyanka, Dhir, Rajiv, DiBiase, Anthony, Diamanti, Klev, Ding, Li, Ding, Shuai, Dinh, Huy Q, Dirix, Luc, Doddapaneni, HarshaVardhan, Donmez, Nilgun, Dow, Michelle T, Drapkin, Ronny, Drechsel, Oliver, Drews, Ruben M, Serge, Serge, Dudderidge, Tim, Dueso-Barroso, Ana, Dunford, Andrew J, Dunn, Michael, Dursi, Lewis Jonathan, Duthie, Fraser R, Dutton-Regester, Ken, Eagles, Jenna, Easton, Douglas F, Edmonds, Stuart, Edwards, Paul A, Edwards, Sandra E, Eeles, Rosalind A, Ehinger, Anna, Eils, Juergen, Eils, Roland, El-Naggar, Adel, Eldridge, Matthew, Ellrott, Kyle, Erkek, Serap, Escaramis, Georgia, Espiritu, Shadrielle MG, Estivill, Xavier, Etemadmoghadam, Dariush, Eyfjord, Jorunn E, Fan, Daiming, Fan, Yu, Farcas, Claudiu, Fassan, Matteo, Fatima, Aquila, Favero, Francesco, Fayzullaev, Nodirjon, Felau, Ina, Fereday, Sian, Ferguson, Martin L, Ferretti, Vincent, Feuerbach, Lars, Field, Matthew A, Fink, J Lynn, Finocchiaro, Gaetano, Fisher, Cyril, Fittall, Matthew W, Fitzgerald, Anna, Fitzgerald, Rebecca C, Flanagan, Adrienne M, Fleshner, Neil E, Flicek, Paul, Foekens, John A, Fong, Kwun M, Fonseca, Nuno A, Foster, Christopher S, Fox, Natalie S, Fraser, Michael, Frazer, Scott, Frenkel-Morgenstern, Milana, Friedman, William, Frigola, Joan, Fronick, Catrina C, Fujimoto, Akihiro, Fujita, Masashi, Fukayama, Masashi, Fulton, Lucinda A, Fulton, Robert S, Furuta, Mayuko, Futreal, P Andrew, Füllgrabe, Anja, Gabriel, Stacey B, Gallinger, Steven, Gambacorti-Passerini, Carlo, Gao, Jianjiong, Gao, Shengjie, Garred, Øystein, Garrison, Erik, Garsed, Dale W, Gehlenborg, Nils, Gelpi, Josep LL, George, Joshy, Gerhard, Daniela S, Gerhauser, Clarissa, Gershenwald, Jeffrey E, Gerstein, Mark, Gerstung, Moritz, Ghori, Mohammed, Ghossein, Ronald, Giama, Nasra H, Gibbs, Richard A, Gibson, Bob, Gill, Anthony J, Gill, Pelvender, Giri, Dilip D, Glodzik, Dominik, Gnanapragasam, Vincent J, Goebler, Maria Elisabeth, Goldman, Mary J, Gomez, Carmen, Gonzalez, Santiago, Gonzalez-Perez, Abel, Gordenin, Dmitry A, Gossage, James, Gotoh, Kunihito, Govindan, Ramaswamy, Grabau, Dorthe, Graham, Janet S, Grant, Robert C, Green, Anthony R, Green, Eric, Greger, Liliana, Grehan, Nicola, Grimaldi, Sonia, Grossman, Robert L, Grundhoff, Adam, Gundem, Gunes, Guo, Qianyun, Gupta, Manaswi, Gupta, Shailja, Gut, Ivo G, Gut, Marta, Göke, Jonathan, Ha, Gavin, Haake, Andrea, Haan, David, Haas, Siegfried, Haase, Kerstin, Haber, James E, Habermann, Nina, Hach, Faraz, Hama, Natsuko, Hamdy, Freddie C, Hamilton, Anne, Hamilton, Mark P, Han, Leng, Hanna, George B, Hansmann, Martin, Haradhvala, Nicholas J, Harismendy, Olivier, Harliwong, Ivon, Harmanci, Arif O, Harrington, Eoghan, Hasegawa, Takanori, Haussler, David, Hawkins, Steve, Hayami, Shinya, Hayashi, Shuto, Hayes, D Neil, Hayes, Stephen J, Hayward, Nicholas K, Hazell, Steven, He, Yao, Heath, Allison P, Heath, Simon C, Hedley, David, Hegde, Apurva M, Heiman, David I, Heinold, Michael C, Heins, Zachary, Heisler, Lawrence E, Hellstrom-Lindberg, Eva, Helmy, Mohamed, Heo, Seong Gu, Hepperla, Austin J, Heredia-Genestar, José María, Herrmann, Carl, Hersey, Peter, Hess, Julian M, Hilmarsdottir, Holmfridur, Hinton, Jonathan, Hirano, Satoshi, Hiraoka, Nobuyoshi, Hobolth, Asger, Hodzic, Ermin, Hoell, Jessica I, Hoffmann, Steve, Hofmann, Oliver, Holbrook, Andrea, Holik, Aliaksei Z, Hollingsworth, Michael A, Holmes, Oliver, Holt, Robert A, Hong, Chen, Hong, Eun Pyo, Hong, Jongwhi H, Hooijer, Gerrit K, Hornshøj, Henrik, Hosoda, Fumie, Hou, Yong, Hovestadt, Volker, Howat, William, Hoyle, Alan P, Hruban, Ralph H, Hu, Jianhong, Hu, Taobo, Hua, Xing, Huang, Kuan-lin, Huang, Mei, Huang, Mi Ni, Huang, Vincent, Huang, Yi, Huber, Wolfgang, Hudson, Thomas J, Hummel, Michael, Hung, Jillian A, Huntsman, David, Hupp, Ted R, Huse, Jason, Huska, Matthew R, Hutter, Barbara, Hutter, Carolyn M, Hübschmann, Daniel, Iacobuzio-Donahue, Christine A, Imbusch, Charles David, Imielinski, Marcin, Imoto, Seiya, Isaacs, William B, Isaev, Keren, Ishikawa, Shumpei, Iskar, Murat, Islam, SM Ashiqul, Ittmann, Michael, Ivkovic, Sinisa, Izarzugaza, Jose MG, Jacquemier, Jocelyne, Jakrot, Valerie, Jamieson, Nigel B, Jang, Gun Ho, Jang, Se Jin, Jayaseelan, Joy C, Jayasinghe, Reyka, Jefferys, Stuart R, Jegalian, Karine, Jennings, Jennifer L, Jeon, Seung-Hyup, Jerman, Lara, Ji, Yuan, Johansson, Peter A, Johns, Amber L, Johns, Jeremy, Johnson, Rory, Johnson, Todd A, Jolly, Clemency, Joly, Yann, Jonasson, Jon G, Jones, Corbin D, Jones, David R, Jones, David TW, Jones, Nic, Jones, Steven JM, Jonkers, Jos, Ju, Young Seok, Juhl, Hartmut, Jung, Jongsun, Juul, Malene, Juul, Randi Istrup, Juul, Sissel, Jäger, Natalie, Kabbe, Rolf, Kahles, Andre, Kahraman, Abdullah, Kakavand, Hojabr, Kalimuthu, Sangeetha, von Kalle, Christof, Kang, Koo Jeong, Karaszi, Katalin, Karlan, Beth, Karlić, Rosa, Karsch, Dennis, Kasaian, Katayoon, Kassahn, Karin S, Katai, Hitoshi, Katoh, Hiroto, Kawakami, Yoshiiku, Kay, Jonathan D, Kazakoff, Stephen H, Kazanov, Marat D, Keays, Maria, Kebebew, Electron, Kefford, Richard F, Kellis, Manolis, Kench, James G, Kennedy, Catherine J, Kerssemakers, Jules NA, Khoo, David, Khoo, Vincent, Khuntikeo, Narong, Khurana, Ekta, Kilpinen, Helena, Kim, Hark Kyun, Kim, Hyung-Lae, Kim, Hyung-Yong, Kim, Hyunghwan, Kim, Jaegil, Kim, Jihoon, Kim, Jong K, Kim, Youngwook, King, Tari A, Klapper, Wolfram, Kleinheinz, Kortine, Klimczak, Leszek J, Knappskog, Stian, Kneba, Michael, Knoppers, Bartha M, Koh, Youngil, Komorowski, Jan, Komura, Daisuke, Komura, Mitsuhiro, Kong, Gu, Kool, Marcel, Korbel, Jan O, Korchina, Viktoriya, Korshunov, Andrey, Koscher, Michael, Koster, Roelof, Kote-Jarai, Zsofia, Koures, Antonios, Kovacevic, Milena, Kremeyer, Barbara, Kretzmer, Helene, Kreuz, Markus, Krishnamurthy, Savitri, Kube, Dieter, Kumar, Kiran, Kumar, Pardeep, Kumar, Sushant, Kumar, Yogesh, Kundra, Ritika, Küppers, Ralf, Lagergren, Jesper, Lai, Phillip H, Laird, Peter W, Lakhani, Sunil R, Lalansingh, Christopher M, Lalonde, Emilie, Lamaze, Fabien C, Lambert, Adam, Lander, Eric, Landgraf, Pablo, Landoni, Luca, Langerød, Anita, Lanzós, Andrés, Larsimont, Denis, Larsson, Erik, Lathrop, Mark, Lau, Loretta MS, Lawerenz, Chris, Lawlor, Rita T, Lawrence, Michael S, Lazic, Ana Mijalkovic, Le, Xuan, Lee, Darlene, Lee, Donghoon, Lee, Eunjung Alice, Lee, Hee Jin, Lee, Jake June-Koo, Lee, Jeong-Yeon, Lee, Juhee, Lee, Ming Ta Michael, Lee-Six, Henry, Lehmann, Kjong-Van, Lehrach, Hans, Lenze, Dido, Leonard, Conrad R, Leongamornlert, Daniel A, Leshchiner, Ignaty, Letourneau, Louis, Letunic, Ivica, Levine, Douglas A, Lewis, Lora, Ley, Tim, Li, Chang, Li, Haiyan Irene, Li, Jun, Li, Lin, Li, Shantao, Li, Siliang, Li, Xiaobo, Li, Xiaotong, Li, Xinyue, Li, Yilong, Liang, Han, Liang, Sheng-Ben, Lichter, Peter, Lin, Pei, Lin, Ziao, Linehan, 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Deurzen, Carolien HM, van de Vijver, Marc J, Veer, L van’t, and von Mering, Christian

Subjects
Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract

In cancer, the primary tumour’s organ of origin and histopathology are the strongest determinants of its clinical behaviour, but in 3% of cases a patient presents with a metastatic tumour and no obvious primary. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we train a deep learning classifier to predict cancer type based on patterns of somatic passenger mutations detected in whole genome sequencing (WGS) of 2606 tumours representing 24 common cancer types produced by the PCAWG Consortium. Our classifier achieves an accuracy of 91% on held-out tumor samples and 88% and 83% respectively on independent primary and metastatic samples, roughly double the accuracy of trained pathologists when presented with a metastatic tumour without knowledge of the primary. Surprisingly, adding information on driver mutations reduced accuracy. Our results have clinical applicability, underscore how patterns of somatic passenger mutations encode the state of the cell of origin, and can inform future strategies to detect the source of circulating tumour DNA.

Published
2023
Full Text
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14. Combined burden and functional impact tests for cancer driver discovery using DriverPower

Author

Shuai, Shimin, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Bandopadhayay, Pratiti, Barenboim, Jonathan, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Brunak, Søren, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Dhingra, Priyanka, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Getz, Gad, Guo, Qianyun, Gut, Ivo G, Haan, David, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Hornshøj, Henrik, Isaev, Keren, Izarzugaza, Jose MG, Johnson, Rory, Johnson, Todd A, Juul, Malene, Juul, Randi Istrup, Kahles, Andre, Kahraman, Abdullah, Kellis, Manolis, Khurana, Ekta, Kim, Jaegil, Kim, Jong K, Kim, Youngwook, Komorowski, Jan, Korbel, Jan O, Kumar, Sushant, Lanzós, Andrés, Larsson, Erik, Lawrence, Michael S, Lee, Donghoon, Lehmann, Kjong-Van, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E, McGillivray, Patrick D, Meyerson, William, Muiños, Ferran, Mularoni, Loris, Nakagawa, Hidewaki, Nielsen, Morten Muhlig, Paczkowska, Marta, Park, Keunchil, Park, Kiejung, Pedersen, Jakob Skou, Pons, Tirso, Pulido-Tamayo, Sergio, Raphael, Benjamin J, Reimand, Jüri, Reyes-Salazar, Iker, Reyna, Matthew A, Rheinbay, Esther, Rubin, Mark A, Rubio-Perez, Carlota, Sahinalp, S Cenk, Saksena, Gordon, Salichos, Leonidas, Sander, Chris, Schumacher, Steven E, Shackleton, Mark, Shapira, Ofer, Shen, Ciyue, Shrestha, Raunak, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stein, Lincoln D, Stuart, Joshua M, Tamborero, David, Tiao, Grace, Tsunoda, Tatsuhiko, Umer, Husen M, Uusküla-Reimand, Liis, Valencia, Alfonso, Vazquez, Miguel, Verbeke, Lieven PC, Wadelius, 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Subjects
Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract

The discovery of driver mutations is one of the key motivations for cancer genome sequencing. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we describe DriverPower, a software package that uses mutational burden and functional impact evidence to identify driver mutations in coding and non-coding sites within cancer whole genomes. Using a total of 1373 genomic features derived from public sources, DriverPower’s background mutation model explains up to 93% of the regional variance in the mutation rate across multiple tumour types. By incorporating functional impact scores, we are able to further increase the accuracy of driver discovery. Testing across a collection of 2583 cancer genomes from the PCAWG project, DriverPower identifies 217 coding and 95 non-coding driver candidates. Comparing to six published methods used by the PCAWG Drivers and Functional Interpretation Working Group, DriverPower has the highest F1 score for both coding and non-coding driver discovery. This demonstrates that DriverPower is an effective framework for computational driver discovery.

