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  1. Škalamera D, Dahmer-Heath M, Stevenson AJ, Pinto C, Shah ET, Daignault SM, et al.
    Oncotarget, 2016 Sep 20;7(38):61000-61020.
    PMID: 27876705 DOI: 10.18632/oncotarget.11314
    Epithelial to mesenchymal transition (EMT) is a developmental program that has been implicated in progression, metastasis and therapeutic resistance of some carcinomas. To identify genes whose overexpression drives EMT, we screened a lentiviral expression library of 17000 human open reading frames (ORFs) using high-content imaging to quantitate cytoplasmic vimentin. Hits capable of increasing vimentin in the mammary carcinoma-derived cell line MDA-MB-468 were confirmed in the non-tumorigenic breast-epithelial cell line MCF10A. When overexpressed in this model, they increased the rate of cell invasion through Matrigel™, induced mesenchymal marker expression and reduced expression of the epithelial marker E-cadherin. In gene-expression datasets derived from breast cancer patients, the expression of several novel genes correlated with expression of known EMT marker genes, indicating their in vivo relevance. As EMT-associated properties are thought to contribute in several ways to cancer progression, genes identified in this study may represent novel targets for anti-cancer therapy.
    Matched MeSH terms: Disease Progression
  2. Üreyen O, Üstuner MA, Argon A, Özbilgin M, Egeli T, Ìlhan E, et al.
    Malays J Pathol, 2018 Aug;40(2):153-160.
    PMID: 30173233
    INTRODUCTION: The aim of this study was to investigate the efficacy of resveratrol and octreotide, agents that are used to prevent intra-abdominal adhesions in experimental models, in preventing intraperitoneal adhesions when used alone or in combination.

    MATERIALS AND METHODS: The study employed 28 young female Wistar albino rats weighing 250-300 grams. An experimental adhesion model was created in each rat using serosal abrasion and peritoneal excision. They were divided into four groups, each comprising seven rats: Group 1, adhesion induction only; Group 2, resveratrol administration only; Group 3, octreotide administration only; and Group 4, administration of resveratrol and octreotide combination. The rats were monitored under appropriate conditions for 14 days and then underwent laparotomy. Macroscopic intensity and extensiveness of adhesions and microscopic changes in the granulation tissue (cellular intensity, reticular and collagen fibers, capillaries, elastic and smooth muscle fibers, fibrosis) were evaluated and graded. Kruskal-Wallis and Mann-Whitney U-test were used in statistical analysis and the level of statistical significance was established as p <0.05.

    RESULTS: There was no significant difference between the groups in terms of the intensity and extensiveness of macroscopic adhesions (p=0.377 and p=0.319). There was a statistically significant difference between the microscopic scores of the groups according to Zühlke's classification (p=0.026). The Bonferroni correction used to test for the differences revealed that the rats in Group 1 achieved significantly higher scores than the rats in Group 3 (p=0.016).

    CONCLUSION: Octreotide showed higher efficiency compared to the control group in microscopic classification; however, the two agents were not superior to each other or their combination was not superior in preventing intra-abdominal adhesions.

    Matched MeSH terms: Disease Models, Animal
  3. Özgüroğlu M, Kilickap S, Sezer A, Gümüş M, Bondarenko I, Gogishvili M, et al.
    Lancet Oncol, 2023 Sep;24(9):989-1001.
    PMID: 37591293 DOI: 10.1016/S1470-2045(23)00329-7
    BACKGROUND: Cemiplimab provided significant survival benefit to patients with advanced non-small-cell lung cancer with PD-L1 tumour expression of at least 50% and no actionable biomarkers at 1-year follow-up. In this exploratory analysis, we provide outcomes after 35 months' follow-up and the effect of adding chemotherapy to cemiplimab at the time of disease progression.

