| 1. |
- Block, Keith I., et al.
(författare)
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Designing a broad-spectrum integrative approach for cancer prevention and treatment
- 2015
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Ingår i: Seminars in Cancer Biology. - : Academic Press. - 1044-579X .- 1096-3650. ; 35, s. S276-S304
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Forskningsöversikt (refereegranskat)abstract
- Targeted therapies and the consequent adoption of "personalized" oncology have achieved notable successes in some cancers; however, significant problems remain with this approach. Many targeted therapies are highly toxic, costs are extremely high, and most patients experience relapse after a few disease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistant immortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are not reliant upon the same mechanisms as those which have been targeted). To address these limitations, an international task force of 180 scientists was assembled to explore the concept of a low-toxicity "broadspectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspects of relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a wide range of high-priority targets (74 in total) that could be modified to improve patient outcomes. For these targets, corresponding low-toxicity therapeutic approaches were then suggested, many of which were phytochemicals. Proposed actions on each target and all of the approaches were further reviewed for known effects on other hallmark areas and the tumor microenvironment Potential contrary or procarcinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixed evidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of the relationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. This novel approach has potential to be relatively inexpensive, it should help us address stages and types of cancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for future research is offered. (C) 2015 The Authors. Published by Elsevier Ltd.
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| 2. |
- Islam, Md. Aminul, et al.
(författare)
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A 30-day follow-up study on the prevalence of SARS-COV-2 genetic markers in wastewater from the residence of COVID-19 patient and comparison with clinical positivity
- 2023
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Ingår i: Science of the Total Environment. - : Elsevier BV. - 0048-9697 .- 1879-1026. ; 858, s. 159350-
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Tidskriftsartikel (refereegranskat)abstract
- Wastewater based epidemiology (WBE) is an important tool to fight against COVID-19 as it provides insights into the health status of the targeted population from a small single house to a large municipality in a cost-effective, rapid, and non-invasive way. The implementation of wastewater based surveillance (WBS) could reduce the burden on the public health system, management of pandemics, help to make informed decisions, and protect public health. In this study, a house with COVID-19 patients was targeted for monitoring the prevalence of SARS-CoV-2 genetic markers in wastewa-ter samples (WS) with clinical specimens (CS) for a period of 30 days. RT-qPCR technique was employed to target non-structural (ORF1ab) and structural-nucleocapsid (N) protein genes of SARS-CoV-2, according to a validated experimental protocol. Physiological, environmental, and biological parameters were also measured following the American Public Health Association (APHA) standard protocols. SARS-CoV-2 viral shedding in wastewater peaked when the highest number of COVID-19 cases were clinically diagnosed. Throughout the study period, 7450 to 23,000 gene copies/1000 mL were detected, where we identified 47 % (57/120) positive samples from WS and 35 % (128/360) from CS. When the COVID-19 patient number was the lowest (2), the highest CT value (39.4; i.e., lowest copy number) was identified from WS. On the other hand, when the COVID-19 patients were the highest (6), the lowest CT value (25.2 i.e., highest copy numbers) was obtained from WS. An advance signal of increased SARS-CoV-2 viral load from the COVID-19 patient was found in WS earlier than in the CS. Using customized primer sets in a traditional PCR approach, we confirmed that all SARS-CoV-2 variants identified in both CS and WS were Delta variants (B.1.617.2). To our knowledge, this is the first follow-up study to determine a temporal relationship be-tween COVID-19 patients and their discharge of SARS-CoV-2 RNA genetic markers in wastewater from a single house including all family members for clinical sampling from a developing country (Bangladesh), where a proper sewage system is lacking. The salient findings of the study indicate that monitoring the genetic markers of the SARS-CoV-2 virus in wastewater could identify COVID-19 cases, which reduces the burden on the public health system during COVID-19 pandemics.
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| 3. |
- Islam, Md. Aminul, et al.