Published
2023
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15. Integrative pathway enrichment analysis of multivariate omics data

Author

Paczkowska, Marta, Barenboim, Jonathan, Sintupisut, Nardnisa, Fox, Natalie S, Zhu, Helen, Abd-Rabbo, Diala, Mee, Miles W, Boutros, Paul C, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Brunak, Søren, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Dhingra, Priyanka, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Getz, Gad, Gonzalez-Perez, Abel, Guo, Qianyun, Gut, Ivo G, Haan, David, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Hornshøj, Henrik, Isaev, Keren, Izarzugaza, Jose MG, Johnson, Rory, Johnson, Todd A, Juul, Malene, Juul, Randi Istrup, Kahles, Andre, Kahraman, Abdullah, Kellis, Manolis, Khurana, Ekta, Kim, Jaegil, Kim, Jong K, Kim, Youngwook, Komorowski, Jan, Korbel, Jan O, Kumar, Sushant, Lanzós, Andrés, Lawrence, Michael S, Lee, Donghoon, Lehmann, Kjong-Van, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Marchal, Kathleen, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E, McGillivray, Patrick D, Meyerson, William, Muiños, Ferran, Mularoni, Loris, Nakagawa, Hidewaki, Nielsen, Morten Muhlig, Park, Keunchil, Park, Kiejung, Pedersen, Jakob Skou, Pich, Oriol, Pons, Tirso, Pulido-Tamayo, Sergio, Raphael, Benjamin J, Reyes-Salazar, Iker, Reyna, Matthew A, Rheinbay, Esther, Rubin, Mark A, Rubio-Perez, Carlota, Sabarinathan, Radhakrishnan, Sahinalp, S Cenk, Saksena, Gordon, Salichos, Leonidas, Sander, Chris, Schumacher, Steven E, Shackleton, Mark, Shapira, Ofer, Shen, Ciyue, Shrestha, Raunak, Shuai, Shimin, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stein, Lincoln D, Stuart, Joshua M, Tamborero, David, Tiao, Grace, Tsunoda, 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Vijver, Marc J, and Veer, L van’t

Subjects
Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract

Multi-omics datasets represent distinct aspects of the central dogma of molecular biology. Such high-dimensional molecular profiles pose challenges to data interpretation and hypothesis generation. ActivePathways is an integrative method that discovers significantly enriched pathways across multiple datasets using statistical data fusion, rationalizes contributing evidence and highlights associated genes. As part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumor types, we integrated genes with coding and non-coding mutations and revealed frequently mutated pathways and additional cancer genes with infrequent mutations. We also analyzed prognostic molecular pathways by integrating genomic and transcriptomic features of 1780 breast cancers and highlighted associations with immune response and anti-apoptotic signaling. Integration of ChIP-seq and RNA-seq data for master regulators of the Hippo pathway across normal human tissues identified processes of tissue regeneration and stem cell regulation. ActivePathways is a versatile method that improves systems-level understanding of cellular organization in health and disease through integration of multiple molecular datasets and pathway annotations.

Published
2023
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16. Pathway and network analysis of more than 2500 whole cancer genomes

Author

Reyna, Matthew A, Haan, David, Paczkowska, Marta, Verbeke, Lieven PC, Vazquez, Miguel, Kahraman, Abdullah, Pulido-Tamayo, Sergio, Barenboim, Jonathan, Wadi, Lina, Dhingra, Priyanka, Shrestha, Raunak, Getz, Gad, Lawrence, Michael S, Pedersen, Jakob Skou, Rubin, Mark A, Wheeler, David A, Brunak, Søren, Izarzugaza, Jose MG, Khurana, Ekta, Marchal, Kathleen, von Mering, Christian, Sahinalp, S Cenk, Valencia, Alfonso, Abascal, Federico, Amin, Samirkumar B, Bader, Gary D, Bandopadhayay, Pratiti, Beroukhim, Rameen, Bertl, Johanna, Boroevich, Keith A, Busanovich, John, Campbell, Peter J, Carlevaro-Fita, Joana, Chakravarty, Dimple, Chan, Calvin Wing Yiu, Chen, Ken, Choi, Jung Kyoon, Deu-Pons, Jordi, Diamanti, Klev, Feuerbach, Lars, Fink, J Lynn, Fonseca, Nuno A, Frigola, Joan, Gambacorti-Passerini, Carlo, Garsed, Dale W, Gerstein, Mark, Guo, Qianyun, Gut, Ivo G, Hamilton, Mark P, Haradhvala, Nicholas J, Harmanci, Arif O, Helmy, Mohamed, Herrmann, Carl, Hess, Julian M, Hobolth, Asger, Hodzic, Ermin, Hong, Chen, Hornshøj, Henrik, Isaev, Keren, Johnson, Rory, Johnson, Todd A, Juul, Malene, Juul, Randi Istrup, Kahles, Andre, Kellis, Manolis, Kim, Jaegil, Kim, Jong K, Kim, Youngwook, Komorowski, Jan, Korbel, Jan O, Kumar, Sushant, Lanzós, Andrés, Larsson, Erik, Lee, Donghoon, Lehmann, Kjong-Van, Li, Shantao, Li, Xiaotong, Lin, Ziao, Liu, Eric Minwei, Lochovsky, Lucas, Lou, Shaoke, Madsen, Tobias, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Maruvka, Yosef E, McGillivray, Patrick D, Meyerson, William, Muiños, Ferran, Mularoni, Loris, Nakagawa, Hidewaki, Nielsen, Morten Muhlig, Park, Keunchil, Park, Kiejung, Pons, Tirso, Reyes-Salazar, Iker, Rheinbay, Esther, Rubio-Perez, Carlota, Saksena, Gordon, Salichos, Leonidas, Sander, Chris, Schumacher, Steven E, Shackleton, Mark, Shapira, Ofer, Shen, Ciyue, Shuai, Shimin, Sidiropoulos, Nikos, Sieverling, Lina, Sinnott-Armstrong, Nasa, Stein, Lincoln D, Tamborero, David, Tiao, Grace, Tsunoda, Tatsuhiko, Umer, Husen M, 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Subjects
Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract

The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.

Published
2023
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17. Divergent mutational processes distinguish hypoxic and normoxic tumours

Author

Bhandari, Vinayak, Li, Constance H, Bristow, Robert G, Boutros, Paul C, Aaltonen, Lauri A, Abascal, Federico, Abeshouse, Adam, Aburatani, Hiroyuki, Adams, David J, Agrawal, Nishant, Ahn, Keun Soo, Ahn, Sung-Min, Aikata, Hiroshi, Akbani, Rehan, Akdemir, Kadir C, Al-Ahmadie, Hikmat, Al-Sedairy, Sultan T, Al-Shahrour, Fatima, Alawi, Malik, Albert, Monique, Aldape, Kenneth, Alexandrov, Ludmil B, Ally, Adrian, Alsop, Kathryn, Alvarez, Eva G, Amary, Fernanda, Amin, Samirkumar B, Aminou, Brice, Ammerpohl, Ole, Anderson, Matthew J, Ang, Yeng, Antonello, Davide, Anur, Pavana, Aparicio, Samuel, Appelbaum, Elizabeth L, Arai, Yasuhito, Aretz, Axel, Arihiro, Koji, Ariizumi, Shun-ichi, Armenia, Joshua, Arnould, Laurent, Asa, Sylvia, Assenov, Yassen, Atwal, Gurnit, Aukema, Sietse, Auman, J Todd, Aure, Miriam RR, Awadalla, Philip, Aymerich, Marta, Bader, Gary D, Baez-Ortega, Adrian, Bailey, Matthew H, Bailey, Peter J, Balasundaram, Miruna, Balu, Saianand, Bandopadhayay, Pratiti, Banks, Rosamonde E, 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Subjects
Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract

Many primary tumours have low levels of molecular oxygen (hypoxia), and hypoxic tumours respond poorly to therapy. Pan-cancer molecular hallmarks of tumour hypoxia remain poorly understood, with limited comprehension of its associations with specific mutational processes, non-coding driver genes and evolutionary features. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we quantify hypoxia in 1188 tumours spanning 27 cancer types. Elevated hypoxia associates with increased mutational load across cancer types, irrespective of underlying mutational class. The proportion of mutations attributed to several mutational signatures of unknown aetiology directly associates with the level of hypoxia, suggesting underlying mutational processes for these signatures. At the gene level, driver mutations in TP53, MYC and PTEN are enriched in hypoxic tumours, and mutations in PTEN interact with hypoxia to direct tumour evolutionary trajectories. Overall, hypoxia plays a critical role in shaping the genomic and evolutionary landscapes of cancer.

Published
2023
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18. Genomic footprints of activated telomere maintenance mechanisms in cancer

Author

Sieverling, Lina, Hong, Chen, Koser, Sandra D, Ginsbach, Philip, Kleinheinz, Kortine, Hutter, Barbara, Braun, Delia M, Cortés-Ciriano, Isidro, Xi, Ruibin, Kabbe, Rolf, Park, Peter J, Eils, Roland, Schlesner, Matthias, Akdemir, Kadir C, Alvarez, Eva G, Baez-Ortega, Adrian, Beroukhim, Rameen, Boutros, Paul C, Bowtell, David DL, Brors, Benedikt, Burns, Kathleen H, Campbell, Peter J, Chan, Kin, Chen, Ken, Dueso-Barroso, Ana, Dunford, Andrew J, Edwards, Paul A, Estivill, Xavier, Etemadmoghadam, Dariush, Feuerbach, Lars, Fink, J Lynn, Frenkel-Morgenstern, Milana, Garsed, Dale W, Gerstein, Mark, Gordenin, Dmitry A, Haan, David, Haber, James E, Hess, Julian M, Imielinski, Marcin, Jones, David TW, Ju, Young Seok, Kazanov, Marat D, Klimczak, Leszek J, Koh, Youngil, Korbel, Jan O, Kumar, Kiran, Lee, Eunjung Alice, Lee, Jake June-Koo, Li, Yilong, Lynch, Andy G, Macintyre, Geoff, Markowetz, Florian, Martincorena, Iñigo, Martinez-Fundichely, Alexander, Meyerson, Matthew, Miyano, Satoru, Nakagawa, 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Qinying, Xu, Yanxun, Xue, Hong, Yachida, Shinichi, Yakneen, Sergei, Yamaguchi, Rui, Yamaguchi, Takafumi N, Yamamoto, Masakazu, Yamamoto, Shogo, Yamaue, Hiroki, Yang, Fan, Yang, Huanming, Yang, Jean Y, Yang, Liming, Yang, Shanlin, Yang, Tsun-Po, Yang, Yang, Yaspo, Marie-Laure, Yates, Lucy, Yau, Christina, Ye, Chen, Ye, Kai, Yellapantula, Venkata D, Yoon, Christopher J, Yousif, Fouad, Yu, Jun, Yu, Kaixian, Yu, Willie, Yu, Yingyan, Yuan, Ke, Yuan, Yuan, Yuen, Denis, Yung, Christina K, Zaikova, Olga, Zapatka, Marc, Zenklusen, Jean C, Zenz, Thorsten, Zeps, Nikolajs, Zhang, Fan, Zhang, Hailei, Zhang, Hongwei, Zhang, Hongxin, Zhang, Jiashan, Zhang, Jing, Zhang, Junjun, Zhang, Xiuqing, Zhang, Xuanping, Zhang, Yan, Zhang, Zemin, Zhao, Zhongming, Zheng, Liangtao, Zheng, Xiuqing, Zhou, Wanding, Zhou, Yong, Zhu, Bin, Zhu, Hongtu, Zhu, Jingchun, Zhu, Shida, Zou, Lihua, Zou, Xueqing, deFazio, Anna, van As, Nicholas, van Deurzen, Carolien HM, van de Vijver, Marc J, Veer, L van’t, and von Mering, Christian

Subjects
Human Biology & Physiology, Ecology,Evolution & Ethology, Tumour Biology, Genetics & Genomics, Structural Biology & Biophysics, Computational & Systems Biology
Abstract

Cancers require telomere maintenance mechanisms for unlimited replicative potential. They achieve this through TERT activation or alternative telomere lengthening associated with ATRX or DAXX loss. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, we dissect whole-genome sequencing data of over 2500 matched tumor-control samples from 36 different tumor types aggregated within the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium to characterize the genomic footprints of these mechanisms. While the telomere content of tumors with ATRX or DAXX mutations (ATRX/DAXXtrunc) is increased, tumors with TERT modifications show a moderate decrease of telomere content. One quarter of all tumor samples contain somatic integrations of telomeric sequences into non-telomeric DNA. This fraction is increased to 80% prevalence in ATRX/DAXXtrunc tumors, which carry an aberrant telomere variant repeat (TVR) distribution as another genomic marker. The latter feature includes enrichment or depletion of the previously undescribed singleton TVRs TTCGGG and TTTGGG, respectively. Our systematic analysis provides new insight into the recurrent genomic alterations associated with telomere maintenance mechanisms in cancer.

