Author: "A Teh" / Topic: humans - Searchworks@Jio Institute Digital Library Search Results

4,037 results on '"A Teh"'

1. PI3K/AKT/mTOR signaling transduction pathway and targeted therapies in cancer.

Author: Glaviano, Antonino, Foo, Aaron, Lam, Hiu, Yap, Kenneth, Jacot, William, Jones, Robert, Eng, Huiyan, Nair, Madhumathy, Makvandi, Pooyan, Geoerger, Birgit, Kulke, Matthew, Baird, Richard, Prabhu, Jyothi, Carbone, Daniela, Pecoraro, Camilla, Teh, Daniel, Sethi, Gautam, Cavalieri, Vincenzo, Lin, Kevin, Javidi-Sharifi, Nathalie, Toska, Eneda, Davids, Matthew, Brown, Jennifer, Diana, Patrizia, Stebbing, Justin, Kumar, Alan, and Fruman, David
Subjects: AKT inhibitors, ATP-competitive mTOR inhibitors, Allosteric mTOR inhibitors, Bi-steric mTOR inhibitors, Cancer, Dual PI3K/mTOR inhibitors, Isoform-specific PI3K inhibitors, PDK1 inhibitors, PI3K/AKT/mTORC pathway, Pan PI3K inhibitors, Humans, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, Signal Transduction, TOR Serine-Threonine Kinases, Neoplasms
Abstract: The PI3K/AKT/mTOR (PAM) signaling pathway is a highly conserved signal transduction network in eukaryotic cells that promotes cell survival, cell growth, and cell cycle progression. Growth factor signalling to transcription factors in the PAM axis is highly regulated by multiple cross-interactions with several other signaling pathways, and dysregulation of signal transduction can predispose to cancer development. The PAM axis is the most frequently activated signaling pathway in human cancer and is often implicated in resistance to anticancer therapies. Dysfunction of components of this pathway such as hyperactivity of PI3K, loss of function of PTEN, and gain-of-function of AKT, are notorious drivers of treatment resistance and disease progression in cancer. In this review we highlight the major dysregulations in the PAM signaling pathway in cancer, and discuss the results of PI3K, AKT and mTOR inhibitors as monotherapy and in co-administation with other antineoplastic agents in clinical trials as a strategy for overcoming treatment resistance. Finally, the major mechanisms of resistance to PAM signaling targeted therapies, including PAM signaling in immunology and immunotherapies are also discussed.
Published: 2023

2. High-throughput telomere length measurement at nucleotide resolution using the PacBio high fidelity sequencing platform

Author: Tham, Cheng-Yong, Poon, LaiFong, Yan, TingDong, Koh, Javier Yu Peng, Ramlee, Muhammad Khairul, Teoh, Vania Swee Imm, Zhang, Suihan, Cai, Yi, Hong, Zebin, Lee, Gina S, Liu, Jin, Song, Hai Wei, Hwang, William Ying Khee, Teh, Bin Tean, Tan, Patrick, Xu, Lifeng, Koh, Angela S, Osato, Motomi, and Li, Shang
Subjects: Biological Sciences, Bioinformatics and Computational Biology, Genetics, Aging, Biotechnology, 2.1 Biological and endogenous factors, Underpinning research, 1.1 Normal biological development and functioning, Aetiology, Generic health relevance, Good Health and Well Being, Humans, Telomere, Shelterin Complex
Abstract: Telomeres are specialized nucleoprotein structures at the ends of linear chromosomes. The progressive shortening of steady-state telomere length in normal human somatic cells is a promising biomarker for age-associated diseases. However, there remain substantial challenges in quantifying telomere length due to the lack of high-throughput method with nucleotide resolution for individual telomere. Here, we describe a workflow to capture telomeres using newly designed telobaits in human culture cell lines as well as clinical patient samples and measure their length accurately at nucleotide resolution using single-molecule real-time (SMRT) sequencing. Our results also reveal the extreme heterogeneity of telomeric variant sequences (TVSs) that are dispersed throughout the telomere repeat region. The presence of TVSs disrupts the continuity of the canonical (5'-TTAGGG-3')n telomere repeats, which affects the binding of shelterin complexes at the chromosomal ends and telomere protection. These findings may have profound implications in human aging and diseases.
Published: 2023

3. Translating periodontal data to knowledge in a learning health system

Author: Tokede, Bunmi, Yansane, Alfa, White, Joel, Bangar, Suhasini, Mullins, Joanna, Brandon, Ryan, Gantela, Swaroop, Kookal, Krishna, Rindal, Donald, Lee, Chun-Teh, Lin, Guo-Hao, Spallek, Heiko, Kalenderian, Elsbeth, and Walji, Muhammad
Subjects: Biomedical and Clinical Sciences, Dentistry, Clinical Research, Dental/Oral and Craniofacial Disease, Prevention, Infectious Diseases, Oral and gastrointestinal, Good Health and Well Being, Dental Informatics, Humans, Learning Health System, Periodontal Diseases, Periodontitis, Population Health, Tooth Loss, &nbsp, Clinical outcomes, big data, decision making, dental informatics, epidemiology, population health
Abstract: BackgroundA learning health system (LHS) is a health system in which patients and clinicians work together to choose care on the basis of best evidence and to drive discovery as a natural outgrowth of every clinical encounter to ensure the right care at the right time. An LHS for dentistry is now feasible, as an increased number of oral health care encounters are captured in electronic health records (EHRs).MethodsThe authors used EHRs data to track periodontal health outcomes at 3 large dental institutions. The 2 outcomes of interest were a new periodontitis case (for patients who had not received a diagnosis of periodontitis previously) and tooth loss due to progression of periodontal disease.ResultsThe authors assessed a total of 494,272 examinations (new periodontitis outcome: n = 168,442; new tooth loss outcome: n = 325,830), representing a total of 194,984 patients. Dynamic dashboards displaying performance on both measures over time allow users to compare demographic and risk factors for patients. The incidence of new periodontitis and tooth loss was 4.3% and 1.2%, respectively.ConclusionsPeriodontal disease, diagnosis, prevention, and treatment are particularly well suited for an LHS model. The results showed the feasibility of automated extraction and interpretation of critical data elements from the EHRs. The 2 outcome measures are being implemented as part of a dental LHS. The authors are using this knowledge to target the main drivers of poorer periodontal outcomes in a specific patient population, and they continue to use clinical health data for the purpose of learning and improvement.Practical implicationsDental institutions of any size can conduct contemporaneous self-evaluation and immediately implement targeted strategies to improve oral health outcomes.
Published: 2022

4. Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Author: Spiers, Harry VM, Kouli, Omar, Ahmed, Waheed U, Varley, Rebecca, Ahari, Daniel, Argus, Leah, McLean, Kenneth A, Kamarajah, Sivesh K, Coe, Peter, Griffiths, Ewen A, Chan, Anthony KC, Macutkiewicz, Christian, Jamdar, Saurabh, Wilson, Michael, Fullwood, Catherine, Toogood, Giles, Siriwardena, Ajith K, McLean, Kenneth, Ahmed, Waheed, Gilchrist, Andrew, Goldsworthy, Matthew, Rashid, Majid, Pockney, P, Varela, J, Brindl, N, Ramirez, J, Marafante, C, Iwao, Y, Ghzawi, A, Elhadi, M, Gacaferi, H, Varghese, C, Adeyeye, A, Alser, O, Teh, C, Prieto, M, Hasan, A, Al-Naggar, H, Salgado, R, Veracierto, F, Lancelotti, T, Solinas, D, Oddi, R, Garcia, FW, Diez, E Mazza, Ramirez, Andrade, Bracco, R, Fernandez, D, Maraschio, MA, Obeide, L, Giordano, E, Alcaraz, A, Marani, MA, Aguirre, N, Luna, F, Francesconi, M, Chiham, F, Cossio, R Ramos, Alvarez, FA, DA Pantoja Pachajoa, Mandojana, F, Merlo, IG, Gonzalez, MH, Cervelo, G, Puma, R, Vardaro, GF, Davis, A, Jurat, D, Guenoff, C, Raubenheimer, K, Goddard, K, Brown, K, Wegrecki, KJ, Cheung, HYC, Yang, M, Cheung, H, Siddiqui, J, Ahn, JH, Huynh, R, Lam, YH, Afzal, M, Ong, BS, Chua, MYM, Ly, K, Thomson, JE, Watson, D, Dawson, AC, Drane, A, Van Ruyven, S, Lun, EWY, Ferguson, M, and Jeong, JY
Subjects: Lung, Clinical Research, Good Health and Well Being, COVID-19, Cholecystectomy, Cholecystitis, Acute, Humans, Pandemics, SARS-CoV-2, CHOLECOVID Collaborative
Abstract: BackgroundThis study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic.MethodsCHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality.ResultsThis study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121).ConclusionCHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic.
Published: 2022

5. Interdisciplinary consensus statements on imaging of scapholunate joint instability

Author: Dietrich, Tobias Johannes, Toms, Andoni Paul, Cerezal, Luis, Omoumi, Patrick, Boutin, Robert Downey, Fritz, Jan, Schmitt, Rainer, Shahabpour, Maryam, Becce, Fabio, Cotten, Anne, Blum, Alain, Zanetti, Marco, Llopis, Eva, Bień, Maciej, Lalam, Radhesh Krishna, Afonso, P Diana, Mascarenhas, Vasco V, Sutter, Reto, Teh, James, Pracoń, Grzegorz, de Jonge, Milko C, Drapé, Jean-Luc, Mespreuve, Marc, Bazzocchi, Alberto, Bierry, Guillaume, Dalili, Danoob, Garcia-Elias, Marc, Atzei, Andrea, Bain, Gregory Ian, Mathoulin, Christophe L, del Piñal, Francisco, Van Overstraeten, Luc, Szabo, Robert M, Camus, Emmanuel J, Luchetti, Riccardo, Chojnowski, Adrian Julian, Grünert, Jörg G, Czarnecki, Piotr, Corella, Fernando, Nagy, Ladislav, Yamamoto, Michiro, Golubev, Igor O, van Schoonhoven, Jörg, Goehtz, Florian, Klich, Maciej, and Sudoł-Szopińska, Iwona
Subjects: Biomedical Imaging, Clinical Research, Bioengineering, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Musculoskeletal, Arthrography, Consensus, Humans, Joint Instability, Ligaments, Articular, Wrist Injuries, Wrist Joint, Wrist injuries, Joint instability, Diagnostic imaging, Guidelines, Surveys and questionnaires, Clinical Sciences, Nuclear Medicine & Medical Imaging
Abstract: ObjectivesThe purpose of this agreement was to establish evidence-based consensus statements on imaging of scapholunate joint (SLJ) instability by an expert group using the Delphi technique.MethodsNineteen hand surgeons developed a preliminary list of questions on SLJ instability. Radiologists created statements based on the literature and the authors' clinical experience. Questions and statements were revised during three iterative Delphi rounds. Delphi panellists consisted of twenty-seven musculoskeletal radiologists. The panellists scored their degree of agreement to each statement on an eleven-item numeric scale. Scores of '0', '5' and '10' reflected complete disagreement, indeterminate agreement and complete agreement, respectively. Group consensus was defined as a score of '8' or higher for 80% or more of the panellists.ResultsTen of fifteen statements achieved group consensus in the second Delphi round. The remaining five statements achieved group consensus in the third Delphi round. It was agreed that dorsopalmar and lateral radiographs should be acquired as routine imaging work-up in patients with suspected SLJ instability. Radiographic stress views and dynamic fluoroscopy allow accurate diagnosis of dynamic SLJ instability. MR arthrography and CT arthrography are accurate for detecting scapholunate interosseous ligament tears and articular cartilage defects. Ultrasonography and MRI can delineate most extrinsic carpal ligaments, although validated scientific evidence on accurate differentiation between partially or completely torn or incompetent ligaments is not available.ConclusionsDelphi-based agreements suggest that standardized radiographs, radiographic stress views, dynamic fluoroscopy, MR arthrography and CT arthrography are the most useful and accurate imaging techniques for the work-up of SLJ instability.Key points• Dorsopalmar and lateral wrist radiographs remain the basic imaging modality for routine imaging work-up in patients with suspected scapholunate joint instability. • Radiographic stress views and dynamic fluoroscopy of the wrist allow accurate diagnosis of dynamic scapholunate joint instability. • Wrist MR arthrography and CT arthrography are accurate for determination of scapholunate interosseous ligament tears and cartilage defects.
Published: 2021

6. Learning hidden elasticity with deep neural networks

Author: Chen, Chun-Teh and Gu, Grace X
Subjects: Clinical Research, Cancer, Bioengineering, Biomedical Imaging, Elasticity Imaging Techniques, Humans, Image Processing, Computer-Assisted, Machine Learning, Models, Biological, Neural Networks, Computer, deep learning&nbsp, neural networks&nbsp, elastography&nbsp, elasticity theory&nbsp, inverse problems, deep learning, elasticity theory, elastography, neural networks
Abstract: Elastography is an imaging technique to reconstruct elasticity distributions of heterogeneous objects. Since cancerous tissues are stiffer than healthy ones, for decades, elastography has been applied to medical imaging for noninvasive cancer diagnosis. Although the conventional strain-based elastography has been deployed on ultrasound diagnostic-imaging devices, the results are prone to inaccuracies. Model-based elastography, which reconstructs elasticity distributions by solving an inverse problem in elasticity, may provide more accurate results but is often unreliable in practice due to the ill-posed nature of the inverse problem. We introduce ElastNet, a de novo elastography method combining the theory of elasticity with a deep-learning approach. With prior knowledge from the laws of physics, ElastNet can escape the performance ceiling imposed by labeled data. ElastNet uses backpropagation to learn the hidden elasticity of objects, resulting in rapid and accurate predictions. We show that ElastNet is robust when dealing with noisy or missing measurements. Moreover, it can learn probable elasticity distributions for areas even without measurements and generate elasticity images of arbitrary resolution. When both strain and elasticity distributions are given, the hidden physics in elasticity-the conditions for equilibrium-can be learned by ElastNet.
Published: 2021

7. Negative Parenting Moderates the Prospective Association of ADHD Symptoms and Youth Social Problems

Author: Fenesy, Michelle C, Teh, Shin Er, and Lee, Steve S
Subjects: Clinical and Health Psychology, Psychology, Pediatric, Brain Disorders, Clinical Research, Mental Health, Behavioral and Social Science, Attention Deficit Hyperactivity Disorder (ADHD), Adolescent, Adolescent Behavior, Attention Deficit Disorder with Hyperactivity, Child, Child Behavior, Child, Preschool, Female, Follow-Up Studies, Humans, Male, Parent-Child Relations, Parenting, Problem Behavior, Prospective Studies, Social Behavior, ADHD, Attention-deficit, hyperactivity disorder, Negative parenting, Social problems, Attention-deficit/hyperactivity disorder, Developmental & Child Psychology, Applied and developmental psychology, Clinical and health psychology, Social and personality psychology
Abstract: Although ADHD and negative parenting are established predictors of youth outcomes, their independent and interactive effects on youth social functioning remain unclear. We tested childhood ADHD symptoms and negative parenting as independent and interactive predictors of prospective change in social problems across a four-year follow-up. At baseline, families of 221 (33% female) children with (n = 94) and without ADHD were rigorously assessed including observed positive and negative parenting behavior, youth ADHD symptoms, as well as multi-informant ratings of youth social problems at multiple occasions. Based on multiple regression with robust standard errors and full-information maximum likelihood procedures to address missing data, ADHD symptoms positively predicted social problems, even with control of observed parenting behavior, child age and sex, oppositional defiant disorder symptoms, and baseline social problems. Additionally, a child ADHD symptoms x negative parenting interaction uniquely predicted separate parent- and teacher-rated social problems where ADHD symptoms positively predicted social problems exclusively in the context of high (+1SD) and very high (+2 SD) negative parenting, respectively. When ADHD was separated into distinct dimensions (i.e., inattention, hyperactivity), an interaction between inattention symptoms and negative parenting approached significance such that inattention symptoms positively predicted parent-rated social problems in the context of high negative parenting. We discuss the interaction between parenting and ADHD symptoms in predictions of youth social problems and implications for intervention.
Published: 2019

8. Variation in Endoscopic Activity Assessment and Endoscopy Score Validation in Adults With Eosinophilic Esophagitis

Author: Schoepfer, Alain M, Hirano, Ikuo, Coslovsky, Michael, Roumet, Marie C, Zwahlen, Marcel, Kuehni, Claudia E, Hafner, David, Alexander, Jeffrey A, Dellon, Evan S, Gonsalves, Nirmala, Leung, John, Bussmann, Christian, Collins, Margaret H, Newbury, Robert O, Smyrk, Thomas C, Woosley, John T, Yang, Guang-Yu, Romero, Yvonne, Katzka, David A, Furuta, Glenn T, Gupta, Sandeep K, Aceves, Seema S, Chehade, Mirna, Spergel, Jonathan M, Falk, Gary W, Meltzer, Brian A, Comer, Gail M, Straumann, Alex, Safroneeva, Ekaterina, Group, International EEsAI Study, Achem, Sami R, Arora, Amindra S, Alpan, Oral, Armstrong, David, Attwood, Stephen E, Butterfield, Joseph H, Crowell, Michael D, DeVault, Kenneth R, Drouin, Eric, Enav, Benjamin, Enders, Felicity T, Fleischer, David E, Foxx-Orenstein, Amy, Francis, Dawn L, Guyatt, Gordon H, Harris, Lucinda A, Kagalwalla, Amir F, Kita, Hirohito, Krishna, Murli, Lee, James J, Lewis, John C, Lim, Kaiser, Locke, G Richard, Murray, Joseph A, Nguyen, Cuong C, Orbelo, Diana M, Pasha, Shabana F, Ramirez, Francisco C, Sheikh, Javed, Umar, Sarah B, Weiler, Catherine R, Wo, John M, Wu, Tsung-Teh, and Yost, Kathleen J
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Digestive Diseases, Clinical Research, Clinical Trials and Supportive Activities, Prevention, Adolescent, Adult, Aged, Anti-Inflammatory Agents, Dose-Response Relationship, Drug, Eosinophilic Esophagitis, Esophagoscopy, Esophagus, Female, Fluticasone, Humans, Male, Middle Aged, Prognosis, Severity of Illness Index, Young Adult, Index, Variability in Endoscopic Assessment, Instrument, International EEsAI Study Group, Gastroenterology & Hepatology, Clinical sciences
Abstract: Background & aimsEosinophilic esophagitis (EoE) is assessed endoscopically (endoscopic activity), based on grades of edema, rings, exudates, furrows, and strictures (EREFS). We examined variations in endoscopic assessments of severity, developed and validated 3 EREFS-based scoring systems, and assessed responsiveness of these systems using data from a randomized placebo-controlled trial of patients with EoE.MethodsFor the development set, 5 gastroenterologists reviewed EREFS findings from 266 adults with EoE and provided endoscopist global assessment scores (EndoGA, scale of 0 to 10); variation (ΔEndoGA) was assessed using linear regression. We evaluated simple scores (features given arbitrary values from 0 to 3) and developed 2 scoring systems (adjusted score range, 0-100). We then fitted our linear regression model with mean EndoGA to data from 146 adults recruited in centers in Switzerland and the United States between April 2011 and December 2012. For the validation set, we collected data from 120 separate adults (recruited in centers in Switzerland and the United States between May 2013 and July 2014), assessing regression coefficient-based scores using Bland-Altman method. We assessed the responsiveness of our scoring systems using data from a randomized trial of patients with EoE given fluticasone (n=16) or placebo (n=8).ResultsThe distribution of EndoGA values differed among endoscopists (mean ΔEndoGA, 2.6±1.8; range 0-6.6). We developed 2 regression-based scoring systems to assess overall and proximal and distal esophageal findings; variation in endoscopic features accounted for more than 90% of the mean EndoGA variation. In the validation group, differences between mean EndoGA and regression-based scores were small (ranging from -4.70 to 2.03), indicating good agreement. In analyses of data from the randomized trial, the baseline to end of study change in patients given fluticasone was a reduction of 24.3 in simple score (reduction of 4.6 in patients given placebo, P=.052); a reduction of 23.5 in regression-based overall score (reduction of 6.56 in patients given placebo, P=.12), and a reduction of 23.8 (reduction of 8.44 in patients given placebo, P=.11).ConclusionAssessments of endoscopic activity in patients with EoE vary among endoscopists. In an analysis of data from a randomized controlled trial, we found that newly developed scoring systems are no better than simple scoring system in detecting changes in endoscopic activity. These results support the use of a simple scoring system in evaluation of endoscopic activity in patients with EoE. clinicaltrials.gov no: NCT00939263 and NCT01386112.
Published: 2019

