Identification of core techniques that enhance genome editing of human T cells expressing synthetic antigen receptors.

Genome editing technologies have seen remarkable progress in recent years, enabling precise regulation of exogenous and endogenous genes. These advances have been extensively applied to the engineering of human T lymphocytes, leading to the development of practice changing therapies for patients with cancer and the promise of synthetic immune cell therapies for a variety of non-malignant diseases. Many distinct conceptual and technical approaches have been used to edit T-cell genomes, however targeted assessments of which techniques are most effective for manufacturing, gene editing and transgene expression are rarely reported. Through extensive comparative evaluation, we identified methods that most effectively enhance engineering of research-scale and pre-clinical T-cell products at critical stages of manufacturing.

Facts and Hopes in Immunotherapy Strategies Targeting Antigens Derived from KRAS Mutations.

In this commentary, we advance the notion that mutant KRAS (mKRAS) is an ideal tumor neoantigen that is amenable for targeting by the adaptive immune system. Recent progress highlights key advances on various fronts that validate mKRAS as a molecular target and support further pursuit as an immunological target. Because mKRAS is an intracellular membrane localized protein and not normally expressed on the cell surface, we surmise that proteasome degradation will generate short peptides that bind to HLA class I (HLA-I) molecules in the endoplasmic reticulum for transport through the Golgi for display on the cell surface. T-cell receptors (TCR)αß and antibodies have been isolated that specifically recognize mKRAS encoded epitope(s) or haptenated-mKRAS peptides in the context of HLA-I on tumor cells. Case reports using adoptive T-cell therapy provide proof of principle that KRAS G12D can be successfully targeted by the immune system in patients with cancer. Among the challenges facing investigators is the requirement of precision medicine to identify and match patients to available mKRAS peptide/HLA therapeutics and to increase the population coverage by targeting additional mKRAS epitopes. Ultimately, we envision mKRAS-directed immunotherapy as an effective treatment option for selected patients that will complement and perhaps synergize with small-molecule mKRAS inhibitors and targeted mKRAS degraders.

Expression of inducible factors reprograms CAR-T cells for enhanced function and safety.

Despite the success of CAR-T cell cancer immunotherapy, challenges in efficacy and safety remain. Investigators have begun to enhance CAR-T cells with the expression of accessory molecules to address these challenges. Current systems rely on constitutive transgene expression or multiple viral vectors, resulting in unregulated response and product heterogeneity. Here, we develop a genetic platform that combines autonomous antigen-induced production of an accessory molecule with constitutive CAR expression in a single lentiviral vector called Uni-Vect. The broad therapeutic application of Uni-Vect is demonstrated in vivo by activation-dependent expression of (1) an immunostimulatory cytokine that improves efficacy, (2) an antibody that ameliorates cytokine-release syndrome, and (3) transcription factors that modulate T cell biology. Uni-Vect is also implemented as a platform to characterize immune receptors. Overall, we demonstrate that Uni-Vect provides a foundation for a more clinically actionable next-generation cellular immunotherapy.

Biochemical and functional characterization of mutant KRAS epitopes validates this oncoprotein for immunological targeting.

Activating RAS missense mutations are among the most prevalent genomic alterations observed in human cancers and drive oncogenesis in the three most lethal tumor types. Emerging evidence suggests mutant KRAS (mKRAS) may be targeted immunologically, but mKRAS epitopes remain poorly defined. Here we employ a multi-omics approach to characterize HLA class I-restricted mKRAS epitopes. We provide proteomic evidence of mKRAS epitope processing and presentation by high prevalence HLA class I alleles. Select epitopes are immunogenic enabling mKRAS-specific TCRαß isolation. TCR transfer to primary CD8+ T cells confers cytotoxicity against mKRAS tumor cell lines independent of histologic origin, and the kinetics of lytic activity correlates with mKRAS peptide-HLA class I complex abundance. Adoptive transfer of mKRAS-TCR engineered CD8+ T cells leads to tumor eradication in a xenograft model of metastatic lung cancer. This study validates mKRAS peptides as bona fide epitopes facilitating the development of immune therapies targeting this oncoprotein.