Published
2023
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19. CHALLENGES IN IMPLEMENTATION OF ANTIMICROBIAL STEWARDSHIP PROGRAMS IN SAUDI HOSPITALS

Author

Saber . M . Alshahrani, Naif. D . Alharbi, Riyadh.A. Alghanmy, Thamer. A . Alsalmi, Sultan . A . Almuhalbidi, Raed . I . Alshaikhi, Sultan . T . Almutairi, Abdulrhman . S . Alghamdi, Ameen W. Alshaikh, Basem M. Albeladi

Abstract

Rising AMR rates, widespread antibiotic abuse, and concerns about the development of resistance to life-saving antibiotics have all been reported by Saudi hospitals in recent years. Appropriate antimicrobial use must be reduced, and so must the rates of antimicrobial resistance, immediately. Improving patient health outcomes, decreasing drug usage, and halting the spread of AMR all result from antimicrobials being used correctly. As such, the Saudi Arabian Ministry of Health's Pharmacists' Strategic Plan included the launch of the country's national antibiotics stewardship program (ASP) in 2014. There is some evidence that ASPs have been implemented in different Saudi tertiary hospitals and medical cities. Some of these implementations include developing antibiotics prescribing policies through drug classification and the target demographics. However, full implementing the ASP guidelines are major issues in Saudi hospitals. Common challenges that clog the wheel of this implementation present as systemic problems. They include patients factors such as the need for patient satisfaction, prescribe factors which include the desire to maintain trusts, hierarchy issues among prescribes, poor team work among healthcare team, etc. Other factors are administrative and facility-based issues which are linked to poor training programs, lack of personnel and poor coordination. These challenges could be effectively overcome if there’s a superior surveillance mechanism from the central ministry of health. At the hospital levels, close monitoring and attention in addition to collaboration will provide solutions to ASP guidelines implementation problems.

Published
2022
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20. Current issues of molecular diagnostics of bladder cancer

Author

Sultan T. Mukashev, Dana G. Nurman, Shokhrukh K. Akhnazarov, Olzhas M. Demissenov, and Akzhol K. Karim

Subjects
Oncology, medicine.medical_specialty, Bladder cancer, business.industry, Internal medicine, Medicine, Current (fluid), business, medicine.disease, Molecular diagnostics, General Nursing, Education
Abstract

Nowadays, it is generally accepted that cancer is a genetic disease. Tumour cells appear due to the accumulation of mutations in critical proto-oncogenes and tumour suppressor genes. Urothelial bladder cancer is a frequent oncological pathology, and therefore it is a significant social problem. The practical relevance of the study is due to the fact that the findings can significantly improve the efficiency of bladder cancer diagnosis. The purpose of the study was to consider all modern methods for diagnosing bladder cancer in one paper. As a research method, the analysis of scientific data obtained from the experimental study of bladder cancer was carried out. According to the data of the investigated sources, a fairly large number of scientists believe that bladder cancer (BC) is one of the most common tumours affecting the urinary tract. It is believed that important prognostic factors include the presence of vascular invasion and tumour complexes in the vessels, which increases the risk of the secondary neoplasm growth even at the pT1 stage. However, when assessing vascular invasion, pathologists often mistake the cracks formed around the tumour complexes for vessels. In this case, the study suggests conducting an immunohistochemical analysis for clear visualisation of blood vessels.

Published
2021

21. Preventing The Next Pandemic: Is Live Vaccine Efficacious Against Monkeypox, or There is a Need for Killed Virus and mRNA Vaccines?

Author

Abdelaziz Abdelaal, Abdullah Reda, Basant Ismail Lashin, Basant E. Katamesh, Aml M. Brakat, Balqees Mahmoud AL-Manaseer, Sayanika Kaur, Ankush Asija, Nimesh K. Patel, Soney Basnyat, Ali A. Rabaan, Saad Alhumaid, Hawra Albayat, Mohammed Aljeldah, Basim R. Al shammari, Amal H. Al-Najjar, Ahmed K. Al-Jassem, Sultan T. AlShurbaji, Fatimah S. Alshahrani, Ahlam Alynbiawi, Zainab H. Alfaraj, Duaa H. Alfaraj, Ahmed H Aldawood, Yub Raj Sedhai, Victoria Mumbo, Alfonso J. Rodriguez-Morales, and Ranjit Sah

Subjects
medicine_pharmacology_other
Abstract

(1) Background: The monkeypox virus (MPV) is a double-stranded DNA virus belonging to the Poxviridae family, Chordopoxvirinae subfamily, and Or-thopoxvirus genu. It was called monkeypox because it was first discovered in monkeys, in a Danish laboratory, in 1958. However, the actual reservoir for MPV is still unknown. (2) Methods & Results: We have reviewed the existing literature on the options for Monkeypox virus. There are three available vaccines for orthopoxviruses: ACAM2000, JYNNEOS, and LC16, with the first being a replicating vaccine and the latter being non or minimally replicating. (3) Conclusions: Smallpox vaccinations previously provided coincidental im-munity to MPV. ACAM2000(a live‐attenuated replicating vaccine) and JYNNEOS (a live‐attenuated, non-replicating vaccine) are two US FDA‐approved vaccines that can prevent monkeypox. However, ACAM2000 may cause serious side effects, including cardiac problems, whereas JYNNEOS is associated with fewer com-plications. The recent outbreaks across the globe have once again highlighted the need for constant monitoring and the development of novel prophylactic and therapeutic modalities. Based on available data, there is still a need to develop an effective and safe new generation of vaccines specific for monkeypox that are killed or mRNA before monkeypox is declared a pandemic.

Published
2022

22. Preventing the Next Pandemic: Is Live Vaccine Efficacious against Monkeypox, or Is There a Need for Killed Virus and mRNA Vaccines?

Author

Abdelaziz Abdelaal, Abdullah Reda, Basant Ismail Lashin, Basant E. Katamesh, Aml M. Brakat, Balqees Mahmoud AL-Manaseer, Sayanika Kaur, Ankush Asija, Nimesh K. Patel, Soney Basnyat, Ali A. Rabaan, Saad Alhumaid, Hawra Albayat, Mohammed Aljeldah, Basim R. Al Shammari, Amal H. Al-Najjar, Ahmed K. Al-Jassem, Sultan T. AlShurbaji, Fatimah S. Alshahrani, Ahlam Alynbiawi, Zainab H. Alfaraj, Duaa H. Alfaraj, Ahmed H. Aldawood, Yub Raj Sedhai, Victoria Mumbo, Alfonso J. Rodriguez-Morales, and Ranjit Sah

Subjects
Pharmacology, Infectious Diseases, Drug Discovery, Immunology, Pharmacology (medical)
Abstract

(1) Background: The monkeypox virus (MPV) is a double-stranded DNA virus belonging to the Poxviridae family, Chordopoxvirinae subfamily, and Orthopoxvirus genus. It was called monkeypox because it was first discovered in monkeys, in a Danish laboratory, in 1958. However, the actual reservoir for MPV is still unknown. (2) Methods and Results: We have reviewed the existing literature on the options for Monkeypox virus. There are three available vaccines for orthopoxviruses—ACAM2000, JYNNEOS, and LC16—with the first being a replicating vaccine and the latter being non- or minimally replicating. (3) Conclusions: Smallpox vaccinations previously provided coincidental immunity to MPV. ACAM2000 (a live-attenuated replicating vaccine) and JYNNEOS (a live-attenuated, nonreplicating vaccine) are two US FDA-approved vaccines that can prevent monkeypox. However, ACAM2000 may cause serious side effects, including cardiac problems, whereas JYNNEOS is associated with fewer complications. The recent outbreaks across the globe have once again highlighted the need for constant monitoring and the development of novel prophylactic and therapeutic modalities. Based on available data, there is still a need to develop an effective and safe new generation of vaccines specific for monkeypox that are killed or developed into a mRNA vaccine before monkeypox is declared a pandemic.

Published
2022

23. A Descriptive Study of the Types and Survival Patterns of Saudi Patients with Multiple Primary Solid Malignancies: A 30-Year Tertiary Care Center Experience

Author

Moustafa S. Alhamadh, Rakan B. Alanazi, Sultan T. Algarni, Ahmed Abdullah R. Alhuntushi, Mohammed Qasim Alshehri, Yusra Sajid Chachar, Mohammad Alkaiyat, and Fouad Sabatin

Subjects
Male, Neoplasms, Multiple Primary, Tertiary Care Centers, Saudi Arabia, Humans, Female, Neoplasms, Second Primary, Thyroid Neoplasms, multiple primary malignancies, multiple primaries, synchronous malignancies, metachronous malignancies, second primary, Colorectal Neoplasms, Retrospective Studies
Abstract

Background and Objective: Cancer survival has improved significantly, which reflects the achievements in screening, diagnosis, and treatment. As a consequence, multiple primary malignancies are diagnosed more frequently, with an incidence ranging from 0.52–11.7%. The types of malignancy that coexist and survival patterns vary notably in different countries and geographical areas. Due to the limited literature in Saudi Arabia, a baseline of prevalent malignancy combinations and their survival patterns would support early detection and disease management. Method: This was a retrospective descriptive study conducted from 1993–2022 at King Abdulaziz Medical City, Department of Medical Oncology, Riyadh, Saudi Arabia. Patients with at least two biopsy-proven solid malignancies were included. Patients with hematological malignancies, missing data, or an uncertain or indecisive pathology report were excluded. Result: In total, 321 patients were analyzed. More than half (57.3%) of the patients were female. A third (33%) of the cases were synchronous, and 67% were metachronous. The most frequent site of the first primary malignancy was breast cancer, followed by colorectal, skin, and thyroid cancers. The most frequent site of the second primary malignancy was colorectal cancer, followed by thyroid, breast, and liver cancers. Only 4% of the cases had a third primary malignancy, with colorectal and appendiceal cancers being the most frequent. The most frequently observed histopathology in the synchronous and metachronous malignancies was adenocarcinoma. Breast–colorectal, breast–thyroid, and kidney–colorectal were the most frequently observed malignancy combinations. Conclusion: The current study offers a baseline of multiple primary malignancies in Saudi Arabia and provides supporting evidence that the pattern of multiple primary malignancies varies among different countries and ethnicities. The possibility of developing another primary malignancy should be considered when treating and monitoring cancer patients.

Published
2022
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25. Antibodies to Combat Fungal Infections: Development Strategies and Progress

Author

Ali A. Rabaan, Amal H. Alfaraj, Amer Alshengeti, Abdulsalam Alawfi, Sara Alwarthan, Mashael Alhajri, Amal H. Al-Najjar, Mona A. Al Fares, Mustafa A. Najim, Souad A. Almuthree, Sultan T. AlShurbaji, Fadwa S. Alofi, Bashayer M. AlShehail, Buthina AlYuosof, Ahlam Alynbiawi, Suha A. Alzayer, Nawal Al Kaabi, Wesam A. Abduljabbar, Zakiyah A. Bukhary, and Ahmed S. Bueid

Subjects
Microbiology (medical), Virology, Microbiology
Abstract

The finding that some mAbs are antifungal suggests that antibody immunity may play a key role in the defense of the host against mycotic infections. The discovery of antibodies that guard against fungi is a significant advancement because it gives rise to the possibility of developing vaccinations that trigger protective antibody immunity. These vaccines might work by inducing antibody opsonins that improve the function of non-specific (such as neutrophils, macrophages, and NK cells) and specific (such as lymphocyte) cell-mediated immunity and stop or aid in eradicating fungus infections. The ability of antibodies to defend against fungi has been demonstrated by using monoclonal antibody technology to reconsider the function of antibody immunity. The next step is to develop vaccines that induce protective antibody immunity and to comprehend the mechanisms through which antibodies mediate protective effects against fungus.

