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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 -
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 -
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 -
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 -
Ageing Research Reviews May 2022Multiple structural brain changes in Alzheimer's disease (AD) and mild cognitive impairment (MCI) have been revealed on magnetic resonance imaging (MRI). There is a... (Review)
Review
INTRODUCTION
Multiple structural brain changes in Alzheimer's disease (AD) and mild cognitive impairment (MCI) have been revealed on magnetic resonance imaging (MRI). There is a fast-growing effort in applying artificial intelligence (AI) to analyze these data. Here, we review and evaluate the AI studies in brain MRI analysis with synthesis.
METHODS
A systematic review of the literature, spanning the years from 2009 to 2020, was completed using the PubMed database. AI studies using MRI imaging to investigate normal aging, mild cognitive impairment, and AD-dementia were retrieved for review. Bias assessment was completed using the PROBAST criteria.
RESULTS
97 relevant studies were included in the review. The studies were typically focused on the classification of AD, MCI, and normal aging (71% of the reported studies) and the prediction of MCI conversion to AD (25%). The best performance was achieved by using the deep learning-based convolution neural network algorithms (weighted average accuracy 89%), in contrast to 76-86% using Logistic Regression, Support Vector Machines, and other AI methods.
DISCUSSION
The synthesized evidence is paramount to developing sophisticated AI approaches to reliably capture and quantify multiple subtle MRI changes in the whole brain that exemplify the complexity and heterogeneity of AD and brain aging.
Topics: Alzheimer Disease; Artificial Intelligence; Brain; Cognitive Dysfunction; Humans; Magnetic Resonance Imaging
PubMed: 35358720
DOI: 10.1016/j.arr.2022.101614 -
Journal of Epidemiology and Global... Mar 2023World Health Organization Eastern Mediterranean Region (WHO EMR) has 40% people in the world in need of humanitarian assistance. This systematic review explores selected... (Review)
Review
BACKGROUND AND OBJECTIVE
World Health Organization Eastern Mediterranean Region (WHO EMR) has 40% people in the world in need of humanitarian assistance. This systematic review explores selected vector-borne and zoonotic diseases (VBZDs) of importance to EMR in terms of disease burden across countries and periods, disaggregated across sex, age groups, education levels, income status, and rural/urban areas, related vector or animal source reduction measures, and public health, social and economic impacts and related interventions.
METHODS
We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and reviewed articles in PubMed, Embase, and WHO Global Index Medicus published between 1st of January 2011 and 27th of June 2022. Thirteen VBZDs with at least one reported outbreak in the last five years in the region or prioritized as per previous analysis at the WHO global and regional level and based on expert consultations, were included as part of the analysis.
RESULTS
The review included 295 studies-55% on leishmaniasis and dengue combined, and 75% studies from Pakistan, Kingdom of Saudi Arabia, and Iran combined. Hospital-based and nationally representative studies constituted 60% and 10% respectively. Males were predominantly affected in most diseases; children reported high burden of Leishmaniasis, whereas elderly had a higher burden of Dengue Fever and Middle East Respiratory Syndrome. Although very few studies reported on socioeconomic differences in burden, the ones that reported showed higher burden of diseases among the disadvantaged socioeconomic groups such as the poor and the less educated. More than 80% studies reported an increase in burden over the years.
CONCLUSION
The literature is scanty for most of the diseases reviewed and the number of studies from countries with humanitarian challenges is very low. The need for more nationally representative, population-based studies calls for prioritizing research investments.
Topics: Male; Animals; Humans; Zoonoses; Iran; Leishmaniasis; World Health Organization; Saudi Arabia
PubMed: 36757670
DOI: 10.1007/s44197-023-00091-7 -
Malaria Journal Jul 2016Haiti has a set a target of eliminating malaria by 2020. However, information on malaria vector research in Haiti is not well known. This paper presents results from a... (Review)
Review
BACKGROUND
Haiti has a set a target of eliminating malaria by 2020. However, information on malaria vector research in Haiti is not well known. This paper presents results from a systematic review of the literature on malaria vector research, bionomics and control in Haiti.
METHODS
A systematic search of literature published in French, Spanish and English languages was conducted in 2015 using Pubmed (MEDLINE), Google Scholar, EMBASE, JSTOR WHOLIS and Web of Science databases as well other grey literature sources such as USAID, and PAHO. The following search terms were used: malaria, Haiti, Anopheles, and vector control.