Adoptive Cellular Therapy for Solid Tumors.

Cancer immunotherapy tools include antibodies, vaccines, cytokines, oncolytic viruses, bispecific molecules, and cellular therapies. This review will focus on adoptive cellular therapy, which involves the isolation of a patient's own immune cells followed by their ex vivo expansion and reinfusion. The majority of adoptive cellular therapy strategies utilize T cells isolated from tumor or peripheral blood, but may utilize other immune cell subsets. T-cell therapies in the form of tumor-infiltrating lymphocytes, T-cell receptor T cells, and CAR T cells may act as "living drugs" as these infused cells expand, engraft, and persist in vivo, allowing adaptability over time and enabling durable remissions in subsets of patients. Adoptive cellular therapy has been less successful in the management of solid tumors because of poor homing, proliferation, and survival of transferred cells. Strategies are discussed, including expression of transgenes to address these hurdles. Additionally, advances in gene editing using CRISPR/Cas9 and similar technologies are described, which allow for clinically translatable gene-editing strategies to enhance the antitumor activity and to surmount the hostilities advanced by the host and the tumor. Finally, the common toxicities and approaches to mitigate these are reviewed.

Pseudoxanthoma elasticum overlaps hereditary spastic paraplegia type 56.

PURPOSE: Pseudoxanthoma elasticum (PXE) is a recessive disorder involving skin, eyes and arteries, mainly caused by ABCC6 pathogenic variants. However, almost one fifth of patients remain genetically unsolved despite extensive genetic screening of ABCC6, as illustrated in a large French PXE series of 220 cases. We searched for new PXE gene(s) to solve the ABCC6-negative patients. METHODS: First, family-based exome sequencing was performed, in one ABCC6-negative PXE patient with additional neurological features, and her relatives. CYP2U1, involved in hereditary spastic paraplegia type 56 (SPG56), was selected based on this complex phenotype, and the presence of two candidate variants. Second, CYP2U1 sequencing was performed in a retrospective series of 46 additional ABCC6-negative PXE probands. Third, six additional SPG56 patients were evaluated for PXE skin and eye phenotype. Additionally, plasma pyrophosphate dosage and functional analyses were performed in some of these patients. RESULTS: 6.4% of ABCC6-negative PXE patients (n = 3) harboured biallelic pathogenic variants in CYP2U1. PXE skin lesions with histological confirmation, eye lesions including maculopathy or angioid streaks, and various neurological symptoms were present. CYP2U1 missense variants were confirmed to impair protein function. Plasma pyrophosphate levels were normal. Two SPG56 patients (33%) presented some phenotypic overlap with PXE. CONCLUSION: CYP2U1 pathogenic variants are found in unsolved PXE patients with neurological findings, including spastic paraplegia, expanding the SPG56 phenotype and highlighting its overlap with PXE. The pathophysiology of ABCC6 and CYP2U1 should be explored to explain their respective role and potential interaction in ectopic mineralization.

Tumor-Derived Myeloid Cell Chemoattractants and T Cell Exclusion in Pancreatic Cancer.

Like many tumor types, pancreatic ductal adenocarcinoma (PDAC) exhibits a rich network of tumor-derived cytokines and chemokines that drive recruitment of myeloid cells to the tumor microenvironment (TME). These cells, which include tumor-associated macrophages and myeloid derived suppressor cells, block the recruitment and priming of T cells, resulting in T cell exclusion within the TME. Genetic or pharmacologic disruption of this chemokine/cytokine network reliably converts the PDAC TME to a T cell-high phenotype and sensitizes tumors to immunotherapy across multiple preclinical models. Thus, neutralization of tumor-derived chemokines/cytokines or blockade of their respective receptors represents a potentially potent strategy to reverse myeloid immunosuppression in PDAC, enabling benefit from checkpoint inhibition not otherwise achievable in this disease. Inhibition of oncogenic pathways that drive tumor-intrinsic expression of chemoattractants may be similarly effective.

