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Journal of Microbiology, Immunology,... Dec 2020Dengue is an arboviral disease caused by dengue virus. Symptomatic dengue infection causes a wide range of clinical manifestations, from mild dengue fever (DF) to...
BACKGROUND
Dengue is an arboviral disease caused by dengue virus. Symptomatic dengue infection causes a wide range of clinical manifestations, from mild dengue fever (DF) to potentially fatal disease, such as dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). We conducted a literature review to analyze the risks of DHF and current perspectives for DHF prevention and control.
METHODS
According to the PRISMA guidelines, the references were selected from PubMed, Web of Science and Google Scholar database using search strings containing a combination of terms that included dengue hemorrhagic fever, pathogenesis, prevention and control. Quality of references were evaluated by independent reviewers.
RESULTS
DHF was first reported in the Philippines in 1953 and further transmitted to the countries in the region of South-East Asia and Western Pacific. Plasma leakages is the main pathophysiological hallmark that distinguishes DHF from DF. Severe plasma leakage can result in hypovolemic shock. Various factors are thought to impact disease presentation and severity. Virus virulence, preexisting dengue antibodies, immune dysregulation, lipid change and host genetic susceptibility are factors reported to be correlated with the development of DHF. However, the exact reasons and mechanisms that triggers DHF remains controversial. Currently, no specific drugs and licensed vaccines are available to treat dengue disease in any of its clinical presentations.
CONCLUSION
This study concludes that antibody-dependent enhancement, cytokine dysregulation and variation of lipid profiles are correlated with DHF occurrence. Prompt diagnosis, appropriate treatment, active and continuous surveillance of cases and vectors are the essential determinants for dengue prevention and control.
Topics: Animals; Antibodies, Viral; Culicidae; Dengue Virus; Female; Humans; Male; Mosquito Vectors; Severe Dengue; Virulence
PubMed: 32265181
DOI: 10.1016/j.jmii.2020.03.007 -
International Journal of Molecular... Mar 2021Alzheimer's disease (AD) is a complex and severe neurodegenerative disease that still lacks effective methods of diagnosis. The current diagnostic methods of AD rely on...
BACKGROUND
Alzheimer's disease (AD) is a complex and severe neurodegenerative disease that still lacks effective methods of diagnosis. The current diagnostic methods of AD rely on cognitive tests, imaging techniques and cerebrospinal fluid (CSF) levels of amyloid-β1-42 (Aβ42), total tau protein and hyperphosphorylated tau (p-tau). However, the available methods are expensive and relatively invasive. Artificial intelligence techniques like machine learning tools have being increasingly used in precision diagnosis.
METHODS
We conducted a meta-analysis to investigate the machine learning and novel biomarkers for the diagnosis of AD.
METHODS
We searched PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews for reviews and trials that investigated the machine learning and novel biomarkers in diagnosis of AD.
RESULTS
In additional to Aβ and tau-related biomarkers, biomarkers according to other mechanisms of AD pathology have been investigated. Neuronal injury biomarker includes neurofiliament light (NFL). Biomarkers about synaptic dysfunction and/or loss includes neurogranin, BACE1, synaptotagmin, SNAP-25, GAP-43, synaptophysin. Biomarkers about neuroinflammation includes sTREM2, and YKL-40. Besides, d-glutamate is one of coagonists at the NMDARs. Several machine learning algorithms including support vector machine, logistic regression, random forest, and naïve Bayes) to build an optimal predictive model to distinguish patients with AD from healthy controls.
CONCLUSIONS
Our results revealed machine learning with novel biomarkers and multiple variables may increase the sensitivity and specificity in diagnosis of AD. Rapid and cost-effective HPLC for biomarkers and machine learning algorithms may assist physicians in diagnosing AD in outpatient clinics.