9. Optimizing drug combinations against multiple myeloma using a quadratic phenotypic optimization platform (QPOP)

Author: Rashid, Masturah Bte Mohd Abdul, Toh, Tan Boon, Hooi, Lissa, Silva, Aleidy, Zhang, Yanzhou, Tan, Pei Fang, Teh, Ai Ling, Karnani, Neerja, Jha, Sudhakar, Ho, Chih-Ming, Chng, Wee Joo, Ho, Dean, and Chow, Edward Kai-Hua
Subjects: Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Hematology, Orphan Drug, Rare Diseases, 6.1 Pharmaceuticals, 5.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Development of treatments and therapeutic interventions, Animals, Antineoplastic Combined Chemotherapy Protocols, Bortezomib, Cell Line, Tumor, Cyclin-Dependent Kinase Inhibitor p21, DNA Damage, DNA Methylation, Decitabine, Dose-Response Relationship, Drug, Drug Resistance, Neoplasm, Drug Synergism, Gene Expression Regulation, Neoplastic, Genes, Tumor Suppressor, High-Throughput Screening Assays, Humans, Mice, Mitomycin, Multiple Myeloma, Phenotype, Protein Tyrosine Phosphatase, Non-Receptor Type 6, RNA, Messenger, Tumor Burden, Biological Sciences, Medical and Health Sciences, Medical biotechnology, Biomedical engineering
Abstract: Multiple myeloma is an incurable hematological malignancy that relies on drug combinations for first and secondary lines of treatment. The inclusion of proteasome inhibitors, such as bortezomib, into these combination regimens has improved median survival. Resistance to bortezomib, however, is a common occurrence that ultimately contributes to treatment failure, and there remains a need to identify improved drug combinations. We developed the quadratic phenotypic optimization platform (QPOP) to optimize treatment combinations selected from a candidate pool of 114 approved drugs. QPOP uses quadratic surfaces to model the biological effects of drug combinations to identify effective drug combinations without reference to molecular mechanisms or predetermined drug synergy data. Applying QPOP to bortezomib-resistant multiple myeloma cell lines determined the drug combinations that collectively optimized treatment efficacy. We found that these combinations acted by reversing the DNA methylation and tumor suppressor silencing that often occur after acquired bortezomib resistance in multiple myeloma. Successive application of QPOP on a xenograft mouse model further optimized the dosages of each drug within a given combination while minimizing overall toxicity in vivo, and application of QPOP to ex vivo multiple myeloma patient samples optimized drug combinations in patient-specific contexts.
Published: 2018

10. Cultivation and sequencing of rumen microbiome members from the Hungate1000 Collection

Author: Seshadri, Rekha, Leahy, Sinead C, Attwood, Graeme T, Teh, Koon Hoong, Lambie, Suzanne C, Cookson, Adrian L, Eloe-Fadrosh, Emiley A, Pavlopoulos, Georgios A, Hadjithomas, Michalis, Varghese, Neha J, Paez-Espino, David, Perry, Rechelle, Henderson, Gemma, Creevey, Christopher J, Terrapon, Nicolas, Lapebie, Pascal, Drula, Elodie, Lombard, Vincent, Rubin, Edward, Kyrpides, Nikos C, Henrissat, Bernard, Woyke, Tanja, Ivanova, Natalia N, and Kelly, William J
Subjects: Biological Sciences, Bioinformatics and Computational Biology, Genetics, Cancer Genomics, Cancer, Microbiome, Human Genome, Animals, Archaea, Bacteria, Biofuels, Gastrointestinal Microbiome, Humans, Lignin, Microbiota, Rumen, Hungate1000 project collaborators
Abstract: Productivity of ruminant livestock depends on the rumen microbiota, which ferment indigestible plant polysaccharides into nutrients used for growth. Understanding the functions carried out by the rumen microbiota is important for reducing greenhouse gas production by ruminants and for developing biofuels from lignocellulose. We present 410 cultured bacteria and archaea, together with their reference genomes, representing every cultivated rumen-associated archaeal and bacterial family. We evaluate polysaccharide degradation, short-chain fatty acid production and methanogenesis pathways, and assign specific taxa to functions. A total of 336 organisms were present in available rumen metagenomic data sets, and 134 were present in human gut microbiome data sets. Comparison with the human microbiome revealed rumen-specific enrichment for genes encoding de novo synthesis of vitamin B12, ongoing evolution by gene loss and potential vertical inheritance of the rumen microbiome based on underrepresentation of markers of environmental stress. We estimate that our Hungate genome resource represents ∼75% of the genus-level bacterial and archaeal taxa present in the rumen.
Published: 2018

11. Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2

Author: Moffitt, Andrea B, Ondrejka, Sarah L, McKinney, Matthew, Rempel, Rachel E, Goodlad, John R, Teh, Chun Huat, Leppa, Sirpa, Mannisto, Susanna, Kovanen, Panu E, Tse, Eric, Au-Yeung, Rex KH, Kwong, Yok-Lam, Srivastava, Gopesh, Iqbal, Javeed, Yu, Jiayu, Naresh, Kikkeri, Villa, Diego, Gascoyne, Randy D, Said, Jonathan, Czader, Magdalena B, Chadburn, Amy, Richards, Kristy L, Rajagopalan, Deepthi, Davis, Nicholas S, Smith, Eileen C, Palus, Brooke C, Tzeng, Tiffany J, Healy, Jane A, Lugar, Patricia L, Datta, Jyotishka, Love, Cassandra, Levy, Shawn, Dunson, David B, Zhuang, Yuan, Hsi, Eric D, and Dave, Sandeep S
Subjects: Genetics, Cancer, Hematology, Lymphoma, Rare Diseases, Clinical Research, Biotechnology, Digestive Diseases, 2.1 Biological and endogenous factors, Aetiology, Animals, DNA Copy Number Variations, Enteropathy-Associated T-Cell Lymphoma, Female, Gene Expression Profiling, Gene Silencing, Histone-Lysine N-Methyltransferase, Humans, Male, Mice, Knockout, Middle Aged, Mutation, Sequence Analysis, DNA, T-Lymphocytes, Medical and Health Sciences, Immunology
Abstract: Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1, JAK3, STAT3, and SOCS1 We also identified mutations in KRAS, TP53, and TERT Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. We modeled the effects of SETD2 loss in vivo by developing a T cell-specific knockout mouse. These mice manifested an expansion of γδ T cells, indicating novel roles for SETD2 in T cell development and lymphomagenesis. Our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease and may inform future classification schemes.
Published: 2017

12. Economic Burden for Lung Cancer Survivors in Urban China.

Author: Zhang, Xin, Liu, Shuai, Liu, Yang, Du, Jian, Fu, Wenqi, Zhao, Xiaowen, Huang, Weidong, Zhao, Xianming, Liu, Guoxiang, Mao, Zhengzhong, and Hu, Teh-Wei
Subjects: Humans, Lung Neoplasms, Incidence, Models, Econometric, Retrospective Studies, Efficiency, Cost of Illness, Socioeconomic Factors, Adult, Aged, Middle Aged, Survivors, Urban Population, Financing, Personal, China, Female, direct cost, economic burden, indirect cost, lung cancer, medical insurance, Financing, Personal, Models, Econometric, Toxicology
Abstract: BackgroundWith the rapid increase in the incidence and mortality of lung cancer, a growing number of lung cancer patients and their families are faced with a tremendous economic burden because of the high cost of treatment in China. This study was conducted to estimate the economic burden and patient responsibility of lung cancer patients and the impact of this burden on family income.MethodsThis study uses data from a retrospective questionnaire survey conducted in 10 communities in urban China and includes 195 surviving lung cancer patients diagnosed over the previous five years. The calculation of direct economic burden included both direct medical and direct nonmedical costs. Indirect costs were calculated using the human capital approach, which measures the productivity lost for both patients and family caregivers. The price index was applied for the cost calculation.ResultsThe average economic burden from lung cancer was $43,336 per patient, of which the direct cost per capita was $42,540 (98.16%) and the indirect cost per capita was $795 (1.84%). Of the total direct medical costs, 35.66% was paid by the insurer and 9.84% was not covered by insurance. The economic burden for diagnosed lung cancer patients in the first year following diagnosis was $30,277 per capita, which accounted for 171% of the household annual income, a percentage that fell to 107% after subtracting the compensation from medical insurance.ConclusionsThe economic burden for lung cancer patients is substantial in the urban areas of China, and an effective control strategy to lower the cost is urgently needed.
Published: 2017

13. Anthropogenic debris in seafood: Plastic debris and fibers from textiles in fish and bivalves sold for human consumption.

Author: Rochman, Chelsea M, Tahir, Akbar, Williams, Susan L, Baxa, Dolores V, Lam, Rosalyn, Miller, Jeffrey T, Teh, Foo-Ching, Werorilangi, Shinta, and Teh, Swee J
Subjects: Animals, Fishes, Humans, Food Contamination, Waste Products, Seafood, Shellfish, United States, Indonesia, Bivalvia, Biochemistry and Cell Biology, Other Physical Sciences
Abstract: The ubiquity of anthropogenic debris in hundreds of species of wildlife and the toxicity of chemicals associated with it has begun to raise concerns regarding the presence of anthropogenic debris in seafood. We assessed the presence of anthropogenic debris in fishes and shellfish on sale for human consumption. We sampled from markets in Makassar, Indonesia, and from California, USA. All fish and shellfish were identified to species where possible. Anthropogenic debris was extracted from the digestive tracts of fish and whole shellfish using a 10% KOH solution and quantified under a dissecting microscope. In Indonesia, anthropogenic debris was found in 28% of individual fish and in 55% of all species. Similarly, in the USA, anthropogenic debris was found in 25% of individual fish and in 67% of all species. Anthropogenic debris was also found in 33% of individual shellfish sampled. All of the anthropogenic debris recovered from fish in Indonesia was plastic, whereas anthropogenic debris recovered from fish in the USA was primarily fibers. Variations in debris types likely reflect different sources and waste management strategies between countries. We report some of the first findings of plastic debris in fishes directly sold for human consumption raising concerns regarding human health.
Published: 2015

14. Facilitating a culture of responsible and effective sharing of cancer genome data

Author: Siu, Lillian L, Lawler, Mark, Haussler, David, Knoppers, Bartha Maria, Lewin, Jeremy, Vis, Daniel J, Liao, Rachel G, Andre, Fabrice, Banks, Ian, Barrett, J Carl, Caldas, Carlos, Camargo, Anamaria Aranha, Fitzgerald, Rebecca C, Mao, Mao, Mattison, John E, Pao, William, Sellers, William R, Sullivan, Patrick, Teh, Bin Tean, Ward, Robyn L, ZenKlusen, Jean Claude, Sawyers, Charles L, and Voest, Emile E
Subjects: Health Services and Systems, Health Sciences, Health Services, Human Genome, Cancer, Clinical Research, Genetics, Biotechnology, Good Health and Well Being, Computational Biology, Culture, Databases, Genetic, Genome, Humans, Information Dissemination, Neoplasms, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract: Rapid and affordable tumor molecular profiling has led to an explosion of clinical and genomic data poised to enhance the diagnosis, prognostication and treatment of cancer. A critical point has now been reached at which the analysis and storage of annotated clinical and genomic information in unconnected silos will stall the advancement of precision cancer care. Information systems must be harmonized to overcome the multiple technical and logistical barriers to data sharing. Against this backdrop, the Global Alliance for Genomic Health (GA4GH) was established in 2013 to create a common framework that enables responsible, voluntary and secure sharing of clinical and genomic data. This Perspective from the GA4GH Clinical Working Group Cancer Task Team highlights the data-aggregation challenges faced by the field, suggests potential collaborative solutions and describes how GA4GH can catalyze a harmonized data-sharing culture.
Published: 2016

15. A Clustered Randomized Controlled Trial to Reduce Secondhand Smoke Exposure Among Nonsmoking Pregnant Women in Sichuan Province, China

Author: Yang, Lian, Tong, Elisa K, Mao, Zhengzhong, Hu, Teh-Wei, and Lee, Anita H
Subjects: Health Services and Systems, Health Sciences, Health Effects of Indoor Air Pollution, Behavioral and Social Science, Pediatric Research Initiative, Prevention, Tobacco Smoke and Health, Clinical Research, Cancer, Tobacco, Clinical Trials and Supportive Activities, Pediatric, 3.1 Primary prevention interventions to modify behaviours or promote wellbeing, 3.2 Interventions to alter physical and biological environmental risks, Prevention of disease and conditions, and promotion of well-being, Reproductive health and childbirth, Good Health and Well Being, Adult, China, Environmental Exposure, Female, Hair, Health Education, Humans, Nicotine, Pregnancy, Prenatal Care, Tobacco Smoke Pollution, Clinical Sciences, Public Health and Health Services, Marketing, Public Health, Epidemiology, Public health
Abstract: IntroductionNonsmoking pregnant women in China have significant exposure to secondhand smoke (SHS). Few interventions have focused on pregnant women reducing their SHS exposure.MethodsThis clustered randomized controlled trial, conducted at eight hospitals in Sichuan, China, compared a prenatal health education intervention with usual clinical care as a control. The primary outcome was self-reported "no SHS exposure" before and 3 months after birth. The intervention consisted of three large group educational sessions, standardized clinician advice, brief monthly follow-up calls, and educational materials and resources. A random sample of participants was biochemically validated before birth with hair nicotine, a long-term biomarker of smoke exposure.ResultsOverall, 1181 participants were randomized to intervention (n = 526) and control (n = 655) groups. More participants in the intervention group than the control group reported no SHS exposure 3 months after birth (Total: 77.9% vs. 52.6%, P < .001; Home: 81.2% vs. 53.3%, P < .001). The intervention group also had greater changes in improved smoke-free homes and SHS knowledge and attitudes. Controlling for covariates, the intervention group was less likely to report SHS exposure than the control group (Total: OR = 0.47, 95% CI = 0.31 to 0.71; Home: OR = 0.33, 95% CI = 0.21 to 0.53), and this effect was sustained 3 months after birth. The adjusted log concentration of hair nicotine for the intervention group decreased by 0.28 log µg/g more than the control group.ConclusionsOur smoke-free health education intervention for nonsmoking pregnant women significantly reduced SHS exposure before and after birth. This intervention model can become part of a standard protocol for the care of pregnant women in hospital settings.
Published: 2016

16. Symptoms Have Modest Accuracy in Detecting Endoscopic and Histologic Remission in Adults With Eosinophilic Esophagitis

Author: Safroneeva, Ekaterina, Straumann, Alex, Coslovsky, Michael, Zwahlen, Marcel, Kuehni, Claudia E, Panczak, Radoslaw, Haas, Nadine A, Alexander, Jeffrey A, Dellon, Evan S, Gonsalves, Nirmala, Hirano, Ikuo, Leung, John, Bussmann, Christian, Collins, Margaret H, Newbury, Robert O, De Petris, Giovanni, Smyrk, Thomas C, Woosley, John T, Yan, Pu, Yang, Guang-Yu, Romero, Yvonne, Katzka, David A, Furuta, Glenn T, Gupta, Sandeep K, Aceves, Seema S, Chehade, Mirna, Spergel, Jonathan M, Schoepfer, Alain M, Group, International Eosinophilic Esophagitis Activity Index Study, Achem, Sami R, Arora, Amindra S, Alpan, Oral, Armstrong, David, Attwood, Stephen E, Butterfield, Joseph H, Crowell, Michael D, DeVault, Kenneth R, Drouin, Eric, Enav, Benjamin, Enders, Felicity T, Fleischer, David E, Foxx-Orenstein, Amy, Francis, Dawn L, Guyatt, Gordon H, Harris, Lucinda A, Kagalwalla, Amir F, Kita, Hirohito, Krishna, Murli, Lee, James J, Lewis, John C, Lim, Kaiser, Locke, G Richard, Murray, Joseph A, Nguyen, Cuong C, Orbelo, Diana M, Pasha, Shabana F, Ramirez, Francisco C, Sheikh, Javed, Umar, Sarah B, Weiler, Catherine R, Wo, John M, Wu, Tsung-Teh, and Yost, Kathleen J
Subjects: Biomedical and Clinical Sciences, Clinical Sciences, Digestive Diseases, Cancer, Clinical Research, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Adolescent, Adult, Aged, Aged, 80 and over, Area Under Curve, Biopsy, Eosinophilic Esophagitis, Eosinophils, Esophagoscopy, Female, Humans, Leukocyte Count, Male, Middle Aged, Predictive Value of Tests, Prospective Studies, ROC Curve, Remission Induction, Reproducibility of Results, Severity of Illness Index, Surveys and Questionnaires, Switzerland, Treatment Outcome, United States, Young Adult, EEsAI, Remission, Endoscopic Grading, Disease Monitoring, International Eosinophilic Esophagitis Activity Index Study Group, Neurosciences, Paediatrics and Reproductive Medicine, Gastroenterology & Hepatology, Clinical sciences, Nutrition and dietetics
Abstract: Background & aimsIt is not clear whether symptoms alone can be used to estimate the biologic activity of eosinophilic esophagitis (EoE). We aimed to evaluate whether symptoms can be used to identify patients with endoscopic and histologic features of remission.MethodsBetween April 2011 and June 2014, we performed a prospective, observational study and recruited 269 consecutive adults with EoE (67% male; median age, 39 years old) in Switzerland and the United States. Patients first completed the validated symptom-based EoE activity index patient-reported outcome instrument and then underwent esophagogastroduodenoscopy with esophageal biopsy collection. Endoscopic and histologic findings were evaluated with a validated grading system and standardized instrument, respectively. Clinical remission was defined as symptom score
Published: 2016

17. The healthcare costs of secondhand smoke exposure in rural China

Author: Yao, Tingting, Sung, Hai-Yen, Mao, Zhengzhong, Hu, Teh-wei, and Max, Wendy
Subjects: Health Services and Systems, Biomedical and Clinical Sciences, Public Health, Health Sciences, Cancer, Tobacco Smoke and Health, Prevention, Behavioral and Social Science, Rural Health, Lung Cancer, Health Effects of Indoor Air Pollution, Health Services, Lung, Burden of Illness, Clinical Research, Tobacco, 2.2 Factors relating to the physical environment, Aetiology, Cardiovascular, Respiratory, Good Health and Well Being, Adult, Asthma, China, Cost of Illness, Environmental Exposure, Family Characteristics, Female, Health Care Costs, Health Expenditures, Heart Diseases, Hospitalization, Humans, Insurance, Health, Male, Neoplasms, Rural Population, Sex Factors, Smoking, Surveys and Questionnaires, Tobacco Smoke Pollution, Tuberculosis, Economics, Global health, Low/Middle income country, Public policy, Secondhand smoke
Abstract: ObjectiveThe goal of this study was to assess the healthcare costs attributable to secondhand smoke (SHS) exposure among non-smoking adults (age ≥ 19) in rural China.MethodsWe analysed data from the 2011 National Rural Household Survey which was conducted among adults in five provinces and one municipality in China (N=12,397). Respondents reported their smoking status, health conditions and healthcare expenditures. Relative risks were obtained from published sources. Healthcare costs included annual outpatient and inpatient hospitalisation expenditures for five SHS-related diseases: asthma, breast cancer (female only), heart disease, lung cancer and tuberculosis. SHS-attributable healthcare costs were estimated using a prevalence-based annual cost approach.FindingsThe total healthcare costs of SHS exposure in rural China amounted to $1.2 billion in 2011, including $559 million for outpatient visits and $612.4 million for inpatient hospitalisations. The healthcare costs for women and men were $877.1 million and $294.3 million, respectively. Heart disease was the most costly condition for both women ($701.7 million) and men ($180.6 million). The total healthcare costs of SHS exposure in rural China accounted to 0.3% of China's national healthcare expenditures in 2011. Over one-fifth of the total healthcare costs of SHS exposure in rural China were paid by health insurance. The out-of-pocket expenditures per person accounted for almost half (47%) of their daily income.ConclusionsThe adverse health effects of SHS exposure result in a large economic burden in China. Tobacco control policies that reduce SHS exposure could have an impact on reducing healthcare costs in China.
Published: 2015

18. The heterogeneous effects of cigarette prices on brand choice in China: implications for tobacco control policy

Author: Li, Jing, White, Justin S, Hu, Teh-wei, Fong, Geoffrey T, and Yuan, Jiang
Subjects: Economics, Applied Economics, Public Health, Health Sciences, Tobacco, Cancer, Tobacco Smoke and Health, Behavioral and Social Science, Good Health and Well Being, Adult, Aged, China, Choice Behavior, Commerce, Data Collection, Female, Humans, Income, Longitudinal Studies, Male, Middle Aged, Poverty, Smoking, Smoking Prevention, Socioeconomic Factors, Taxes, Tobacco Products, Price, Low, Middle income country, Socioeconomic status, Taxation, Low/Middle income country
Abstract: BackgroundChina has long kept its tobacco taxes below international standards. The Chinese government has cited two rationales against raising tobacco tax, namely, the unfair burden it places on low-income smokers and the ability of consumers to switch to cheaper brands.ObjectiveThis study examines how different socioeconomic subgroups of Chinese smokers switch brands in response to cigarette price changes.MethodsWe model smokers' choice of cigarette tier as a function of tier-specific prices. We examine heterogeneous responses to prices by estimating mixed logit models for different income and education subgroups that allow for random variation in smokers' preferences. We use data from three waves of the longitudinal International Tobacco Control China Survey, collected in six large Chinese cities between 2006 and 2009.FindingsLow-income and less educated smokers are considerably more likely to switch tiers (including both up-trading and down-trading) than are their high-socioeconomic status (SES) counterparts. For those in the second-to-lowest tier, a ¥1 ($0.16, or roughly 25%) rise in prices increases the likelihood of switching tiers by 5.6% points for low-income smokers and 7.2% points for less educated smokers, compared to 1.6% and 3.0% points for the corresponding high-SES groups. Low-income and less educated groups are also more likely to trade down compared to their high-SES counterparts.ConclusionsOnly a small percentage of low-income and less educated Chinese smokers switched to cheaper brands in response to price increases. Hence, the concern of the Chinese government that a cigarette tax increase will lead to large-scale brand switching is not supported by this study.
Published: 2015

19. Type three secretion system-mediated escape of Burkholderia pseudomallei into the host cytosol is critical for the activation of NFκB