Challenges and Opportunities for Pancreatic Cancer Immunotherapy.

Pancreatic ductal adenocarcinoma (PDA) is among the most immune-resistant tumor types. Its unique genomic landscape shaped by oncogenic drivers promotes immune suppression from the earliest stages of tumor inception to subvert adaptive T cell immunity. Single-agent immune modulators have thus far proven clinically ineffective, and multi-modal therapies targeting mechanisms of immunotherapy resistance are likely needed. Here, we review novel immunotherapy strategies currently under investigation to (1) confer antigen specificity, (2) enhance T cell effector function, and (3) neutralize immunosuppressive elements within the tumor microenvironment that may be rationally combined to untangle the web of immune resistance in PDA and other tumors.

Osmotic pressure estimation using the Pitzer equation for forward osmosis modelling.

Forward osmosis (FO) has received widespread recognition in the past decade due to its potential low energy production of water. This study presents a new model analysis for predicting the water flux in FO systems when inorganic-based draw solutions are used under variable experimental conditions for using a laboratory scale cross-flow single cell unit. The new model accounts for the adverse impact of concentration polarization (both ICP and ECP) incorporating the water activity by Pitzer to calculate the bulk osmotic pressures. Using the water activity provides a better correlation of experimental data than the classical van't Hoff equation. The nonlinear model also gave a better estimate for the structural parameter factor (S) of the membrane in its solution. Furthermore, the temperature and concentration of both the draw and feed solutions played a significant role in increasing the water flux, which could be interpreted in terms of the mass transfer coefficient representing ECP; a factor sensitive to the hydraulics of the system. The model provides greatly improved correlations for the experimental water fluxes.

Bibliometric analysis of global publications in medication adherence (1900-2017).

OBJECTIVES: Medication non-adherence is a worldwide problem. The aim of this study was to assess the global research output, research trends and topics that shaped medication adherence research. METHODS: A bibliometric methodology was applied. Keywords related to 'medication adherence' were searched in Scopus database for all times up to 31 December 2017. Retrieved data were analyzsd, and bibliometric indicators and maps were presented. KEY FINDINGS: In total, 16 133 documents were retrieved. Most frequently encountered author keywords, other than adherence/compliance, were HIV, hypertension, diabetes mellitus, schizophrenia, depression, osteoporosis, asthma and quality of life. The number of documents published from 2008 to 2017 represented 62.0% (n = 10 005) of the total retrieved documents. The h-index of the retrieved documents was 223. The USA ranked first (43.1%; n = 6959), followed by the UK (8.6%; n = 1384) and Canada (4.5%; n = 796). The USA dominated the lists of active authors and institutions. Top active journals in publishing research on medication adherence were mainly in the field of AIDS. Top-cited articles in the field focused on adherence to anti-HIV medications, the impact of depression on medication adherence and barriers to adherence. CONCLUSION: Adherence among HIV patients dominated the field of medication adherence. Research on medication adherence needs to be strengthened in all countries and in different types of chronic diseases. Research collaboration should also be encouraged to increase research activity on medication adherence in developing countries.

[Statins in primary prevention of cardiovascular disease]. / Statines en prévention primaire des événements cardiovasculaires.

Cardiovascular events are the second leading cause of death in France. The assessment of overall cardiovascular risk using a personalized assessment with weighting risk factors can predict the risk of cardiovascular events in ten years. The validated treatments to reduce cardiovascular mortality in primary prevention are few. The use of statins in primary prevention is discussed. We report in this review the updated conclusions from clinical trials regarding the treatment with statins in primary prevention.

Global research output in antimicrobial resistance among uropathogens: A bibliometric analysis (2002-2016).