    METHODS: EMPOWER-Lung 1 was a multicentre, open-label, randomised, phase 3 trial. We enrolled patients (aged ≥18 years) with histologically confirmed squamous or non-squamous advanced non-small-cell lung cancer with PD-L1 tumour expression of 50% or more. We randomly assigned (1:1) patients to intravenous cemiplimab 350 mg every 3 weeks for up to 108 weeks, or until disease progression, or investigator's choice of chemotherapy. Central randomisation scheme generated by an interactive web response system governed the randomisation process that was stratified by histology and geographical region. Primary endpoints were overall survival and progression free survival, as assessed by a blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumours version 1.1. Patients with disease progression on cemiplimab could continue cemiplimab with the addition of up to four cycles of chemotherapy. We assessed response in these patients by BICR against a new baseline, defined as the last scan before chemotherapy initiation. The primary endpoints were assessed in all randomly assigned participants (ie, intention-to-treat population) and in those with a PD-L1 expression of at least 50%. We assessed adverse events in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03088540.

    FINDINGS: Between May 29, 2017, and March 4, 2020, we recruited 712 patients (607 [85%] were male and 105 [15%] were female). We randomly assigned 357 (50%) to cemiplimab and 355 (50%) to chemotherapy. 284 (50%) patients assigned to cemiplimab and 281 (50%) assigned to chemotherapy had verified PD-L1 expression of at least 50%. At 35 months' follow-up, among those with a verified PD-L1 expression of at least 50% median overall survival in the cemiplimab group was 26·1 months (95% CI 22·1-31·8; 149 [52%] of 284 died) versus 13·3 months (10·5-16·2; 188 [67%] of 281 died) in the chemotherapy group (hazard ratio [HR] 0·57, 95% CI 0·46-0·71; p<0·0001), median progression-free survival was 8·1 months (95% CI 6·2-8·8; 214 events occurred) in the cemiplimab group versus 5·3 months (4·3-6·1; 236 events occurred) in the chemotherapy group (HR 0·51, 95% CI 0·42-0·62; p<0·0001). Continued cemiplimab plus chemotherapy as second-line therapy (n=64) resulted in a median progression-free survival of 6·6 months (6·1-9·3) and overall survival of 15·1 months (11·3-18·7). The most common grade 3-4 treatment-emergent adverse events were anaemia (15 [4%] of 356 patients in the cemiplimab group vs 60 [17%] of 343 in the control group), neutropenia (three [1%] vs 35 [10%]), and pneumonia (18 [5%] vs 13 [4%]). Treatment-related deaths occurred in ten (3%) of 356 patients treated with cemiplimab (due to autoimmune myocarditis, cardiac failure, cardio-respiratory arrest, cardiopulmonary failure, septic shock, tumour hyperprogression, nephritis, respiratory failure, [n=1 each] and general disorders or unknown [n=2]) and in seven (2%) of 343 patients treated with chemotherapy (due to pneumonia and pulmonary embolism [n=2 each], and cardiac arrest, lung abscess, and myocardial infarction [n=1 each]). The safety profile of cemiplimab at 35 months, and of continued cemiplimab plus chemotherapy, was generally consistent with that previously observed for these treatments, with no new safety signals INTERPRETATION: At 35 months' follow-up, the survival benefit of cemiplimab for patients with advanced non-small-cell lung cancer was at least as pronounced as at 1 year, affirming its use as first-line monotherapy for this population. Adding chemotherapy to cemiplimab at progression might provide a new second-line treatment for patients with advanced non-small-cell lung cancer.

    FUNDING: Regeneron Pharmaceuticals and Sanofi.