Topics: Aged; Alzheimer Disease; Biomarkers; Chromatography, High Pressure Liquid; Diagnosis, Computer-Assisted; Female; Humans; Machine Learning; Middle Aged
PubMed: 33803217
DOI: 10.3390/ijms22052761 -
Frontiers in Immunology 2021There is a significant research gap in meta-analysis on the efficacy and safety of coronavirus disease 2019 (COVID-19) vaccines. This study analyzed the efficacy of... (Meta-Analysis)
Meta-Analysis
There is a significant research gap in meta-analysis on the efficacy and safety of coronavirus disease 2019 (COVID-19) vaccines. This study analyzed the efficacy of COVID-19 vaccines. Published phase I, phase II, and phase III trials analyzing safety and immunogenicity and phase III randomized clinical trials evaluating the efficacy of COVID-19 vaccines were included. We searched MEDLINE, Scopus, and The Lancet for published articles evaluating the relative reduction in COVID-19 risk after vaccination. Selected literatures were published between December 15, 2019 and May 15, 2021 on the safety, efficacy, and immunogenicity of COVID-19 vaccines. This meta-analysis included studies that confirmed cases of COVID-19 using reverse transcriptase polymerase chain reaction. This study detected 8,926 eligible research articles published on COVID-19 vaccines. Of these, 25 studies fulfilled the inclusion criteria. Among the selected articles, 19 randomized clinical trials, 2 non-randomized clinical trials, and 3 observational studies were analyzed. Seven (28%) studies were included in the meta-analysis. The efficacy of the adenovirus vector vaccine was 73% (95% CI = 69-77) and that of the messenger RNA (mRNA) vaccine was 85% (95% CI = 82-88) in participants aged ≥18 years. There are no reports of clinical trials in participants aged under 16 years. The production of neutralizing antibodies against receptor-binding domains (RBDs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in >90% of the vaccinated samples was reported within 0-30 days of the first or the second dose of the vaccine. Pain at the injection site was the most common local symptom in people receiving mRNA vaccines (29%-85% of participants). Fever (0.2%-95%) was the most prevalent in people receiving adenovirus vector vaccines, and fatigue (8.4%-55%) was the most common side effect in people receiving the mRNA vaccines. Studies suggest that mRNA vaccines and adenovirus vector vaccines can provide moderate to high protection against COVID-19 infection in people over 18 years. Evidence of the long-term protection of the vaccines in people aged under 16 years against the multiple variants of COVID-19 are limited. This study will provide an integrated evaluation on the efficacy, safety, and immunogenicity of the COVID-19 vaccines.
Topics: Adolescent; Adult; Aged; Antibodies, Neutralizing; COVID-19; COVID-19 Vaccines; Humans; Immunogenicity, Vaccine; Injections, Intramuscular; Middle Aged; Pain; Randomized Controlled Trials as Topic; SARS-CoV-2; Young Adult
PubMed: 34707602
DOI: 10.3389/fimmu.2021.714170 -
Revista Panamericana de Salud Publica =... 2023To characterize the distribution profile of dengue, chikungunya, and Zika virus infections in Latin America and the Caribbean and to identify possible factors associated... (Review)
Review
OBJECTIVES
To characterize the distribution profile of dengue, chikungunya, and Zika virus infections in Latin America and the Caribbean and to identify possible factors associated with the risk of dissemination and severity of these arboviruses.
METHODS
The protocol of this review was registered on the PROSPERO platform. Searches were carried out in the following databases: Virtual Health Library, MEDLINE/PubMed, and Embase. The search terms were: Zika virus, Zika virus infection, dengue, dengue virus, chikungunya virus, chikungunya fever, epidemiology, observational study, Latin America, and Caribbean region. Studies that addressed the distribution of these arboviruses and the risk factors associated with dengue, Zika virus disease, and chikungunya, published between January 2000 and August 2020 in English, Portuguese, and Spanish, were included.
RESULTS
Of 95 studies included, 70 identified risk factors, clinical manifestations, and outcomes for arbovirus infections and 25 described complications and/or deaths. The highest frequency of confirmed cases was for dengue. Brazil reported most cases of the three arboviruses in the period analyzed. Environmental and socioeconomic factors facilitated the proliferation and adaptation of vectors, and host-related factors were reported to aggravate dengue. Most deaths were due to chikungunya, Zika virus disease caused most neurological alterations, and dengue resulted in greater morbidity leading to more frequent hospitalization.
CONCLUSIONS
The review provides a broad view of the three arboviruses and the intrinsic aspects of infections, and highlights the factors that influence the spread of these viruses in the populations studied.
PubMed: 36788963
DOI: 10.26633/RPSP.2023.34 -
Frontiers in Immunology 2021The World Health Organization declared the coronavirus disease 2019 (COVID-19) pandemic on March 11, 2020. Two vaccine types were developed using two different...
INTRODUCTION
The World Health Organization declared the coronavirus disease 2019 (COVID-19) pandemic on March 11, 2020. Two vaccine types were developed using two different technologies: viral vectors and mRNA. Thrombosis is one of the most severe and atypical adverse effects of vaccines. This study aimed to analyze published cases of thrombosis after COVID-19 vaccinations to identify patients' features, potential pathophysiological mechanisms, timing of appearance of the adverse events, and other critical issues.