OBJECTIVES: Antimicrobial resistance (AMR) among uropathogens contributes to treatment failure. Research in AMR among uropathogens is important to establish treatment options. This study assessed global research trends in AMR among uropathogens. METHODS: SciVerse Scopus was used to retrieve relevant documents for the period 2002-2016. Only journal articles were included in the analysis. Analysis of author keywords was carried out using VOSviewer. RESULTS: A total of 1087 journal articles were retrieved with an h-index of 50. The number of publications increased noticeably in the past decade. Analysis of subject areas of retrieved documents showed that 275 (25.3%) articles were in molecular biology/genetics/microbiology/immunology, 197 (18.1%) were in pharmacological/therapeutic approaches for treatment of urinary tract infections and 615 (56.6%) were in epidemiology/public health. Terms such as multidrug-resistant and extended-spectrum ß-lactamases (ESBLs) appeared more frequently in documents published in the period 2012-2016. The mean number of authors per article was 5.3. Most active authors in this field were from Japan. The USA ranked first with 148 documents (13.6%), followed by India (97; 8.9%) and Iran (84; 7.7%). The top productive institution was Tehran University of Medical Sciences (21 publications), followed by Kobe University in Japan (20 publications). The Journal of Antimicrobial Chemotherapy ranked first with 33 publications. CONCLUSION: Research in AMR among uropathogens showed a noticeable increase in the past decade. Reports of increasing incidence of resistance among uropathogens were published from different parts of the world. Empirical therapy should be based on updated research in AMR.

Bibliometric Analysis of Worldwide Publications on Antimalarial Drug Resistance (2006-2015).

BACKGROUND: In response to international efforts to control and eradicate malaria, we designed this study to give a bibliometric overview of research productivity in antimalarial drug resistance (AMDR). METHODS: Keywords related to AMDR were used to retrieve relevant literature using Scopus database. RESULTS: A total of 976 publications with an h-index of 63 were retrieved. The number of publications showed a noticeable increase starting in the early 1990s. The USA was the most productive country with 337 publications equivalent to one-third of worldwide publications in this field. More than two-thirds of publications by the USA (236, 70.03%) were made by international collaboration. Of the top ten productive countries, two countries were from Mekong subregion, particularly Thailand and Cambodia. The Malaria Journal was the most productive journal (136, 13.93%) in this field. Mahidol University (80, 8.20%) in Thailand was the most productive institution. Seven articles in the top-ten list were about artemisinin resistance in Plasmodium falciparum, one was about chloroquine resistance, one was about sulfadoxine-pyrimethamine resistance, and the remaining one was about general multidrug resistance. CONCLUSION: Eradication and control of AMDR require continuing research activity to help international health organizations identify spots that require an immediate action to implement appropriate measures.

Bibliometric analysis of worldwide scientific literature in mobile - health: 2006-2016.

BACKGROUND: The advancement of mobile technology had positively influenced healthcare services. An emerging subfield of mobile technology is mobile health (m-Health) in which mobile applications are used for health purposes. The aim of this study was to analyze and assess literature published in the field of m-Health. METHODS: SciVerse Scopus was used to retrieve literature in m-Health. The study period was set from 2006 to 2016. ArcGIS 10.1 was used to present geographical distribution of publications while VOSviewer was used for data visualization. Growth of publications, citation analysis, and research productivity were presented using standard bibliometric indicators. RESULTS: During the study period, a total of 5465 documents were published, giving an average of 496.8 documents per year. The h-index of retrieved documents was 81. Core keywords used in literature pertaining to m-Health included diabetes mellitus, adherence, and obesity among others. Relative growth rate and doubling time of retrieved literature were stable from 2009 to 2015 indicating exponential growth of literature in this field. A total of 4638 (84.9%) documents were multi-authored with a mean collaboration index of 4.1 authors per article. The United States of America ranked first in productivity with 1926 (35.2%) published documents. India ranked sixth with 183 (3.3%) documents while China ranked seventh with 155(2.8%) documents. VA Medical Center was the most prolific organization/institution while Journal of Medical Internet Research was the preferred journal for publications in the field of m-Health. Top cited articles in the field of m-Health included the use of mobile technology in improving adherence in HIV patients, weight loss, and improving glycemic control in diabetic patients. CONCLUSION: The size of literature in m-Health showed a noticeable increase in the past decade. Given the large volume of citations received in this field, it is expected that applications of m-Health will be seen into various health aspects and health services. Research in m-Health needs to be encouraged, particularly in the fight against AIDS, poor medication adherence, glycemic control in Africa and other low income world regions where technology can improve health services and decrease disease burden.