Author: Teh, Boon Eng, French, Christopher Todd, Chen, Yahua, Chen, Isabelle Gek Joo, Wu, Ting-Hsiang, Sagullo, Enrico, Chiou, Pei-Yu, Teitell, Michael A, Miller, Jeff F, and Gan, Yunn-Hwen
Subjects: Microbiology, Biological Sciences, Biomedical and Clinical Sciences, Emerging Infectious Diseases, Prevention, Biodefense, Infectious Diseases, Vaccine Related, Aetiology, 2.2 Factors relating to the physical environment, Infection, Bacterial Secretion Systems, Burkholderia pseudomallei, Cell Line, Cytosol, Epithelial Cells, Humans, NF-kappa B, Virulence Factors, Agricultural and Veterinary Sciences, Medical and Health Sciences, Medical microbiology
Abstract: BackgroundBurkholderia pseudomallei is the causative agent of melioidosis, a potentially fatal disease endemic in Southeast Asia and Northern Australia. This Gram-negative pathogen possesses numerous virulence factors including three "injection type" type three secretion systems (T3SSs). B. pseudomallei has been shown to activate NFκB in HEK293T cells in a Toll-like receptor and MyD88 independent manner that requires T3SS gene cluster 3 (T3SS3 or T3SSBsa). However, the mechanism of how T3SS3 contributes to NFκB activation is unknown.ResultsKnown T3SS3 effectors are not responsible for NFκB activation. Furthermore, T3SS3-null mutants are able to activate NFκB almost to the same extent as wildtype bacteria at late time points of infection, corresponding to delayed escape into the cytosol. NFκB activation also occurs when bacteria are delivered directly into the cytosol by photothermal nanoblade injection.ConclusionsT3SS3 does not directly activate NFκB but facilitates bacterial escape into the cytosol where the host is able to sense the presence of the pathogen through cytosolic sensors leading to NFκB activation.
Published: 2014