Published
2023

27. Quantum mechanical investigations of base-catalyzed cycloaddition reaction between phenylacetylene and azidobenzene

Author

Sultan T. Abu-Orabi and Mohammad Abd Al-Hakim Badawi

Subjects
chemistry.chemical_classification, chemistry.chemical_compound, Phenylacetylene, chemistry, Base (chemistry), Polymer chemistry, General Chemistry, Azidobenzene, Cycloaddition, Catalysis
Abstract

In this study, the mechanism for both the Huisgen 1,3-dipolar cycloaddition and the base-catalyzed cycloaddition reactions between phenylacetylene and azidobenzene has been investigated with density functional theory, namely at the M06-2X/6-31G(d) computational level. Later, the reaction has been modeled with a representative simple alkyne and a simple azide to concentrate solely on how the difference bases affect the mechanism of the reaction between phenylacetylene and azidobenzene as charged components. In this study, another mechanism of this reaction with uncharged components has been proposed to compare the calculated thermodynamic and kinetic properties for charged and uncharged systems. The calculated activation barrier differences between the catalyzed and the uncatalyzed reactions are consistent with the faster and the regioselective synthesis of the triazole product in the presence of solvents. The calculated barrier of the rate-determining step in the base-catalyzed mechanism with the uncharged system is lower than that with charged systems. Finally, the reaction leading to final product formation in uncharged system is more spontaneous than that in the charged system, and the same applies to the total reaction in the presence of solvents.

Published
2020

28. Inhibition of G-protein signalling in cardiac dysfunction of intellectual developmental disorder with cardiac arrhythmia (IDDCA) syndrome

Author

De Nittis P., Efthymiou S., Sarre A., Guex N., Chrast J., Putoux A., Sultan T., Raza Alvi J., Ur Rahman Z., Zafar F., Rana N., Rahman F., Anwar N., Maqbool S., Zaki M. S., Gleeson J. G., Murphy D., Galehdari H., Shariati G., Mazaheri N., Sedaghat A., Lesca G., Chatron N., Salpietro V., Christoforou M., Houlden H., Simonds W. F., Pedrazzini T., Maroofian R., Reymond A., SYNAPS STUDY GROUP: SYNAPS Study Group: Stanislav Groppa, Blagovesta Marinova Karashova, Wolfgang Nachbauer, Sylvia Boesch, Larissa Arning, Dagmar Timmann, Bru Cormand, Belen Pérez-Dueñas, Jatinder S Goraya, Tipu Sultan, Jun Mine, Daniela Avdjieva, Hadil Kathom, Radka Tincheva, Selina Banu, Mercedes Pineda-Marfa, Pierangelo Veggiotti, Michel D. Ferrari, Arn M. J. M. van den Maagdenberg, Alberto Verrotti, Giangluigi Marseglia, Salvatore Savasta, Mayte García-Silva, Alfons Macaya Ruiz, Barbara Garavaglia, Eugenia Borgione, Simona Portaro, Benigno Monteagudo Sanchez, Richard Boles, Savvas Papacostas, Michail Vikelis, Eleni Zamba Papanicolaou, Efthymios Dardiotis, Shazia Maqbool, Shahnaz Ibrahim, Salman Kirmani, Nuzhat Noureen Rana, Osama Atawneh, George Koutsis, Salvatore Mangano, Carmela Scuderi, Giovanna Morello, Tanya Stojkovic, Massimo Zollo, Gali Heimer, Yves A. Dauvilliers, Pasquale Striano, Issam Al-Khawaja, Fuad Al-Mutairi, Hamed Sherifa., University of Lausanne (UNIL), University College of London [London] (UCL), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Children's Hospital [Lahore], Institute of Child Health [Lahore], Children's Hospital [Multan], Institute of Child Health [Multan], National Research Centre - NRC (EGYPT), Howard Hughes Medical Institute (HHMI), Shahid Chamran University of Ahvaz (SCU), Ahvaz Jundishapur University of Medical Sciences (AJUMS), National Institutes of Health [Bethesda] (NIH), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lausanne = University of Lausanne (UNIL), Herrada, Anthony, P., De Nitti, S., Efthymiou, A., Sarre, N., Guex, J., Chrast, A., Putoux, T., Sultan, J., Raza Alvi, Z., Ur Rahman, F., Zafar, N., Rana, F., Rahman, N., Anwar, S., Maqbool, M. S., Zaki, J. G., Gleeson, D., Murphy, H., Galehdari, G., Shariati, N., Mazaheri, A., Sedaghat, G., Lesca, N., Chatron, V., Salpietro, M., Christoforou, H., Houlden, W. F., Simond, T., Pedrazzini, R., Maroofian, A., Reymond, STUDY GROUP: SYNAPS Study Group: Stanislav Groppa, Synap, Marinova Karashova, Blagovesta, Nachbauer, Wolfgang, Boesch, Sylvia, Arning, Larissa, Timmann, Dagmar, Cormand, Bru, Pérez-Dueñas, Belen, S Goraya, Jatinder, Sultan, Tipu, Mine, Jun, Avdjieva, Daniela, Kathom, Hadil, Tincheva, Radka, Banu, Selina, Pineda-Marfa, Mercede, Veggiotti, Pierangelo, Ferrari, Michel D., van den Maagdenberg, Arn M. J. M., Verrotti, Alberto, Marseglia, Giangluigi, Savasta, Salvatore, García-Silva, Mayte, Macaya Ruiz, Alfon, Garavaglia, Barbara, Borgione, Eugenia, Portaro, Simona, Monteagudo Sanchez, Benigno, Boles, Richard, Papacostas, Savva, Vikelis, Michail, Zamba Papanicolaou, Eleni, Dardiotis, Efthymio, Maqbool, Shazia, Ibrahim, Shahnaz, Kirmani, Salman, Noureen Rana, Nuzhat, Atawneh, Osama, Koutsis, George, Mangano, Salvatore, Scuderi, Carmela, Morello, Giovanna, Stojkovic, Tanya, Zollo, Massimo, Heimer, Gali, Dauvilliers, Yves A., Striano, Pasquale, Al-Khawaja, Issam, Al-Mutairi, Fuad, and Sherifa., Hamed

Subjects
Male, 0301 basic medicine, Developmental Disabilities, Batecs cardíacs, 0302 clinical medicine, Neurodevelopmental disorder, Heart Rate, Medicine, Child, Genetics (clinical), Mice, Knockout, Gnb5-null mouse models, GTP-Binding Protein beta Subunits, Cardiac muscle, Heart, Syndrome, IDDCA, Functional Genomics, Pedigree, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, cardiac conduction anomalies, Gnb5 -null mouse models, GNB5 variants, medicine.anatomical_structure, Child, Preschool, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, medicine.symptom, Signal Transduction, Bradycardia, Cardiac function curve, Gnb5 -null mouse model, medicine.medical_specialty, Adolescent, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Contractility, Young Adult, Brain damage, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, GNB5variants, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Internal medicine, Exome Sequencing, Heart rate, Genetics, Animals, Humans, business.industry, Gene Expression Profiling, Heart beat, Proteins, Cardiac arrhythmia, Arrhythmias, Cardiac, GNB5 variant, medicine.disease, Mice, Inbred C57BL, Autonomic nervous system, 030104 developmental biology, Endocrinology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, Lesions cerebrals, cardiac conduction anomalie, business, Proteïnes, 030217 neurology & neurosurgery
Abstract

BackgroundPathogenic variants of GNB5 encoding the β5 subunit of the guanine nucleotide-binding protein cause IDDCA syndrome, an autosomal recessive neurodevelopmental disorder associated with cognitive disability and cardiac arrhythmia, particularly severe bradycardia.MethodsWe used echocardiography and telemetric ECG recordings to investigate consequences of Gnb5 loss in mouse.ResultsWe delineated a key role of Gnb5 in heart sinus conduction and showed that Gnb5-inhibitory signalling is essential for parasympathetic control of heart rate (HR) and maintenance of the sympathovagal balance. Gnb5−/− mice were smaller and had a smaller heart than Gnb5+/+ and Gnb5+/−, but exhibited better cardiac function. Lower autonomic nervous system modulation through diminished parasympathetic control and greater sympathetic regulation resulted in a higher baseline HR in Gnb5−/− mice. In contrast, Gnb5−/− mice exhibited profound bradycardia on treatment with carbachol, while sympathetic modulation of the cardiac stimulation was not altered. Concordantly, transcriptome study pinpointed altered expression of genes involved in cardiac muscle contractility in atria and ventricles of knocked-out mice. Homozygous Gnb5 loss resulted in significantly higher frequencies of sinus arrhythmias. Moreover, we described 13 affected individuals, increasing the IDDCA cohort to 44 patients.ConclusionsOur data demonstrate that loss of negative regulation of the inhibitory G-protein signalling causes HR perturbations in Gnb5−/− mice, an effect mainly driven by impaired parasympathetic activity. We anticipate that unravelling the mechanism of Gnb5 signalling in the autonomic control of the heart will pave the way for future drug screening.

Published
2020

30. Physiological and biochemical parameters among a population of bakers exposed to environmental heat

Author

Sultan T Al-Otaibi

Subjects
Cross-Sectional Studies, Hot Temperature, Occupational Exposure, Public Health, Environmental and Occupational Health, Humans, General Medicine, Heat Stress Disorders, Workplace
Abstract

The aim of this study was to determine the physiological and biochemical changes among bakers, induced by heat exposure at the workplace.Information was collected by means of a self-administered questionnaire. Vital signs were measured and recorded by a trained nurse before and after each work shift. A venous blood sample was drawn at the end of each work shift. The mean wet-bulb globe temperature (WBGT) index in the bakeries and offices was measured.This was a cross-sectional study involving 137 bakers working in 20 bakeries, and 107 control subjects comparable in terms of age, race, marital status, years of service, income, and cigarette smoking. There was a significant weight loss and increase in the respiratory rate, the heart rate, and oral body temperature among the bakers compared to the control group. Sodium levels were significantly lower, while blood urea nitrogen levels were significantly higher, among the bakers than in the control group. There were unfavorably hot working conditions in the bakeries: the WBGT index in the bakeries was 37.4°C while the average WBGT for the offices was 25.5°C.The changes in the physiological and biochemical parameters among the bakers were found to be associated with exposure to high environmental heat in the bakeries, as judged by the WBGT index. Preventive measures should be aimed at reducing the adverse effects of heat exposure among bakers and should be directed towards the man-machine-environment triad. Int J Occup Med Environ Health. 2022;35(3):265-72.

Published
2022

31. Hematological parameters in a population of male bakers exposed to high heat work environment

Author

Sultan T. Al-Otaibi

Subjects
Male, Multidisciplinary, Cross-Sectional Studies, Hot Temperature, Occupational Exposure, Humans, Humidity, Heat Stress Disorders, Workplace
Abstract

Objectives The aim of this study was to determine the hematological changes associated with heat exposure in a population of bakers. Materials and methods Personal information was collected using a questionnaire, and a venous blood sample was drawn at the end of a work shift from the bakers and from a control group. The average wet-bulb globe temperature (WBGT) index was measured in the workplaces of both the bakers and the controls. Results This cross-sectional study involved 137 bakers working in 20 bakeries and 107 controls who were comparable in terms of likely confounding factors. Hemoglobin and platelet values were abnormal among the bakers and statistically significantly different to the control group (P = 0.026, and P = 0.016 respectively). The average WBGT index in the bakeries was 37.4°C, while the average WBGT in the workplaces of the controls was 25.5°C, (P Conclusions The changes in the bakers’ hematological parameters were found to be associated with exposure to high environmental heat at bakeries, as measured by the WBGT index. Preventive measures should be introduced to reduce the adverse effect of heat exposure among bakers and directed toward the worker–equipment–environment triad.

Published
2022

32. Antioxidant activity of crude extracts and essential oils from flower buds and leaves of Cistus creticus and Cistus salviifolius

Author

Hasan Tashtoush, Sultan T. Abu-Orabi, Noura R. Saleh, Jamil N. Lahham, Tareq T. Bataineh, Hala I. Al-Jaber, Safwan M. Obeidat, Mahmoud A. Al-Qudah, and Mohammed Sharif Al-Sheraideh

Subjects
Antioxidant, General Chemical Engineering, medicine.medical_treatment, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Sclarene, lcsh:Chemistry, chemistry.chemical_compound, Antioxidant activity, medicine, Organic chemistry, chemistry.chemical_classification, PCA, biology, Butanol, General Chemistry, 021001 nanoscience & nanotechnology, biology.organism_classification, Ascorbic acid, Cistus salviifolius L, 0104 chemical sciences, Cistus creticus, Hydrocarbon, chemistry, lcsh:QD1-999, Essential oils, Cistus salviifolius, Camphene, 0210 nano-technology, Cistus creticus L
Abstract

Volatile oils from flowers and leaves of C. creticus L. and C. salviifolius L. were extracted by two extraction methods; namely, hydrodistillation and solid-phase micro-extraction (SPME). The chemical composition of essential oils was analyzed by GC and GC–MS. The volatile extracted from leaves and flowers of C. criticus using SPME was dominated by monoterpenes and sesquiterpenes hydrocarbon with α-pinene, camphene and α-cubebene as major components. In hydrodistillation, the oil extracted from leaves was dominated by oxygenated diterpenes and diterpenes hydrocarbon with manoyl oxide and sclarene as major components, whereas, the oil extracted from flowers was dominated by oxygenated diterpenes and diterpenes hydrocarbon with manoyl oxide and abietatriene as major components. The volatile from flowers and leaves of C. salviifolius obtained by SPME were dominated by monoterpenes and sesquiterpenes with δ-3-carene, α-pinene, β-pinene, and E-caryophyllene as major constituents. On the other hand, the oils from flowers and leaves of C. salviifolius obtained by hydrodistillation were dominated by oxygenated diterpenes, diterpenes hydrocarbon and esters with dehydro abietol, abietol, manoyl oxide and methyl octadecenoate as major components. In the leaves, the major components of the oil were manoyl oxide, E-ethyl cinnamate, and Z-ethyl cinnamate. These oils showed weak antioxidant activity when compared to the positive controls α-tocopherol, ascorbic acid, and EDTA, while the crude extracts aq. MeOH, butanol, and water showed good antioxidant activity. Discriminating between the studied plants based on the extraction method was also possible upon applying Principle component analysis (PCA) to the obtained GC–MS data.