    Matched MeSH terms: Disease Progression
  4. Öner S, Watson LA, Adıgüzel Z, Ergen İ, Bilgin E, Curci A, et al.
    Mem Cognit, 2023 Apr;51(3):729-751.
    PMID: 35817990 DOI: 10.3758/s13421-022-01329-8
    The COVID-19 pandemic created a unique set of circumstances in which to investigate collective memory and future simulations of events reported during the onset of a potentially historic event. Between early April and late June 2020, we asked over 4,000 individuals from 15 countries across four continents to report on remarkable (a) national and (b) global events that (i) had happened since the first cases of COVID-19 were reported, and (ii) they expected to happen in the future. Whereas themes of infections, lockdown, and politics dominated global and national past events in most countries, themes of economy, a second wave, and lockdown dominated future events. The themes and phenomenological characteristics of the events differed based on contextual group factors. First, across all conditions, the event themes differed to a small yet significant degree depending on the severity of the pandemic and stringency of governmental response at the national level. Second, participants reported national events as less negative and more vivid than global events, and group differences in emotional valence were largest for future events. This research demonstrates that even during the early stages of the pandemic, themes relating to its onset and course were shared across many countries, thus providing preliminary evidence for the emergence of collective memories of this event as it was occurring. Current findings provide a profile of past and future collective events from the early stages of the ongoing pandemic, and factors accounting for the consistencies and differences in event representations across 15 countries are discussed.
    Matched MeSH terms: Communicable Disease Control
  5. von Delft A, Dramowski A, Sifumba Z, Mosidi T, Xun Ting T, von Delft D, et al.
    Clin Infect Dis, 2016 05 15;62 Suppl 3:S275-80.
    PMID: 27118858 DOI: 10.1093/cid/ciw037
    "Occupational MDR-TB"  …  "XDR-TB"  …  "Treatment-induced hearing loss": 3 life-changing messages imparted over the phone. Three personal accounts are shared highlighting the false belief held by many healthcare workers (HCWs) and students in low-resource settings-that they are immune to tuberculosis despite high levels of occupational tuberculosis exposure. This misconception reflects a lack of awareness of tuberculosis transmission and disease risk, compounded by the absence of accurate occupational tuberculosis estimates. As the global problem of drug-resistant (DR) tuberculosis evolves, HCWs are increasingly infected and suffer considerable morbidity and mortality from occupational DR tuberculosis disease. Similarly, healthcare students are emerging as a vulnerable and unprotected group. There is an urgent need for improved detection, vaccines, preventive therapy, treatment, and support for affected HCWs and those they care for, as well as destigmatization of all forms of tuberculosis. Finally, efforts to protect HCWs and prevent DR tuberculosis transmission by universal implementation of tuberculosis infection control measures should be prioritized.
    Matched MeSH terms: Infectious Disease Transmission, Patient-to-Professional/prevention & control*
  6. van Zonneveld M, Rakha M, Tan SY, Chou YY, Chang CH, Yen JY, et al.
    Sci Rep, 2020 02 07;10(1):2111.
    PMID: 32034221 DOI: 10.1038/s41598-020-58646-8
    This study provides insights in patterns of distribution of abiotic and biotic stress resilience across Vigna gene pools to enhance the use and conservation of these genetic resources for legume breeding. Vigna is a pantropical genus with more than 88 taxa including important crops such as V. radiata (mung bean) and V. unguiculata (cowpea). Our results show that sources of pest and disease resistance occur in at least 75 percent of the Vigna taxa, which were part of screening assessments, while sources of abiotic stress resilience occur in less than 30 percent of screened taxa. This difference in levels of resilience suggests that Vigna taxa co-evolve with pests and diseases while taxa are more conservative to adapt to climatic changes and salinization. Twenty-two Vigna taxa are poorly conserved in genebanks or not at all. This germplasm is not available for legume breeding and requires urgent germplasm collecting before these taxa extirpate on farm and in the wild. Vigna taxa, which tolerate heat and drought stress are rare compared with taxa, which escape these stresses because of short growing seasons or with taxa, which tolerate salinity. We recommend prioritizing these rare Vigna taxa for conservation and screening for combined abiotic and biotic stress resilience resulting from stacked or multifunctional traits. The high presence of salinity tolerance compared with drought stress tolerance, suggests that Vigna taxa are good at developing salt-tolerant traits. Vigna taxa are therefore of high value for legume production in areas that will suffer from salinization under global climate change.
    Matched MeSH terms: Disease Resistance/genetics