20. Effects of hospital facilities on patient outcomes after cancer surgery

Author: Knight, Sr, Chu, K, Lapitan, Mc, Dare, Aj, Pius, R, Shaw, Ca, Drake, Tm, Norman, L, Ademuyiwa, Ao, Adisa, Ao, Aguilera, Ml, Al-Saqqa, Sw, Al-Slaibi, I, Bhangu, A, Biccard, Bm, Brocklehurst, P, Costas-Chavarri, A, Elhadi, M, Fairfield, Cj, Fitzgerald, Je, Ghosh, D, Glasbey, J, Henegouwen, Miv, Ingabire, Jca, Kingham, Tp, Lawani, I, Lieske, B, Lilford, R, Martin, J, Mclean, Ka, Moore, R, Morton, D, Nepogodiev, D, Ntirenganya, F, Pata, F, Pinkney, T, Stephen, R Knight, Catherine, A Shaw, Riinu, Pius, Thomas, M Drake, Lisa, Norman, Adesoji, O Ademuyiwa, Adewale, O Adisa, Maria Lorena Aguilera, Sara, W Al-Saqqa, Ibrahim, Al-Slaibi, Aneel, Bhangu, Bruce, M Biccard, Peter, Brocklehurst, Ainhoa, Costas-Chavarri, Kathryn, Chu, Anna, Dare, Muhammed, Elhadi, Cameron, J Fairfield, J Edward Fitzgerald, Dhruv, Ghosh, James, Glasbey, Mark, I van Berge Henegouwen, C Allen Ingabire, J, T Peter Kingham, Marie Carmela Lapitan, Ismaïl, Lawani, Bettina, Lieske, Richard, Lilford, Janet, Martin, Kenneth, A McLean, Rachel, Moore, Dion, Morton, Dmitri, Nepogodiev, Faustin, Ntirenganya, Francesco, Pata, Thomas, Pinkney, Ahmad Uzair Qureshi, Antonio Ramos-De la Medina, Aya, Riad, Hosni Khairy Salem, Joana, Simões, Richard, Spence, Neil, Smart, Stephen, Tabiri, Hannah, Thomas, Thomas, G Weiser, Malcolm, West, John, Whitaker, Ewen, M Harrison, Arben, Gjata, Maria Marta Modolo, Sebastian, King, Erick, Chan, Sayeda Nazmun Nahar, Ade, Waterman, Dominique, Vervoort, Alemayehu Ginbo Bedada, Bernardo De Azevedo, Ana Gabriela Figueiredo, Manol, Sokolov, Venerand, Barendegere, Gerald, Ekwen, Arnav, Agarwal, Qinyang, Liu, Juan Camilo Correa, Kalisya Luc Malemo, Jacques, Bake, Jakov, Mihanovic, Kamila, Kunčarová, Julius, Orhalmi, Hosni, Salem, Jyri, Teras, Aristotelis, Kechagias, Alexis, P Arnaud, Judith, Lindert, Vasileios, Kalles, Maria-Lorena, Aguilera-Arevalo, Gustavo, Recinos, Zsolt, Baranyai, Basant, Kumar, Harish Neelamraju Lakshmi, Sanoop Koshy Zachariah, Philip, Alexander, Sunil Kumar Venkatappa, Pramesh, C, Radhian, Amandito, Christina, Fleming, Luca, Ansaloni, Gianluca, Pellino, Ahmed, M Altibi, Ibrahim, Nour, Intisar, Hamdun, Ali, M Ghellai, Donatas, Venskutonis, Tomas, Poskus, Justas, Zilinskas, Precious, Malemia, Yong Yong Tew, Elaine, Borg, Sarah, Ellul, Fatima Zahraa Wafqui, David, W Borowski, Anne Sophie van Dalen, Cameron, Wells, Harissou, Adamou, Adesoji, Ademuyiwa, Adewale, Adisa, Kjetil, Søreide, Sara Al Saqqa, Osaid, Alser, Haya, Tahboub, Helmut Alfredo Segovia Lohse, Sebastian Shu Yip, Piotr, Major, António Sampaio Soares, Matei Razvan Bratu, Andrey, Litvin, Armen, Vardanyan, Ahmad, Gudal, Naif, Albati, Jovan, Juloski, Miran, Rems, Sarah, Rayne, Stephanie Van Straten, Yoshan, Moodley, Irene Ortega Vázquez, Jaime, Ruiz-Tovar, Kithsiri Janakantha Senanayake, Sujeewa Priyantha Bandara Thalgaspitiya, Omer Abdelbagi Omer, Anmar, Homeida, Yucel, Cengiz, Daniel, Clerc, Muhammad, Alshaar, Hanen, Bouaziz, Yuksel, Altinel, Matthew, Doe, Maryna, Freigofer, Ella, Teasdale, Rakan, Kabariti, Joshua Michael Clements, Stephen Richard Knight, Ahsan, Ashfaq, Ijeoma, Azodo, Gabriela, Wagner, Ivan, Trostchansky, Mayaba, Maimbo, David, Linyama, Helidon, Nina, Amanda, Zeko, Claudio Gabriel Fermani, Santiago, Villalobos, Federico, Carballo, Pablo, Farina, Sebastian, Guckenheimer, Marilla, Dickfos, Ankit, Ajmera, Chester, Chong, Ralph, Gourlay, Sikandar, Hussaini, Yi Jia Lee, Adeeb, Majid, Peter, Martin, Rebecca, Miles, Owen James Morris, Jamie, Phua, William, Ridley, Tarunpreet, Saluja, Ryan Renxin Tan, Jen, Teh, Anna, Wells, Bharti, Arora, Qaasim, Dollie, Debbie, Ho, Yanru, Ma, Omattage Mahasha Perera, Anthony, Truong, Amanda Caroline Dawson, Bryan, Lim, Upuli, Pahalawatta, Jacqueline, Phan, Xiao-Ming Sarah Woon-Shoo-Tong, Andrea, Yeoh, Lillian, Charman, Andrew, Drane, Sharon, Laura, Charmaine Chu Wen Lo, Amy, Mozes, Rita, Poon, Hao Han Tan, Ellen, Wall, Prakshi, Chopra, Jasmine De Giovanni, Bal, Dhital, Brian, Draganic, Alexander, Duller, Jonathan, Gani, Yao Kuan Goh, Jun Young Jeong, Brendan, Mcmanus, Prakash, Nagappan, Peter, Pockney, Anya, Rugendyke, Mahsa, Sarrami, Stephen, Smith, Vanessa, Wills, Hsu Ven Wong, Geoffrey, Ye, Geoffrey, Zhang, Ethan, Brooker, Daniel, Feng, Bonnie, Lau, Carlin, Ngai, Sarah, Birks, David, Gyorki, Jaime Otero de Pablos, Ali, Abbosh, Chris, Gillespie, Ahmed, Mahmoud, Bianca, Kwan, Joshua, Lawson, Andrea, Warwick, Janne, Bingham, Andrew, J Cockbain, Nagendra Naidu Dudi-Venkata, Jordan, Ellaby-Hall, Ben, Finlay, Emily, Humphries, Jade, Pisaniello, Monique, Pisaniello, Salma, Salih, Tarik, Sammour, Haidar Hadri Abd Wahab, April De Silva, Nicola, Hayward, Kartik, Iyer, Guy, Maddern, Gian Andrea Prevost, Naga, Annapureddy, Krishna Pranathi Settipalli, Jeremy, Yeo, Lucy, Hempenstall, Lily, Pham, Shaun, Purcell, Cherry, Talavera, Ashish, I Vaska, Gurpreet, Chaggar, Phillip, Chrapko, Annelise, Cocco, Sarah Michelle Crystal Jade Coulter-Nile, Grahame, Ctercteko, James, French, Houchen, Gong, Martijn, Gosselink, Thuvarahan, Jegathees, Ivan, Jin, Michelle, Kalachov, Kathryn, Kiefhaber, Katherine, Lee, Jason, Luong, Steven, Phan, Henry, Pleass, Kelly, Veale, Zhi, Zeng, Angela, Au, Ashe, Debiasio, Idy, Deng, Jananee, Myooran, Amrita, Nair, Peter, Stewart, Anton, Stift, Lukas Walter Unger, Kerstin, Wimmer, Nabila, Ahmed, Syed, Hasan, Saber, Rahman, Margaret, O'Shea, Greg, Padmore, Adrian, Peters, Pietro, Perduca, Guenda, Pulcina, Nicolas, Tinton, Frederic, Buxant, Elsa, Dabin, Giulia, Garofalo, Francis, Dossou, Freddy Houehanou Rodrigue Gnangnon, Yacoubou Imorou Souaibou, Pako, Motlaleselelo, Omphile, Tlhomelang, Igor Lima Buarque, Gustavo Mendonça Ataíde Gomes, Aldo Vieira Barros, Ilia, Batashki, Nikolai, Damianov, Vladislav, Stoyanov, Dragomir, Dardanov, Svilen, Maslyankov, Plamen, Petkov, George, Todorov, Evgeni, Zhivkov, Aygulya, Akisheva, Miguel Angel Castilla Moreno, Geno, Genov, Ivelina, Ilieva, Tsvetomir, Ivanov, Martin, Karamanliev, Azhar, Khan, Emil, Mitkov, Tsanko, Yotsov, Boyko, Atanasov, Nikolay, Belev, Mihail, Slavchev, Carlos, Nsengiyumva, Elgan, Jones, Simon, Stock, Steve, Kyota, James, Brown, Tresor Mabanza, K, Lemery Nigo Samuel, Chidi, Otuneme, Ngwang, Prosper, Franklin, Umenze, Marylise, Boutros, Natasha, Caminsky, Sinziana, Dumitra, Richard, Garfinkle, Dominique, Morency, Ebram, Salama, Alexander, Banks, Lorenzo, Ferri, Haitian, He, Amit, Katz, Alexander Sender Liberman, Sarkis, Meterissian, Allison, Pang, Elena, Parvez, Usmaan, Hameed, Fahima, Osman, Sangita, Sequeira, Natalie, Coburn, Alisha, Jaffer, Paul, Karanicolas, Matthew, Mosseler, Reilly, Musselman, Xinyuan, Liu, Ching Wan Yip, Juan Sebastian Garces-Otero, Carolina, Guzman, Sebastian, Sierra, Andres Uribe Valencia, Paulo Andrés Cabrera Rivera, Saul, Camelo, Andrea, Gonzalez, Alejandro, González-Orozco, Manuel Santiago Mosquera Paz, Carlos J- Perez Rivera, Felipe, Gonzalez, Andres, Isaza-Restrepo, Laura, Nino-Torres, Natalia Arias Madrid, Maria Clara Mendoza Arango, Justin, Tsandiraki, Damir, Jemendžić, Branislav, Kocman, Oliver, Šuman, Renata, Canic, Darko, Jurišić, Ivana, Karakas, Ana Krizanovic Rupcic, Vlatka, Pitlovic, Josip, Samardžić, Mario, Kopljar, Ivan, Bacic, Edgar, Domini, Robert, Karlo, Danijela, Miljanić, Andrea, Simic, Mariam, Ahmed, Majdi Al Nassrallah, Rabiya, Altaf, Talal, Amjad, Ruba, Eltoum, Heba, Haidar, Alhassan, Hassan, Omar, Khalil, Marwan, Qasem, Rommel, Ramesh, Gautham, Sajith, Maham, Wisal, Jan, Žatecký, Michele, Bujda, Katerina, Jirankova, Ales, Paclik, Aya, Abdallah, Mariam Abdulgawad Almogy, Esraa Ayman El-Sawy, Ahmed Moustafa ElFayoumy, Nourhan, Elghareeb, Nourhan Ahmed Esmat, Ahmed, Fadel, Abdullah, Habater, Heba, Hamdy, Amr, Hefni, Marwa, Kamal, Norhan Mohamed Abobakr, Ahmed, Sayed, Nancy, Shaker, Ehab, Taha, Hoda, Tharwat, Omar, Zakaria, Ibrahem, Abdelmotaleb, Ali, Al-Dhufri, Hamza, S Al-Himyari, Enas El Sheikh, Asmaa, Eldmaty, Aya, Elkhalawy, Ahmed, M Elkhashen, Kithara, Magdy, Safa, Mostafa, Habib Doutoum Sadia, Mohamed Mahmoud Saleh, Dina, Samir, Mohamed Yahia Mohamed Ali, Mahmoud, A Nassar, Samar, Abdelhady, Aly, Abdelrazek, Israa, Abdelsalam, Aya, El-Sawy, Eman, Essam, Mohamed, Gadelkarim, Khaled, Ghaly, Mohamed, Hassabalnaby, Rana, Masarani, Nourhan Mohamed Shaaban, Ahmed, Sabry, Menatalla, Salem, Nourhan Akram Soliman, Diaaaldin, Zahran, Moustafa Ramadan Abou El Soud, Esraa Tarek Badr, Hala, Borham, Nehal, Elmeslemany, Mohammad, Elsayed, Fawzia, Elsherif, Sara, Eslam, Gehad, Gaber, Sondos, Ibrahim, Yara, Kamh, Abdelrahman, Mahmoud, Shimaa Gamal Mohamed, Eman, Morshedy, Cinderella, Omar, Fatima Salem Soliman, Shaza, Abdelkawy, Naglaa, Abdelmohsen, Mahmoud, Abdelshakour, Ahmed, Dahy, Norhan, Gamal, Mohammed, Gamal, Ahmad, Hasan, Helal, Hetta, Nehad, Mousa, Mohamed, Omar, Somia, Rabie, Mahmoud, Saad, Bakeer, Saleh, Marwa Sayed Mohamed, Muhammad, Shawqi, Heba Abdelhady Mousa, Mostafa, Alnoury, Mohamed, Elbealawy, Ahmed, Elshafey, Muhammad Essam Ibrahim El Desouki Muhammad Ahmed, Mennatullah, Ghonaim, Fawzy, Hgag, Mohamed, Ibrahim, Mahmoud, Morsy, Mohamed Reda Loaloa, Ahmed, Refaat, Hadeer, Samir, Fatma, Shahien, Mohamed, Sobhy, Fathy, Sroor, Esraa, Abdellatif, Marina, Adel, Amr Abdelghani Afifi, Eman, Afifi, Marco, Antaky, Amr, Dawoud, Naira El Zoghby, Amira, El-Remaily, Ali Abdelazez Elzanfaly, Ahmed, Gadallah, Fatma Alzahraa Gamal, Omar, Hashem, Shrouk Medhat Youssef, Aliaa Muhammad Attyah, Malak, Munir, Omar, Shazly, Esraa, Taha, Karim, Wilson, Sawsan, Adel, Asmaa, Ali, Esraa, Eid, Esraa, Elhelow, Marwa, Elmahdy, Bassant, Elshatby, Amany Hossam El-Din Zakaria, Ahmad, Hossny, Eman, Ibrahim, Ahmed, M Yonis, Maram, Metwalli, Basant, Yousry, Esraa, Zid, Mina, A Yacoub, Ahmed, Abdelhakim, Nervana, Abouelsoad, Mo'Min, Alkhatib, Ahmed, Ashraf, Alaa, Ashraf, Yasmin, Elazab, Mahmoud, Elfanty, Osama, Elkabir, Mai, Elsayed, Ahmed, Elshimy, Hager, Elsobky, John, Eskander, Ahmed, Gad, Ward, Hamsho, Noura Khaled Abdelwahed, Menna, Magdy, Dalia, Moharam, Abeer, Osama, Shereen, Ramadan, Radwa, Roum, Taqwa, Sayed, Tarneem, Shehada, Ahmed Mohy Zidan, Khalid, Abbas, Amr, Ali, Mohamed, Attia, Mohamed, Balata, Ayman El Nakeeb, Mohamed Ibrahim Elsayed Elewaily, Ahmed, Elfallal, Hossam, Elfeki, Ahmed, Elkhadragy, Sameh, Emile, Helmy, Ezzat, Hasnaa, Hosni, Islam, Mansour, Waleed, Omar, Gehad, Othman, Kareem, Sadek, Mostafa, Shalaby, Noura, Shehab-Eldeen, Rawda Anas Khalifa, Helmy, Badr, Mostafa, Eldeep, Ahmed, Eldeep, Amany Eldoseuky Mohammed, Salwa, Khallaf, Eman Magdy Hegazy, Rokia, Mahmoud, Pola, Mikhail, Mahmoud, Morsi, Sara, Mowafy, Dina, Raafat, Amina, Safy, Marwa, Sera, Ahmed Shible Sera, Mostafa Salim Mohamed AbdAllah, Muhammad, Abdelkader, Abdulrahman Osama Abdou, Ahmedgaber, Ahmed, Shireen, Gaafar, Fatma Ibrahim Negm, Mina, Lapic, Ahmed, Maher, Hagar, Mahmoud, Ahmed, Mostafa, Mohamed, Samir, Fatma, Samy, Nourhan, Semeda, Hind, I Shalaby, Alaa, El-Taweel, Ahmed Galal Elnagar, Ahmed Gamal Hemidan, Mohamed, Hussein, Ahmed, A Kandil, Moawad, Mf, Ayat Allah Nasser Hamamah, Mostafa, Soliman, Mohamed, Abdelkhalek, Noura Abdelmaksoud Tawakel, Ahmed Mohamed Abdelwahed, Alrawy, Abdou, Khalid, Atallah, Mohammed Yasser Elsherbeny, Eman, Emara, Mohamed, Hamdy, Omar, Hamdy, Amira, Haron, Salma, Ismail, Islam Hany Metwally, Nihal Mohamed Hamed Elgaml, Ahmed, Nassar, Basel, Refky, Mirna, Sadek, Mahmoud, Saleh, Asmaa, Yunes, Mai, Zakaria, Mohammed, Zuhdy, Notila, Fayed, Mohammed Mustafa Hassan Mohammed, Sander, Kütner, Priit, Melnik, Indrek, Seire, Toomas, Ümarik, Eppu, Ainoa, Verner, Eerola, Hanna, Koppatz, Laura, Koskenvuo, Ville, Sallinen, Sini, Takala, Jevgeni, Katunin, Arto, Turunen, Niki, Christou, Muriel, Mathonnet, Vincent, Lavoue, Krystel Nyangoh Timoh, Lucie, Soulabaille, Romain, Lesourd, Aude, Merdrignac, Laurent, Sulpice, Benoît, André, Elodie, Chantalat, Charlotte, Vaysse, Bertrand, Dousset, Sebastien, Gaujoux, Gregory, Martin, Octavian, Clonda, Domantas, Juodis, Klaus, Kienle, Andras, Mravik, Samuel, Palmer, Gabor, Szabadhegyi, Anita Eseenam Agbeko, 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Telma, Fonseca, Jorge, Pereira, Juan, Rachadell, Ana, Torre, Filipe Madeira Martins, Ana Cristina Carvalho, Joana Rodrigues Ferreira, Bruno Ribeiro da Silva, Helena, Devesa, Ana, Vieira, Inês, Mónica, Margarida, Amaro, Diogo, Sousa, Marta, Reia, João, Louro, Ana, Martins, Joaquina, Dominguez, Inês, Santos, Nuno Miguel Freitas Oliveira, José Carlos Pereira, Pedro, Silva-Vaz, Ligia, Freire, Ricardo, Escrevente, Valentina Madalina Negoita, Dmitry, Shakhmatov, Yves, Nezerwa, Radosav, Radulovic, Gareth, Obery, Francois, Viljoen, Tome, Mendes, Antonio, Suarez, Enrique, Moncada, Maria, Fernandez-Hevia, Carolina Curtis Martínez, Julia Maria Gil Garcia, Mariana González Zunzarren, Tarig, Idris, Karolina, Eklöv, Oskar, Grahn, Leila, Amin, Malin, Blomqvist, Costanza, Ajani, Rebecca, Kraus, Nico, Seeger, Melissa, Willemin, Fadi, Rayya, Mohammad, Ayash, Raneem, Msouti, Israa, Kannas, Eias, Abazid, Asil, Esper, Skander, Slim, Akil Serdar Kavcar, Erman, Aytac, Ahmet Cem Dural, Ayse, Ilker, Ismail Cem 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Harmony Impellizzeri, Marco Inama, Gianluigi Moretto, Sylvie Mochet, Elisa Ponte, Antonella Usai, Stefano Mancini, Andrea Sagnotta, Luigi Solinas, Elisa Bolzonaro, Nicolò Tamini, Gianluca Curletti, Raffaele Galleano, Michele Malerba, Sofia Campanella, Gianfranco Cocorullo, Francesco Colli, Paolino De Marco, Nicolò Falco, Tommaso Fontana, Leonel Jospin Kamdem Mambou, Antonella La Brocca, Leo Licari, Brenda Randisi, Giovanna Rizzo, Giulia Rotolo, Giuseppe Salamone, Roberta Tutino, Paolina Venturelli, Stefano Malabarba, Alessandro Sgrò, Ivan Vella, Bruno Cirillo, Daniele Crocetti, Giorgio De Toma, Pierfrancesco Lapolla, Andrea Mingoli, Paolo Sapienza, Angela Belvedere, Stefania Bianchini, Margherita Binetti, Arianna Birindelli, Valeria Tonini, Mauro Podda, Fabio Pulighe, Michele De Rosa, Lorenzo Bono, Felice Borghi, Paolo Geretto, Maria Carmela Giuffrida, Corrado Lauro, Alessandra Marano, Luca Pellegrino, Paola Salusso, Diego Sasia, Michela Campanelli, Alberto Realis Luc, Mario Trompetto, Roberto Cardia, Nicola Cillara, Antonio Nicola Giordano, Antonio Costanzo, Mario Alessandro Giovilli, Luca Turati, Silvestro Canonico, Gianluca Pellino, Guido Sciaudone, Francesco Selvaggi, Lucio Selvaggi, Nader Albsoul, Ahmad AlBsoul, Ala'a Aldeen Alkhatib, Osama Alsallaq, Justin Z Amarin, Rami Ayoub, Isam Bsisu, M S El Muhtaseb, Mohammad Jabaiti, Jamal Melhem, Ibrahim Nour, Yasmeen Z Qwaider, Mohammad Hasan Salameh, Ahmad Suleihat, Haya H Suradi, Mohammad Alammarin, Almoutuz Aljaafreh, Mohammad Bani Hani, Zeina Bani Hani, Farah Bani Hani, Toqa Fahmawee, Shadi Hamouri, Cyrine Katanani, Ra'fat Tawalbeh, Tamara Tawalbeh, Hassan Zawahrah, Mohamad K Abou Chaar, Lana Abusalem, Mahmoud Al-Masri, Hani Al-Najjar, Lutfi Barghuthi, Zahra Ahmed, Adnan Maulana, Omar Ngotho, Charbel Kamau, Aruyaru Stanley Mwenda, Fridah Bosire, Elizabeth Mwachiro, Robert Parker, Ian Simel, Kimutai Sylvester, Abdulmunem Ahmed Mustafa Althini, Sofian Elbarouni, Aya Elseed Elbeshina, Ahmed Gwea, Ans Malek, Wedad Albashir Masoud Farag, Abdulwahab Abdalei, Abu Baker Abdel Malik, Areej Abo-Khammash, Ma'aly Abuhlaiga, Nour Adnan, Marwa Albaggar, Asma Alfitory, Asma Aljanfi, Fakhruddin Almuzghi, Zohoor Altumei, Fatima Alzabti, Hana Ashoushan, Mohamed Assalhi, Joma Azzubia, Sondos Bnhameida, Malik Delhen, Houssein Elshafei, Hana Elteir, Fatima Esbaga, Abdel Aziz Gobbi, Fatma Hamouda, Hamdan Hilan, Rania Ismail, Fieruz Jebran, Muataz Kasbour, Galia Maderi, Saja Mohammad, Burooj Mohammed, Habib Murtadi, Hamassat Mustafa, Mohamed Rajab, Sarah Trenba, Mariam Wafaa, Eman Al Sagheir, Alabas Almigheerbi, Ahmed Alzahaf, Sumayyah Ghayth Bahroun, Najah Ben Dallah, Mahmoud Elshaibani, Haitem Eswaye, Maha Karar, Samah Omar, Eman Younes, Maha Younes, Dafer Zreeg, Saleh Abujamra, Firas Ashour, Mala Elgammudi, Wesal Omar F Aljadidi, Enas Saddouh, Randa Sharif, Aya Alabuzidi, AbdulMawlay Alwerfally, Sarra Aribi, Fatma Bibas, Taha Elfaituri, Yasmine Elhajjaji, Ala Khaled, Wegdan Khalil, Tesneem Layas, Enas Soula, Ahmed Tarek, Muad Fathi Khalleefah Abu Hallalah, Saleh Abujamra, Hazem Abdelkarem Ahmed, Tagwa Alsharef, Abdulsalam Ali Ben Saoud, Tasnim El Gharmoul, Ahmed Elhadi, Safa Elrais, Abdulhalim Shebani, Heba Zarti, Asaid Zeiton, Marijus Ambrazevicius, Nerijus Kaselis, Migle Stakyte, Oleg Aliosin, Agne Cizauskaite, Sarunas Dailidenas, Vitalijus Eismontas, Migle Kybransiene, Vitalija Nutautiene, Narimantas Samalavicius, Dainius Simcikas, Algirdas Slepavicius, Albinas Tamosiunas, Nerijus Ubartas, Paulius Zeromskas, Saulius Bradulskis, Edvinas Dainius, Juozas Juočas, Egle Kubiliute, Juozas Kutkevičius, Aurimas Opolskis, Audrius Parseliunas, Andrejus Subocius, Donatas Venskutonis, Egle Virbickaite, Diana Zuikyte, Algirdas Bogusevicius, Kristina Buzaite, Daiva Čepuliené, Ieva Cesleviciene, Vaidotas Cesna, Jolanta Gribauskaite, Povilas Ignatavicius, Mantas Jokubauskas, Monika Liugailaitè, Ernest Margelis, Ruta Mazelyte, Lina Pankratjevaitè, Matas Pažusis, Agne Rackeviciute, Justina Saladyte, Monika Škimelytè, Vygintas Šlenfuktas, Monika Sudeikyte, Algimantas Tamelis, Tomas Vanagas, Žygimantas Žumbakys, Aivaras Atkociunas, Audrius Dulskas, Justas Kuliavas, Justas Birutis, Sigitas Paškevičius, Mindaugas Šatkauskas, Donatas Danys, Matas Jakubauskas, Lina Jakubauskiene, Marius Kryzauskas, Vytautas Lipnickas, Gabija Makūnaitè, Fanjandrainy Rasoaherinomenjanahary, Herizo Rasolofonarivo, Luc Hervé Samison, Bitiel Banda, Precious Malemia, Vanessa Msosa, Ahmad Imran Ahmad Izzuddin, Andre Das, Ying Yee Gan, Tan Shong Sheng, Jia Yng Siaw, Mohd Fadliyazid Ab Rahim, Dyg Zahratul Hamrak Abang Jamari, Nurfariza Che Husin, Muhd Yusairi Kamarulzaman, Yi Ping Lim, Nil Amri Mohamed Kamil, Mohd Razeen Mohd Hassan, Saidah Mohd Sahid, Johari Mustafa, Elaine Hui Been Ng, Wan Khamizar Wan Khazim, Ng Chang Ern, P G Lingeshan, Syariz Ezuan Sulaiman, Sue Ean Ang, Muhammad Navid Bin Mohamad Sithik, Yih Jeng Cheong, Mahadevan Deva Tata, Law Jia Xian, Aravinthan Kadravello, I-Ern Koh, Li-Yen Ng, Yuki 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Orozco, Alejandro Gonzalez Ojeda, Samantha Corro Díaz González, Laura Martinez, Antonio Ramos-De la Medina, Bonifacio Mosqueda Amador, Armando Novoa, Dennet Arturo Olazo Espejo, Alejandro Jimenez, Federico Lopez Rosales, Elva Gabriela Vanoye, Luis Alberto Garcia Gonzalez, Roberto Carlos Miranda-Ackerman, Manuel Solano-Genesta, Alethia Alvarez-Cano, Hector Hugo Romero-Garza, Heriberto Medina-Franco, Lorelí Mejía-Fernández, Noel Salgado-Nesme, Omar Vergara-Fernandez, Guadalupe Montserrat Gutiérrez-Mota, Francisco Xavier Hernandez Vera, Anabella Llantada Lopez, Gilberto Morgan Villela, Felipe de Jesus Ramirez Padilla, Walezka Tapia Marin, Mónica Martínez Maldonado, Ramses Sánchez Suárez, José Manuel Troche, Chaymae Benyaiche, Oumaima Outani, Souadka Amine, Amine Benkabbou, Anass Mohammed Majbar, Raouf Mohsine, Ali Rafik, Thida Oung, Moe Moe Tin, David W Borowski, Philipp Plarre, David W Borowski, Philipp Plarre, Anna Alberga, Nina Sluiter, Jurriaan Tuynman, Robin Blok, Didem Cömert, Roel Hompes, Marianne Kalff, Merel Elisabeth Stellingwerf, Pieter Tanis, Mark van Berge Henegouwen, Elise Maria van Praag, Daan Wisselink, Michael Gerhards, Josephine Lopes Cardozo, Emma Westerduin, Joske de Jonge, Aaw van Geloven, Kaz van Schilt, Frank den Boer, Simone Stoots, Stijn Vlek, Jamie Adams, Ibrahim S Al-Busaidi, Gabrielle Budd, Seung Il Choi, Michael Jen Jie Chu, Anurag Ganugapati, Lucy McKinstry, Rebecca Pascoe, Simon Richards, Kenrick Rosser, Annie Stevenson, Rebecca White, Shebani Farik, Jin Kwun, Ahmed Murad, Sarah Cowan, Timothy Hall, Michael Hayton, Laminou Malam Sani, Souleymane Oumarou Garba, Harissou Adamou, Ibrahim Amadou Magagi, Oumarou Habou, Halima Aliyu, Muhammad Daniyan, Tunde T Sholadoye, Lawal Abdullahi, Lofty-John Anyanwu, Aminu Mohammad Mohammad, Abubakar Bala Muhammad, Abdurrahman Abba Sheshe, Ibrahim Suleiman, Alaba Adesina, Ajibola Awolowo, Clement Onuoha, Omotayo Salami, Ogechukwu Taiwo, Agboola Taiwo, Stephen Kache, Jerry Godfrey Makama, Danjuma Sale, Olajide Abiola, Akinlabi Ajao, Anthony Ajiboye, Amarachukwu Etonyeaku, Julius Olaogun, Ademola Adebanjo, Opeoluwa Adesanya, Michael Olatunji Afolayan, Olanrewaju Balogun, Ayomide Makanjuola, Samuel Nwokocha, Rufus Wale Ojewola, Thomas Olagboyega Olajide, Adewale Aderounmu, Abdul-Rashid Adesunkanmi, Adewale Adisa, Augustine Agbakwuru, Adeleke Akeem Aderogba, Olusegun Isaac Alatise, Olukayode Arowolo, Oladejo Lawal, Tajudeen Mohammed, Chinedu Ndegbu, Olalekan Olasehinde, Funmilola Wuraola, Akinbolaji Akinkuolie, Amarachukwu Etonyeaku, Arinzechukwu Mosanya, Omobolaji Ayandipo, Peter Elemile, Taiwo Akeem Lawal, Samuel Ali Sani, Stephen Garba, Rebecca Hauwa Sani, Samson Olori, Henry Onyebuashi, Ifeanyi Umoke, Adedire Adenuga, Ademola Adeyeye, Olufemi Habeeb, Bashir Lawal, Abdulrasheed Nasir, Eirik Kjus Aahlin, Didrik Kjønås, Elisabeth Myrseth, Jibran Abbasy, Abdul Alvi, Omair Saleem, Asma Afzal, Anam Nazir, Muhammad Farooq, Ayesha Liaqat, Syed Asghar Naqi, Ali Raza, Muzna Sarfraz, Muhammad Sarwar, Muntaha Banglani, Ambreen Munir, Rahmat Sehrish, Bushra Ayub, Raza Sayyed, Amna Altaf, Saima Ayub, Ahmad Uzair Qureshi, Komal Saeed, Bilal Syed, Sana Amir Akbar, Abdul Wahid Anwer, Ruqayya Naheed Khan, Amina Iqbal Khan, Shahid Khattak, Sameen Mohtasham, Muhammad Asad Parvaiz, Aamir Ali Syed, Abdul Basit Ansari, Noman Shahzad, Tanwir Khaliq, Isbah Rashid, Shahzad Hussain Waqar, Hasan Abu Al-Saleem, Amjad Abu Alqumboz, Mohammad Alqadi, Adham Amro, Rawan Assa, Eman Awesat, Rawan Ayyad, Mohammed Hammad, Ayat Haymony, Bassel Hijazi, Bara Hmeidat, Rowaa Lahaseh, Aseel Qawasmi, Alaa Rajabi, Mohammed Shehada, Sundus Shkokani, Yasmine Yaghi, Nadine Yaghi, Mohammad AlZohour, Mohammad Farid, Yousef Mahmoud Habes, Wesam Juba, Yanal Nubani, Abdelrahman Rabee, Mohammad Sa'deh, Saeed Abed, Iyad Al Basos, Mohammad Alswerki, Dina Ashour, Israa Awad, Samar Diab, Alaa El Jamassi, Sahar El-Kahlout, Somaya Elhout, Ahmed N K Hajjaj, Doaa Hasanain, Baraa Nabil Hajjaj, Mohammed Obaid, Eman Saikaly, Ahmed Salhi, Hiba Al-Tammam, Murad Almasri, Muath Baniowda, Doha Beshtawi, Ali Horoub, Rami Misk, Bayan Mohammad, Rami Qasrawi, Tasnim Sholi, Samar Abu-Nimeh, Abrar Abu-Srour, Sadi A Abukhalaf, Samer Adawi, Barah Alsalameh, Kholoud Ayesh, Muawiyah Elqadi, Ahmad Hammouri, Fatima Karim Mustafa, Natalie Marzouqa, Shatha Melhem, Dima Miqdad, Balqees Mohamad, Mhammed Rawhi, Ayman B Abu Ahammala, Ahmed Abu Ataya, Israa