Published
2020

33. Effect of Geographic Location, Ontogenesis on Essential Oil Composition and Spontaneously Emitted Volatile Organic Compounds of Inula viscosa (L.) Greuter. (Astraceae) Grown in Jordan

Author

Fatma U. Afifi, Mahmoud A. Al-Qudah, Sultan T. Abu-Orabi, Reem N. Dabibeh, Hala I. Al-Jaber, Lina M. Barhoumi, M. Abu-Zarga, Ismaeil F. Abaza, and Omar M. Bdair

Subjects
010404 medicinal & biomolecular chemistry, 010405 organic chemistry, Chemistry, Ontogeny, Botany, General Chemistry, 01 natural sciences, 0104 chemical sciences
Abstract

The present study aimed at investigating the variation in the chemical composition of emitted volatile organic compounds (VOCs) and essential oils obtained from fresh aerial parts of Inula viscosa (Asteraceae) as affected by growth stage and geographical location zone. VOCs were extracted by solid phase microextraction (SPME) method from whole aerial parts of I. viscosa during the vegetative (spring-August) period, and from fresh leaves, closed pre-flowering buds and fully expanded flowers during the full flowering season (October). The essential oils were extracted by hydrodistillation form fresh organs during the flowering stage. GC/MS analysis of VOCs during the vegetative period revealed sesquiterpene hydrocarbons as main components in the samples collected from the Mediterranean zone (MID-1: 64.72-27.48%, MID-2: 32.09-76.77%). The profile of the samples from the Irano-Turanian zone (IT) was quite different. Myrcenol was the main component in the leaves, pre-flowering buds and fully expanded flowers from all locations (0.61-39.01%). E-nerolidol was the main component in the hydrodistilled oil of all organs from the different locations (73.72-88.66 %). Principle component and cluster analysis revealed that the chemical composition of the essential oils and VOCs belonging to MID-zone were similar and quite different when compared to the composition of the samples belonging to IT-zone. The results indicated the possible use of E-nerolidole as a stable chemotype marker in I. viscosa taxonomy.

Published
2020

34. Aryl ferrocenylmethylesters: Synthesis, solid-state structure and electrochemical investigations

Author

Khaled Al Khalyfeh, Marcus Korb, Rasha K. Al-Shewiki, Sultan T. Abu-Orabi, Naim H. Al-Said, Heinrich Lang, Saddam Weheabby, Firas F. Awwadi, Wissam Helal, Asma Ghazzy, and Deeb Taher

Subjects
Chemistry, Supporting electrolyte, General Chemical Engineering, Aryl, Infrared spectroscopy, 02 engineering and technology, General Chemistry, 010402 general chemistry, 021001 nanoscience & nanotechnology, Electrochemistry, 01 natural sciences, Redox, 0104 chemical sciences, lcsh:Chemistry, chemistry.chemical_compound, Crystallography, lcsh:QD1-999, Ferrocene, 0210 nano-technology, Single crystal, HOMO/LUMO
Abstract

The reaction of [Fe(η5-C5H4CH2OH)2] (1) with 2 equiv of ClC(O)R (2) (a, R = C6H5; b, R = 2-CH3-C6H4; c, R = 3-CH3-C6H4, d, R = 4-CH3-C6H4) produced the corresponding ferrocenyl carboxylates [Fe(η5-C5H4CH2OC(O)R)2] (3a–d). Treatment of [FcCH2OLi] (4-Li) (Fc = Fe(η5-C5H5)(η5-C5H4)) with (ClC(O))2C6H4 (5) (a, 1,2-((ClC(O))2-C6H4; b, 1,3-((ClC(O))2-C6H4; c, 1,4-((ClC(O))2-C6H4) in a 2:1 M ratio gave (FcCH2OC(O))2-C6H4 (6a–c), while with 1,3,5-(ClC(O))3-C6H3 (7) in a 3:1 M ratio produced 1,3,5-(FcCH2OC(O))3-C6H3 (8). All compounds were characterized by NMR (1H, 13C{1H}) and IR spectroscopy, ESI-TOF mass spectrometry and elemental analysis. The molecular structures of 3a–d and 6b in the solid state were determined by single crystal X-ray structure analysis, showing anti-periplanar orientations of the 1,1′-positioned substituents at ferrocene (3a–d). In the cyclic voltammograms of 3a–d, 6a–d and 8 reversible electrochemical redox processes (Fc/Fc+) were observed, ranging between 146 and 164 mV for 3a–d, ca. 100 mV for 6a–d and at 113 mV for 8 using [NnBu4][B(C6F5)4] as the supporting electrolyte. The molecular electronic structure of 3, 6 and 8 was calculated by DFT methods in order to obtain the HOMO and LUMO absolute and relative energies in addition to electron density and distribution within the molecular arrangements. It was found that different degrees of HOMO-LUMO energy gaps within the series, due to a lowering in the LUMO energy depending on the positions of the carboxylic ester substituents on the aryl rings, are in agreement with the electrochemical results obtained. Keywords: Ferrocenylmethyl, Mono-dicarboxy benzene, Trimesic acid, Solid state structure, Electrochemistry, DFT

Published
2020

35. 1,2,3-Triazole derivatives as highly selective cannabinoid receptor type 2 (CB2) agonists

Author

Stephen J. Cutler, Robert J. Doerksen, Anastassiya V. Gadetskaya, Amer H. Tarawneh, Lo’ay Al-Momani, Sultan T. Abu-Orabi, and Pankaj Pandey

Subjects
Cannabinoid receptor, biology, Molecular model, Chemistry, General Chemical Engineering, Active site, General Chemistry, Docking, Biochemistry, Opioid, Radioligand binding assay, biology.protein, medicine, Functional selectivity, Cannabinoid receptor type 2, lipids (amino acids, peptides, and proteins), Receptor binding, Triazole, Receptor, Cannabinoid receptors, QD1-999, medicine.drug, G protein-coupled receptor
Abstract

The cannabinoid receptor 2 (CB2 receptor) has attracted considerable interest, mainly due to its potential as a target for therapeutics for treating various diseases that have a neuroinflammatory or neurodegenerative component while avoiding the adverse psychotropic effects that accompany CB1 receptor-based therapies. With the appreciation that CB2-selective ligands show marked functional selectivity, there is a renewed opportunity to explore this promising area of research from both a mechanistic as well as a therapeutic perspective. In this research, we are interested in the discovery of new chemotypes as highly selective CB2 modulators, which may serve as good starting points for further optimization towards the development of CB2 therapeutics. In search of new chemotypes as CB2 selective agents, we screened a series of triazole derivatives with interesting bioactive scaffolds, which led to the discovery of two novel and highly selective ligands for CB2 receptors. Compounds 6 and 11 produced a concentration-dependent inhibition of specific [3H]-CP55,940 (CB2) binding with Ki ± SEM values of 105.3 ± 22.6 and 116.4 ± 19.5 nM, respectively, while no binding affinity towards CB1 receptors or opioid receptors was observed. The CB2 functional activity of 6 and 11, as measured by a GPCR Tango assay (G-protein independent β-arrestin translocation assay), revealed that these compounds act as CB2 agonists with EC50 values ± SEM of 1.83 ± 0.16 and 1.14 ± 0.52 µM, respectively. Molecular modeling results showed that both compounds fit well into the active site of the CB2 receptor and showed strong hydrophobic interactions with key residues. In conclusion, the new triazole derivatives (6 and 11) showed promising activity towards CB2 receptors and have great potential to be developed into therapeutically useful CB2 agonists through hit-to-lead optimization.

Published
2022

36. Biallelic variants in PCDHGC4 cause a novel neurodevelopmental syndrome with progressive microcephaly, seizures, and joint anomalies

Author

Iqbal, M, Maroofian, R, Çavdarlı, B, Riccardi, F, Field, M, Banka, S, Bubshait, DK, Li, Y, Hertecant, J, Baig, SM, Dyment, D, Efthymiou, S, Abdullah, U, Makhdoom, EUH, Ali, Z, Scherf de Almeida, T, Molinari, F, Mignon-Ravix, C, Chabrol, B, Antony, J, Ades, L, Pagnamenta, AT, Jackson, A, Douzgou, S, Genomics England Research Consortium, Beetz, C, Karageorgou, V, Vona, B, Rad, A, Baig, JM, Sultan, T, Alvi, JR, Maqbool, S, Rahman, F, Toosi, MB, Ashrafzadeh, F, Imannezhad, S, Karimiani, EG, Sarwar, Y, Khan, S, Jameel, M, Noegel, AA, Budde, B, Altmüller, J, Motameny, S, Höhne, W, Houlden, H, Nürnberg, P, Wollnik, B, Villard, L, Alkuraya, FS, Osmond, M, Hussain, MS, and Yigit, G

Abstract

PURPOSE: We aimed to define a novel autosomal recessive neurodevelopmental disorder, characterize its clinical features, and identify the underlying genetic cause for this condition. METHODS: We performed a detailed clinical characterization of 19 individuals from nine unrelated, consanguineous families with a neurodevelopmental disorder. We used genome/exome sequencing approaches, linkage and cosegregation analyses to identify disease-causing variants, and we performed three-dimensional molecular in silico analysis to predict causality of variants where applicable. RESULTS: In all affected individuals who presented with a neurodevelopmental syndrome with progressive microcephaly, seizures, and intellectual disability we identified biallelic disease-causing variants in Protocadherin-gamma-C4 (PCDHGC4). Five variants were predicted to induce premature protein truncation leading to a loss of PCDHGC4 function. The three detected missense variants were located in extracellular cadherin (EC) domains EC5 and EC6 of PCDHGC4, and in silico analysis of the affected residues showed that two of these substitutions were predicted to influence the Ca2+-binding affinity, which is essential for multimerization of the protein, whereas the third missense variant directly influenced the cis-dimerization interface of PCDHGC4. CONCLUSION: We show that biallelic variants in PCDHGC4 are causing a novel autosomal recessive neurodevelopmental disorder and link PCDHGC4 as a member of the clustered PCDH family to a Mendelian disorder in humans.

Published
2021

37. Knowledge, attitude, and awareness regarding dental implants in a Saudi subpopulation

Author

Sultan T. Alshammari, Badreyah M. Alwajaan, Saad A. Alshammari, Ahmed A. Madfa, and Ahmed H. Albaqawi

Subjects
Automotive Engineering
Abstract

Background: The aim of the present study evaluated and elevated the knowledge, attitude and awareness of people life in Hail region to dental implants as option of treatment to replace the missing teeth.Methods: The present study was conducted in dental clinics in Hail region. Study sample was consisted of total 428 individuals. Individuals, who were meted the determined inclusion criteria in this study, will be selected for answer the structured questioners. Chi-square test to determine the significant differences of the study parametersResults: Among of participants, females were 161 (37.6%) and males were 267 (62.4%) of the participants. The subjects that heard about dental implants from internet was 126 (29.4%). Majority of the subjects 207 (48.4.2%) had a friend treated with an implant. Around 326 (76.2%) responders want to learn more about implants. Most of subjects 206 (48.1%) thought that dental implant require 6 months from the first examination until your prosthesis is finished. About of 148 (34.60) believed that survival rate will be life. Around 326 (76.2%) responders wished to get dental implants inserted from a specialist. Majority of the responders 281 (65.7%) thought implants required superior cleanliness and care and that it cannot be cleansed like natural dentition.Conclusions: Patients have little information and awareness regarding dental implants.