  7. van Prooije T, Ibrahim NM, Azmin S, van de Warrenburg B
    Parkinsonism Relat Disord, 2021 11;92:112-118.
    PMID: 34711523 DOI: 10.1016/j.parkreldis.2021.10.023
    This paper reviews and summarizes three main aspects of spinocerebellar ataxias (SCA) in the Asian population. First, epidemiological studies were comprehensively reviewed. Overall, the most common subtypes include SCA1, SCA2, SCA3, and SCA6, but there are large differences in the relative prevalence of these and other SCA subtypes between Asian countries. Some subtypes such as SCA12 and SCA31 are rather specific to certain Asian populations. Second, we summarized distinctive phenotypic manifestations of SCA patients of Asian origin, for example a frequent co-occurrence of parkinsonism in some SCA subtypes. Lastly, we have conducted an exploratory survey study to map SCA-specific expertise, resources, and management in various Asian countries. This showed large differences in accessibility, genetic testing facilities, and treatment options between lower and higher income Asian countries. Currently, many Asian SCA patients remain without a final genetic diagnosis. Lack of prevalence data on SCA, lack of patient registries, and insufficient access to genetic testing facilities hamper a wider understanding of these diseases in several (particularly lower income) Asian countries.
    Matched MeSH terms: Disease Management*
  8. van Panhuis WG, Choisy M, Xiong X, Chok NS, Akarasewi P, Iamsirithaworn S, et al.
    Proc Natl Acad Sci U S A, 2015 Oct 20;112(42):13069-74.
    PMID: 26438851 DOI: 10.1073/pnas.1501375112
    Dengue is a mosquito-transmitted virus infection that causes epidemics of febrile illness and hemorrhagic fever across the tropics and subtropics worldwide. Annual epidemics are commonly observed, but there is substantial spatiotemporal heterogeneity in intensity. A better understanding of this heterogeneity in dengue transmission could lead to improved epidemic prediction and disease control. Time series decomposition methods enable the isolation and study of temporal epidemic dynamics with a specific periodicity (e.g., annual cycles related to climatic drivers and multiannual cycles caused by dynamics in population immunity). We collected and analyzed up to 18 y of monthly dengue surveillance reports on a total of 3.5 million reported dengue cases from 273 provinces in eight countries in Southeast Asia, covering ∼ 10(7) km(2). We detected strong patterns of synchronous dengue transmission across the entire region, most markedly during a period of high incidence in 1997-1998, which was followed by a period of extremely low incidence in 2001-2002. This synchrony in dengue incidence coincided with elevated temperatures throughout the region in 1997-1998 and the strongest El Niño episode of the century. Multiannual dengue cycles (2-5 y) were highly coherent with the Oceanic Niño Index, and synchrony of these cycles increased with temperature. We also detected localized traveling waves of multiannual dengue epidemic cycles in Thailand, Laos, and the Philippines that were dependent on temperature. This study reveals forcing mechanisms that drive synchronization of dengue epidemics on a continental scale across Southeast Asia.
    Matched MeSH terms: Disease Outbreaks
  9. van Doremalen N, Lambe T, Sebastian S, Bushmaker T, Fischer R, Feldmann F, et al.
    PLoS Negl Trop Dis, 2019 06;13(6):e0007462.
    PMID: 31170144 DOI: 10.1371/journal.pntd.0007462
    Nipah virus (NiV) is a highly pathogenic re-emerging virus that causes outbreaks in South East Asia. Currently, no approved and licensed vaccine or antivirals exist. Here, we investigated the efficacy of ChAdOx1 NiVB, a simian adenovirus-based vaccine encoding NiV glycoprotein (G) Bangladesh, in Syrian hamsters. Prime-only as well as prime-boost vaccination resulted in uniform protection against a lethal challenge with NiV Bangladesh: all animals survived challenge and we were unable to find infectious virus either in oral swabs, lung or brain tissue. Furthermore, no pathological lung damage was observed. A single-dose of ChAdOx1 NiVB also prevented disease and lethality from heterologous challenge with NiV Malaysia. While we were unable to detect infectious virus in swabs or tissue of animals challenged with the heterologous strain, a very limited amount of viral RNA could be found in lung tissue by in situ hybridization. A single dose of ChAdOx1 NiVB also provided partial protection against Hendra virus and passive transfer of antibodies elicited by ChAdOx1 NiVB vaccination partially protected Syrian hamsters against NiV Bangladesh. From these data, we conclude that ChAdOx1 NiVB is a suitable candidate for further NiV vaccine pre-clinical development.
    Matched MeSH terms: Disease Models, Animal
  10. de la Rosette J, Laguna P, Álvarez-Maestro M, Eto M, Mochtar CA, Albayrak S, et al.
    Int J Urol, 2020 11;27(11):981-989.
    PMID: 32772434 DOI: 10.1111/iju.14340
    OBJECTIVES: To determine the well-being of urologists worldwide during the coronavirus disease 2019 pandemic, and whether they have adequate personal protective equipment knowledge and supplies appropriate to their clinical setting.