Abu Jayyab, Samar Al-Shwaikh, Othman Alagha, Mohammed Alasttal, Haneen Awadallah, Mahmood Elblbessy, Jehad Fares, Akram Jarbou, Ibtisam Mahfouz, Moath A Albahnasawi, Asmaa' Abo Mahadi, Hasan Abuelhatal, Ayham Abuelqomboz, Abdelrahman Almoqayyad, Abdallah Alwali, Reem Balaawi, Mahmoud Hamouda, Mohammed Humeid, Abdullah Jedyan, Tasneem Mahmoud Abu Hamam, Ghadeer Matar, Ali Salem, Tahani Samra, Nureddin Shaheen, Karam Shihada, Ayoob A Nemer, Mahmoud Abu Al Amrain, Abdulwhhab Abu Alamrain, Najlaa Abu Jamie, Mohammed R Abu-Rous, Nada Alfarra, Mohammed AlTaweel, Noor Alwhaidi, Ramadan Hamed, Bader Saqqa, Ahmad Shaheen, Dana Aljaber, Loay Aljaberi, Malak Alwaheidi, Assef Jawaada, Hani Khaldi, Rami Qahoush, Jalil Qari, Rana Saadeh, Ahlam Salim, Aseel Yacoub, Abbas Abbas, Rana Abu Shua'ib, Baraa Abu Zainah, Mahmoud AbuSirrees, Basheer Babaa, Ola Barhoush, Asef Belal Qadomi, Laith Daraghmeh, Reema Haji, Alaa Khatatbeh, Lana Khatib, Salsabeel Qarariah, Yara Quzmar, Khalil Safadi, Roqaya Salameh, Mohammad Hassan, Shifaa Herzallah, Loai Massad, Ahmed Nazzal, Ranin Nazzal, Dennis Escobar, Gustavo Miguel Machain V, Agustin Rodriguez Gonzalez, Jorge Emerson Chachaima Mar, Nathaly Olga Chinchihualpa Paredes, Vicente Cuba, Walter Lopez, Maria Milagros Niquen Jimenez, Nestor Alberto Sanchez Bartra, Olenka Sapallanay Ojeda, Diego Sequeiros, Andrea Toscano Pacheco, María Vergara, Sol Abarca, Rodrigo Alcorta, Giuliano Borda-Luque, Ivan Edward Eusebio Zegarra, Claudia Luján López, Mirella Marrufo, Cinthya Mogrovejo, Andrea Nomura, Yamile Rodríguez Angeles, Maitza Rosario Vidal Meza, Gabriela Zavala, José Neiser Castillo Arrascue, Jomara Caroline Hidrogo Cabrera, José Julio Mariano Larrea Vera, Miguel Osorio, Edgar Alcides Ylatoma Díaz, Mark Anthony Fontanilla, Joseph Roy Fuentes, Anna Leah Salazar, Genieve Dominguez, Marc Paul Lopez, Shiela Macalindong, Mark Augustine Onglao, Arjel Ramirez, Marie Dione Sacdalan, Mayou Martin Tampo, Gemma Leonora Uy, Jeremiah Mangahas, Kenneth Yabut, Joannes Paul Cañete, Bernalynn Eris Cansana, Ernes John Castro, Maria Kaiserin Lipana, Manuel Francisco Roxas, Vlu Jean Zara, Maciej Chroł, Paula Franczak, Michał Orłowski, Piotr Budzyński, Andrzej Budzyński, Pawel Bury, Agata Czerwińska, Jadwiga Dworak, Jacek Dziedzic, Michał Kisielewski, Jan Kulawik, Anna Lasek, Piotr Major, Piotr Małczak, Marcin Migaczewski, Michał Pędziwiatr, Magdalena Pisarska, Dorota Radkowiak, Mateusz Rubinkiewicz, Anna Rzepa, Tomasz Skoczylas, Maciej Stanek, Katarzyna Truszkiewicz, Mateusz Wierdak, Marek Winiarski, Piotr Zarzycki, Anna Zub-Pokrowiecka, Piotr Kowalewski, Rafał Roszkowski, Maciej Walędziak, Miguel Tomé, Sara Patrocinio, Ines Guerreiro, Filipe Almeida, Xavier de Sousa, Nuno Monteiro, Maria Teresa Costa Santos, Daniela de Oliveira, Marta Lopes Serra, Daniela Morgado, Christian Neves, Ana Carolina Oliveira, Alice Pimentel, Sofia Silva, Márcia Carvalho, Lúcia Carvalho, Joana Magalhães, Leonor Matos, Tânia Monteiro, Carlota Ramos, Vanessa Santos, José Barbosa, Jose Costa-Maia, Vítor Devezas, Ana Fareleira, Cristina Fernandes, Diana Gonçalves, Henrique Mora, Marina Morais, Fabiana Silva de Sousa, Sara Catarino Santos, Ana Logrado, André Tojal, Edgar Amorim, Miguel F Cunha, Ana Fazenda, João Pedro Melo Neves, Inês Isabel Sampaio da Nóvoa Gomes Miguel, Diogo Veiga, José Azevedo, Hugo Cardoso Louro, Mariana Leite, José Azevedo, Maria Bairos Menezes, Bárbara Gama, Diana Brito, Marta Cristina Cruz Martins, André Graça E Magalhães, Ana Catarina Longras, Rita Lourenço, Diana Matos, Luis Castro, Filipa Policarpo, Joana Romano, Mariana Leite, Cristina Monteiro, Diogo Pinto, Marina Duarte, Sónia Fortuna Martins, Mariline Oliveira, Diogo Galvão, Lisandra Martins, Anaisa Silva, Viorel Taranu, Bárbara Vieira, Jessica Neves, Simone Oliveira, Hugo Ribeiro, Margarida Cinza, Rosa Felix, Arnaldo Machado, Joana Oliveira, Joana Patrício, Rita Pedroso de Lima, Mário Pereira, Miguel Rocha Melo, Cristina Velez, Alberto Abreu da Silva, Mariana Claro, Daniel Costa Santos, Andreia Ferreira, Hugo Capote, Daniela Rosado, Filipa Taré, Oriana Nogueira, Miguel Ângelo, José Miguel Baiao, Andreia Guimarães, João Marques, Miguel Nico Albano, Marta Silva, Ana Valente da Costa, Teresa Vieira Caroço, Sara Almeida Braga, Ines Capunge, Marta Fragoso, João Guimarães, Bruno Pinto, João Ribeiro, Miguel Angel, Guilherme Fialho, Monica Guerrero, Filipa Campos Costa, Diogo Cardoso, Vasco Cardoso, Magda Alves, Inês Estalagem, Tiago Louro, Cláudia Marques, Rita Martelo, Miguel Morgado, Rita Canotilho, Ana Margarida Correia, Pedro 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B., Abu Ataya, A., Abu Jayyab, I., Al-Shwaikh, S., Alagha, O., Alasttal, M., Awadallah, H., Elblbessy, M., Fares, J., Jarbou, A., Mahfouz, I., Albahnasawi, M. A., Abo mahadi, A., Abuelhatal, H., Abuelqomboz, A., Almoqayyad, A., Alwali, A., Balaawi, R., Hamouda, M., Humeid, M., Jedyan, A., Mahmoud Abu hamam, T., Matar, G., Salem, A., Samra, T., Shaheen, N., Shihada, K., A. Nemer, A., Abu Al Amrain, M., Abu Alamrain, A., Abu Jamie, N., Abu-Rous, M. R., Alfarra, N., Altaweel, M., Alwhaidi, N., Hamed, R., Saqqa, B., Shaheen, A., Aljaber, D., Aljaberi, L., Alwaheidi, M., Jawaada, A., Khaldi, H., Qahoush, R., Qari, J., Saadeh, R., Salim, A., Yacoub, A., Abbas, A., Abu shua'ib, R., Abu Zainah, B., Abusirrees, M., Babaa, B., Barhoush, O., Belal qadomi, A., Daraghmeh, L., Haji, R., Khatatbeh, A., Khatib, L., Qarariah, S., Quzmar, Y., Safadi, K., Salameh, R., Hassan, M., Herzallah, S., Massad, L., Nazzal, A., Nazzal, R., Escobar, D., Machain V, G. M., Rodriguez Gonzalez, A., Chachaima Mar, J. E., Chinchihualpa Paredes, N. O., Cuba, V., Lopez, W., Niquen Jimenez, M. M., Sanchez Bartra, N. A., Sapallanay Ojeda, O., Sequeiros, D., Toscano Pacheco, A., Vergara, M., Abarca, S., Alcorta, R., Borda-Luque, G., Eusebio Zegarra, I. E., Lujan Lopez, C., Marrufo, M., Mogrovejo, C., Nomura, A., Rodriguez Angeles, Y., Vidal Meza, M. R., Zavala, G., Castillo Arrascue, J. N., Hidrogo Cabrera, J. C., Larrea vera, J. J. M., Osorio, M., Ylatoma Diaz, E. A., Fontanilla, M. A., Fuentes, J. R., Salazar, A. L., Dominguez, G., Lopez, M. P., Macalindong, S., Onglao, M. A., Ramirez, A., Sacdalan, M. D., Tampo, M. M., Uy, G. L., Mangahas, J., Yabut, K., Canete, J. P., Cansana, B. E., Castro, E. J., Lipana, M. K., Roxas, M. F., Zara, V. J., Chrol, M., Franczak, P., Orlowski, M., Budzynski, P., Budzynski, A., Bury, P., Czerwinska, A., Dworak, J., Dziedzic, J., Kisielewski, M., Kulawik, J., Lasek, A., Malczak, P., Migaczewski, M., Pedziwiatr, M., Pisarska, M., Radkowiak, D., Rubinkiewicz, M., Rzepa, A., Skoczylas, T., Stanek, M., Truszkiewicz, K., Wierdak, M., Winiarski, M., Zarzycki, P., Zub-Pokrowiecka, A., Kowalewski, P., Roszkowski, R., Waledziak, M., Tome, M., Patrocinio, S., Guerreiro, I., Almeida, F., de Sousa, X., Monteiro, N., Costa Santos, M. T., de Oliveira, D., Lopes Serra, M., Morgado, D., Neves, C., Oliveira, A. C., Pimentel, A., Silva, S., Carvalho, M., Carvalho, L., Magalhaes, J., Matos, L., Monteiro, T., Ramos, C., Santos, V., Barbosa, J., Costa-Maia, J., Devezas, V., Fareleira, A., Fernandes, C., Goncalves, D., Mora, H., Morais, M., Silva de Sousa, F., Catarino Santos, S., Logrado, A., Tojal, A., Amorim, E., Cunha, M. F., Fazenda, A., Melo Neves, J. P., Sampaio da Novoa Gomes Miguel, I. I., Veiga, D., Azevedo, J., Cardoso Louro, H., Leite, M., Bairos Menezes, M., Gama, B., Brito, D., Cruz Martins, M. C., Graca e Magalhaes, A., Longras, A. C., Lourenco, R., Matos, D., Castro, L., Policarpo, F., Romano, J., Monteiro, C., Pinto, D., Duarte, M., Fortuna Martins, S., Oliveira, M., Galvao, D., Martins, L., Silva, A., Taranu, V., Vieira, B., Neves, J., Oliveira, S., Ribeiro, H., Cinza, M., Felix, R., Machado, A., Oliveira, J., Patricio, J., Pedroso de Lima, R., Pereira, M., Rocha Melo, M., Velez, C., Abreu da Silva, A., Claro, M., Costa Santos, D., Ferreira, A., Capote, H., Rosado, D., Tare, F., Nogueira, O., Angelo, M., Baiao, J. M., Guimaraes, A., Marques, J., Nico Albano, M., Silva, M., Valente da Costa, A., Vieira Caroco, T., Almeida Braga, S., Capunge, I., Fragoso, M., Guimaraes, J., Pinto, B., Ribeiro, J., Angel, M., Fialho, G., Guerrero, M., Campos Costa, F., Cardoso, D., Cardoso, V., Alves, M., Estalagem, I., Louro, T., Marques, C., Martelo, R., Morgado, M., Canotilho, R., Correia, A. M., Martins, P., Peyroteo, M., Gomes, J., Monteiro, R., Romano, M., Alves, D. M., Peixoto, R., Quintela, C., Jervis, M. J., Melo, D., Pacheco, A., Paixao, V., Pedro, V., Pimenta, J., Pimenta de Castro, J., Rocha, A., Beuran, M., Ciubotaru, C., Diaconescu, B., Hostiuc, S., Negoi, I., Stoica, B., Anokhin, E., Kuznetsov, G., Oganezov, G., Paramzin, F., Romanova, E., Rutkovskii, V., Shushval, M., Zabiyaka, M., Dzhumabaev, K., Ivanov, V., Mamedli, Z., Achkasov, S., Balkarov, A., Nabiev, E., Nagudov, M., Rybakov, E., Saifutdinova, K., Sushkov, O., Joseph, L., Ndayishimiye, I., Faustin, N., Mutabazi, A. Z., Mvukiyehe, J. P., Nsengimana, V. J. P., Uwakunda, C., Abbas, M. M., Akeel, N., Aljiffry, M., Awaji, K., Farsi, A., Jamjoum, G., Khoja, A., Maghrabi, A., Malibary, N., Nassif, M., Saleem, A., Sultan, A., Tashkandi, W., Tashkandi, H., Trabulsi, N., Ba, M. B., Diallo, A. C., Ndong, A., Cuk, V., Jankovic, U., Koh, S. Z., Koh, F., Lee, K. C., Lee, K. Y., Lee, S., Leong, W. Q., Lui, S. A., Prakash, P., Grosek, J., Norcic, G., Tomazic, A., Fitchat, N., Jaich, R., Wineberg, D., Koto, M. Z., Baiocchi, D., Clarke, D., Steenkamp, C. J., Bannister, S., Boutall, A., Chinnery, G., Coccia, A., Dell, A., Karjiker, P., Kloppers, C., Loxton, N., Mabogoane, T., Malherbe, F., Panieri, E., Rayamajhi, S., van Wyngaard, T., Warden, C., Madiba, T. E., Pillay, N., Brooks, S., Kruger, C., Van Der Merwe, L. H., Gool, F., Kariem, M., Bougard, H., Kariem, N., Noor, F., Pillay, R., Steynfaardt, L., Gonzalez Gonzalez, L., Marin Santos, J. M., Martin-Borregon, P., Martinez Caballero, J., Nevado Garcia, C., Rodriguez Fraga, P., De Castro Parga, G., Fernandez Veiga, M. P., Garrido Lopez, L., Infante Pino, H., Lages Cal, I., Lopez Otero, M., Nogueira Sixto, M., Paniagua Garcia Senorans, M., Rodriguez Fernandez, L., Ruano Poblador, A., Rufo Crespo, E., Sanchez-Santos, R., Vigorita, V., Alonso Batanero, E., Asnel, D., Cifrian Canales, I., Contreras Saiz, E., De Santiago Alvarez, I., Diaz Vico, T., Fernandez Arias, S., Fernandez Martinez, D., Garcia Bernardo, C., Garcia Florez, L. J., Garcia Gutierrez, C., Garcia Munar, M., Marquez Zorrilla Molina, C. A., Merayo, M., Michi Campos, J. L., Moreno Gijon, M., Otero-Diez, J. L., Rodicio Miravalles, J. L., Solar-Garcia, L., Suarez Sanchez, A., Truan, N., Alejandre Villalobos, C., Caballero Diaz, Y., Jimenez, M., Montesdeoca, D., Navarro-Sanchez, A., Vega, V., Beltran de Heredia, J., Gomez, Z., Jezieniecki, C., Legido Moran, A. P., Montes-Manrique, M., Rodriguez-Lopez, M., Ruiz Soriano, M., Trujillo Diaz, J., Vazquez Fernandez, A., Argudo, N., Pera, M., Torrent Jansa, L., Garcia Dominguez, M., Goded, I., Roldon Golet, M., Talal El-Abur, I., Utrilla Fornals, A., Zambrana Campos, V., Aguilar Martinez, M. D. M., Bosch, M., Garcia-Catala, L., Sanchez-Guillen, L., Artigau, E., Gomez Romeu, N., Julia Bergkvist, D., Espina Perez, B., Morato, O., Olona, C., Dieguez, B., Forero-Torres, A., Losada, M., Gomez-Abril, S., Gonzalvez, P., Martinez, R., Navarro Martinez, S., Paya-Llorente, C., Perez Rubio, A., Santarrufina Martinez, S., Sebastian Tomas, J. C., Trullenque Juan, R., Gegundez Simon, A., Mate, P., Prieto-Nieto, M. I., Rubio-Perez, I., Urbieta, A., Vicario Bravo, M., Abello, D., Frasson, M., Garcia-Granero, A., Abad Gurumeta, A., Abad-Motos, A., Lucena-de Pablo, E., Nozal, B., Ripolles-Melchor, J., Salvachua, R., Ferrero, E., Garcia-Sancho Tellez, L., Picardo, A. L., Rojo Lopez, J. A., Zorrilla Matilla, L. P., Cagigas Fernandez, C., Castanedo Bezanilla, S., Estevez Tesouro, J., Fernandez-Diaz, M. J., Garcia Cardo, J., Gomez Ruiz, M., Gonzalez-Tolaretxipi, E., Jimeno Fraile, J., Poch, C., Rodriguez-Aguirre, M., Troche Pesqueira, N., Trugeda-Carrera, M. S., de la Torre, J., Blanco-Colino, R., Espin-Basany, E., Espinosa-Bravo, M., Morales Comas, C., Reyes Afonso, E., Rivero Deniz, J., Siso Raber, C., Verdaguer Tremolosa, M., Chandrasinghe, P., Kumarage, S., Wijekoon Arachchilage, N., Abdalla Ahmed Elkamel, A., A. Adam, M., Blomme, N., Thorell, A., Wogensen, F., Alga, A., Ansarei, D., Celebioglu, F., Heinius, G., Nigard, L., Pieniowski, E., Ahlqvist, S., Bjorklund, I., Franberg, A., Hakansson, M., Adamo, K., Franklin, O., Sund, M., Wiberg, R., Andersson, Y., Chabok, A., Nikberg, M., Kugelberg, A., Canonica, C., Christoforidis, D., Fasolini, F., Gaffuri, P., Giuliani, M., Meani, F., Popeskou, S. G., Pozza, S., Wandschneider, W., Peterer, L., Widmer, L. W., Zimmermann, B., Bakoleas, P., Chanousi, I., Charalampidou, L., Grochola, L. F., Heid, F., Ntaoulas, S., Outos, M., Peros, G., Podolska-Skoczek, H., Reinisch, K. B., Zielasek, C., Demartines, N., Gilgien, J., Kefleyesus, A., St-Amour, P., Toussaint, A., Alhimyar, M., Alsaid, B., Alyafi, A., Alkhaledi, A., Kouz, B., Omarain, A., Al-Sabbagh, Y., Alkhatib, H., Sara, S., Alhaj, A., Danial, A., Kadoura, L., Maa Albared, S., Monawar, Y., Nahas, L., Abd, B., Saad, A., Wakkaf, H., Bouzaiene, H., Ghalleb, M., Akaydin, E., Akbaba, A. C., Atakul, O., Baltaci, E., Besli, S., Burgu, G., Cenal, U., de Muijnck, C., Demirkaya, H. C., Dogruoz, A., Gezer, Z. I., Gundogdu, Y., Kara, M., Korkmaz, H. K., Kurtoglu, G. K., Ozben, V., Ozmen, B. B., Pektas, A. M., Sel, E. K., Yenidunya, N., Bengur, F. B., Oral, B. M., Yozgatli, T. K., Abdullayev, S., Gunes, M. E., Sahbaz, N. A., Banaz, T., Kargici, K., Kuyumcu, O. F., Yanikoglu, E., Yesilsancak, M., Yilmaz, D., Aktas, M. K., Rencuzogullari, A., Isik, A., Leventoglu, S., Yalcinkaya, A., Yuksel, O., Kalayci, M. U., Kara, Y., Sarici, I. S., Akin, A., Alemdag, G. N., Arslan, E., Baki, B. E., Bodur, M. S., Calik, A., Candas Altinbas, B., Cihanyurdu, I., Erkul, O., Gul, B., Guner, A., Kose, B., Semiz, A., Sevim, Tayar, S., Tomas, K., Tufek, O. Y., Turkyilmaz, S., Ulusahin, M., Usta, A., Yildirim, R., Guler, S. A., Tatar, O. C., Varol, E., Kirimtay, B., Uysal, M., Yildiz, A., Kose, E., Ciftci, A. B., Colak, E., Eraslan, H., Kucuk, G. O., Yemez, K., Lule, H., Bienfait, M., Bua, E., Okalany, N., Basarab, M., Bielosludtsev, O., Kolhanova, K., Perepelytsia, K., Romanukha, K., Savenkov, D., Siryi, S., Tereshchenko, M., Viacheslav, N., Volovetskyi, A., Kebkalo, A., Tryliskyy, Y., Tyselskiy, V., Bruce, E., Chow, B. L., Iddles, E., Mcguckin, S., Newall, N., Ramsay, G., Sharma, P., Stewart, C., Wong, J., Badran, A., Bath, M., Belais, F., Butt, E., Joshi, K., Kapur, M., Shaw, M., Townson, A., Williams, C. Y. K., Gray, T., Greig, R., Husain, M., Murray, E., Mustafa, A., Asif, A., Gokul, A., Shah, M., Akitikori, M. T., Charalabopoulos, A., Davidson, S., Mcnally, S., Rupani, S., Juma, F., Mills, S. C., Muirhead, L., Sellars, K., Walsh, U., Warren, O., Chambers, A., Hunt, R., Boyce, S., Cornwall, H., Tol, I., Argyriou, E. O., Eardley, N., Povey, M., Aithie, J. M. S., Irfan, A., Mcguigan, M. -C., Starr, R., Warren, C. R., Archibald, J., Kirby, G., Kisyov, I., Khoo, C. K., Lee, R., Photiou, D., Davis, R., Prasad, U., Yang, P. Z., Bird, J., Leung, E., Summerour, V., Currow, C., Kiam, J., Tan, G. J. S., Muthusami, A., Pegba-Otemolu, I., Urbonas, T., Nunoo-Mensah, J., Smolskas, E., Boddy, A., Gravante, G., Hunter, D., Andrew, D., Koh, A., Thompson, A., Adams, L., Clements, H. A., De Silva, K., Ekpete, O., Haque, S., Henderson, S., Ibrahim, B., Jayasinghe, T., Livie, J., Mailley, K., Nair, G., Tan, D., Baggaley, C., Dawidziuk, A., Szyszka, B., Barter, C., Gandhi, N., Hassell, K., Hitchin, S., Kelsall, J., Nagy, E., Nessa, A., Whisker, L., Yanni, F., Ali, M., Arora, D., Hediwattege, S., Kumarasinghe, N., Rathore, M., Tennakoon, A., Ali Ahmad, S. M., Bajomo, O., Nadira, F., Celentano, V., Griffiths, E., Karri, R. S., Mak, J. K. C., Pipe, M., Bhatti, M. I., Rabie, M., Boyle, C., Hamilton, D., Mihuna, A., Ng, J. C. K., Nicholson, G., Oliwa, A., Pearson, R., Rose, A., Yong, S. Q., Boereboom, C., Hanna, M., Walter, C., Greensmith, T. S., Mitchell, R., Monaghan, E., Crawford, J., Moug, S., Blackwell, J., Boyd-Carson, H., Herrod, P., Al-Allaf, O., Beattie, M., Bullock, C., Burman, S., Clark, G., Flamey, N., Flannery, O., Harding, A., Kodiatt, B., Lawday, S., Mahapatra, S., Mukundu Nagesh, N., Ng, M., Rye, D., Yoong, A., Clark, L., Deans, C., Edirisooriya, M., Carrington, E. V., Wong, T. L. E., Yusuf, B., Chamberlain, C., Duke, K., Kmiotek, E., Botes, A., Condie, N., Schrire, T., Shah, R., Thomas-Jones, I., Yates, C., Anthony, N., Matthews, E., Sahnan, K., Tankel, J., Tucker, S., Winter Beatty, J., Ziprin, P., Duggan, W., Kantartzi, A., Sridhar, S., Khaw, R. A., Srivastava, P., Underwood, C., Alves do Canto Brum, H., Chopra, S., Davis, L., Hughes, R., Tulley, J., Alberts, J., Athisayaraj, T., Olugbemi, M., Ahmad, K., Chan, C., Chapman, G., Fleming, H., Fox, B., Grewar, J., Hulse, K., Rutherford, D., Sinead, M., Speake, D., Vaughan-Shaw, P. G., Christodoulides, N., Kudhail, S., Welch, M., Husaini, S. M., Lambracos, S., Anyanwu, C., Suresh, R., Thomas, J. S., Gleeson, E., Platoff, R., Saif, A., Enumah, Z., Etchill, E., Gabre-Kidan, A., Bernstein, M., Carrano, F. M., Connors, J., Lynn, P., Melis, M., Newman, E., Foster, D. S., Perrone, K., Titan, A., Ahmad, S., Bafford, A. C. M. D., Dal Molin, M., Hanna, N., Zafar, S. N., Hemmila, M., Napolitano, L., Wong, J. J., Chandler, J., Wood, L., Wren, S., Ottesen, T., You, L., Yu, K., Arcienega Yanez, M. D. P., Ferreira Fernandes, M., Gonzalez, D., Cubas, S., Gonzalez, M. C., Zubiaurre, V., Demolin, R., Giroff, N., Sciuto, P., Campos, M., Rodriguez Cantera, G., Deepika, G., Simuchimba, E., Bulaya, A., Chibuye, C., Chirengendure, B., Kabale, M. -R., Kabongo, K., Munthali, J., Mweso, O., Pikiti, F., Otieno, J., Lai, L. T., Blackman, B., Subramaniam, S., Karim, R., Kok, N., Lee, Y. D., Ali, S., Sinha, A., Corrigan, R., Barnes, N., Wong, F., Dennis, G., Jedamzik, J., Phillips, E., Piette, W., Van hentenryck, M., Koco, H., Lawani, S., Kassa, M. W., Santos Bezerra, T., Gribnev, P., Dimitrov, D., Krastev, P., Oum, S., Bonghaseh, D. T., Al Farsi, M., Alsharqawi, N., Acevedo, V., Castillo Barbosa, A. C., Giron, F., Leon Rodriguez, J. P., Kucan, D., Rosko, D., Barsic, N., Zupan, D., Hegazi, A., Truncikova, V., Fryba, V., Mohamed, M., Nagi, A., Rashad Temerik, A., Elshawy, M. E., Mahmoud, M. I., Anwar, M., Rageh, T., Elmokadem, A., Gaballa, K., Teppo, S., Pengerma, P., Ballouhey, Q., Bergeat, D., Weyl, A., Hain, E., Gyedu, A., Yenli, E., Osei-Poku, D., Rompou, V. -A., Zoikas, A., Gaitanidis, A., Koukis, G., Perivoliotis, K., Tavlas, P., Galanos-Demiris, K., Zografos, G., Karavokyros, I., Xanthopoulou, G., Iordanidou, E., Ayau, F., Garcia, A., Damjan, P., Wason, D., B L, A., Rangganata, E., Kamath, P., O'Connor, D. B., Pinto, M., Perrone, F., Tropeano, F. P., Troilo, F., Bossi, D., Scala, D., Pulitano, L., Carella, M., Pietrabissa, A., Gori, A., Giraudo, G., De Simone, V., Russo, A. A., Braccio, B., Al-Taher, R., Athamneh, S., Parker, A., Sawiee, A., Kattia, A., Tababa, O., Shaeeb, Z., Syminas, V., Jurgaitis, J., Damuleviciene, G., Svagzdys, S., Razafimanjato, N. N. M., Chieng Loo, L., Tiong, I. C., Wan Muhmad, W. F., Vijeyan, H., Li Ying, T., Grech, G., Arrangoiz, R., Jimenez Ley, V. B., Arizpe, D., Lagunes Lara, E., Castro Lopez, E. V., Eaazim, J., Gordinou de Gouberville, M., Bastiaenen, V., Rottier, S., Nahab, F., Ji, M. Y., Seyoji, M., Nwachukwu, C., Emeghara, O., Muhammed, S. E., Idowu, A., Sowemimo, O., Ogundoyin, O., Akande, O., Lott, A., Nadeem, M., Laghari, A. A., Loya, A., Mushtaq, H., Abdullah, M. T., Abuhilal, B., Atawneh, M., Hamdan, H., Alhabil, B., Srour, A., Mousa, I., Da Silva Medina, L., Bartosiak, K., Ferreira, P., Francisco, V., Lemos, R., Frutuoso, L., Fernandes, S., Fonseca, T., Pereira, J., Rachadell, J., Torre, A., Madeira Martins, F., Carvalho, A. C., Rodrigues Ferreira, J., Ribeiro da Silva, B., Devesa, H., Vieira, A., Monica, I., Amaro, M., Sousa, D., Reia, M., Louro, J., Martins, A., Dominguez, J., Santos, I., Freitas Oliveira, N. M., Pereira, J. C., Silva-Vaz, P., Freire, L., Escrevente, R., Negoita, V. M., Shakhmatov, D., Nezerwa, Y., Radulovic, R., Obery, G., Viljoen, F., Mendes, T., Suarez, A., Moncada, E., Fernandez-Hevia, M., Curtis Martinez, C., Gil Garcia, J. M., Gonzalez Zunzarren, M., Idris, T., Eklov, K., Grahn, O., Amin, L., Blomqvist, M., Ajani, C., Kraus, R., Seeger, N., Willemin, M., Rayya, F., Ayash, M., Msouti, R., Kannas, I., Abazid, E., Esper, A., Slim, S., Kavcar, A. S., Aytac, E., Dural, A. C., Ilker, A., Eray, I. C., Kurnaz, E., Altiner, S., Tepe, M. D., Sahin, C., Savli, E., Innocent, A., Babirye, L., Diachenko, A., Hordoskiy, V., Curry, H., Chau, C. Y. C., Robertson, H., Lennon, H., Loi, L., Kirkham, E., Mccann, C., Watts, D., Gurung, B., Wilson, M., Tribedi, T., Garofalo, E., Zahra, B., Macdonald, S., Daniels, I., Ng, N., Khosla, S., Olivier, J., Yue, S. Y. P., Suresh, G., Wellington, J., Lorejo, E., Mossaad, M., Crutcher, M., Alimi, M., Baiu, I., Abdou, H., Conway, A., Peck, C., Perdomo Perez, M. A., Zulu, S., Nakazwe, M., Burger, S., Davies, J., Donaldson, R., Ede, C., Garden, O. J., Lesetedi, C., Mabedi, C., Magill, L., Makinde Alakaloko, F., Makupe, A., Monahan, M., Mulira, S., Muller, E., Musowoyo, J., Olory-Togbe, J. L., Roberts, T., Smith, M., Tayler, V., Windsor, J., Yepez, R., Sundar, S., Runigamugabo, E., Verjee, A., Chen, J., Daya, L., El Aroussi, N., Farina, V., Gnintedeme Olivier, T., Gonzales Nacarino, M., Hammani, A., Honjo, S., Jacobs, R., Kimura, H., Nkoronko, M., Oscullo Yepez, J. J., Pin Hung, W., Raj, A., Romani Pozo, A., Rommaneh, M., Sassamela Fabiano, S. C., Shiroma Gago, C. M., Srinivas, A., Sung, C. -Y., Tai, A., Valle Aranda, Y. C., Venturini, S., Wilguens Lartigue, J., Public and occupational health, AMS - Sports, APH - Health Behaviors & Chronic Diseases, CCA - Cancer Treatment and quality of life, Amsterdam Gastroenterology Endocrinology Metabolism, Cancer Center Amsterdam, and Albarella, Sara
Subjects: global surgery, hospitals, humans, income, neoplasms, postoperative period, poverty, prospective studies, no keywords listed, General Medicine, Prospective Studie, Hospital, Settore MED/18 - Chirurgia Generale, outcome, Hospitals, Humans, Income, Neoplasms, surgery, Postoperative Period, Poverty, Prospective Studies, cancer surgery, Human, hospital facilities
Abstract: © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p
Published: 2022

