CodeBreak 200: study limitations, and future directions.
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ABSTRACT:
SUBMITTER: Alharbi M
PROVIDER: S-EPMC10894345 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
Publications
CodeBreak 200: study limitations, and future directions.
Alharbi Malak M Awidi Muhammad M Dy Grace K GK
Translational cancer research 20240105 1
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Project description:Crimean-Congo hemorrhagic fever (CCHF) is the most prevalent tick-borne viral disease affecting humans. The disease is life-threatening in many regions of the developing world, including Africa, Asia, the Middle East, and Southern Europe. In line with the rapidly increasing disease prevalence, various vaccine strategies are under development. Despite a large number of potential vaccine candidates, there are no approved vaccines as of yet. This paper presents a detailed comparative analysis of current efforts to develop vaccines against CCHFV, limitations associated with current efforts, and future research directions.
| S-EPMC10518622 | biostudies-literature
Project description:Estimating total infection levels, including unreported and asymptomatic infections, is important for understanding community disease transmission. Wastewater can provide a pooled community sample to estimate total infections that is independent of case reporting biases toward individuals with moderate to severe symptoms and by test-seeking behavior and access. We derive three mechanistic models for estimating community infection levels from wastewater measurements based on a description of the processes that generate SARS-CoV-2 RNA signals in wastewater and accounting for the fecal strength of wastewater through endogenous microbial markers, daily flow, and per-capita wastewater generation estimates. The models are illustrated through two case studies of wastewater data collected during 2020-2021 in Virginia Beach, VA, and Santa Clara County, CA. Median simulated infection levels generally were higher than reported cases, but at times, were lower, suggesting a discrepancy between the reported cases and wastewater data, or inaccurate modeling results. Daily simulated infection estimates showed large ranges, in part due to dependence on highly variable clinical viral fecal shedding data. Overall, the wastewater-based mechanistic models are useful for normalization of wastewater measurements and for understanding wastewater-based surveillance data for public health decision-making but are currently limited by lack of robust SARS-CoV-2 fecal shedding data.
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Project description:Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous entity with complex pathophysiology and manifestations. Phenomapping is the process of applying statistical learning techniques to patient data to identify distinct subgroups based on patterns in the data. Phenomapping has emerged as a technique with potential to improve the understanding of different HFpEF phenotypes. Phenomapping efforts have been increasing in HFpEF over the past several years using a variety of data sources, clinical variables, and statistical techniques. This review summarizes methodologies and key takeaways from these studies, including consistent discriminating factors and conserved HFpEF phenotypes. We argue that phenomapping results to date have had limited implications for clinical care and clinical trials, given that the phenotypes, as currently described, are not reliably identified in each study population and may have significant overlap. We review the inherent limitations of aggregating and utilizing phenomapping results. Lastly, we discuss potential future directions, including using phenomapping to optimize the likelihood of clinical trial success or to drive discovery in mechanisms of the disease process of HFpEF.
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Project description:ObjectivesWhile various clinical and pharmacological determinants for chemotherapy-associated cognitive impairment have been identified, conflicting evidence suggests that cytokines might play an intermediary role. The objective of this systematic review was to evaluate the current evidence pertaining to the associations among chemotherapy, cytokines induction and cognitive impairment in cancer patients.MethodsA literature search with PubMed and SciVerse Scopus was conducted in March 2013 to gather relevant articles and abstracts that fulfilled the inclusion and exclusion criteria. This review included studies that had performed objective and/or subjective cognitive assessments and cytokine measurements on defined populations of cancer patients who received chemotherapy.ResultsHigh methodological heterogeneity existed among the selected studies which differed in cancer populations, subject characteristics, cognitive endpoints, types of cytokines tested and their measurement methods. Weak to moderate correlations were observed between IL-1?, IL-6, TNF-? levels, and different degrees of cognitive impairment. Different types of chemotherapy treatments might lead to varying presentations and severities of cytokine-induced cognitive impairment. Notably, the time concordance between the onset of cytokine induction and occurrence of cognitive impairment was not well elucidated. A number of confounding factors was identified to interfere with the expression levels of cytokines; these confounders included subjects' cancer types, ages, genders, genetics and psychosocial characteristics such as anxiety, depression and fatigue.ConclusionAlthough existing studies observed cognitive impairment and cytokine dysregulation in patients who receive chemotherapy, our results suggest that the intermediary role of cytokines in post-chemotherapy cognitive impairment is still controversial and requires further evaluation. A list of methodological recommendations is proposed to harmonize future studies of this subject matter.