MATERIALS AND METHODS
We performed a systematic electronic search of scientific articles regarding COVID-19 vaccine-related thrombosis and its complications on the PubMed (MEDLINE) database and through manual searches. We selected 10 out of 50 articles from February 1 to May 5, 2021 and performed a descriptive analysis of the adverse events caused by the mRNA-based Pfizer and Moderna vaccines and the adenovirus-based AstraZeneca vaccine.
RESULTS
In the articles on the Pfizer and Moderna vaccines, the sample consisted of three male patients with age heterogeneity. The time from vaccination to admission was ≤3 days in all cases; all patients presented signs of petechiae/purpura at admission, with a low platelet count. In the studies on the AstraZeneca vaccine, the sample consisted of 58 individuals with a high age heterogeneity and a high female prevalence. Symptoms appeared around the ninth day, and headache was the most common symptom. The platelet count was below the lower limit of the normal range. All patients except one were positive for PF4 antibodies. The cerebral venous sinus was the most affected site. Death was the most prevalent outcome in all studies, except for one study in which most of the patients remained alive.
DISCUSSION
Vaccine-induced thrombotic thrombocytopenia (VITT) is an unknown nosological phenomenon secondary to inoculation with the COVID-19 vaccine. Several hypotheses have been formulated regarding its physiopathological mechanism. Recent studies have assumed a mechanism that is assimilable to heparin-induced thrombocytopenia, with protagonist antibodies against the PF4-polyanion complex. Viral DNA has a negative charge and can bind to PF4, causing VITT. New experimental studies have assumed that thrombosis is related to a soluble adenoviral protein spike variant, originating from splicing events, which cause important endothelial inflammatory events, and binding to endothelial cells expressing ACE2.
CONCLUSION
Further studies are needed to better identify VITT's pathophysiological mechanisms and genetic, demographic, or clinical predisposition of high-risk patients, to investigate the correlation of VITT with the different vaccine types, and to test the significance of the findings.
Topics: 2019-nCoV Vaccine mRNA-1273; Antigen-Antibody Complex; BNT162 Vaccine; COVID-19; Cerebral Veins; ChAdOx1 nCoV-19; Female; Headache; Humans; Mass Vaccination; Platelet Factor 4; SARS-CoV-2; Sex Factors; Survival Analysis; Thrombosis
PubMed: 34912330
DOI: 10.3389/fimmu.2021.729251 -
Neuroepidemiology 2011Population incidence of Guillain-Barré syndrome (GBS) is required to assess changes in GBS epidemiology, but published estimates of GBS incidence vary greatly depending... (Meta-Analysis)
Meta-Analysis Review
Population incidence of Guillain-Barré syndrome (GBS) is required to assess changes in GBS epidemiology, but published estimates of GBS incidence vary greatly depending on case ascertainment, definitions, and sample size. We performed a meta-analysis of articles on GBS incidence by searching Medline (1966-2009), Embase (1988-2009), Cinahl (1981-2009) and CABI (1973-2009) as well as article bibliographies. We included studies from North America and Europe with at least 20 cases, and used population-based data, subject matter experts to confirm GBS diagnosis, and an accepted GBS case definition. With these data, we fitted a random-effects negative binomial regression model to estimate age-specific GBS incidence. Of 1,683 nonduplicate citations, 16 met the inclusion criteria, which produced 1,643 cases and 152.7 million person-years of follow-up. GBS incidence increased by 20% for every 10-year increase in age; the risk of GBS was higher for males than females. The regression equation for calculating the average GBS rate per 100,000 person-years as a function of age in years was exp[-12.0771 + 0.01813(age in years)] × 100,000. Our findings provide a robust estimate of background GBS incidence in Western countries. Our regression model may be used in comparable populations to estimate the background age-specific rate of GBS incidence for future studies.