Bibliometric analysis of publications on Campylobacter: (2000-2015).

BACKGROUND: Campylobacter species are widespread zoonotic pathogens. Campylobacter jejuni causes a form of gastroenteritis called campylobacteriosis. Campylobacter drug resistance is considered a serious threat. In order to better understand national and international research output on Campylobacter, we conducted this bibliometric overview of publications on Campylobacter. This study can be used to assess extent of interaction and response of researchers, food regulators, and health policy makers to global burden of campylobacateriosis. METHODS: Scopus database was used to retrieve publications with the following keywords (Campylobacter/campylobacteriosis, C. jejuni, C. coli). The study period was set from 2000 to 2015. All types of journal documents, excluding errata, were considered. Bibliometric indicators such as annual growth of publications, country contribution, international collaboration, and citation analysis were presented. The quality of retrieved data was indirectly assessed by Hirsch index and impact factor of journals. RESULTS: A total of 5522 documents were retrieved with median (Q1-Q3) citations of 9 (2-23) and h-index of 113. Annual number of publications showed a fluctuating increase. The core leading journals were Applied and Environmental Microbiology journal and Journal of Food Protection with 246 (4.46%) publications for each. The USA (1309; 23.6%) was the most productive country while Danmarks Tekniske Universitet (150; 2.7%) was the most productive institution. Half of the top ten productive countries were European. France had the lowest percentage (33.5%) of articles with international collaboration while Netherlands (57.7%) had the highest percentage of articles with international collaboration. Approximately half (50.1%) of retrieved articles were published in journals under the subject area of "immunology/microbiology". Main themes in highly cited articles were molecular biology/genetics and public health burden of campylobacteriosis. There were 728 (13.1%) articles on campylobacter-related drug resistance, and the top cited articles focused mainly on increasing resistance to quinolones and fluoroquinolones. CONCLUSIONS: There was a clear increase in number of publications on Campylobacter. Rational use of antimicrobials in humans, poultry, and animals is highly recommended. International collaboration is highly required particularly in implementing new diagnostic screening technologies to minimize global health burden of Campylobacter and ensure food safety.

Bibliometric analysis of medicine-related publications on poverty (2005-2015).

BACKGROUND: Poverty is a global problem. The war against poverty requires not only financial support, but also poverty-related research to pinpoint areas of high need of intervention. In line with international efforts to fight poverty and negative consequences, we carried out this study to give a bibliometric overview of medicine-related literature on poverty. Such a s study is an indicator of the extent of interaction of various international key players on the war against poverty-related health problems. METHODS: Scopus was used to achieve the objective of this study. The time span set for this study was 2005-2015. Poverty-related articles under the subject area "Medicine" were used to give bibliometric indicators such as annual growth of publications, international collaboration, highly cited articles, active countries, institutions, journals, and authors. RESULTS: The total number of retrieved articles was 1583. The Hirsh-index of retrieved articles was 56. A modest and fluctuating increase was seen over the study period. Visualization map of retrieved articles showed that "HIV", infectious diseases, mental health, India, and Africa were most commonly encountered terms. No significant dominance of any particular author or journal was observed in retrieved articles. The United States of America had the largest share in the number of published articles. The World Health Organization and Centers for Disease Prevention and Control were among top active institutions/organizations. International collaboration was observed in less than one third of publications. Top cited articles focused on three poverty-related health issues, mainly, infectious diseases, malnutrition, and child development/psychology. Most of top articles were published in high impact journals. CONCLUSIONS: Data indicated that articles on poverty were published in high influential medical journals indicative of the importance of poverty as a global health problem. However, the number publications and the extent of international collaborations was lower than expected given the huge burden of poverty-related health problems.