21. Oestrogen‐induced angiogenesis promotes adenomyosis by activating the Slug‐VEGF axis in endometrial epithelial cells

Author: Huang, Tze‐Sing, Chen, Yi‐Jen, Chou, Teh‐Ying, Chen, Chih‐Yao, Li, Hsin‐Yang, Huang, Ben‐Shian, Tsai, Hsiao‐Wen, Lan, Hsin‐Yi, Chang, Cheng‐Hsuan, Twu, Nae‐Fang, Yen, Ming‐Shyen, Wang, Peng‐Hui, Chao, Kuan‐Chong, Lee, Chun‐Chung, and Yang, Muh‐Hwa
Subjects: 2.1 Biological and endogenous factors, Aetiology, Cardiovascular, Adenomyosis, Animals, Blotting, Western, Cells, Cultured, Endometriosis, Endometrium, Epithelial Cells, Estrogens, Female, Humans, Immunoenzyme Techniques, Mice, Mice, Inbred NOD, Mice, SCID, Myometrium, Neovascularization, Pathologic, Snail Family Transcription Factors, Transcription Factors, Vascular Endothelial Growth Factor A, Slug, adenomyosis, angiogenesis, epithelial-mesenchymal transition, oestrogen, Medicinal and Biomolecular Chemistry, Biochemistry and Cell Biology, Clinical Sciences, Biochemistry & Molecular Biology
Abstract: Adenomyosis is an oestrogen-dependent disease characterized by the invasion of endometrial epithelial cells into the myometrium of uterus, and angiogenesis is thought to be required for the implantation of endometrial glandular tissues during the adenomyotic pathogenesis. In this study, we demonstrate that compared with eutopic endometria, adenomyotic lesions exhibited increased vascularity as detected by sonography. Microscopically, the lesions also exhibited an oestrogen-associated elevation of microvascular density and VEGF expression in endometrial epithelial cells. We previously reported that oestrogen-induced Slug expression was critical for endometrial epithelial-mesenchymal transition and development of adenomyosis. Our present studies demonstrated that estradiol (E2) elicited a Slug-VEGF axis in endometrial epithelial cells, and also induced pro-angiogenic activity in vascular endothelial cells. The antagonizing agents against E2 or VEGF suppressed endothelial cells migration and tubal formation. Animal experiments furthermore confirmed that blockage of E2 or VEGF was efficient to attenuate the implantation of adenomyotic lesions. These results highlight the importance of oestrogen-induced angiogenesis in adenomyosis development and provide a potential strategy for treating adenomyosis through intercepting the E2-Slug-VEGF pathway.
Published: 2014

22. The effect of cigarette prices on brand-switching in China: a longitudinal analysis of data from the ITC China Survey

Author: White, Justin S, Li, Jing, Hu, Teh-wei, Fong, Geoffrey T, and Jiang, Yuan
Subjects: Health Sciences, Public Health, Commerce, Management, Tourism and Services, Human Society, Clinical Research, Tobacco Smoke and Health, Tobacco, Cancer, Good Health and Well Being, Adult, China, Commerce, Data Collection, Female, Humans, Longitudinal Studies, Male, Middle Aged, Smoking, Taxes, Tobacco Products, Economics, Low/Middle income country, Price
Abstract: BackgroundRecent studies have found that Chinese smokers are relatively unresponsive to cigarette prices. As the Chinese government contemplates higher tobacco taxes, it is important to understand the reasons for this low response. One possible explanation is that smokers buffer themselves from rising cigarette prices by switching to cheaper cigarette brands.ObjectiveThis study examines how cigarette prices influence consumers' choices of cigarette brands in China.MethodsThis study uses panel data from the first three waves of the International Tobacco Control China Survey, drawn from six large cities in China and collected between 2006 and 2009. The study sample includes 3477 smokers who are present in at least two waves (8552 person-years). Cigarette brands are sorted by price into four tiers, using excise tax categories to determine the cut-off for each tier. The analysis relies on a conditional logit model to identify the relationship between price and brand choice.FindingsOverall, 38% of smokers switched price tiers from one wave to the next. A ¥1 change in the price of cigarettes alters the tier choice of 4-7% of smokers. Restricting the sample to those who chose each given tier at baseline, a ¥1 increase in price in a given tier would decrease the share choosing that tier by 4% for Tier 1 and 1-2% for Tiers 2 and 3.ConclusionsChina's large price spread across cigarette brands appears to alter the brand selection of some consumers, especially smokers of cheaper brands. Tobacco pricing and tax policy can influence consumers' incentives to switch brands. In particular, whereas ad valorem taxes in a tiered pricing system like China's encourage trading down, specific excise taxes discourage the practice.
Published: 2014

23. Oral serum-derived bovine immunoglobulin improves duodenal immune reconstitution and absorption function in patients with HIV enteropathy

Author: Asmuth, David M, Ma, Zhong-Min, Albanese, Anthony, Sandler, Netanya G, Devaraj, Sridevi, Knight, Thomas H, Flynn, Neil M, Yotter, Tammy, Garcia, Juan-Carlos, Tsuchida, Emily, Wu, Tsung-Teh, Douek, Daniel C, and Miller, Christopher J
Subjects: Clinical Research, HIV/AIDS, Digestive Diseases, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, Oral and gastrointestinal, Administration, Oral, Adsorption, Adult, Animals, CD4 Lymphocyte Count, Cattle, Diet, Duodenum, HIV Enteropathy, Humans, Immunity, Mucosal, Immunoglobulins, Male, Pilot Projects, Serum Globulins, Treatment Outcome, bovine immunoglobulin, d-xylose absorption, gastrointestinal associated lymphoid tissue, gut permeability, HIV enteropathy, immune reconstitution, immunohistochemistry, intestinal fatty acid binding protein, monocyte chemotaxis protein-1, Biological Sciences, Medical and Health Sciences, Psychology and Cognitive Sciences, Virology
Abstract: ObjectivesTo examine the impact of serum-derived bovine immunoglobulin, an oral medical food known to neutralize bacterial antigen and reduce intestinal inflammation, on restoration of mucosal immunity and gastrointestinal function in individuals with HIV enteropathy.DesignOpen-label trial with intensive 8-week phase of bovine serum immunoglobulin (SBI) 2.5 g twice daily with a 4-week washout period and an optional 9-month extension study.MethodsHIV enteropathy was defined as chronic gastrointestinal symptoms including frequent loose or watery stools despite no identifiable, reversible cause. Upper endoscopy for tissue immunofluorescent antibody assay and disaccharide gut permeability/absorption studies were performed before and after 8 weeks of SBI to test mucosal immunity and gastrointestinal function. Blood was collected for markers of microbial translocation, inflammation, and collagen kinetics. A validated gastrointestinal questionnaire assessed changes in symptoms.ResultsAll eight participants experienced profound improvement in symptoms with reduced bowel movements/day (P = 0.008) and improvements in stool consistency (P = 0.008). Gut permeability was normal before and after the intervention, but D-xylose absorption increased in seven of eight participants. Mucosal CD4 lymphocyte densities increased by a median of 139.5 cells/mm2 from 213 to 322 cells/mm2 (P = 0.016). Intestinal-fatty acid binding protein (I-FABP), a marker of enterocyte damage, initially rose in seven of eight participants after 8 weeks (P = 0.039), and then fell below baseline in four of five who continued receiving SBI (P = 0.12). Baseline serum I-FABP levels were negatively correlated with subsequent rise in mucosal CD4 lymphocyte densities (r = -0.74, P = 0.046).ConclusionSBI significantly increases intestinal mucosal CD4 lymphocyte counts, improves duodenal function, and showed evidence of promoting intestinal repair in the setting of HIV enteropathy.
Published: 2013

24. Is the Association of Subjective SES and Self-Rated Health Confounded by Negative Mood? An Experimental Approach

Author: Kraus, Michael W, Adler, Nancy, and Chen, Teh-Way David
Subjects: Epidemiology, Clinical and Health Psychology, Social and Personality Psychology, Public Health, Health Sciences, Psychology, Mental Health, Behavioral and Social Science, Clinical Research, Depression, Adolescent, Adult, Affect, Aged, Female, Health Status, Humans, Male, Middle Aged, Social Class, Young Adult, socioeconomic status, subjective status, negative affect, self-rated health, Medical and Health Sciences, Education, Psychology and Cognitive Sciences, Health sciences
Abstract: ObjectiveLower subjective socioeconomic status (SSS) consistently shows associations with poorer health with the strongest relationships emerging with global self-rated health. Though often interpreted as reflecting the impact of low SSS on health, the association could also arise from confounding SSS with negative affect. In this research we sought to determine if negative affect confounds, or alternatively, is on the causal pathway linking SSS to self-rated health.MethodThree-hundred adult participants--recruited from throughout the United States--were randomized to experience sadness, shame, or a neutral mood induction in which they wrote about and visualized a particularly emotionally evocative event. Participants subsequently completed measures of SSS, self-rated health, depression, and negative mood.ResultsConsistent with predictions, neither SSS scores nor the association of SSS with self-rated health, depression, and chronic negative affect differed by mood induction condition, controlling for demographic factors that covary with SSS (e.g., age, gender, education, income). Moreover, chronic negative affect partially explained the relationship between SSS and self-rated health, independent of manipulated mood.ConclusionsThese findings support the utility of the measurement of SSS, and provide evidence suggesting that chronic negative affect is a likely mediator of the SSS association with global health rather than a confounder.
Published: 2013

25. Severe hyperkalaemia in the setting of tumour lysis syndrome

Author: Timothy G Scully, Geoffrey R. Wong, Han S. Lim, and Andrew W Teh
Subjects: medicine.medical_specialty, Lysis, business.industry, Septic shock, medicine.medical_treatment, Acute kidney injury, General Medicine, Emergency department, medicine.disease, medicine.disease_cause, Gastroenterology, Renal transplant, Internal medicine, Beta-lactamase, medicine, Humans, Hyperkalemia, business, Tumor Lysis Syndrome, Escherichia coli, Normal heart
Abstract: A 49-year-old man with a structurally normal heart presented to the emergency department with pyelonephritis secondary to extended spectrum beta lactamase Escherichia coli , resulting in both septic shock and an acute kidney injury. He had a background history of a renal transplant for adult
Published: 2023

26. Evaluation of Care Outcomes of Patients Receiving Hyperkalemia Treatment With Insulin in Acute Care Tertiary Hospital Emergency Department

Author: Siew Hoon Lim, Siti Namira B.A. Wahab, Shin Yuh Ang, Ming Ming Teh, and Fazila Aloweni
Subjects: Adult, Blood Glucose, Tertiary Care Centers, Blood Glucose Self-Monitoring, Humans, Insulin, Hyperkalemia, Emergency Nursing, Emergency Service, Hospital, Hypoglycemia, Retrospective Studies
Abstract: Treatment of hyperkalemia using intravenous insulin can result in severe hypoglycemia, but regular blood glucose monitoring is not standardized. This study aimed to (i) explore the demographics of adult patients receiving hyperkalemia treatment and (ii) identify the incidence rate of hypoglycemia and associated demographic or clinical characteristics.A descriptive design with prospective data collection was used. This study recruited 135 patients who received hyperkalemia treatment in the emergency department. Structured blood glucose monitoring was conducted at 1, 2, 4, and 6 hours after receiving intravenous insulin. Univariate analyses of association between demographic and clinical variables and hypoglycemia outcome were performed.There were 31 hypoglycemic events, with 11.9%, 7.4%, 2.2%, and 1.5% occurring at the 1, 2, 4, and 6 hours after treatment. The logit regression showed no significantly increased risk of hypoglycemia in terms of the demographic and clinical variables.The variation in blood glucose response observed in this study combined with the high incidences of hypolycaemia indicated the need for frequent and longer duration of monitoring for patients who were being treated for hyperkalaemia with IDT.
Published: 2023

27. Obscurin and KCTD6 regulate cullin-dependent small ankyrin-1 (sAnk1.5) protein turnover

Author: Lange, Stephan, Perera, Sue, Teh, Phildrich, and Chen, Ju
Subjects: Biochemistry and Cell Biology, Biological Sciences, 1.1 Normal biological development and functioning, 2.1 Biological and endogenous factors, Acetylation, Adaptor Proteins, Signal Transducing, Animals, Ankyrins, COP9 Signalosome Complex, COS Cells, Chlorocebus aethiops, Cullin Proteins, Gene Expression, Gene Expression Regulation, Developmental, Gene Knockdown Techniques, Guanine Nucleotide Exchange Factors, Humans, Mice, Mice, Knockout, Multiprotein Complexes, Muscle Proteins, Muscle, Skeletal, Myocardium, NEDD8 Protein, Peptide Hydrolases, Phosphorylation, Protein Binding, Protein Interaction Domains and Motifs, Protein Isoforms, Protein Processing, Post-Translational, Protein Serine-Threonine Kinases, Protein Structure, Quaternary, RNA Interference, Rats, Rho Guanine Nucleotide Exchange Factors, Two-Hybrid System Techniques, Ubiquitination, Ubiquitins, Medical and Health Sciences, Developmental Biology, Biochemistry and cell biology
Abstract: Protein turnover through cullin-3 is tightly regulated by posttranslational modifications, the COP9 signalosome, and BTB/POZ-domain proteins that link cullin-3 to specific substrates for ubiquitylation. In this paper, we report how potassium channel tetramerization domain containing 6 (KCTD6) represents a novel substrate adaptor for cullin-3, effectively regulating protein levels of the muscle small ankyrin-1 isoform 5 (sAnk1.5). Binding of sAnk1.5 to KCTD6, and its subsequent turnover is regulated through posttranslational modification by nedd8, ubiquitin, and acetylation of C-terminal lysine residues. The presence of the sAnk1.5 binding partner obscurin, and mutation of lysine residues increased sAnk1.5 protein levels, as did knockdown of KCTD6 in cardiomyocytes. Obscurin knockout muscle displayed reduced sAnk1.5 levels and mislocalization of the sAnk1.5/KCTD6 complex. Scaffolding functions of obscurin may therefore prevent activation of the cullin-mediated protein degradation machinery and ubiquitylation of sAnk1.5 through sequestration of sAnk1.5/KCTD6 at the sarcomeric M-band, away from the Z-disk-associated cullin-3. The interaction of KCTD6 with ankyrin-1 may have implications beyond muscle for hereditary spherocytosis, as KCTD6 is also present in erythrocytes, and erythrocyte ankyrin isoforms contain its mapped minimal binding site.
Published: 2012

28. Predictive Biomarkers for Immunotherapy in Lung Cancer: Perspective From the International Association for the Study of Lung Cancer Pathology Committee

Author: Mari, Mino-Kenudson, Kurt, Schalper, Wendy, Cooper, Sanja, Dacic, Fred R, Hirsch, Deepali, Jain, Fernando, Lopez-Rios, Ming Sound, Tsao, Yasushi, Yatabe, Mary Beth, Beasley, Hui, Yu, Lynette M, Sholl, Elizabeth, Brambilla, Teh-Ying, Chou, Casey, Connolly, Ignacio, Wistuba, Keith M, Kerr, and Sylvie, Lantuejoul
Subjects: Pulmonary and Respiratory Medicine, Lung Neoplasms, Oncology, Carcinoma, Non-Small-Cell Lung, Biomarkers, Tumor, Tumor Microenvironment, Humans, Immunotherapy, B7-H1 Antigen
Abstract: Immunotherapy including immune checkpoint inhibitors (ICIs) has become the backbone of treatment for most lung cancers with advanced or metastatic disease. In addition, they have increasingly been used for early stage tumors in neoadjuvant and adjuvant settings. Unfortunately, however, only a subset of patients experiences meaningful response to ICIs. Although programmed death-ligand 1 (PD-L1) protein expression by immunohistochemistry (IHC) has played a role as the principal predictive biomarker for immunotherapy, its performance may not be optimal, and it suffers multiple practical issues with different companion diagnostic assays approved. Similarly, tumor mutational burden (TMB) has multiple technical issues as a predictive biomarker for ICIs. Now, ongoing research on tumor- and host immune-specific factors has identified immunotherapy biomarkers that may provide better response and prognosis prediction, in particular in a multimodal approach. This review by the International Association for the Study of Lung Cancer Pathology Committee provides an overview of various immunotherapy biomarkers, including updated data on PD-L1 IHC and TMB, and assessments of neoantigens, genetic and epigenetic signatures, immune microenvironment by IHC and transcriptomics, and microbiome and pathologic response to neoadjuvant immunotherapies. The aim of this review is to underline the efficacy of new individual or combined predictive biomarkers beyond PD-L1 IHC and TMB.
Published: 2022

29. Correlations between Clinical and Histopathologic Characteristics in Idiopathic Epiretinal Membrane

Author: Lei-Chi Wang, Wen-Jung Lo, Ya-Yun Huang, Yu-Bai Chou, An-Fei Li, Shih-Jen Chen, Teh-Ying Chou, and Tai-Chi Lin
Subjects: Ophthalmology, Vitrectomy, Visual Acuity, Humans, Epiretinal Membrane, Tomography, Optical Coherence, Retrospective Studies
Abstract: To investigate correlations between clinical and histopathologic characteristics of idiopathic epiretinal membrane (ERM).Retrospective interventional case series.In total, 87 eyes from 87 patients with idiopathic ERM who underwent pars plana vitrectomy with peeling of the ERM from 2019 to 2020 were included.The outcomes of clinical ophthalmic examination, including measurement of best-corrected visual acuity (BCVA) and spectral-domain OCT (SD-OCT), before and after surgery were reviewed. Surgical specimens were fixed in formalin and embedded in paraffin for histologic and immunohistochemical analysis.The association between morphological characteristics revealed on SD-OCT images and the cellular composition of the surgically excised ERM demonstrated with immunohistochemical staining were the main outcome measures. Changes in the BCVA and central macular thickness (CMT) were assessed through a comparison of preoperative and postoperative measurements.Based on SD-OCT morphological characteristics in the foveal area, 15 cases were classified into group 1A (mainly outer retinal thickening), 39 into group 1B (more tenting of the outer retina and distorted inner retina), and 33 into group 1C (prominent inner retina thickening). Overall, postoperative final BCVA and CMT at 1 year improved in all groups. Patients who presented with a better initial BCVA exhibited a more favorable final BCVA. Epiretinal membranes in group 1C demonstrated the greatest decrease in CMT compared with those in groups 1B and 1A, but the final CMT did not differ among the groups. A negative correlation between the density of hyalocytes (P = 0.003) and myofibroblasts (P = 0.047) was noted between the 3 groups. Total cell density and glial cell density of the ERMs were strongly associated with poor final BCVA and BCVA improvement.The present study provides new histopathologic information regarding the formation and progression of idiopathic ERM. Glial cell proliferation plays a predominant role in these processes. Epiretinal membranes with high cellularity and glial cell density may cause damage to the retina structure, resulting in poor postoperative visual outcomes. These findings provide additional evidence supporting early surgical intervention in patients with idiopathic ERM reported with visual disturbance.
Published: 2022

30. The role of taxation in tobacco control and its potential economic impact in China

Author: Hu, Teh-wei, Mao, Zhengzhong, Shi, Jian, and Chen, Wendong
Subjects: Applied Economics, Economics, Public Health, Health Sciences, Human Society, Prevention, Cancer, Tobacco, Tobacco Smoke and Health, Good Health and Well Being, China, Cost-Benefit Analysis, Humans, Models, Economic, Smoking, Smoking Cessation, Smoking Prevention, Taxes, Tobacco Industry
Abstract: ObjectivesTo identify key economic issues involved in raising the tobacco tax and to recommend possible options for tobacco tax reform in China.MethodsEstimated price elasticities of the demand for cigarettes, prevalence data and epidemiology are used to estimate the impact of a tobacco tax increase on cigarette consumption, government tax revenue, lives saved, employment and revenue loss in the cigarette industry and tobacco farming.ResultsThe recent Chinese tax adjustment, if passed along to the retail price, would reduce the number of smokers by 630,000 saving 210,000 lives, at a price elasticity of -0.15. A tax increase of 1 RMB (or US$0.13) per pack of cigarettes would increase the Chinese government's tax revenue by 129 billion RMB (US 17.2 billion), decrease consumption by 3.0 billion packs of cigarettes, reduce the number of smokers by 3.42 million and save 1.14 million lives.ConclusionThe empirical economic analysis and tax simulation results clearly indicate that increasing the tobacco tax in China is the most cost-effective instrument for tobacco control.
Published: 2010