Topics: Age Factors; Animals; Guillain-Barre Syndrome; Humans; Incidence; Population Surveillance; Risk Factors
PubMed: 21422765
DOI: 10.1159/000324710 -
Frontiers in Immunology 2022Recombinant Adeno-associated virus (rAAV) is one of the main delivery vectors for gene therapy. To assess immunogenicity, toxicity, and features of AAV gene therapy in... (Meta-Analysis)
Meta-Analysis
Recombinant Adeno-associated virus (rAAV) is one of the main delivery vectors for gene therapy. To assess immunogenicity, toxicity, and features of AAV gene therapy in clinical settings, a meta-analysis of 255 clinical trials was performed. A total of 7,289 patients are planned to be dosed. AAV2 was the most dominantly used serotype (29.8%, n=72), and 8.3% (n=20) of trials used engineered capsids. 38.7% (n=91) of trials employed neutralizing antibody assays for patient enrollment, while 15.3% (n=36) used ELISA-based total antibody assays. However, there was high variability in the eligibility criteria with cut-off tiers ranging from 1:1 to 1:1,600. To address potential immunogenicity, 46.3% (n=118) of trials applied immunosuppressants (prophylactic or reactive), while 32.7% (n=18) of CNS and 37.5% (n=24) of ocular-directed trials employed immunosuppressants, possibly due to the immune-privileged status of CNS and retina. There were a total of 11 patient deaths across 8 trials, and 18 out of 30 clinical holds were due to toxicity findings in clinical studies. 30.6% (n=78) of trials had treatment-emergent serious adverse events (TESAEs), with hepatotoxicity and thrombotic microangiopathy (systemic delivery) and neurotoxicity (CNS delivery) being the most prominent. Additionally, the durability of gene therapy may be impacted by two distinct decline mechanisms: 1) rapid decline presumably due to immune responses; or 2) gradual decline due to vector dilution. The durability varied significantly depending on disease indication, dose, serotypes, and patient individuals. Most CNS (90.0%) and muscle trials (73.3%) achieved durable transgene expression, while only 43.6% of ocular trials had sustained clinical outcomes. The rAAV production system can affect rAAV quality and thus immunogenicity and toxicity. Out of 186 trials that have disclosed production system information, 63.0% (n=126) of trials used the transient transfection of the HEK293/HEK293T system, while 18.0% (n=36) applied the baculovirus/Sf9 (rBac/Sf9) system. There were no significant differences in TESAEs and durability between AAV generated by rBac/Sf9 and HEK293/HEK293T systems. In summary, rAAV immunogenicity and toxicity poses significant challenges for clinical development of rAAV gene therapies, and it warrants collaborative efforts to standardize monitoring/measurement methods, design novel strategies to overcome immune responses, and openly share relevant information.
Topics: Humans; Dependovirus; HEK293 Cells; Genetic Vectors; Genetic Therapy; Immunosuppressive Agents
PubMed: 36389770
DOI: 10.3389/fimmu.2022.1001263 -
Journal of Hematology & Oncology Dec 2020B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T-cell therapy is an emerging treatment option for multiple myeloma. The aim of this systematic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor (CAR)-T-cell therapy is an emerging treatment option for multiple myeloma. The aim of this systematic review and meta-analysis was to determine its safety and clinical activity and to identify factors influencing these outcomes.
METHODS
We performed a database search using the terms "BCMA," "CAR," and "multiple myeloma" for clinical studies published between 01/01/2015 and 01/01/2020. The methodology is further detailed in PROSPERO (CRD42020125332).
RESULTS
Twenty-three different CAR-T-cell products have been used so far in 640 patients. Cytokine release syndrome was observed in 80.3% (69.0-88.2); 10.5% (6.8-16.0) had neurotoxicity. A higher neurotoxicity rate was reported in studies that included more heavily pretreated patients: 19.1% (13.3-26.7; I = 45%) versus 2.8% (1.3-6.1; I = 0%) (p < 0.0001). The pooled overall response rate was 80.5% (73.5-85.9); complete responses (CR) were observed in 44.8% (35.3-54.6). A pooled CR rate of 71.9% (62.8-79.6; I = 0%) was noted in studies using alpaca/llama-based constructs, whereas it was only 18.0% (6.5-41.1; I = 67%) in studies that used retroviral vectors for CAR transduction. Median progression-free survival (PFS) was 12.2 (11.4-17.4) months, which compared favorably to the expected PFS of 1.9 (1.5-3.7) months (HR 0.14; p < 0.0001).
CONCLUSIONS
Although considerable toxicity was observed, BCMA-targeted CAR-T-cell therapy is highly efficacious even in advanced multiple myeloma. Subgroup analysis confirmed the anticipated inter-study heterogeneity and identified potential factors contributing to safety and efficacy. The results of this meta-analysis may assist the future design of CAR-T-cell studies and lead to optimized BCMA CAR-T-cell products.