A bibliometric analysis of literature on malaria vector resistance: (1996 - 2015).

BACKGROUND: Emergence of insecticide resistance in malaria vectors is a real threat to future goals of elimination and control of malaria. Therefore, the objective of this study was to assess research trend on insecticide resistance of Anopheles mosquito. In specific, number of publications, countries, institutions, and authors' research profile, citation analysis, international collaborations, and impact of journals publishing documents on insecticide resistance will be presented. It was conducted via Scopus search engine which was used to retrieve relevant data. Keywords used were based on literature available on this topic. The duration of study was set from 1996-2015. RESULTS: A total of 616 documents, mainly as original research articles (n = 569; 92.37%) were retrieved. The average number of citations per article was 26.36. Poisson log-linear regression analysis indicated that there was a 6.00% increase in the number of publications for each extra article on pyrethroid resistance. A total of 82 different countries and 1922 authors participated in publishing retrieved articles. The United Kingdom (UK) ranked first in number of publications followed by the United States of America (USA) and France. The top ten productive countries included seven African countries. The UK had collaborations mostly with Benin (relative link strength = 46). A total of 1817 institution/ organizations participated in the publication of retrieved articles. The most active institution/ organization was Liverpool School of Tropical Medicine. Retrieved articles were published in 134 different scientific peer reviewed journals. The journal that published most on this topic was Malaria Journal (n = 101; 16.4%). Four of the top active authors were from South Africa and two were from the UK. Three of the top ten cited articles were published in Insect Molecular Biology journal. Six articles were about pyrethroid resistance and at least two were about DDT resistance. CONCLUSION: Publications on insecticide resistance in malaria vector has gained momentum in the past decade. International collaborations enhanced the knowledge about the situation of vector resistance in countries with endemic malaria. Molecular biology of insecticide resistance is the key issue in understanding and overcoming this emerging problems.

Bibliometric analysis of global scientific research on carbapenem resistance (1986-2015).

BACKGROUND: Antimicrobial resistance is a global public health challenge and carbapenem resistance, in particular, is considered an urgent global health threat. This study was carried out to give a bibliometric overview of literature on carbapenem resistance. In specific, number of publications, top productive countries and institutes, highly cited articles, citation analysis, co-authorships, international collaboration, top active authors, and journals publishing articles on carbapenem resistance were analyzed and discussed. METHODS: Specific keywords pertaining to carbapenem resistance were used in Scopus database. Quantitative and qualitative analysis of retrieved data were presented using appropriate bibliometric indicators and visualization maps. RESULTS: A total of 2617 journal articles were retrieved. The average number of citations per article was of 21.47. The growth of publications showed a dramatic increase from 2008 to 2015. Approximately 9 % of retrieved articles on carbapenem resistance were published in Antimicrobial Agents and Chemotherapy journal. Retrieved articles were published by 102 different countries. The United States of America (USA) contributed most with 437 (16.70 %) articles followed by China with 257 (9.82 %) articles. When productivity was stratified by population size, Greece ranked first followed by France. Greece also ranked first when data were stratified by gross domestic product (GDP). Asian countries have lesser international collaboration compared with other countries in the top ten list. Five of top ten productive institutes were Europeans (France, the UK, Greece, Italy, and Switzerland) and two were Asians (China and South Korea). Other active institutes included an Israeli and a Brazilian institute. Four of the top ten cited articles were published in Antimicrobial Agents and Chemotherapy journal and two were published in The Lancet Infectious Diseases. CONCLUSION: There was a dramatic increase in number of publications on carbapenem resistance in the past few years. These publications were produced from different world regions including Asia, Europe, Middle East, and Latin America. International collaboration needs to be encouraged particularly for researchers in Asia. Molecular biology and epidemiology dominated the theme of the top ten cited articles on carbapenem resistance. This bibliometric study will hopefully help health policy makers in planning future research and allocating funds pertaining to carbapenem resistance.