Published
2022

40. Factors associated with needlestick injuries among healthcare workers: implications for prevention

Author

Hatem A Alqahtani, Sultan T Al-Otaibi, and Kifah Habib Alfulayw

Subjects
medicine.medical_specialty, Health-care workers, Health Personnel, Health informatics, Health administration, Physicians, Health care, medicine, Training, Humans, Needlestick Injuries, Retrospective Studies, business.industry, Health Policy, Nursing research, Public health, Incidence (epidemiology), Research, Incidence, Retrospective cohort study, Needle stick injury, Hepatitis b vaccination, Family medicine, Public aspects of medicine, RA1-1270, business
Abstract

Background Our study sought to determine the frequency of Needlestick injuries (NSIs) among Healthcare Workers (HCWs) working at governmental hospital and to study the factors that associated with occurrence of NSIs, and to develop recommendations for a comprehensive program for prevention. Methods Retrospective study of all reported cases of NSIs in the period from April 2016 to May 2018 among healthcare workers at a governmental hospital. Results Incidence of NSIs over 26 months was 8.4% among all participants. Nurses were the most affected staff (52.5%) resulted commonly from disposing syringes (58.9%). In contrast, the incidence of NSIs among physicians was 24.9% where surgical devices were the primary source of NSIs among them (40%). Failure to complete all required hepatitis B vaccination was common among expatriates of the participants of this study. Conclusions NSIs was common among HCWs participated in this study. Preventive measures should be implemented including adequate hepatitis B immunization.

Published
2021

41. Refractory Salmonella Prosthetic Valve Endocarditis Complicated by Splenic Infarction and Aortic Pseudoaneurysm in a Patient with Double Prosthetic Valves: A Case Report

Author

Moustafa S. Alhamadh, Rakan B. Alanazi, Thamer Saad Alhowaish, Abdulrahman Yousef Alhabeeb, Sultan T. Algarni, Osama Mohaamad Wadaan, Ihab Suliman, and Mohammed Ghormalla Al-Ghamdi

Subjects
Clinical Biochemistry
Abstract

Endocarditis is an extremely rare complication of Salmonellosis with an incidence of 0.2–0.4%. It is a destructive and invasive infection that follows a highly complicated course and carries a high mortality rate that exceeds 45%. Multiple predisposing factors for Salmonella endocarditis have been described in the literature, including human immunodeficiency virus infection, congenital heart diseases, and the presence of a prosthetic valve. Herein, we report a case of Salmonella prosthetic valve endocarditis complicated by splenic infarction and aortic pseudoaneurysm presenting as a month-long history of fluctuating fever, chills, and rigors, accompanied by occasional cough and shortness of breath in a 55-year-old female with aortic and mitral valves replacement and multiple comorbidities. She was diagnosed by multiple radiographic studies and successfully treated with the Commando procedure and a long course of IV antibiotics.

Published
2022

42. Biallelic mutations in neurofascin cause neurodevelopmental impairment and peripheral demyelination

Author

Efthymiou, S., Salpietro, V., Malintan, N., Poncelet, M., Kriouile, Y., Fortuna, S., Zorzi, R. de, Payne, K., Henderson, L.B., Cortese, A., Maddirevula, S., Alhashmi, N., Wiethoff, S., Ryten, M., Botia, J.A., Provitera, V., Schuelke, M., Vandrovcova, J., Groppa, S., Karashova, B.M., Nachbauer, W., Boesch, S., Arning, L., Timmann, D., Cormand, B., Perez-Duenas, B., Goraya, J.S., Sultan, T., Mine, J., Avdjieva, D., Kathom, H., Tincheva, R., Banu, S., Pineda-Marfa, M., Veggiotti, P., Ferrari, M.D., Maagdenberg, A.M.J.M. van den, Verrotti, A., Marseglia, G., Savasta, S., Garcia-Silva, M., Ruiz, A.M., Garavaglia, B., Borgione, E., Portaro, S., Sanchez, B.M., Boles, R., Papacostas, S., Vikelis, M., Rothman, J., Kullmann, D., Papanicolaou, E.Z., Dardiotis, E., Maqbool, S., Ibrahim, S., Kirmani, S., Rana, N.N., Atawneh, O., Lim, S.Y., Shaikh, F., Koutsis, G., Breza, M., Mangano, S., Scuderi, C., Morello, G., Stojkovic, T., Zollo, M., Heimer, G., Dauvilliers, Y.A., Minetti, C., Al-Khawaja, I., Al-Mutairi, F., Hamed, S., Pipis, M., Bettencourt, C., Rinaldi, S., Walsh, L., Torti, E., Iodice, V., Najafi, M., Karimiani, E.G., Maroofian, R., Siquier-Pernet, K., Boddaert, N., Lonlay, P. de, Cantagrel, V., Aguennouz, M., Khorassani, M. el, Schmidts, M., Alkuraya, F.S., Edvardson, S., Nolano, M., Devaux, J., Houlden, H., SYNAPS Study Grp, Efthymiou, S., Salpietro, V., Malintan, N., Poncelet, M., Kriouile, Y., Fortuna, S., De Zorzi, R., Payne, K., Henderson, L. B., Cortese, A., Maddirevula, S., Alhashmi, N., Wiethoff, S., Ryten, M., Botia, J. A., Provitera, V., Schuelke, M., Vandrovcova, J., Walsh, L., Torti, E., Iodice, V., Najafi, M., Karimiani, E. G., Maroofian, R., Siquier-Pernet, K., Boddaert, N., De Lonlay, P., Cantagrel, V., Aguennouz, M., El Khorassani, M., Schmidts, M., Alkuraya, F. S., Edvardson, S., Nolano, M., Devaux, J., Houlden, H., Groppa, S., Karashova, B. M., Nachbauer, W., Boesch, S., Arning, L., Timmann, D., Cormand, B., Perez-Duenas, B., Goraya, J. S., Sultan, T., Mine, J., Avdjieva, D., Kathom, H., Tincheva, R., Banu, S., Pineda-Marfa, M., Veggiotti, P., Ferrari, M. D., Van Den Maagdenberg, A. M. J. M., Verrotti, A., Marseglia, G., Savasta, S., Garcia-Silva, M., Ruiz, A. M., Garavaglia, B., Borgione, E., Portaro, S., Sanchez, B. M., Boles, R., Papacostas, S., Vikelis, M., Rothman, J., Kullmann, D., Papanicolaou, E. Z., Dardiotis, E., Maqbool, S., Ibrahim, S., Kirmani, S., Rana, N. N., Atawneh, O., Lim, S. -Y., Shaikh, F., Koutsis, G., Breza, M., Mangano, S., Scuderi, C., Morello, G., Stojkovic, T., Zollo, M., Heimer, G., Dauvilliers, Y. A., Minetti, C., Al-Khawaja, I., Al-Mutairi, F., Hamed, S., Pipis, M., Bettencourt, C., Rinaldi, S., Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Laboratory of Molecular Biophysics, Department of Biochemistry, Department of Biochemistry, Hertie Institute for Clinical Brain Research and Center for Neurology, University of Tübingen, Department of Medical and Molecular Genetics, King‘s College London, Department of Human Genetics, Ruhr University Bochum (RUB), Universitat de Barcelona (UB), Fondazione, Leiden University Medical Center (LUMC), Department of Physiology and Cellular Biophysics [New York, NY, USA], Columbia University College of Physicians and Surgeons, Department of Microbiology, Università degli studi di Catania [Catania], Institut de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ceinge, centro di Ingegneria Genetica e Biotecnologie Avanzate, Unité des troubles du sommeil, Centre de référence national sur les maladies rares (narcolepsie, hypersomnie idiopathique, syndrome de Kleine-Levin)-Hôpital Gui-de-Chauliac, Muscular and Neurodegenerative Disease Unit, University of Genoa (UNIGE), Department of Molecular Neuroscience, University College of London [London] (UCL)-Institute of Neurology, Indiana University, Indiana University [Bloomington], Indiana University System-Indiana University System, Molecular and Clinical Sciences Institute - St George’s [London, UK] (Genetics Research Centre), University of London [London], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neuroimagerie en psychiatrie (U1000), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service métabolisme, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-CHU Necker - Enfants Malades [AP-HP], Department of Genetics and Metabolic Diseases and the Monique and Jacques Roboh Department of Genetic Research, Hadassah Hebrew University Medical Center [Jerusalem], Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Efthymiou S., Salpietro V., Malintan N., Poncelet M., Kriouile Y., Fortuna S., De Zorzi R., Payne K., Henderson L.B., Cortese A., Maddirevula S., Alhashmi N., Wiethoff S., Ryten M., Botia J.A., Provitera V., Schuelke M., Vandrovcova J., Walsh L., Torti E., Iodice V., Najafi M., Karimiani E.G., Maroofian R., Siquier-Pernet K., Boddaert N., De Lonlay P., Cantagrel V., Aguennouz M., El Khorassani M., Schmidts M., Alkuraya F.S., Edvardson S., Nolano M., Devaux J., Houlden H., Groppa S., Karashova B.M., Nachbauer W., Boesch S., Arning L., Timmann D., Cormand B., Perez-Duenas B., Goraya J.S., Sultan T., Mine J., Avdjieva D., Kathom H., Tincheva R., Banu S., Pineda-Marfa M., Veggiotti P., Ferrari M.D., Van Den Maagdenberg A.M.J.M., Verrotti A., Marseglia G., Savasta S., Garcia-Silva M., Ruiz A.M., Garavaglia B., Borgione E., Portaro S., Sanchez B.M., Boles R., Papacostas S., Vikelis M., Rothman J., Kullmann D., Papanicolaou E.Z., Dardiotis E., Maqbool S., Ibrahim S., Kirmani S., Rana N.N., Atawneh O., Lim S.-Y., Shaikh F., Koutsis G., Breza M., Mangano S., Scuderi C., Morello G., Stojkovic T., Zollo M., Heimer G., Dauvilliers Y.A., Minetti C., Al-Khawaja I., Al-Mutairi F., Hamed S., Pipis M., Bettencourt C., Rinaldi S., Efthymiou, Stephanie, Salpietro, Vincenzo, Malintan, Nancy, Poncelet, Mallory, Kriouile, Yamna, Fortuna, Sara, De Zorzi, Rita, Payne, Katelyn, Henderson, Lindsay B, Cortese, Andrea, Maddirevula, Sateesh, Alhashmi, Nadia, Wiethoff, Sarah, Ryten, Mina, Botia, Juan A, Provitera, Vincenzo, Schuelke, Marku, Vandrovcova, Jana, Walsh, Laurence, Torti, Erin, Iodice, Valeria, Najafi, Maryam, Karimiani, Ehsan Ghayoor, Maroofian, Reza, Siquier-Pernet, Karine, Boddaert, Nathalie, De Lonlay, Pascale, Cantagrel, Vincent, Aguennouz, Mhammed, El Khorassani, Mohamed, Schmidts, Miriam, Alkuraya, Fowzan S, Edvardson, Simon, Nolano, Maria, Devaux, Jérôme, Houlden, Henry, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-CHU Necker - Enfants Malades [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11)

Subjects
Male, [SDV]Life Sciences [q-bio], [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Nerve Fibers, Myelinated, Gene Frequency, Neurodevelopmental Disorder, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Nerve Growth Factor, Protein Isoforms, Child, ComputingMilieux_MISCELLANEOUS, Myelin Sheath, neurofascin, neurodevelopment, peripheral demyelination, Allele, Demyelinating Disease, Genomics, neurodevelopment, neurofascin, peripheral demyelination, Settore MED/39 - Neuropsichiatria Infantile, Pedigree, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, Child, Preschool, Peripheral Nerve, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, Neuroglia, Human, Adult, Adolescent, Nervous System Malformations, Guillain-Barre Syndrome, Axon, Nervous System Malformation, Ranvier's Nodes, Humans, Nerve Growth Factors, Peripheral Nerves, Alleles, Autoantibodies, Infant, Protein Isoform, Original Articles, Axons, nervous system, Neurodevelopmental Disorders, Cell Adhesion Molecule, Mutation, Cell Adhesion Molecules, Demyelinating Diseases
Abstract

See Karakaya and Wirth (doi:10.1093/brain/awz273) for a scientific commentary on this article. Neurofascin (NFASC) isoforms are immunoglobulin cell adhesion molecules involved in node of Ranvier assembly. Efthymiou et al. identify biallelic NFASC variants in ten unrelated patients with a neurodevelopmental disorder characterized by variable degrees of central and peripheral involvement. Abnormal expression of Nfasc155 is accompanied by severe loss of myelinated fibres., Axon pathfinding and synapse formation are essential processes for nervous system development and function. The assembly of myelinated fibres and nodes of Ranvier is mediated by a number of cell adhesion molecules of the immunoglobulin superfamily including neurofascin, encoded by the NFASC gene, and its alternative isoforms Nfasc186 and Nfasc140 (located in the axonal membrane at the node of Ranvier) and Nfasc155 (a glial component of the paranodal axoglial junction). We identified 10 individuals from six unrelated families, exhibiting a neurodevelopmental disorder characterized with a spectrum of central (intellectual disability, developmental delay, motor impairment, speech difficulties) and peripheral (early onset demyelinating neuropathy) neurological involvement, who were found by exome or genome sequencing to carry one frameshift and four different homozygous non-synonymous variants in NFASC. Expression studies using immunostaining-based techniques identified absent expression of the Nfasc155 isoform as a consequence of the frameshift variant and a significant reduction of expression was also observed in association with two non-synonymous variants affecting the fibronectin type III domain. Cell aggregation studies revealed a severely impaired Nfasc155-CNTN1/CASPR1 complex interaction as a result of the identified variants. Immunofluorescence staining of myelinated fibres from two affected individuals showed a severe loss of myelinated fibres and abnormalities in the paranodal junction morphology. Our results establish that recessive variants affecting the Nfasc155 isoform can affect the formation of paranodal axoglial junctions at the nodes of Ranvier. The genetic disease caused by biallelic NFASC variants includes neurodevelopmental impairment and a spectrum of central and peripheral demyelination as part of its core clinical phenotype. Our findings support possible overlapping molecular mechanisms of paranodal damage at peripheral nerves in both the immune-mediated and the genetic disease, but the observation of prominent central neurological involvement in NFASC biallelic variant carriers highlights the importance of this gene in human brain development and function.