    METHODS: Urologists worldwide completed a Société Internationale d'Urologie online survey from 16 April 2020 until 1 May 2020. Analysis was carried out to evaluate their knowledge about protecting themselves and others in the workplace, including their confidence in their ability to remain safe at work, and any regional differences.

    RESULTS: There were 3488 respondents from 109 countries. Urologists who stated they were moderately comfortable that their work environment offers good protection against coronavirus disease 2019 showed a total mean satisfaction level of 5.99 (on a "0 = not at all" to "10 = very" scale). A large majority (86.33%) were confident about protecting themselves from coronavirus disease 2019 at work. However, only about one-third reported their institution provided the required personal protective equipment (35.78%), and nearly half indicated their hospital has or had limited personal protective equipment availability (48.08%). Worldwide, a large majority of respondents answered affirmatively for testing the healthcare team (83.09%). Approximately half of the respondents (52.85%) across all regions indicated that all surgical team members face an equal risk of contracting coronavirus disease 2019 (52.85%). Nearly one-third of respondents reported that they had experienced social avoidance (28.97%).

    CONCLUSIONS: Our results show that urologists lack up-to-date knowledge of preferred protocols for personal protective equipment selection and use, social distancing, and coronavirus disease 2019 testing. These data can provide insights into functional domains from which other specialties could also benefit.