RESULTS
A total of 132 references were identified with 40 high quality references deemed relevant and included in this review. Six references dealt with mosquito distribution, seven with larval mosquito ecology, 16 with adult mosquito ecology, three with entomological indicators of malaria transmission, eight with insecticide resistance, one with sero-epidemiology and 16 with vector control. In the last 15 years (2000-2015), there have only been four published papers and three-scientific meeting abstracts on entomology for malaria in Haiti. Overall, the general literature on malaria vector research in Haiti is limited and dated.
DISCUSSION
Entomological information generated from past studies in Haiti will contribute to the development of strategies to achieve malaria elimination on Hispaniola. However it is of paramount importance that malaria vector research in Haiti is updated to inform decision-making for vector control strategies in support of malaria elimination.
Topics: Animals; Anopheles; Disease Transmission, Infectious; Entomology; Haiti; Humans; Malaria; Mosquito Control; Mosquito Vectors
PubMed: 27443992
DOI: 10.1186/s12936-016-1436-x -
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 -
Diagnostics (Basel, Switzerland) Jan 2022Lyme disease (LD) can have significant consequences for the health of workers. The frequency of infection can be estimated by using prevalence and incidence data on... (Review)
Review
Lyme disease (LD) can have significant consequences for the health of workers. The frequency of infection can be estimated by using prevalence and incidence data on antibodies against Borrelia Burgdoferi (BB). A systematic search of studies published in English between 2002 and 2021 and a meta-analysis were conducted in PubMed/Medline, Web of Science, Scopus, and Google Scholar databases. Out of a total of 1125 studies retrieved, 35 articles were included in the systematic review. Overall, in these studies, outdoor workers showed a 20.5% BB seroprevalence rate. Meta-analysis, performed on 15 studies (3932 subjects), revealed a significantly increased risk in outdoor activities (OR 1.93 95%CI 1.15-3.23), with medium-level heterogeneity (I = 69.2%), and non-significant publication bias. The estimated OR in forestry and agricultural workers was 2.36 (CI95% 1.28; 4.34) in comparison with the controls, while a non-significant increase in risk (OR = 1.05, CI95% 0.28; 3.88) was found in the remaining categories of workers (veterinarians, animal breeders, soldiers). The estimated pooled risk was significantly higher in the studies published until 2010 (OR 3.03 95%CI 1.39-6.61), while in more recent studies the odds became non-significant (OR 1.08 95% CI 0.63-1.85). The promotion of awareness campaigns targeting outdoor workers in endemic areas, and the implementation of local programs aimed at controlling range expansion of vectors, are key strategies for protecting workers.
PubMed: 35204387
DOI: 10.3390/diagnostics12020296 -
Therapeutic Advances in Infectious... 2021Chagas disease (CD) is caused by . When acquired, the disease develops in stages. For diagnosis, laboratory confirmation is required, and an extensive assessment of the... (Review)
Review
INTRODUCTION
Chagas disease (CD) is caused by . When acquired, the disease develops in stages. For diagnosis, laboratory confirmation is required, and an extensive assessment of the patient's health should be performed. Treatment consists of the administration of trypanocidal drugs, which may cause severe adverse effects. The objective of our systematic review was to analyze data contained in the CD published case reports to understand the challenges that patients and clinicians face worldwide.
MATERIALS AND METHODS
We performed a systematic review following the PRISMA guidance. PubMed database was explored using the terms 'American trypanosomiasis' or 'Chagas disease'. Results were limited to human case reports written in English or Spanish. A total of 258 reports (322 patients) were included in the analysis. Metadata was obtained from each article. Following this, it was analyzed to obtain descriptive measures.
RESULTS
From the sample, 56.2% were males and 43.8% were females. Most cases were from endemic countries (85.4%). The most common clinical manifestations were fever during the acute stage (70.0%), dyspnea during the chronic stage in its cardiac form (53.7%), and constipation during the chronic stage in its digestive form (73.7%). Most patients were diagnosed in the chronic stage (72.0%). Treatment was administered in 56.2% of cases. The mortality rate for the acute stage cases was 24.4%, while for the chronic stage this was 28.4%.
DISCUSSION
CD is a parasitic disease endemic to Latin America, with increasing importance due to human and vector migration. In this review, we report reasons for delays in diagnosis and treatment, and trends in medical practices. Community awareness must be increased to improve CD's diagnoses; health professionals should be appropriately trained to detect and treat infected individuals. Furthermore, public health policies are needed to increase the availability of screening and diagnostic tools, trypanocidal drugs, and, eventually, vaccines.
PubMed: 34408874
DOI: 10.1177/20499361211033715