(författare)
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Variant-specific deleterious mutations in the SARS-CoV-2 genome reveal immune responses and potentials for prophylactic vaccine development
- 2023
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Ingår i: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has had a disastrous effect worldwide during the previous three years due to widespread infections with SARS-CoV-2 and its emerging variations. More than 674 million confirmed cases and over 6.7 million deaths have been attributed to successive waves of SARS-CoV-2 infections as of 29th January 2023. Similar to other RNA viruses, SARS-CoV-2 is more susceptible to genetic evolution and spontaneous mutations over time, resulting in the continual emergence of variants with distinct characteristics. Spontaneous mutations of SARS-CoV-2 variants increase its transmissibility, virulence, and disease severity and diminish the efficacy of therapeutics and vaccines, resulting in vaccine-breakthrough infections and re-infection, leading to high mortality and morbidity rates.Materials and methods: In this study, we evaluated 10,531 whole genome sequences of all reported variants globally through a computational approach to assess the spread and emergence of the mutations in the SARS-CoV-2 genome. The available data sources of NextCladeCLI 2.3.0 () and NextStrain () were searched for tracking SARS-CoV-2 mutations, analysed using the PROVEAN, Polyphen-2, and Predict SNP mutational analysis tools and validated by Machine Learning models.Result: Compared to the Wuhan-Hu-1 reference strain NC 045512.2, genome-wide annotations showed 16,954 mutations in the SARS-CoV-2 genome. We determined that the Omicron variant had 6,307 mutations (retrieved sequence:1947), including 67.8% unique mutations, more than any other variant evaluated in this study. The spike protein of the Omicron variant harboured 876 mutations, including 443 deleterious mutations. Among these deleterious mutations, 187 were common and 256 were unique non-synonymous mutations. In contrast, after analysing 1,884 sequences of the Delta variant, we discovered 4,468 mutations, of which 66% were unique, and not previously reported in other variants. Mutations affecting spike proteins are mostly found in RBD regions for Omicron, whereas most of the Delta variant mutations drawn to focus on amino acid regions ranging from 911 to 924 in the context of epitope prediction (B cell & T cell) and mutational stability impact analysis protruding that Omicron is more transmissible.Discussion: The pathogenesis of the Omicron variant could be prevented if the deleterious and persistent unique immunosuppressive mutations can be targeted for vaccination or small-molecule inhibitor designing. Thus, our findings will help researchers monitor and track the continuously evolving nature of SARS-CoV-2 strains, the associated genetic variants, and their implications for developing effective control and prophylaxis strategies.
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| 4. |
- Islam, Md Aminul, et al.
(författare)
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A bibliometric study on Marburg virus research with prevention and control strategies
- 2022
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Ingår i: Frontiers in Tropical Diseases. - : Frontiers Media SA. - 2673-7515. ; 3
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Forskningsöversikt (refereegranskat)abstract
- Marburg virus (MARV) is a pathogenic zoonotic RNA virus etiologic for Marburg virus disease (MVD), a severe hemorrhagic fever. This is a rare disease, with a high fatality rate, that spreads via infected blood or body fluids or indirectly via fomites (contaminated objects and substances such as clothed, beds, personal protective equipment, or medical equipments). A few vaccines to protect against MARV are undergoing clinical trials, but there is not yet an approved vaccine against this disease. Eventually, prevention and control guidelines should be adhered to rigorously to alleviate this infection. This bibliometric analysis aimed to harness narrative evaluation, emphasizing the significance of quantitative approaches and delineating the most thought-provoking concerns for researchers using VOSviewer software (Centre for Science and Technology Studies, Leiden University, the Netherlands). “Marburg Virus” OR “MARV” AND “Diseases” search criteria were used for the analysis of articles published between 1962 and 2022. Co-occurrence analysis was carried out, which characterized different thematic clusters. From this analysis, we found that 1688 published articles, and the number of publications increased across that period annually, with a growth rate of 8.78%. It is also conspicuous that the number of publications in the United States reached its acme during this period (i.e., 714 publications, accounting for 42.29% of the total), and the United States Army Medical Research Institute of Infectious Diseases published the most literature (i.e., 146 papers). Our study found that the three pre-eminent authors of Marburg virus papers were “FELDMANN, HEINZ“ of the National Institute of Allergy and Infectious Diseases, United States, “BECKER, STEPHAN” of the Philipps University of Marburg, Germany, and “GEISBERT, THOMAS W” of the University of Texas Medical Branch, United States. In this study we found that “JOURNAL OF VIROLOGY” has published the most pertinent literature, totaling 88 articles, followed by “The journal of Infectious Diseases”, which published 76 relevant papers, and “VIRUSES”, which published 52 corresponding papers. The most cited paper on the Marburg virus was published in Nature Medicine, with 522 total citations and 29 citations/year. Studies of the changing epidemiology and evolving nature of the virus and its ecological niche are required; breakthrough and implementation of the efficacious vaccine candidate(s), prophylaxis and therapeutic alternatives and supervision strategies, unveiling awareness-raising programs, and developing apposite and timely preparedness, prevention, and proactive control strategies are of utmost importance.