    Matched MeSH terms: Infectious Disease Transmission, Patient-to-Professional/prevention & control*
  11. de Silva JR, Amir A, Lau YL, Ooi CH, Fong MY
    PLoS One, 2019;14(9):e0222681.
    PMID: 31536563 DOI: 10.1371/journal.pone.0222681
    The Duffy blood group plays a key role in Plasmodium knowlesi and Plasmodium vivax invasion into human erythrocytes. The geographical distribution of the Duffy alleles differs between regions with the FY*A allele having high frequencies in many Asian populations, the FY*B allele is found predominately in European populations and the FY*Bes allele found predominantly in African regions. A previous study in Peninsular Malaysia indicated high homogeneity of the dominant FY*A/FY*A genotype. However, the distribution of the Duffy genotypes in Malaysian Borneo is currently unknown. In the present study, the distribution of Duffy blood group genotypes and allelic frequencies among P. knowlesi infected patients as well as healthy individuals in Malaysian Borneo were determined. A total of 79 P. knowlesi patient blood samples and 76 healthy donor samples were genotyped using allele specific polymerase chain reaction (ASP-PCR). Subsequently a P. knowlesi invasion assay was carried out on FY*AB/ FY*A and FY*A/ FY*A Duffy genotype blood to investigate if either genotype conferred increased susceptibility to P. knowlesi invasion. Our results show almost equal distribution between the homozygous FY*A/FY*A and heterozygous FY*A/FY*B genotypes. This is in stark contrast to the Duffy distribution in Peninsular Malaysia and the surrounding Southeast Asian region which is dominantly FY*A/FY*A. The mean percent invasion of FY*A/FY*A and FY*A/FY*B blood was not significantly different indicating that neither blood group confers increased susceptibility to P. knowlesi invasion.
    Matched MeSH terms: Genetic Predisposition to Disease/genetics*
  12. de Azevedo JP, Nascimento LR, Cortinovis MC, Oliveira SS, da Costa EV, da Silva EE
    J Clin Virol, 2004 Dec;31(4):248-52.
    PMID: 15494264 DOI: 10.1016/j.jcv.2004.04.007
    BACKGROUND: Human adenoviruses are classified into six species, A-F, and 51 serotypes are recognized. Adenoviruses can cause a broad range of diseases. Serotypes 3, 7 and 21 are most commonly associated with CNS disease. Serotype 21 (specie B) was isolated from brain tissue and CSF of patients with acute flaccid paralysis (AFP) in Malaysia.
    OBJECTIVES: Characterize, by molecular methods, species B adenoviruses isolated from poliomyelitis-suspected cases and investigate the possible etiological role of adenoviruses in acute flaccid paralysis (AFP).
    STUDY DESIGN: 622 virus isolates, including Sabin-related polioviruses, non-polio enteroviruses (NPEV) and adenoviruses, were recovered from fecal specimens in our laboratory during the period of 1997-2002 from AFP cases occurring in Brazil, Peru and Bolivia. Negative controls consisted of 528 fecal specimens collected from healthy children <==5 of age. Of these, 478 were contacts of AFP negative cases and 50 were from a day-care center.
    RESULTS: Sixty-four adenovirus strains isolated in HEp2 (human laryngeal tumor cells) cells were confirmed as such by an adenovirus-group specific PCR. Nucleotide sequencing identified the following adenovirus species: A (3 isolates), B (20 isolates), C (38 isolates), D (2 isolates) and E (1 isolate). The following serotypes belonging to the species B were identified: Ad3 (1 strain), Ad7 (17 strains) and, Ad16 (2 strains).
    CONCLUSION: Other viral agents became more recognized in association with CNS diseases in areas where wild polioviruses have been eradicated. The possible role of species B adenoviruses in the etiology of AFP cases similar to that caused by wild poliovirus is discussed.
    Matched MeSH terms: Acute Disease
  13. da Silva Voorham JM
    Ned Tijdschr Geneeskd, 2014;158:A7946.
    PMID: 25227888
    Sylvatic dengue viruses are both evolutionarily and ecologically distinguishable from the human dengue virus (DENV). Sporadic episodes of sylvatic human infections in West Africa and Southeast Asia suggest that sylvatic DENV regularly come into contact with human beings. Following a study on the sylvatic transmission cycle in Malaysia in 2007, researchers announced that a new DENV serotype, DENV-5, had been discovered. Scientists are still sceptical about these new findings, and indicate that more data is necessary to determine whether this 'new' virus really is a different serotype or whether it is a variant of one of the four DENV serotypes already known. The good news is that this new variant has not yet established itself in the human transmission cycle. However, if it really is a new serotype this will have implications for the long-term control of dengue using vaccines currently under development.
    Matched MeSH terms: Disease Susceptibility
  14. Zyoud SH, Waring WS, Al-Jabi SW, Sweileh WM, Rahhal B, Awang R
    Basic Clin Pharmacol Toxicol, 2016 Nov;119(5):512-519.
    PMID: 27098056 DOI: 10.1111/bcpt.12609
    In recent years, there has been increasing interest in the role of intravenous lipid formulations as potential antidotes in patients with severe cardiotoxicity caused by drug toxicity. The aim of this study was to conduct a comprehensive bibliometric analysis of all human and animal studies featuring lipid emulsion as an antidote for the treatment of acute poisoning. The Scopus database search was performed on 5 February 2016 to analyse the research output related to intravenous lipid emulsion as an antidote for the treatment of acute poisoning. Research indicators used for analysis included total number of articles, date (year) of publication, total citations, value of the h-index, document types, countries of publication, journal names, collaboration patterns and institutions. A total of 594 articles were retrieved from Scopus database for the period of 1955-2015. The percentage share of global intravenous lipid emulsion research output showed that research output was 85.86% in 2006-2015 with yearly average growth in this field of 51 articles per year. The USA, United Kingdom (UK), France, Canada, New Zealand, Germany, Australia, China, Turkey and Japan accounted for 449 (75.6%) of all the publications. The total number of citations for all documents was 9,333, with an average of 15.7 citations per document. The h-index of the retrieved documents for lipid emulsion research as antidote for the treatment of acute poisoning was 49. The USA and the UK achieved the highest h-indices, 34 and 14, respectively. New Zealand produced the greatest number of documents with international collaboration (51.9%) followed by Australia (50%) and Canada (41.4%) out of the total number of publications for each country. In summary, we found an increase in the number of publications in the field of lipid emulsion after 2006. The results of this study demonstrate that the majority of publications in the field of lipid emulsion were published by high-income countries. Researchers from institutions in the USA led scientific production on lipid emulsion research. There is an obvious need to promote a deeper engagement through international collaborative research projects and funding mechanisms.
    Matched MeSH terms: Acute Disease
  15. Zuo XY, Feng QS, Sun J, Wei PP, Chin YM, Guo YM, et al.
    Biol Sex Differ, 2019 03 25;10(1):13.
    PMID: 30909962 DOI: 10.1186/s13293-019-0227-9
    BACKGROUND: The male predominance in the incidence of nasopharyngeal carcinoma (NPC) suggests the contribution of the X chromosome to the susceptibility of NPC. However, no X-linked susceptibility loci have been examined by genome-wide association studies (GWASs) for NPC by far.