Published
2019

43. Early-infantile onset epilepsy and developmental delay caused by bi-allelic GAD1 variants

Author

Neuray, C., Maroofian, R., Scala, M., Sultan, T., Pai, G. S., Mojarrad, M., Khashab, H. E., Deholl, L., Yue, W., Alsaif, H. S., Zanetti, M. N., Bello, O., Person, R., Eslahi, A., Khazaei, Z., Feizabadi, M. H., Efthymiou, S., El-Bassyouni, H. T., Soliman, D. R., Tekes, S., Ozer, L., Baltaci, V., Khan, S., Beetz, C., Amr, K. S., Salpietro, V., Jamshidi, Y., Alkuraya, F. S., Houlden, H., Groppa, S., Karashova, B. M., Nachbauer, W., Boesch, S., Arning, L., Timmann, D., Cormand, B., Perez-Duenas, B., Synaps, Group, Di Rosa, G., Aguennouz, M., Goraya, J. S., Mine, J., Avdjieva, D., Kathom, H., Tincheva, R., Banu, S., Pineda-Marfa, M., Veggiotti, P., Ferrari, M. D., Verrotti, A., Marseglia, G., Savasta, S., Garcia-Silva, M., Ruiz, A. M., Garavaglia, B., Borgione, E., Portaro, S., Sanchez, B. M., Boles, R., Papacostas, S., Vikelis, M., Papanicolaou, E. Z., Dardiotis, E., Maqbool, S., Ibrahim, S., Kirmani, S., Rana, N. N., Atawneh, O., Koutsis, G., Breza, M., Mangano, S., Scuderi, C., Morello, G., Stojkovic, T., Zollo, M., Heimer, G., Dauvilliers, Y. A., Striano, P., Al-Khawaja, I., Al-Mutairi, F., Sherifa, H., Neuray C., Maroofian R., Scala M., Sultan T., Pai G.S., Mojarrad M., Khashab H.E., deHoll L., Yue W., Alsaif H.S., Zanetti M.N., Bello O., Person R., Eslahi A., Khazaei Z., Feizabadi M.H., Efthymiou S., El-Bassyouni H.T., Soliman D.R., Tekes S., Ozer L., Baltaci V., Khan S., Beetz C., Amr K.S., Salpietro V., Jamshidi Y., Alkuraya F.S., Houlden H., Mangano S., Dicle Üniversitesi, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü, Tıbbi Biyoloji Ana Bilim Dalı, Tekeş, Selahattin, University College of London [London] (UCL), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), University of Genoa (UNIGE), IRCCS Istituto Giannina Gaslini [Genoa, Italy], Children's Hospital [Lahore], Institute of Child Health [Lahore], Medical University of South Carolina [Charleston] (MUSC), Mashhad University of Medical Sciences, Ain Shams University (ASU), University of Oxford [Oxford], GeneDx [Gaithersburg, MD, USA], Khorasan Razavi Agricultural and Natural Resources Research and Education Center, National Research Centre [Cairo, Egypt], Benha University (BU), Dicle University, CENTOGENE AG, University of London [London], King Faisal Specialist Hospital [Riyadh, Saudi Arabia] (Research Centre), and SYNaPS Study Group: Stanislav Groppa, Blagovesta Marinova Karashova, Wolfgang Nachbauer, Sylvia Boesch, Larissa Arning, Dagmar Timmann, Bru Cormand, Belen Pérez-Dueñas, Gabriella Di Rosa, Jatinder S Goraya, Tipu Sultan, Jun Mine, Daniela Avdjieva, Hadil Kathom, Radka Tincheva, Selina Banu, Mercedes Pineda-Marfa, Pierangelo Veggiotti, Michel D Ferrari, Alberto Verrotti, Giangluigi Marseglia, Salvatore Savasta, Mayte García-Silva, Alfons Macaya Ruiz, Barbara Garavaglia, Eugenia Borgione, Simona Portaro, Benigno Monteagudo Sanchez, Richard Boles, Savvas Papacostas, Michail Vikelis, Eleni Zamba Papanicolaou, Efthymios Dardiotis, Shazia Maqbool, Shahnaz Ibrahim, Salman Kirmani, Nuzhat Noureen Rana, Osama Atawneh, George Koutsis, Marianthi Breza, Salvatore Mangano, Carmela Scuderi, Eugenia Borgione, Giovanna Morello, Tanya Stojkovic, Massimi Zollo, Gali Heimer, Yves A Dauvilliers, Pasquale Striano, Issam Al-Khawaja, Fuad Al-Mutairi, Hamed Sherifa

Subjects
Male, 0301 basic medicine, Glutamate decarboxylase, Malalties cerebrals, Neurotransmissors, Neurodevelopmental delay, Epilepsy, 0302 clinical medicine, MESH: Child, Age of Onset, Child, cleft palate, GAD1, AcademicSubjects/SCI01870, Glutamate Decarboxylase, Glutamate receptor, Muscle weakness, purl.org/becyt/ford/3.1 [https], Neurotransmitters, MESH: Infant, Hypotonia, muscle weakne, Cleft palate, MESH: Epilepsy, Child, Preschool, Muscle Hypotonia, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], purl.org/becyt/ford/3 [https], Female, Brain diseases, Abnormalities, medicine.symptom, Multiple, medicine.drug, epilepsy, muscle weakness, neurodevelopmental delay, MESH: Glutamate Decarboxylase, medicine.medical_specialty, MESH: Abnormalities, Multiple, MESH: Mutation, MESH: Age of Onset, Biology, Inhibitory postsynaptic potential, GAD1, cleft palate, epilepsy, muscle weakness, neurodevelopmental delay, gamma-Aminobutyric acid, 03 medical and health sciences, Excitatory synapse, Internal medicine, medicine, Humans, Abnormalities, Multiple, Preschool, Alleles, MESH: Neurodevelopmental Disorders, MESH: Humans, MESH: Muscle Hypotonia, MESH: Alleles, MESH: Child, Preschool, Infant, medicine.disease, MESH: Male, Epilèpsia, Editor's Choice, 030104 developmental biology, Endocrinology, Neurodevelopmental Disorders, Mutation, AcademicSubjects/MED00310, Neurology (clinical), MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery, Reports
Abstract

Mice lacking GAD1 show neonatal mortality, but the human phenotype associated with GAD1 disruption is poorly characterized. Neuray et al. describe six patients with biallelic GAD1 mutations, presenting with early-infantile onset epilepsy, neurodevelopmental delay, muscle weakness and non-CNS manifestations., Gamma-aminobutyric acid (GABA) and glutamate are the most abundant amino acid neurotransmitters in the brain. GABA, an inhibitory neurotransmitter, is synthesized by glutamic acid decarboxylase (GAD). Its predominant isoform GAD67, contributes up to ∼90% of base-level GABA in the CNS, and is encoded by the GAD1 gene. Disruption of GAD1 results in an imbalance of inhibitory and excitatory neurotransmitters, and as Gad1−/− mice die neonatally of severe cleft palate, it has not been possible to determine any potential neurological dysfunction. Furthermore, little is known about the consequence of GAD1 disruption in humans. Here we present six affected individuals from six unrelated families, carrying bi-allelic GAD1 variants, presenting with developmental and epileptic encephalopathy, characterized by early-infantile onset epilepsy and hypotonia with additional variable non-CNS manifestations such as skeletal abnormalities, dysmorphic features and cleft palate. Our findings highlight an important role for GAD1 in seizure induction, neuronal and extraneuronal development, and introduce GAD1 as a new gene associated with developmental and epileptic encephalopathy.

Published
2020

44. Epidemiology of hand fractures at a tertiary care setting in Saudi Arabia

Author

Sultan T Alturki, Fahad A. Alhumaid, Nawaf S. Alohaideb, Omar S. Alobaidan, Sayaf H. Alshareef, Arwa A. Alhuwaymil, and Asif Z. Bhatti

Subjects
Adult, Male, medicine.medical_specialty, Pediatrics, Adolescent, Saudi Arabia, lcsh:Medicine, 030204 cardiovascular system & hematology, Wrist, Brief Communication, Tertiary care, First metacarpal, Tertiary Care Centers, Crush Injuries, Fractures, Bone, Fractures, Open, Young Adult, 03 medical and health sciences, 0302 clinical medicine, falls, Epidemiology, medicine, Humans, 030212 general & internal medicine, Young adult, Carpal fractures, Road traffic, Retrospective Studies, Fracture Healing, business.industry, lcsh:R, Accidents, Traffic, Hand Injuries, Retrospective cohort study, General Medicine, Wrist Injuries, Closed Fracture Reduction, Open Fracture Reduction, medicine.anatomical_structure, Hand Bones, epidemiology, Accidental Falls, Female, hand, business
Abstract

Objectives: To examine the epidemiology of hand fractures including common bones affected, causes, interventions, outcomes, and complications. Methods: This retrospective records-based study included patients who were admitted to King Saud Medical City, Riyadh, Kingdom of Saudi Arabia, with traumatic metacarpal or phalangeal fractures between January 2016 and September 2017. Carpal fractures, wrist fractures, and all pathological fractures were excluded. Results: A total of 82 patients (90.2% of them men with an average age of 27.6±13.4 years) with 101 fractures were included. The fifth (25.5%) and first (24.5%) rays were the most commonly affected ones. The fifth finger (27.8%) and first metacarpal (28.9%) were the most commonly affected finger and metacarpal bone. Approximately 32.7% of the fractures were open fractures. The most frequent causes of hand fractures included falls (40.5%), road traffic accidents (20.3%), crushing injuries (9.5%), and machinery injuries (9.5%). Approximately 90.1% of the patients underwent operative interventions including open reduction (50.5%) and closed reduction (34.3%). The majority of fractures (79.2%) healed, and only 14.7% of fractures developed complications. Conclusion: In this study of hand fractures, patients were predominantly males and the main causes of fractures were falls and road traffic accidents. Saudi Med J 2019; Vol. 40 (7): 732-736 doi:10.15537/smj.2019.7.24286 How to cite this article: Alhumaid FA, Alturki ST, Alshareef SH, Alobaidan OS, Alhuwaymil AA, Alohaideb NS, Bhatti AZ. Epidemiology of hand fractures at a tertiary care setting in Saudi Arabia. Saudi Med J 2019; 40 (7): 732-736. doi:10.15537/smj.2019.7.24286.

Published
2019

45. Chemical constituents of the aerial parts of Salvia judaica Boiss. from Jordan

Author

Hala I. Al-Jaber, Ethar F Khlaifat, Sahar O Ibrahim, Hasan Tashtoush, Musa H. Abu Zarga, Mahmoud A. Al-Qudah, Sultan T. Abu Orabi, and Ayman M. Saleh

Subjects
Salvia judaica, biology, 010405 organic chemistry, Tormentic acid, Rosmarinic acid, Organic Chemistry, Plant Science, Ascorbic acid, biology.organism_classification, 01 natural sciences, Biochemistry, Cirsilineol, 0104 chemical sciences, Analytical Chemistry, 010404 medicinal & biomolecular chemistry, chemistry.chemical_compound, chemistry, Glucoside, Apigenin, Tricin, Nuclear chemistry
Abstract

Investigation of the chemical constituents of Salvia judaica growing wild in Jordan led to the isolation and identification of 15 known compounds. These included: luteolin-3'-methyl ether (1), indole-3-carboxyaldehyde (2), p-hydroxybenzaldehyde (3), tricin (4), apigenin (5), methyl isoferuloyl-7-(3,4-dihydroxyphenyl) lactate (6), methyl rosmarinate (7), rosmarinic acid (8), salvigenin (9), β-sitosterol (10), 3β, 28-dihydroxyurs-12-ene (11), cirsilineol (12), 2,3-dihydroxyurs-12-en-28-oic acid (13), β-sitosteryl glucoside (14), and tormentic acid (15). Compounds 6 and 7 exhibited strong radical scavenging and chelating activities as compared to α-tocopherol and ascorbic acid, compound 7 showed a 2-fold greater antioxidant activity as compared to compound 6. Furthermore, low doses of compounds 6 and 7 were able to inhibit the growth of leukemic (HL-60, Jurkat, K562 and CCRF-SB) and solid tumor cells (MCF-7, MDA-MB-231 and Caco-2). Compound 7 showed a ca. 3-4-fold stronger cytotoxicity against the tested cells as compared to compound 6.