31. Immunogenicity of COVID-19 vaccines in patients with hematologic malignancies: a systematic review and meta-analysis

Author: Monica A. Slavin, Smaro Lazarakis, Tim Spelman, Benjamin W Teh, Joanne S.K. Teh, Zoe C.F. Neoh, and Julien Coussement
Subjects: medicine.medical_specialty, COVID-19 Vaccines, Malignancy, immune response, Immune system, Internal medicine, medicine, Humans, Adverse effect, SARS-CoV-2, business.industry, Immunogenicity, COVID-19, Hematology, Odds ratio, vaccination, medicine.disease, Antibodies, Neutralizing, Confidence interval, Vaccination, Hematologic Neoplasms, Meta-analysis, Systematic Review, business, haematological, malignancy
Abstract: The objectives of this study were to assess the immunogenicity and safety of COVID-19 vaccines in patients with hematologic malignancies. A systematic review and meta-analysis of clinical studies of immune responses to COVID-19 vaccination stratified by underlying malignancy and published from January 1, 2021, to August 31, 2021, was conducted using MEDLINE, EMBASE, and Cochrane CENTRAL. Primary outcome was the rate of seropositivity after 2 doses of COVID-19 vaccine with rates of seropositivity after 1 dose, rates of positive neutralizing antibodies, cellular responses, and adverse events as secondary outcomes. Rates were pooled from single-arm studies while rates of seropositivity were compared against the rate in healthy controls for comparator studies using a random effects model and expressed as a pooled odds ratios with 95% confidence intervals. Forty-four studies (16 mixed group, 28 disease specific) with 7064 patients were included in the analysis (2331 after first dose, 4733 after second dose). Overall seropositivity rates were 62% to 66% after 2 doses of COVID-19 vaccine and 37% to 51% after 1 dose. The lowest seropositivity rate was 51% in patients with chronic lymphocytic leukemia and was highest in patients with acute leukemia (93%). After 2 doses, neutralizing antibody response rates were 57% to 60%, and cellular response rates were 40% to 75%. Active treatment, ongoing or recent treatment with targeted and CD-20 monoclonal antibody therapies within 12 months were associated with poor immune responses to COVID-19 vaccine. New approaches to prevention are urgently required to reduce COVID-19 infection morbidity and mortality in high-risk patient groups that respond poorly to COVID-19 vaccination.
Published: 2022

32. Comparison of Clinical Outcomes Between Low- and High-Risk Groups of Early Breast Cancer Patients Treated with Intraoperative Radiotherapy in Addition to External Beam Radiation: A Multi-Centre Prospective Study

Author: J. A. Mosiun, Mee-Hoong See, Li-Ying Teoh, Mahmoud Danaee, Lee-Lee Lai, Char-Hong Ng, Cheng-Har Yip, Mei-Sze Teh, Nur Aishah Md Taib, Anita Bustam, Rozita Abdul Malik, Marniza Saad, Suniza Jamaris, and Ngie-Min Ung
Subjects: Humans, Female, Breast Neoplasms, Surgery, Prospective Studies, Social Group
Abstract: There is a paucity of data on the use of intraoperative radiotherapy (IORT) with low-energy X-rays in Malaysian women with early breast cancer. The aim of this study is to evaluate the clinical, cosmetic, and patient-reported outcomes in low- and high-risk early breast cancer patients treated with breast conserving surgery (BCS) and IORT.Patients suitable for BCS who were treated with IORT between January 2016 and June 2019 from three centres were analysed. They were divided into low-risk and high-risk groups based on the risk of recurrence according to the TARGeted Intraoperative radioTherapy (TARGIT) A and B study criteria. Outcomes of interest included local recurrence, wound complications, and radiation toxicity, with a subset analysed for cosmetic and patient-reported outcomes.Within a median follow-up of 31 months, there were 104 and 211 patients in the low- and high-risk groups, respectively. No significant difference was observed in local recurrence rates (low-risk, 1.0% vs. high-risk, 1.4%; p = 1.000). Both cohorts exhibited low frequencies of severe wound complications ranging between 1.4 and 1.9%. No major radiation toxicities were reported in either group. In the subgroup analysis, low-risk patients had significantly better mean scores in the subscales of inframammary fold and scar. Based on the BREAST-Q patient-reported outcomes questionnaire, seven out of nine parameters were scored similarly between both groups with no significant difference.This study showed that the use of IORT in both low- and high-risk early breast cancers is efficacious and safe with low recurrence rates and an acceptable toxicity profile.
Published: 2022

33. Genomic profiling with whole‐exome sequencing revealed distinct mutations and novel pathways in Asian melanoma

Author: Yu‐Jen Chiu, Hui‐Ying Weng, Yen‐Yu Lin, Yung‐Feng Lin, Yi‐Chen Yeh, Chern‐Kang Perng, Hsu Ma, Shih‐Feng Tsai, and Teh‐Ying Chou
Subjects: Skin Neoplasms, Exome Sequencing, Mutation, Humans, Genomics, Dermatology, General Medicine, Melanoma
Abstract: The clinical characteristics of malignant melanoma are highly variable between patient populations of different ethnicities. To explore the underlining genetic variations, we reviewed the clinical data of 242 malignant melanoma cases from Taiwan and among them submitted formalin-fixed paraffin-embedded tissue samples from 37 patients for whole-exome sequencing to identify the mutational signatures, tumor mutation burden and specific gene mutations. The genomic profiles and clinical outcomes were compared with the information derived from the publicly available TCGA and TGEN databases. Mutation signature 12 was the dominant signature in Taiwanese patients and represented approximately 45% of the mutation signatures observed. In contrast, mutation signature 7 was the most prominent among cases available in the TCGA database. Common gene mutations found in the TCGA melanoma dataset were not frequently found in melanomas from Taiwanese patients. There were a significant number of specific gene mutations that exclusively occurred in acral subtype but not in non-acral subtype melanomas, and vice versa. While certain common mutations form a shared core of genetic features, there appear to be specific genetic pathways that are involved in the occurrence of melanomas that grow in non-UV-exposed areas. Our findings have shed light on the tumorigenesis pathways involved in malignant melanoma.
Published: 2022

34. Emicizumab assay evaluations and results from an Australian field study of emicizumab measurement

Author: Geoffrey Kershaw, Caroline Dix, Vivien M. Chen, Nancy Cai, and Teh-Liane Khoo
Subjects: Sleep Apnea, Obstructive, Factor VIII, Antibodies, Bispecific, Australia, Humans, Antibodies, Monoclonal, Humanized, Hemophilia A, Pathology and Forensic Medicine
Abstract: Emicizumab is a recombinant, humanised bispecific antibody which acts as a FVIII mimetic and is a therapeutic option for haemophilia A. Plasma emicizumab levels may sometimes be required. Multiple one-stage clotting assays (OSA) and one human component chromogenic assay (CSA) were used to measure emicizumab both centrally and by a field study. The study samples drug concentrations range included within therapy range of 35-70 μg/mL. All assays were modified from traditional FVIII assays to enable replacement of plasma calibrators with emicizumab calibrators. Central laboratory OSA mean recovery levels (target) for six spike levels of emicizumab were close to target at 120.5 (120), 81.6 (80), 40.9 (40), 21.4 (20), 10.7 (10) and 5.5 (5) μg/mL. Field study OSA mean recoveries were similarly close to target. Between method coefficients of variation were9% in both the central laboratory and field study assays, except for the 5 μg/mL sample which was 12.3%. CSA mean recoveries were within 10% of target at 80, 50 and 20 μg/mL levels. This study affirms that emicizumab can be measured by OSA using many types of activated partial thromboplastin time (APTT) reagents and is also measurable by the human CSA. The assays showed good precision, accuracy and linearity both locally and in a field study setting.
Published: 2022

35. Predictors of histologic response to dietary therapy in eosinophilic oesophagitis

Author: Lillian Wang, Kristin C. Mara, Karthik Ravi, Tsung‐Teh Wu, Thomas C. Smyrk, David A. Katzka, and Jeffrey A. Alexander
Subjects: Adult, Hepatology, Food, Biopsy, Gastroenterology, Humans, Pharmacology (medical), Eosinophilic Esophagitis, Retrospective Studies, Diet
Abstract: Dietary therapy successfully treats eosinophilic oesophagitis (EoE), but limited data exist on predictors of patient response.To determine response rates and to identify predictors of histologic response to elimination diets in adults with EoE METHODS: This was a retrospective, single-centre study of adults with PPI-refractory EoE undergoing dietary therapy with six food elimination diet (SFED) or extended six food elimination diet (ExSFED) in an outpatient setting from January 2012 to January 2019. Patient demographics, radiologic and endoscopic findings, endoscopic reference (EREF) scores, histology and symptoms were evaluated before and after food elimination. Histologic response was assessed via tissue obtained from endoscopically-guided biopsy or Cytosponge. Dietary therapy adherence was assessed via structured phone interview. Multivariable logistic regression analysis was performed to identify predictors of dietary response.We included 68 patients, of whom 62% had a histologic response to dietary therapy (81% to SFED, 19% to ExSFED). Median duration of follow-up was 45 months (IQR, 34-53 months). On multivariable analysis, higher pre-SFED EREF score was the only variable associated with dietary non-response (OR 0.07, 95% CI 0.49, 0.98; p = 0.04).In adults with EoE, histologic dietary non-response to SFED was associated with a higher pre-SFED EREF score, suggesting that fixed structural disease may predict dietary non-response. Our additional observations of poor correlation between symptomatic and histologic flares, and identification of ExSFED responders, suggest that histologic confirmation should be sought before committing patients to lifelong dietary changes. We also recommend the consideration of restricting legumes and corn in SFED non-responders as ExSFED detected additional dietary responders.
Published: 2022

36. Tumor burden score as a new prognostic surrogate in patients with hepatocellular carcinoma undergoing radiofrequency ablation: role of albumin-bilirubin (ALBI) grade vs easy ALBI grade

Author: Shu-Yein, Ho, Po-Hong, Liu, Chia-Yang, Hsu, Yi-Hsiang, Huang, Jia-I, Liao, Chien-Wei, Su, Ming-Chih, Hou, and Teh-Ia, Huo
Subjects: Radiofrequency Ablation, Carcinoma, Hepatocellular, Hepatology, Liver Neoplasms, Gastroenterology, Humans, Bilirubin, alpha-Fetoproteins, Neoplasm Recurrence, Local, Prognosis, Serum Albumin, Tumor Burden, Retrospective Studies
Abstract: Tumor burden score (TBS) was proposed to represent tumor burden in solid tumors, including hepatocellular carcinoma (HCC). The prognostic role of TBS in HCC patients in relation to recently introduced liver reserve markers, albumin-bilirubin (ALBI) grade, and easy (EZ)-ALBI grade, is unclear. We aimed to investigate the feasibility of TBS in HCC patients undergoing radiofrequency ablation (RFA).A total of 576 treatment-naïve patients with HCC undergoing RFA were analyzed. The multivariate Cox analysis was used to identify independent predictors associated with tumor recurrence and long-term survival.Patients with high TBS had increased risk of tumor recurrence and mortality compared with those with low TBS. The Cox analysis showed that serum ɑ-fetoprotein (AFP) level20 ng/mL, medium and high TBS, ALBI grade 2 and grade 3, EZ-ALBI grade 2 and grade 3 were associated with tumor recurrence and decreased patient survival (all p0.05). In addition, TBS can reliably stratify tumor recurrence and overall survival in different ALBI and EZ-ALBI grade groups.TBS is a simple and feasible prognostic surrogate to predict tumor recurrence and survival in HCC patients undergoing RFA. Its prognostic ability remains stable in patients with variable liver functional reserve.
Published: 2022

37. 21-Gene recurrence score predictive for prognostic benefit of radiotherapy in patients age ≥ 70 with T1N0 ER/PR + HER2- breast cancer treated with breast conserving surgery and endocrine therapy

Author: Neil, Chevli, Waqar, Haque, Kevin T, Tran, Andrew M, Farach, Mary R, Schwartz, Sandra S, Hatch, E Brian, Butler, and Bin S, Teh
Subjects: Cohort Studies, ErbB Receptors, Oncology, Humans, Breast Neoplasms, Female, Radiotherapy, Adjuvant, Radiology, Nuclear Medicine and imaging, Hematology, Neoplasm Recurrence, Local, Mastectomy, Segmental, Prognosis, Retrospective Studies
Abstract: Based on the results of the Cancer and Leukemia Group B (CALGB) 9343 trial, patients age ≥70 with T1N0 hormone receptor positive (ER/PR+), human epidermal growth factor receptor-2 negative (HER2-) breast cancer who are treated with breast conserving surgery (BCS) and endocrine therapy (ET) are candidates for omission of radiotherapy (RT). Because the CALGB 9343 trial did not stratify based on recurrence score (RS) test (Oncotype Dx), we conducted the present retrospective study to determine whether RS is predictive of who may benefit from RT following BCS in this cohort.The National Cancer Database (NCDB) was queried (2004-2017) for patients age ≥ 70 with pT1N0 ER+/PR + HER2- breast cancer treated with BCS and ET. Patients were stratified based on their RS (low risk [LR] = 1-10, intermediate risk [IR] = 11-25, high risk [HR] = 26-99). Propensity score matching (PSM) created 1:1 matched cohorts of patients who received radiotherapy and those who did not. Kaplan-Meier analysis evaluated overall survival (OS). Univariable (UVA) and multivariable (MVA) Cox proportional hazard analyses identified clinical and treatment factors prognostic for OS.A total of 11,891 patients met the selection criteria: 3364 in the LR cohort, 7305 in the IR cohort, and 1222 in the HR cohort. A total of 79 % received RT: 77 % in the LR cohort, 79 % in the IR cohort, and 85 % in the HR cohort. Because PSM could not be efficiently performed in the HR cohort alone, the IR and HR cohort were merged (IRHR) for matching. After PSM, the 5-year OS in the LR cohort was 91 % for those who received RT and 89 % for those who did not (p = 0.605). In the IRHR cohort, the 5-year OS was 91 % for those who received RT and 87 % for those who did not (p = 0.003). On MVA in the LR cohort, RT (p = 0.727) was not predictive of improved OS. On MVA in the IRHR cohort, RT (p = 0.010) was a positive prognostic factor for OS.In this older cohort of patients, there is an OS benefit with the use of RT in patients with IRHR RS but not in patients with LR RS. Pending prospective evaluation, assessment of RS in this older subset of patients is recommended with consideration of RT when RS is ≥11.
Published: 2022

38. Rapid Histological Assessment of Prostate Specimens in the Three-dimensional Space by Hydrophilic Tissue Clearing and Confocal Microscopy

Author: Yu-Ching Peng, Yu-Chieh Lin, Yu-Ling Hung, Chien-Chung Fu, Margaret Dah-Tsyr Chang, Yen-Yin Lin, and Teh-Ying Chou
Subjects: Male, Prostatectomy, Histology, Microscopy, Confocal, Prostate, Humans, Prostatic Neoplasms, Anatomy, Neoplasm Grading, Coloring Agents
Abstract: Microscopic examination of biopsied and resected prostatic specimens is the mainstay in the diagnosis of prostate cancer. However, conventional analysis of hematoxylin and eosin (H&E)-stained tissue is time-consuming and offers limited two-dimensional (2D) information. In the current study, we devised a method—termed Prostate Rapid Optical examination for cancer STATus (proSTAT)—for rapid screening of prostate cancer using high-resolution 2D and three-dimensional (3D) confocal images obtained after hydrophilic tissue clearing of 100-µm-thick tissue slices. The results of the proSTAT method were compared with those of traditional H&E stains for the analysis of cores ( n=15) obtained from radical prostatectomy specimens ( n=5). Gland lumen formation, consistent with Gleason pattern 3, was evident following tracking of multiple optical imaging sections. In addition, 3D rendering allowed visualizing a tubular network of interconnecting branches. Rapid 3D fluorescent labeling of tumor protein p63 accurately distinguished prostate adenocarcinoma from normal tissue and benign lesions. Compared with conventional stains, the 3D spatial and molecular information extracted from proSTAT may significantly increase the amount of available data for pathological assessment of prostate specimens. Our approach is amenable to automation and—subject to independent validation—can find a wide spectrum of clinical and research applications.
Published: 2023

39. Oncogenic circRNA C190 Promotes Non–Small Cell Lung Cancer via Modulation of the EGFR/ERK Pathway

Author: Yuh Min Chen, Jerry Chieh-Yu Chen, Chian Shiu Chien, Yueh Chien, Teh Ia Huo, Afeez Adekunle Ishola, Shih Hwa Chiou, Po-Kuei Hsu, Aliaksandr A. Yarmishyn, Mong Lien Wang, Ping-Hsing Tsai, Ming-Teh Chen, Yuan-Tzu Lan, Yung-Hung Luo, Yi-Ping Yang, Hsin-I Ma, and Kung-Hao Liang
Subjects: Male, MAPK/ERK pathway, Cancer Research, Lung Neoplasms, Cell, Mice, Nude, Mice, Cyclin-dependent kinase, Carcinoma, Non-Small-Cell Lung, medicine, Animals, Humans, Gene knockdown, Cyclin-dependent kinase 1, biology, Chemistry, Kinase, Oncogenes, RNA, Circular, Cell cycle, ErbB Receptors, Disease Models, Animal, medicine.anatomical_structure, Oncology, Cancer research, biology.protein, Cyclin-dependent kinase 6
Abstract: Lung cancers are the leading cause of cancer-related mortality worldwide, and the majority of lung cancers are non–small cell lung carcinoma (NSCLC). Overexpressed or activated EGFR has been associated with a poor prognosis in NSCLC. We previously identified a circular noncoding RNA, hsa_circ_0000190 (C190), as a negative prognostic biomarker of lung cancer. Here, we attempted to dissect the mechanistic function of C190 and test the potential of C190 as a therapeutic target in NSCLC. C190 was upregulated in both NSCLC clinical samples and cell lines. Activation of the EGFR pathway increased C190 expression through a MAPK/ERK-dependent mechanism. Transient and stable overexpression of C190 induced ERK1/2 phosphorylation, proliferation, and migration in vitro and xenograft tumor growth in vivo. RNA sequencing and Expression2Kinases (X2K) analysis indicated that kinases associated with cell-cycle and global translation are involved in C190-activated networks, including CDKs and p70S6K, which were further validated by immunoblotting. CRISPR/Cas13a-mediated knockdown of C190 decreased proliferation and migration of NSCLC cells in vitro and suppressed tumor growth in vivo. TargetScan and CircInteractome databases predicted that C190 targets CDKs by sponging miR-142-5p. Analysis of clinical lung cancer samples showed that C190, CDK1, and CDK6 expressions were significantly higher in advanced-stage lung cancer than in early-stage lung cancer. In summary, C190 is directly involved in EGFR–MAPK–ERK signaling and may serve as a potential therapeutic target for the treatment of NSCLC. Significance: The circRNA C190 is identified as a mediator of multiple pro-oncogenic signaling pathways in lung cancer and can be targeted to suppress tumor progression.
Published: 2022

40. The BILAG-2004 index is associated with development of new damage in SLE

Author: Chee-Seng Yee, Caroline Gordon, Mohammed Akil, Peter Lanyon, Christopher J Edwards, David A Isenberg, Anisur Rahman, Lee-Suan Teh, Sofia Tosounidou, Robert Stevens, Athiveeraramapandian Prabu, Bridget Griffiths, Neil McHugh, Ian N Bruce, Yasmeen Ahmad, Munther A Khamashta, Vernon T Farewell, Yee, Chee-Seng [0000-0003-1715-4869], Gordon, Caroline [0000-0002-1244-6443], Isenberg, David A [0000-0001-9514-2455], Rahman, Anisur [0000-0003-2346-4484], Teh, Lee-Suan [0000-0002-7452-2659], McHugh, Neil [0000-0003-2765-658X], Bruce, Ian N [0000-0003-3047-500X], and Apollo - University of Cambridge Repository
Subjects: Rheumatology, Heart Disease Risk Factors, SLE, Humans, Lupus Erythematosus, Systemic, Pharmacology (medical), Longitudinal Studies, BILAG-2004, damage, disease activity, mortality, Severity of Illness Index, Article
Abstract: Objective To determine whether BILAG-2004 index is associated with the development of damage in a cohort of SLE patients. Mortality and development of damage were examined. Methods This was a multicentre longitudinal study. Patients were recruited within 12 months of achieving fourth ACR classification criterion for SLE. Data were collected on disease activity, damage, SLE-specific drug exposure, cardiovascular risk factors, antiphospholipid syndrome status and death at every visit. This study ran from 1 January 2005 to 31 December 2017. Descriptive statistics were used to analyse mortality and development of new damage. Poisson regression was used to examine potential explanatory variables for development of new damage. Results A total of 273 SLE patients were recruited with total follow-up of 1767 patient-years (median 73.4 months). There were 6348 assessments with disease activity scores available for analysis. During follow-up, 13 deaths and 114 new damage items (in 83 patients) occurred. The incidence rate for development of damage was higher in the first 3 years before stabilizing at a lower rate. Overall rate for damage accrual was 61.1 per 1000 person-years (95% CI: 50.6, 73.8). Analysis showed that active disease scores according to BILAG-2004 index (systems scores of A or B, counts of systems with A and BILAG-2004 numerical score) were associated with development of new damage. Low disease activity (LDA) states [BILAG-2004 LDA and BILAG Systems Tally (BST) persistent LDA] were inversely associated with development of damage. Conclusions BILAG-2004 index is associated with new damage. BILAG-2004 LDA and BST persistent LDA can be considered as treatment targets.
Published: 2023