Topics: B-Cell Maturation Antigen; Cytokine Release Syndrome; Humans; Immunotherapy, Adoptive; Multiple Myeloma; Neurotoxicity Syndromes; Progression-Free Survival; Receptors, Chimeric Antigen; Treatment Outcome
PubMed: 33272302
DOI: 10.1186/s13045-020-01001-1 -
Human Brain Mapping Jun 2021Resting-state fMRI (rs-fMRI) detects functional connectivity (FC) abnormalities that occur in the brains of patients with Alzheimer's disease (AD) and mild cognitive...
Resting-state fMRI (rs-fMRI) detects functional connectivity (FC) abnormalities that occur in the brains of patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). FC of the default mode network (DMN) is commonly impaired in AD and MCI. We conducted a systematic review aimed at determining the diagnostic power of rs-fMRI to identify FC abnormalities in the DMN of patients with AD or MCI compared with healthy controls (HCs) using machine learning (ML) methods. Multimodal support vector machine (SVM) algorithm was the commonest form of ML method utilized. Multiple kernel approach can be utilized to aid in the classification by incorporating various discriminating features, such as FC graphs based on "nodes" and "edges" together with structural MRI-based regional cortical thickness and gray matter volume. Other multimodal features include neuropsychiatric testing scores, DTI features, and regional cerebral blood flow. Among AD patients, the posterior cingulate cortex (PCC)/Precuneus was noted to be a highly affected hub of the DMN that demonstrated overall reduced FC. Whereas reduced DMN FC between the PCC and anterior cingulate cortex (ACC) was observed in MCI patients. Evidence indicates that the nodes of the DMN can offer moderate to high diagnostic power to distinguish AD and MCI patients. Nevertheless, various concerns over the homogeneity of data based on patient selection, scanner effects, and the variable usage of classifiers and algorithms pose a challenge for ML-based image interpretation of rs-fMRI datasets to become a mainstream option for diagnosing AD and predicting the conversion of HC/MCI to AD.
Topics: Alzheimer Disease; Cognitive Dysfunction; Connectome; Humans; Machine Learning; Magnetic Resonance Imaging; Predictive Value of Tests
PubMed: 33942449
DOI: 10.1002/hbm.25369 -
Acta Tropica Jul 2022Mosquito-borne diseases are emerging and re-emerging across the globe, especially after the COVID19 pandemic. The recent advances in text mining in infectious diseases... (Review)
Review
Mosquito-borne diseases are emerging and re-emerging across the globe, especially after the COVID19 pandemic. The recent advances in text mining in infectious diseases hold the potential of providing timely access to explicit and implicit associations among information in the text. In the past few years, the availability of online text data in the form of unstructured or semi-structured text with rich content of information from this domain enables many studies to provide solutions in this area, e.g., disease-related knowledge discovery, disease surveillance, early detection system, etc. However, a recent review of text mining in the domain of mosquito-borne disease was not available to the best of our knowledge. In this review, we survey the recent works in the text mining techniques used in combating mosquito-borne diseases. We highlight the corpus sources, technologies, applications, and the challenges faced by the studies, followed by the possible future directions that can be taken further in this domain. We present a bibliometric analysis of the 294 scientific articles that have been published in Scopus and PubMed in the domain of text mining in mosquito-borne diseases, from the year 2016 to 2021. The papers were further filtered and reviewed based on the techniques used to analyze the text related to mosquito-borne diseases. Based on the corpus of 158 selected articles, we found 27 of the articles were relevant and used text mining in mosquito-borne diseases. These articles covered the majority of Zika (38.70%), Dengue (32.26%), and Malaria (29.03%), with extremely low numbers or none of the other crucial mosquito-borne diseases like chikungunya, yellow fever, West Nile fever. Twitter was the dominant corpus resource to perform text mining in mosquito-borne diseases, followed by PubMed and LexisNexis databases. Sentiment analysis was the most popular technique of text mining to understand the discourse of the disease and followed by information extraction, which dependency relation and co-occurrence-based approach to extract relations and events. Surveillance was the main usage of most of the reviewed studies and followed by treatment, which focused on the drug-disease or symptom-disease association. The advance in text mining could improve the management of mosquito-borne diseases. However, the technique and application posed many limitations and challenges, including biases like user authentication and language, real-world implementation, etc. We discussed the future direction which can be useful to expand this area and domain. This review paper contributes mainly as a library for text mining in mosquito-borne diseases and could further explore the system for other neglected diseases.
Topics: Animals; COVID-19; Data Mining; Dengue; Humans; Mosquito Vectors; Vector Borne Diseases; Zika Virus; Zika Virus Infection
PubMed: 35430265
DOI: 10.1016/j.actatropica.2022.106447