Published
2019

46. Temporal trends in the incidence and demographics of cancers, communicable diseases, and non-communicable diseases in Saudi Arabia over the last decade

Author

Hatem K. Herzallah, Mohammed H. Shafee, Belavendra R. Antonisamy, and Sultan T Al-Otaibi

Subjects
Lung Diseases, Male, lcsh:Medicine, Coronary Artery Disease, Communicable diseases, 030204 cardiovascular system & hematology, Dengue fever, Dengue, Chickenpox, 0302 clinical medicine, Quality of life, Neoplasms, Medicine, 030212 general & internal medicine, education.field_of_study, Leukemia, Incidence, Lymphoma, Non-Hodgkin, Incidence (epidemiology), General Medicine, Hepatitis B, Hypertension, Original Article, Female, Colorectal Neoplasms, Cancers, Population, Saudi Arabia, Breast Neoplasms, Measles, Brucellosis, 03 medical and health sciences, Sex Factors, Breast cancer, Environmental health, Diabetes Mellitus, Humans, Obesity, Thyroid Neoplasms, Non-communicable diseases, Noncommunicable Diseases, education, business.industry, lcsh:R, medicine.disease, Trends, business
Abstract

Objectives: To describe the trends in the incidence rates of 5 most common cancers, communicable diseases, and non-communicable diseases in Saudi Arabia over the last decade. Methods: The incidence rates of cancers (2001-2014), communicable diseases (2003-2016), and non-communicable diseases (1990-2017) were retrieved, classified, and analyzed retrospectively during November 2017, based on data available with the Ministry of Health and were analyzed at the Imam Abdulrahman Bin Faisal University in Dammam, Kingdom of Saudi Arabia. Results: Age-standardized incidence rate (ASR) (per 100,000 population) of breast cancer among women increased dramatically from 11.8 in 2001 to 22.7 in 2014, indicating a 92.4% increase over the decade. Colorectal cancer incidence was the highest among men, and its ASR per 100,000 population increased from 5.0 to 10.6 in men and from 5.0 to 8.2 in women. Among communicable diseases, incidences of hepatitis B, measles, chickenpox, and brucellosis decreased while dengue fever increased. An alarming increase was observed in the incidence rate of non-communicable diseases namely, obesity, diabetes, and hypertension. Conclusion: The incidence rate of non-communicable diseases increased over the decade and was associated with increased mortality and disability, reduced quality of life, and increased health-care costs, indicating an urgent need to establish prevention and control programs. The rising trend in the incidence of cancers may also become a health care issue in Saudi Arabia in the coming years. Saudi Med J 2019; Vol. 40 (3): 277-286 doi: 10.15537/smj.2019.3.23585 How to cite this article: Herzallah HK, Antonisamy BR, Shafee MH, Al-Otaibi ST. Temporal trends in the incidence and demographics of cancers, communicable diseases, and non-communicable diseases in Saudi Arabia over the last decade. Saudi Med J . 2019 Mar;40(3):277-286. doi: 10.15537/smj.2019.3.23585.

Published
2019

47. Occupational Violence and Staff Safety in Health-Care: A Cross-Sectional Study in a Large Public Hospital

Author

Sultan T Al-Otaibi, Hatem A Alqahtani, and Zainab R Al-Shaban

Subjects
medicine.medical_specialty, health-care, Cross-sectional study, media_common.quotation_subject, Convenience sample, 03 medical and health sciences, violence, 0302 clinical medicine, Health care, Medicine, Quality (business), 030212 general & internal medicine, occupational, Productivity, large hospital, media_common, Original Research, Risk Management and Healthcare Policy, Workplace violence, business.industry, 030503 health policy & services, Health Policy, Public Health, Environmental and Occupational Health, Family medicine, Public hospital, 0305 other medical science, business
Abstract

Zainab R Al-Shaban,1 Sultan T Al-Otaibi,2 Hatem A Alqahtani3 1Primary Healthcare Centers, Department of Occupational Medicine, Ministry of Health, Qatif, Kingdom of Saudi Arabia; 2Department of Public Health, College of Public Health, Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi Arabia; 3Department of Family and Community Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Kingdom of Saudi ArabiaCorrespondence: Sultan T Al-OtaibiImam Abdulrahman Bin Faisal University, Po Box 1982, Dammam, 31441, Saudi ArabiaTel +966 13-8948964Fax +966 13-8645612Email salotaibi@iau.edu.saBackground: Physical and psychological workplace violence in health-care settings has serious implications for the health of workers, as well as a negative effect on productivity and health-care quality.Methods: A cross-sectional study was conducted from May to July 2018 among physicians and nurses using a convenience sample (n = 213) for the previous 12 months at a tertiary hospital in Dammam, Saudi Arabia. The participants completed a self-administered questionnaire that assessed their personal and professional characteristics, whether they had experienced physical violence (assault) or psychological violence as health-care practitioners, and whether they had reported the incidents.Results: Among the respondents, 57% had experienced psychological violence, 6% had experienced physical violence, and 37% had experienced both psychological and physical violence in the previous 12 months. Shiftwork and working in the inpatient department were associated with a significant increase in the risk of physical violence. However, these factors showed no difference with regard to psychological violence. Both physical and psychological violence had diverse causes, without any single predominant cause. Similarly, both forms of violence occurred in multiple departments. Many of the incidents were unreported (75% of incidents involving psychological violence and 39% involving physical violence).Conclusion: Physical and psychological violence against health-care workers (HCWs) in the hospital under study was found to be very common. The results of this study suggest the need to develop and evaluate a violence prevention program to achieve quality health-care services.Keywords: occupational, health-care, violence, large hospital

Published
2021

48. The battle against Coronavirus disease 2019 (COVID-19) in the Kingdom of Saudi Arabia. Public health perspective

Author

Sultan T Al-Otaibi

Subjects
medicine.medical_specialty, Battle, media_common.quotation_subject, Saudi Arabia, Context (language use), Disease, Review Article, 030204 cardiovascular system & hematology, 03 medical and health sciences, 0302 clinical medicine, COVID-19 Testing, Environmental health, Pandemic, Medicine, Humans, 030212 general & internal medicine, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Pandemics, Health policy, media_common, business.industry, Public health, Mortality rate, Health Policy, pandemic, Outbreak, COVID-19, Coronavirus disease (COVID-19), General Medicine, public health perspective, Public Health, business
Abstract

Coronavirus disease 2019 (COVID-19) which was initially reported in the Chinese city of Wuhan has now spread unprecedented all over the world, including the Kingdom of Saudi Arabia (KSA). The World Health Organization declared this outbreak as a public health emergency of international concern during late January 2020 while the announcement of this viral infectious condition was made as COVID-19 disease during February 2020. As of late May 2020, the global death rate due to COVID-19 was 357,714 and 441 in KSA alone. This review provides an overview of COVID-19 and the public health measures adopted by KSA in the context of COVID-19.

Published
2020

49. Theory-Based Model and Prediction Analysis of Information Security Compliance Behavior in the Saudi Healthcare Sector

Author

Hadeer A. Al-Ani, Sultan T. Alanazi, Shankar Karuppayah, Mohammed Anbar, and Shouki A. Ebad

Subjects
behavioral theory, health information system, information security, information security compliance behavior, Physics and Astronomy (miscellaneous), General Mathematics, Developing country, 02 engineering and technology, Health informatics, 020204 information systems, 0502 economics and business, Health care, 0202 electrical engineering, electronic engineering, information engineering, Computer Science (miscellaneous), Big Five personality traits, Government, business.industry, lcsh:Mathematics, 05 social sciences, Information security, Public relations, lcsh:QA1-939, Work experience, Chemistry (miscellaneous), Marital status, business, Psychology, 050203 business & management
Abstract

The adoption of health information systems provides many potential healthcare benefits. The government of the Kingdom of Saudi Arabia has subsidized this field. However, like those of other less developed countries, organizations in the Kingdom of Saudi Arabia struggle to secure their health information systems. This issue may stem from a lack of awareness regarding information security. To date, most related studies have not considered all of the factors affecting information security compliance behavior (ISCB), which include psychological traits, cultural and religious beliefs, and legal concerns. This paper aims to investigate the usefulness of a theory-based model and determine the predictors of ISCB among healthcare workers at government hospitals in the Kingdom of Saudi Arabia. The study investigated 433 health workers in Arar, the capital of the Northern Borders Province in the Kingdom of Saudi Arabia. Two phases involved in this study were the hypothetical model formulation and identification of ISCB predictors. The results suggest that moderating and non-common factors (e.g., religion and morality) impact ISCB, while demographic characteristics (e.g., age, marital status, and work experience) do not. All published instruments and theories were embedded to determine the most acceptable theories for Saudi culture. The theory-based model of ISCB establishes the main domains of theory for this study, which were religion/morality, self-efficacy, legal/punishment, personality traits, cost of compliance/noncompliance, subjective norms, information security policy, general information security, and technology awareness. Predictors of ISCB indicate that general information security, followed by self-efficacy and religion/morality, is the most influential factor on ISCB among healthcare workers in the Kingdom of Saudi Arabia. This study is considered as the first to present the symmetry between theory and actual descriptive results, which were not investigated before.

Published
2020

50. Synthesis and characterization of 1,4-chalcogenesters bearing 5-membered heterocycles

Author

Alexander Hildebrandt, Khaled Al Khalyfeh, Ammar H. Al-Dujaili, Randa M. Al-As’ad, Heinrich Lang, Wissam Helal, Hana Hammad, Imad Hamadneh, Amer Imraish, Marcus Korb, Sultan T. Abu-Orabi, and Deeb Taher

Subjects
010405 organic chemistry, Aryl, Heteroatom, Substituent, Infrared spectroscopy, Mesophase, General Chemistry, 010402 general chemistry, 01 natural sciences, 0104 chemical sciences, chemistry.chemical_compound, Crystallography, Differential scanning calorimetry, chemistry, Phenylene, HOMO/LUMO
Abstract

Treatment of 1,4-(SeSiMe3)2-C6H4 (1) with two equiv of ClC(O)R (2) (a, R = 2-cC4H3O; b, R = 2-cC4H3S; c, R = 3-cC4H3S) produced the corresponding phenylene carboselenolates 1,4-(SeC(O)R)2-C6H4 (3a–c), while the reaction of 1,4-(SLi)2-C6H4 (4) with ClC(O)R (2) in a 1:2 molar ratio gave phenylene carbothiolates 1,4-(SC(O)R)2-C6H4 (5a–c). Compounds 3a–c and 5a–c were characterized by elemental analysis, NMR (1H, 13C{1H}, 77Se{1H}) and IR spectroscopy. The molecular structures of 3a–c and 5a–c in the solid state were determined by single-crystal X-ray structure analysis. The carbochalcogenato groups and the heteroatoms of the 5-membered rings are in an anti-arrangement with respect to each other. Cyclic voltammetry measurements show irreversible reduction processes for the 5-membered heterocyclic redox moiety in which reduction of these compounds lead to decomposition of the original compounds to unidentified species and show redox potentials between 1480 and 1580 mV for 3a-c and 1470−1490 mV for 5a-c, relative to the FcH/FcH+ redox couple. Also, thioester-functionalized systems 5a-c show significantly higher reduction potentials as compared to selenoesters 3a-c, reflecting the minor electron-donating effect of the sulfur atoms. The molecular electronic structures of the title compounds were additionally investigated by DFT calculations, revealing different degrees of HOMO-LUMO energy gaps within the series of 3a–c and 5a–c, due to a lowering in LUMO energy, depending on the nature of the heterocyclic ring. The calculations showed that the HOMO and LUMO are mainly located on the selenoester/thioester functionalized heterocyclic. The phase transition temperatures and enthalpies of the title compounds were detected by differential scanning calorimetry (DSC) analysis and the phases are confirmed by polarizing optical microscopy (POM). The mesomorphic investigation shows that compound 5a only exhibits enantiotropic smectic B (SmB) mesophase. In contrast, the other compounds do not show mesomorphic behavior, but simply changes from the solid crystalline state to the isotropic liquid. Biological activity of the compounds was evaluated using cytotoxicity assay on different cancer cell lines. Only compound 3c showed selective cytotoxic effect against MDA-231 and PC-3 cancer cell lines. The synthesis and characterization of phenylene carboselenolates 1,4-(SeC(O)R)2-C6H4 (3a–c) and phenylene carbothiolates 1,4-(SC(O)R)2-C6H4 (5a–c) were discussed. The solid state structures of the six compounds are reported. Electrochemical investigations show irreversible redox events. DFT calculations reveal different HOMO-LUMO gaps depending on the aryl substituent pattern. In addition, the liquid crystalline properties and the bioactivity test were carried out too.

Published
2020

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