41. Deep exploration of immune function in EGFR wild-type and mutated lung adenocarcinomas by gene expression profiling: role of TRAIL-R2 (TNFRSF10B) in patient treatment and outcome

Author: Wei-Chin Chang, Yi-Chen Yeh, Hsiang-Ling Ho, and Teh-Ying Chou
Subjects: Lung Neoplasms, Gene Expression Profiling, Immunity, Adenocarcinoma of Lung, Adenocarcinoma, Prognosis, Pathology and Forensic Medicine, ErbB Receptors, Receptors, TNF-Related Apoptosis-Inducing Ligand, Treatment Outcome, Mutation, Tumor Microenvironment, Humans, RNA, Messenger
Abstract: The tumor microenvironment is important in the initiation and progression of lung adenocarcinoma (LUAD). In this study, we aim to analyze the expression profile of immune-related genes in LUADs, examine the differential expression of immune-related genes in epidermal growth factor receptor (EGFR) wild-type and mutant LUADs, and the clinicopathologic significance of these differentially expressed genes. We used the NanoString PanCancer Immune Profiling Panel to examine 34 cases of LUADs (18 EGFR wild-type, 16 EGFR mutant). In EGFR wild-type LUADs, the macrophage and neutrophil signatures are significantly higher, and significantly higher expression of chemokines, interleukins, leukocyte, macrophage, natural killer cell, pathogen defense, Tumor necrosis factor superfamily, and transporter function signatures are also observed. TNFRSF10B mRNA was preferentially expressed in EGFR wild-type LUADs (P = 6.15e-6, adjusted P = .0244). Immunohistochemical staining for TRAIL-R2 (encoded by TNFRSF10B) on 134 tissue microarray LUAD cases demonstrated strong, moderate, and weak staining in 75 (56.0%), 46 (34.3%), and 13 (9.7%) cases, respectively. Strong TRAIL-R2 expression was significantly associated with poor overall survival (OS) in all stages and EGFR wild-type LUADs, but not in EGFR-mutant tumors. Furthermore, strong TRAIL-R2 expression (P = .004) was an independent risk factor for poor OS. In summary, TNFRSF10B mRNA revealed significantly higher expression in EGFR wild-type LUADs, and strong TRAIL-R2 expression predicts an unfavorable prognosis for these tumors. These patients may benefit from additional treatment with TRAIL-R2-targeted therapies.
Published: 2022

42. Predictive Accuracy of Digital Biomarker Technologies for Detection of Mild Cognitive Impairment and Pre-Frailty Amongst Older Adults: A Systematic Review and Meta-Analysis

Author: Seng-Khoon Teh, Iris Rawtaer, and Hwee Pink Tan
Subjects: Early Diagnosis, Frailty, Health Information Management, Alzheimer Disease, Humans, Cognitive Dysfunction, Health Informatics, Electrical and Electronic Engineering, Sensitivity and Specificity, Biomarkers, Aged, Computer Science Applications
Abstract: Digital biomarker technologies coupled with predictive models are increasingly applied for early detection of age-related potentially reversible conditions including mild cognitive impairment (MCI) and pre-frailty (PF). We aimed to determine the predictive accuracy of digital biomarker technologies to detect MCI and PF with systematic review and meta-analysis. A computer-assisted search on major academic research databases including IEEE-Xplore was conducted. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines were adopted for reporting in this study. Summary receiver operating characteristic curve based on random-effect bivariate model was used to evaluate overall sensitivity and specificity for detection of the respective age-related conditions. A total of 43 studies were selected for final systematic review and meta-analysis. 26 studies reported on detection of MCI with sensitivity and specificity of 0.48-1.00 and 0.55-1.00, respectively. On the other hand, there were 17 studies that reported on the detection of PF with reported sensitivity of 0.53-1.00 and specificity of 0.61-1.00. Meta-analysis further revealed pooled sensitivities of 0.84 (95% CI: 0.79-0.88) and 0.82 (95% CI: 0.74-0.88) for in-home detection of MCI and PF, respectively, while pooled specificities were 0.85 (95% CI: 0.80-0.89) and 0.82 (95% CI: 0.75-0.88), respectively. Besides MCI, and PF, in this work during systematic review, we also found one study which reported a sensitivity of 0.93 and a specificity of 0.57 for detection of cognitive frailty (CF). The meta-analytic result, for the first time, quantifies the predictive efficacy of digital biomarker technologies for detection of MCI and PF. Additionally, we found the number of studies for detection of CF to be notably lower, indicating possible research gaps to explore predictive models on digital biomarker technology for detection of CF.
Published: 2022

43. Burden of pertussis among young infants in Malaysia: A hospital-based surveillance study

Author: Thahira J. Mohamed, Siew M. Fong, Thiyagar Nadarajaw, Chong M. Choo, Nik Khairulddin Nik Yusoff, Jeyaseelan P. Nachiappan, Kwai Cheng Chan, M.T. Koh, Fairuz Amran, Rohaidah Hashim, Kartini A. Jabar, Cindy Shuan Ju Teh, Denis Macina, and Hishamshah Mohd Ibrahim
Subjects: Pertussis Vaccine, General Veterinary, General Immunology and Microbiology, Whooping Cough, Vaccination, Malaysia, Public Health, Environmental and Occupational Health, Infant, Hospitals, Cross-Sectional Studies, Infectious Diseases, Humans, Molecular Medicine, Female, Child
Abstract: The case fatality rate and the risk of complications due to pertussis is very high in infants. Asia has the second highest childhood pertussis burden. The study aimed to assess the prevalence, clinical complications, and mortality rates of pertussis disease requiring hospitalization among young infants in Malaysia.The study was a one-year, hospital-based, multi-site surveillance of infants less than six months of age with symptoms consistent with pertussis and a cross-sectional analysis of their mothers for recent pertussis infection. Information was obtained from medical records and interviews with the parents. Pertussis diagnosis was confirmed for all infants through serum anti-PT titration test or PCR test.441 possible cases of pertussis were included in this study. Of these, 12.7 % had laboratory confirmation of pertussis. Infants with confirmed pertussis had significantly higher rates of cyanosis (37.5 % vs 8.6 %; p 0.0001) and apnea (12.5 % vs 3.9 %; p = 0.027) than test-negative infants. Most infants from both groups were in recovery/recovered at discharge. Those with confirmed pertussis had higher case fatality rate than test-negative cases (5.4 % vs 1.0 %; p = 0.094), but the difference did not reach significance. The majority of confirmed pertussis cases (89.3 %) occurred in infants too young to be fully vaccinated or under-vaccinated for their age. Both test-negative and confirmed pertussis resulted in work-day losses and incurred costs for both parents.A high pertussis disease burden persists in infants less than six months of age, especially among those un- and under-vaccinated. Maternal and complete, on-time infant vaccination is important to reduce disease burden.
Published: 2022

44. Evaluating suggested stricter gamma criteria for linac-based patient-specific delivery QA in the conventional and SBRT environments

Author: Robert A, Price, Iavor, Veltchev, Teh, Lin, Ahmed, Eldib, Lili, Chen, Lihui, Jin, Xiaoming, Chen, Jie, Liu, Lu, Wang, and C-M Charlie, Ma
Subjects: Gamma Rays, Radiotherapy Planning, Computer-Assisted, Biophysics, Humans, General Physics and Astronomy, Radiotherapy Dosage, Radiology, Nuclear Medicine and imaging, Radiotherapy, Intensity-Modulated, General Medicine, Particle Accelerators, Radiosurgery
Abstract: To evaluate AAPM TG-218 recommended tolerances for IMRT QA for conventional and SBRT delivery.QA analysis was repeated for 150 IMRT/VMAT patients with varying gamma criteria. True composite delivery was utilized, corrected for detector and output variation. Universal tolerance (TLThe IMRT/VMAT TLThe AL
Published: 2022

45. Clinicohistological and immunopathological features of patients with cutaneous lupus erythematosus at tertiary dermatology centre in Malaysia

Author: Yeon Chiat Teh, Chai Har Loo, Norazlima Mohd Ali, Ai Lee Lim, and Wooi Chiang Tan
Subjects: Male, Cross-Sectional Studies, Lupus Erythematosus, Discoid, Lupus Erythematosus, Cutaneous, Malaysia, Humans, Lupus Erythematosus, Systemic, Female, Dermatology, Severity of Illness Index
Abstract: Background Cutaneous lupus erythematosus (CLE) is a chronic, autoimmune skin disease with a wide spectrum of clinical presentations in different populations. Aim To study the clinicohistological and immunological features of CLE in a multiethnic population and to identify the predictive factors of disease severity based on the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Methods This was a cross-sectional study of CLE conducted from March 2019 to February 2020. Results In total, 111 patients were recruited with a female/male ratio of 4.9 : 1. Acute CLE contributed 47.7%, followed by chronic CLE at 46.9% and subacute CLE at 5.4%. A large majority (84%) of patients had systemic lupus erythematosus. Of patients with chronic CLE, about 67.3% developed systemic involvement. Antinuclear antibody (ANA) was detected in 90.0%. Skin biopsy was taken from 42 patients and showed perivascular lymphocytic infiltration (95.2%), epidermal atrophy (47.6%) and hydropic degeneration of the basal layer (47.6%). Immunoglobulin deposition at the dermoepidermal junction was seen in > 40% of patients, predominantly in a granular pattern. Mean CLASI Total was 6.44 ± 7.70, while CLASI Activity (CLASI-A) was 2.75 ± 4.10 and CLASI Damage (CLASI-D) was 3.71 ± 4.76. Involved body surface area (BSA) was found to be an independent predictive factor for CLASI-A (OR = 1.34, P Conclusions We observed a high percentage of patients with CLE with systemic manifestations and positive ANA result. More aggressive treatment of patients with positive predictive factors for severe disease combined with significant clinical activity may be warranted.
Published: 2022

46. Chromatin Rewiring by Mismatch Repair Protein MSH2 Alters Cell Adhesion Pathways and Sensitivity to BET Inhibition in Gastric Cancer

Author: Amrita M. Nargund, Chang Xu, Amit Mandoli, Atsushi Okabe, Gao Bin Chen, Kie Kyon Huang, Taotao Sheng, Xiaosai Yao, Jia Ming Nickolas Teo, Raghav Sundar, Yee Jiun Kok, Yi Xiang See, Manjie Xing, Zhimei Li, Chern Han Yong, Aparna Anand, Zul Fazreen Bin Adam Isa, Lai Fong Poon, Michelle Shu Wen Ng, Javier Yu Peng Koh, Wen Fong Ooi, Su Ting Tay, Xuewen Ong, Angie Lay Keng Tan, Duane T. Smoot, Hassan Ashktorab, Heike I. Grabsch, Melissa J. Fullwood, Bin Tean Teh, Xuezhi Bi, Atsushi Kaneda, Shang Li, Patrick Tan, Pathologie, RS: GROW - R2 - Basic and Translational Cancer Biology, School of Biological Sciences, and National University of Singapore
Subjects: Cancer Research, MUTATIONS, Protein, HMSH2, INSTABILITY, DNA Helicases, Nuclear Proteins, PROTEIN, DNA MISMATCH REPAIR, ONCOGENES, TUMORS, Chromatin, DNA-Binding Proteins, MutS Homolog 2 Protein, Oncology, Stomach Neoplasms, Cell Adhesion, Humans, Medicine [Science], MutL Protein Homolog 1, Mutations, Germ-Line Mutation, Transcription Factors
Abstract: Mutations in the DNA mismatch repair gene MSH2 are causative of microsatellite instability (MSI) in multiple cancers. Here, we discovered that besides its well-established role in DNA repair, MSH2 exerts a novel epigenomic function in gastric cancer. Unbiased CRISPR-based mass spectrometry combined with genome-wide CRISPR functional screening revealed that in early-stage gastric cancer MSH2 genomic binding is not randomly distributed but rather is associated specifically with tumor-associated super-enhancers controlling the expression of cell adhesion genes. At these loci, MSH2 genomic binding was required for chromatin rewiring, de novo enhancer-promoter interactions, maintenance of histone acetylation levels, and regulation of cell adhesion pathway expression. The chromatin function of MSH2 was independent of its DNA repair catalytic activity but required MSH6, another DNA repair gene, and recruitment to gene loci by the SWI/SNF chromatin remodeler SMARCA4/BRG1. Loss of MSH2 in advanced gastric cancers was accompanied by deficient cell adhesion pathway expression, epithelial-mesenchymal transition, and enhanced tumorigenesis in vitro and in vivo. However, MSH2-deficient gastric cancers also displayed addiction to BAZ1B, a bromodomain-containing family member, and consequent synthetic lethality to bromodomain and extraterminal motif (BET) inhibition. Our results reveal a role for MSH2 in gastric cancer epigenomic regulation and identify BET inhibition as a potential therapy in MSH2-deficient gastric malignancies. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) National Medical Research Council (NMRC) National Research Foundation (NRF) This study was supported by National Medical Research Council grants NMRC/STaR/0026/2015, MOH-000967-00 and OFLCG18May-0003, and A*ccelerate GAP fund ETPL/15-R15 GAP-0021 (to P. Tan) and MOE tier 2 grant (MOE2017-T2-1-105) and NMRC CS-IRG grant (NMRC/CIRG/1481/2017 to S. Li) and SCISSOR (A*STAR IAF-PP) H18/01/a0/020. Funding was also provided by Cancer Science Institute of Singapore, NUS, under the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centers of Excellence initiative, and block funding from Duke-NUS Medical School. A.M. Nargund is also supported by St. Baldrick's Foundation Research Award. R. Sundar is supported by a National Medical Research Council (NMRC) Fellowship, Singapore. M.J. Fullwood is supported by the RNA Biology Center at the Cancer Science Institute of Singapore, NUS, as part of funding under the Singapore Ministry of Education Academic Research Fund Tier 3 awarded to Daniel Tenen (MOE2014-T3-1-006) and the National Research Foundation Singapore and the Singapore Ministry of Education under its Research Centers of Excellence initiative.
Published: 2022

47. Paediatric <scp> BCOR </scp> ‐associated sarcomas with a novel long spliced internal tandem duplication of <scp> BCOR </scp> exon 15

Author: Jian Yuan Goh, Chik Hong Kuick, Masahiro Sugiura, Sze Jet Aw, Manli Zhao, Hongfeng Tang, Sandini Gunaratne, Fucun Zhu, Lin Cai, Bin Tean Teh, Paul S Thorner, and Kenneth Tou En Chang
Subjects: Repressor Proteins, Proto-Oncogene Proteins, Mutation, Humans, RNA, Sarcoma, Exons, Child, Kidney Neoplasms, Pathology and Forensic Medicine
Abstract: Clear cell sarcoma of the kidney (CCSK) and primitive myxoid mesenchymal tumour of infancy (PMMTI) are paediatric sarcomas that most commonly harbour internal tandem duplications (ITDs) of exon 15 of the BCOR gene, in the range of 87-114 base pairs (bp). Some cases, instead, have BCOR-CCNB3 or YWHAE-NUTM2 gene fusions. About 10% of cases lack any of these genetic alterations when tested by standard methods. Two cases of CCSK and one PMMTI lacking the aforementioned mutations were analysed using Archer FusionPlex technology. Two related BCOR exon 15 RNA transcripts with ITDs of lengths 388 and 96 bp were detected in each case; only the 388 bp transcript was identified when genomic DNA was sequenced. In silico analysis of this transcript revealed acceptor and donor splice sites indicating that, at the RNA level, the 388-bp transcript was likely spliced to form the 96-bp transcript. The results were confirmed by Sanger sequencing using primers targeting the ITD breakpoint. This novel and unusually long ITD segment is difficult to identify by DNA sequencing using typical primer design strategies flanking entire duplicated segments because it exceeds the typical read lengths of most sequencing platforms as well as the usual fragment lengths obtained from formalin-fixed paraffin-embedded material. As diagnosis of CCSK and PMMTI may be challenging by morphology and immunohistochemistry alone, it is important to identify mutations in these cases. Knowledge of this novel BCOR ITD is important in relation to primer design for detection by sequencing, and using RNA versus DNA for sequencing.
Published: 2022

48. A genomic‐augmented multivariate prognostic model for the survival of natural‐killer/T‐cell lymphoma patients from an international cohort

Author: Jing Quan Lim, Dachuan Huang, Jason Yongsheng Chan, Yurike Laurensia, Esther Kam Yin Wong, Daryl Ming Zhe Cheah, Burton Kuan Hui Chia, Wen‐Yu Chuang, Ming‐Chung Kuo, Yi‐Jiun Su, Qing‐qing Cai, Yanfen Feng, Huilan Rao, Li‐Na Feng, Pan‐Pan Wei, Jie‐Rong Chen, Bo‐Wei Han, Guo‐Wang Lin, Jun Cai, Yu Fang, Jing Tan, Huangming Hong, Yanhui Liu, Fen Zhang, Wenyu Li, Michelle L. M. Poon, Siok‐Bian Ng, Anand Jeyasekharan, Jeslin Chian Hung Ha, Lay Poh Khoo, Suk Teng Chin, Wan Lu Pang, Rebecca Kee, Chee Leong Cheng, Nicholas Francis Grigoropoulos, Tiffany Tang, Miriam Tao, Mohamad Farid, Kia Joo Puan, Jie Xiong, Wei‐Li Zhao, Chiea Chuen Khor, William Hwang, Won Seog Kim, Elias Campo, Patrick Tan, Bin Tean Teh, Wee‐Joo Chng, Olaf Rötzschke, Thomas Tousseyn, Hui‐Qiang Huang, Steve Rozen, Soon Thye Lim, Lee‐Yung Shih, Jin‐Xin Bei, and Choon Kiat Ong
Subjects: EXPRESSION, Epstein-Barr Virus Infections, Herpesvirus 4, Human, Science & Technology, MUTATIONS, BLOCKADE, Genomics, GENETIC RISK, Hematology, Prognosis, Disease-Free Survival, VARIABLES, Lymphoma, Extranodal NK-T-Cell, PERIPHERAL T-CELL, Humans, BARR-VIRUS-DNA, NASAL, SMILE, Life Sciences & Biomedicine, Retrospective Studies
Abstract: With lowering costs of sequencing and genetic profiling techniques, genetic drivers can now be detected readily in tumors but current prognostic models for Natural-killer/T cell lymphoma (NKTCL) have yet to fully leverage on them for prognosticating patients. Here, we used next-generation sequencing to sequence 260 NKTCL tumors, and trained a genomic prognostic model (GPM) with the genomic mutations and survival data from this retrospective cohort of patients using LASSO Cox regression. The GPM is defined by the mutational status of 13 prognostic genes and is weakly correlated with the risk-features in International Prognostic Index (IPI), Prognostic Index for Natural-Killer cell lymphoma (PINK), and PINK-Epstein-Barr virus (PINK-E). Cox-proportional hazard multivariate regression also showed that the new GPM is independent and significant for both progression-free survival (PFS, HR: 3.73, 95% CI 2.07-6.73; p
Published: 2022

49. Prevalence of Loneliness and Its Association With General and Health-Related Measures of Subjective Well-Being in a Longitudinal Bicultural Cohort of Older Adults in Advanced Age Living in New Zealand: LiLACS NZ

Author: Roy Lay-Yee, Barry J Milne, Valerie A Wright-St Clair, Joanna Broad, Tim Wilkinson, Martin Connolly, Ruth Teh, Karen Hayman, Marama Muru-Lanning, and Ngaire Kerse
Subjects: Cohort Studies, Aging, Clinical Psychology, Social Psychology, Loneliness, Prevalence, Quality of Life, Humans, Geriatrics and Gerontology, Gerontology, Aged, New Zealand
Abstract: Objectives There is evidence that loneliness is detrimental to the subjective well-being of older adults. However, little is known on this topic for the cohort of those in advanced age (80 years or older), which today is the fastest-growing age group in the New Zealand population. We examined the relationships between loneliness and selected subjective well-being outcomes over 5 years. Methods We used a regional, bicultural sample of those in advanced age from 2010 to 2015 (Life and Living in Advanced Age: a Cohort Study in New Zealand). The first wave enrolled 937 people (92% of whom were living in the community): 421 Māori (Indigenous New Zealanders aged 80–90 years) and 516 non-Māori aged 85 years. We applied standard regression techniques to baseline data and mixed-effects models to longitudinal data, while adjusting for sociodemographic factors. Results For both Māori and non-Māori, strong negative associations between loneliness and subjective well-being were found at baseline. In longitudinal analyses, we found that loneliness was negatively associated with life satisfaction as well as with mental health-related quality of life. Discussion Our findings of adverse impacts on subjective well-being corroborate other evidence, highlighting loneliness as a prime candidate for intervention—appropriate to cultural context—to improve well-being for adults in advanced age.
Published: 2022

50. Hyperleukocytosis associated with delayed presentation among patients with acute leukemia during the COVID-19 pandemic

Author: Aditya Tedjaseputra, James A. Kuzich, Nisha Thiagarajah, Tse-Chieh Teh, Julia McClelland, Marzia Rahman, Rowena Brook, Chong Chyn Chua, Doen Ming Ong, Shuh-Ying Tan, Robin Filshie, Chun Yew Fong, Pasquale Fedele, Ashish Bajel, Jake Shortt, and Andrew H. Wei
Subjects: Leukemia, Myeloid, Acute, Cancer Research, Oncology, Leukocytosis, Acute Disease, Humans, COVID-19, Hematology, Pandemics
Published: 2022

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