    METHODS: To understand the contribution of the X chromosome in NPC susceptibility, we conducted an X chromosome-wide association analysis on 1615 NPC patients and 1025 healthy controls of Guangdong Chinese, followed by two validation analyses in Taiwan Chinese (n = 562) and Malaysian Chinese (n = 716).

    RESULTS: Firstly, the proportion of variance of X-linked loci over phenotypic variance was estimated in the discovery samples, which revealed that the phenotypic variance explained by X chromosome polymorphisms was estimated to be 12.63% (non-dosage compensation model) in males, as compared with 0.0001% in females. This suggested that the contribution of X chromosome to the genetic variance of NPC should not be neglected. Secondly, association analysis revealed that rs5927056 in DMD gene achieved X chromosome-wide association significance in the discovery sample (OR = 0.81, 95% CI 0.73-0.89, P = 1.49 × 10-5). Combined analysis revealed rs5927056 for DMD gene with suggestive significance (P = 9.44 × 10-5). Moreover, the female-specific association of rs5933886 in ARHGAP6 gene (OR = 0.62, 95%CI: 0.47-0.81, P = 4.37 × 10-4) was successfully replicated in Taiwan Chinese (P = 1.64 × 10-2). rs5933886 also showed nominally significant gender × SNP interaction in both Guangdong (P = 6.25 × 10-4) and Taiwan datasets (P = 2.99 × 10-2).

    CONCLUSION: Our finding reveals new susceptibility loci at the X chromosome conferring risk of NPC and supports the value of including the X chromosome in large-scale association studies.