Bibliometric analysis of worldwide publications on multi-, extensively, and totally drug - resistant tuberculosis (2006-2015).

BACKGROUND: The year 2015 marked the end of United Nations Millennium Development Goals which was aimed at halting and reversing worldwide tuberculosis (TB). The emergence of drug resistance is a major challenge for worldwide TB control. The aim of this study was to give a bibliometric overview of publications on multi-, extensively, and totally drug-resistant TB. METHODS: Scopus database was used to retrieve articles on multidrug resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) tuberculosis for the study period (2006-2015). The number of publications, top productive countries and institutions, citation analysis, co-authorships, international collaboration, active authors, and active journals were retrieved and analyzed. RESULTS: A total of 2260 journal articles were retrieved. The mean ± SD citations per article was 7.04 ± 16.0. The h-index of retrieved data was 76. The number of publications showed a three - fold increase over the study period compared with less than two - fold increase in tuberculosis research during the same study period. Stratified by number of publications, the United States of America ranked first while Switzerland ranked first in productivity per 100 million people, and South Africa ranked first in productivity stratified per one trillion Gross Domestic Product. Three of the High Burden Countries (HBC) MDR-TB (India, China, and South Africa) were present in top productive countries. High percentage of international collaboration was seen among most HBC MDR-TB. Except for Plos One journal, most active journals in publishing articles on MDR, XDR, TDR-TB were in infection - related fields and in general medicine. Top 20 cited articles were published in prestigious journal such as Lancet and New England Journal of Medicine. The themes in top 20 cited articles were diverse, ranging from molecular biology, diagnostic tools, co-infection with HIV, and results of new anti-TB drugs. CONCLUSION: Publications on MDR, XDR and TDR - TB are increasing in the past decade. International collaboration was common. Many low resourced African and Asian countries will benefit from research leading to new diagnostic and screening technology of TB. The exchange of expertise, ideas and technology is of paramount importance in this field.

Assessment of research productivity of Arab countries in the field of infectious diseases using Web of Science database.

BACKGROUND: To meet the future challenges of infectious diseases and limit the spread of multidrug resistant microorganisms, a better understanding of published studies in the field of infectious diseases is needed. The objective of this study was to analyze the quantity and quality of research activity in the field of infectious diseases in Arab countries and compare it with that in non-Arab countries. METHODS: Documents published in Arab countries within the research category of "infectious diseases" were extracted and analyzed using the Web of Science database. The data analyzed represent research productivity during the time interval between 1900 - 2012. RESULTS: Worldwide, the total number of documents published in the field of infectious diseases up to 2012 was 227,188. A total of 2,408 documents in the field of infectious diseases were published in Arab countries, which represents 1.06% of worldwide research output. Research output from Arab countries in the field of infectious diseases was low for decades. However, approximately a five-fold increase was observed in the past decade. Arab countries ranked 56(th) to 218(th) on the standard competition ranking (SCR) in worldwide publications in the field of infectious diseases. Egypt, with a total publication of 464 (19.27%) documents ranked first among Arab countries, while Kuwait University was the most productive institution with a total of 158 (6.56%) documents. Average citation per document published in Arab countries was 13.25 and the h-index was 64. Tuberculosis (230; 9.55%), malaria (223; 9.26%), and hepatitis (189; 7.8%) were the top three infectious diseases studied as according to the retrieved documents. CONCLUSION: The present data reveals that some Arab countries contribute significantly to the field of infectious diseases. However, Arab countries need to work harder to bridge the gap in this field. Compared with non-Arab countries in the Middle East, research output from Arab countries was high, but more efforts are needed to enhance the quality of this output. Future research in the field should be encouraged and correctly directed.