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| 5. |
- Islam, Md Aminul, et al.
(författare)
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Old Enemy with a New Face : Re-emerging Monkeypox Disease - An Update
- 2022
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Ingår i: JOURNAL OF PURE AND APPLIED MICROBIOLOGY. - : DR M N KHAN. - 0973-7510. ; 16, s. 2972-2988
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Forskningsöversikt (refereegranskat)abstract
- Human monkeypox (MPX), a multi-country re-emerging disease, is rapidly spreading around the world. The etiological agent of this disease, Monkeypox virus (MPXV), is a DNA virus classified into three genetic types (West Africa, Congo Basin clade, and one new clade-3). Atypical or unusual symptoms as well as asymptomatic infection of MPXV has also been reported. Transmission among humans is possible by droplets, contact, sexual intercourse, and fomites. Secondary transmission of this disease has been reported to occur in less than 10% of cases where it was found 35%-88% of smallpox. Mother-to-fetus transmission by vertical route is also possible for this disease. Modern equipment, biosafety level-3 laboratory facilities, and trained expert persons are needed to diagnose this disease. Previous data support that similar to 85% clinical protection is provided by smallpox vaccines for monkeypox, although initially non-human primates models were used for various experiments, and also side-effects of this vaccine have been notably mentioned in various studies. Limited research findings of JYNNEOS vaccine has supported the comparatively lower prevalence of MPX cases with vaccination. Few drugs, including cidofovir, tecovirimat, brincidofovir, and vaccinia immune globulin intravenous are preferable against this disease, although clinical trial data is limited and FDA-approval is also pending. This review-based study presents an overall scenario of Monkeypox disease (MPXD) based on previously published studies. Recommended clinical treatment and vaccination, appropriate infection prevention and control strategies, adopting one health approach, and quick identification of hotspots using a wastewater-based surveillance system need to be followed to check the further spread of MPX outbreaks.
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| 6. |
- Suleiman, Adeiza Shuaibu, et al.
(författare)
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A meta-meta-analysis of co-infection, secondary infections, and antimicrobial resistance in COVID-19 patients
- 2023
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Ingår i: Journal of Infection and Public Health. - : Elsevier BV. - 1876-0341 .- 1876-035X. ; 16:10, s. 1562-1590
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Forskningsöversikt (refereegranskat)abstract
- The newly discovered coronavirus SARS-CoV-2 has sparked a worldwide pandemic of COVID-19, which has caused havoc on medical infrastructures, economies, and cultures around the world. Determining the whole scenario is essential since SARS-CoV-2 variants and sub-variants keep appearing after vaccinations and booster doses. The objective of this secondary meta-analysis is to analysis co-infection, secondary infections, and antimicrobial resistance (AMR) in COVID-19 patients. This study used five significant databases to conduct a systematic review and an overlap meta-analysis to evaluate the pooled estimates of co-infections and secondary infections. The summary of the meta-analysis showed an overall co-infection effect of 26.19% (95% confidence intervals CI: 21.39–31.01, I2 =98.78, n = 14 meta-analysis) among patients with COVID-19. A coinfection effect of 11.13% (95% CI: 9.7–12.56, I2 =99.14, n = 11 meta-analysis) for bacteria; 9.69% (95% CI: 1.21–7.90, I2 =98.33) for fungal and 3.48% (95% CI: 2.15–4.81, I2 =95.84) for viruses. A secondary infection effect of 19.03% (95% CI: 9.53–28.54, I2 =85.65) was pooled from 2 meta-analyses (Ave: 82 primary studies). This is the first study that compiles the results of all the previous three years meta-analyses into a single source and offers strong proof of co-infections and secondary infections in COVID-19 patients. Early detection of co-infection and AMR is crucial for COVID-19 patients in order to effective treatment.
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