    Matched MeSH terms: Genetic Predisposition to Disease*
  16. Zulkifli, Y., Alitheen, N.B., Raha, A.R., Yeap, S.K., Marlina, Son, R., et al.
    MyJurnal
    Vibrio parahaemolyticus is one of the most widely recognized pathogenic Vibrio species due to numerous outbreaks and its’ wide occurrence in marine environment. In this study, 32 isolates of V. parahaemolyticus isolated from cockles were tested for sensitivity to 16 antibiotics and the presence of plasmids. All the isolates were multi-resistance, defined as resistant to atleast three different antibiotics with multiple antibiotic resistance indexes ranging from 0.31 to 0.69, indicating the isolates originate from high risk sources of contamination where antibiotics are often used. In the plasmid profiling test, only 15 isolates (47%) harbored plasmid DNA, which ranged in size from 2.7 to 56.2 kb, separating the isolates into 14 plasmid profiles. Hence, food contaminated with antibiotic resistant V. parahaemolyticus could be a major threat to public health due to the distinct possibility that they can be a significant reservoir of genes encoding antibiotic resistance determinants that can be transferred intra or interspecies. As in many developing countries, raw food hygiene and antimicrobial resistance epidemiology is still in the infancy stage in the locality of the study and thus our data provide a current baseline profile of antimicrobial resistance and plasmid of V. parahaemolyticusfrom cockles in Padang, Indonesia.
    Matched MeSH terms: Disease Outbreaks
  17. Zulkifli MM, Ibrahim R, Ali AM, Aini I, Jaafar H, Hilda SS, et al.
    Neurol Res, 2009 Feb;31(1):3-10.
    PMID: 18937888 DOI: 10.1179/174313208X325218
    Newcastle disease virus (NDV) is a virus of paramyxovirus family and lately has been studied for the treatment of cancer in human. In this study, we successfully determined the oncolysis potential of NDV vaccine, V4UPM tested on the human glioblastoma multiform cell line (DBTRG.05MG) and human glioblastoma astrocytoma cell line (U-87MG) in vitro and in vivo. The V4UPM strain is a modified V4 strain developed as thermostable feed pellet vaccine for poultry.
    Matched MeSH terms: Newcastle disease virus
  18. Zulkifli MH, Viswenaden P, Jasamai M, Azmi N, Yaakob NS
    Biomed Pharmacother, 2019 Feb 20;112:108630.
    PMID: 30797147 DOI: 10.1016/j.biopha.2019.108630
    5-HT3R antagonists such as ondansetron, granisetron and tropisetron have been clinically used to treat nausea and vomiting in chemotherapy patients. However, current study and research revealed novel potentials of these ligands in other diseases like inflammation, Alzheimer's, and drug abuse. Towards utilising these drugs as anti-smoking agents to treat nicotine dependence problem, there are conflicting reports regarding the potential of these ligands in modulating the effects of nicotine in both human and animal behavioural studies. This is complicated by the heterogeneity of 5-HT3R itself, cross regulation between nicotinic acetylcholinergic receptor (nAChR) and distinct pharmacological profiles of 5-HT3R antagonists. This review gathered existing studies conducted investigating the potential of "-setron" class of 5-HT3R antagonists in modulating nicotine effects. We proposed that the mechanism where 5-HT3R antagonists mediate the effects of nicotine could be attributed by both direct at 5-HT3R and indirect mechanism in nicotine addiction downstream regulation. The indirect mechanism mediated by the 5-HT3R antagonist could be through α7 nAChR, 5-HT1B receptor (5-HT1BR), 5-HT1C receptor (5-HT1CR), calcineurin activity, p38 MAPK level, PPAR-γ and NF-κβ. Our review suggested that future studies should focus on newer 5-HT3R antagonist with superior pharmacological profile or the one with multitarget action rather than high selectivity at single receptor.
    Matched MeSH terms: Alzheimer Disease
  19. Zulkifli I, Abdulllah N, Azrin NM, Ho YW
    Br Poult Sci, 2000 Dec;41(5):593-7.
    PMID: 11201439
    1. Hubbard x Hubbard (HH) and Shaver x Shaver (SS) chicks given a dietary supplement of either 50 mg/kg oxytetracycline (OTC) or 1 g/kg Lactobacillus culture (LC) were exposed to 36 +/- 1 degrees C for 3 h daily from day (d) 21 to 42. 2. Prior to heat treatment, body weight (d 21) and weight gain (d 1 to d 21) of OTC and LC birds were greater than those fed the control diet. Chicks given LC had the best food efficiency followed by OTC and control birds during d 1 to d 21. Body weight (d 1 and d 21) and weight gain (d 1 to d 21) were greater for HH tlhan SS chicks. 3. After 3 weeks of heat exposure, birds receiving the LC diet had greater body weight and weight gain, higher food intake and lower food efficiency than OTC and control chicks. 4. Antibody production against Newcastle discase vaccine on d 21 was not affected by strain or diet. On d 42, while diet had negligible effect on this variable among the SS broilers, HH birds fed LC had higher antibody production than those on the control diet. 5. Neither strain nor diet had a significant effect on mortality.
    Matched MeSH terms: Newcastle disease virus/immunology
  20. Zulkhernain NS, Teo SH, Patel V, Tan PJ
    Curr Cancer Drug Targets, 2014;14(8):764-73.
    PMID: 25348017 DOI: 10.2174/1568009614666141028121347
    Targeted therapy, the treatment of cancer based on an underlying genetic alteration, is rapidly gaining favor as the preferred therapeutic approach. To date, although natural products represent a rich resource of bio-diverse drug candidates, only a few have been identified to be effective as targeted cancer therapies largely due to the incompatibilities to current high-throughput screening methods. In this article, we review the utility of a zebrafish developmental screen for bioactive natural product-based compounds that target signaling pathways that are intimately shared with those in humans. Any bioactive compound perturbing signaling pathways identified from phenotypic developmental defects in zebrafish embryos provide an opportunity for developing targeted therapies for human cancers. This model provides a promising tool in the search for targeted cancer therapeutics from natural products.
    Matched MeSH terms: Disease Models, Animal*
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