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Project description:Nutritional epigenetics is a rapidly expanding field of research, and the natural modulation of the genome is a non-invasive, sustainable, and personalized alternative to gene-editing for chronic disease management. Genetic differences and epigenetic inflexibility resulting in abnormal gene expression, differential or aberrant methylation patterns account for the vast majority of diseases. The expanding understanding of biological evolution and the environmental influence on epigenetics and natural selection requires relearning of once thought to be well-understood concepts. This research explores the potential for natural modulation by the less understood epigenetic modifications such as ubiquitination, nitrosylation, glycosylation, phosphorylation, and serotonylation concluding that the under-appreciated acetylation and mitochondrial dependant downstream epigenetic post-translational modifications may be the pinnacle of the epigenomic hierarchy, essential for optimal health, including sustainable cellular energy production. With an emphasis on lessons learned, this conceptional exploration provides a fresh perspective on methylation, demonstrating how increases in environmental methane drive an evolutionary down regulation of endogenous methyl groups synthesis and demonstrates how epigenetic mechanisms are cell-specific, making supplementation with methyl cofactors throughout differentiation unpredictable. Interference with the epigenomic hierarchy may result in epigenetic inflexibility, symptom relief and disease concomitantly and may be responsible for the increased incidence of neurological disease such as autism spectrum disorder.
| S-EPMC7750768 | biostudies-literature
Project description:Chlamydia is a major bacterial pathogen that infects humans, as well as a wide range of animals, including marsupials, birds, cats, pigs, cattle, and sheep. Antibiotics are the only treatment currently available, however, with high rates of re-infection, there is mounting pressure to develop Chlamydia vaccines. In this review, we analyzed how Chlamydia vaccine trials have developed over the past 70 years and identified where future trials need to be focused. There has been a strong bias toward studies targeting C. muridarum and C. trachomatis within mice and a lack of studies matching chlamydial species to their end target host. Even though a large number of specific antigenic targets have been studied, the results from whole-cell vaccine targets show slightly more promising results overall. There has also been a strong bias toward systemic vaccine delivery systems, despite the finding that mucosal delivery systems have shown more promising outcomes. However, the only successful vaccines with matched chlamydial species/infecting host are based on systemic vaccine delivery methods. We highlight the extensive work done with mouse model trials and indicate that whole cell antigenic targets are capable of inducing an effective response, protecting from disease and reducing shedding rates. However, replication of these results using antigen preparations more conducive to commercial vaccine production has proven difficult. To date, the Major Outer Membrane Protein (MOMP) has emerged as the most suitable substitute for whole cell targets and its delivery as a combined systemic and mucosal vaccine is most effective. Finally, although mouse model trials are useful, differences between hosts and infecting chlamydial strains are preventing vaccine formulations from mouse models to be translated into larger animals or intended hosts.
| S-EPMC6365973 | biostudies-literature
Project description:Currently, the guidelines for audiological and vestibular follow-up in children with congenital cytomegalovirus (CMV) are not well-defined. The general recommendation is to evaluate hearing in all children with congenital CMV at the same intervals: once every 3-6 months up to 1 year of age, once every 6 months from 1 to 3 years of age, and once a year from 3 to 6 years of age. Additionally, there are no universally accepted protocols for the vestibular follow-up of children with congenital CMV, although video head impulse test (v-HIT) and cervical vestibular-evoked myogenic potentials (cVEMPs) are sometimes used. This narrative review critically evaluates existing audiological and vestibular follow-up approaches for children with congenital CMV, highlighting the need for personalized protocols. Tailoring follow-up schedules with different timing and methods based on risk factors, such as the trimester of maternal infection, CMV PCR results in amniotic fluid, and valganciclovir use, would indeed allow for more precise evaluations, timely interventions, and optimized resource allocation. This strategy would also alleviate the logistical and emotional burdens on families by ensuring that high-risk children receive more frequent and appropriate assessments and early interventions, while lower-risk children avoid unnecessary testing.
| S-EPMC11506510 | biostudies-literature
Project description:IntroductionRecently, interest in quantifying upper limb function in cerebral palsy has grown. However, the lack of reference tasks and protocols, have hindered the development of quantified movement analysis in clinical practice. This study aimed to evaluate existing instrumented assessments of upper limb function in cerebral palsy, with a focus on their clinical applicability, to identify reasons for the lack of adoption and provide recommendations for improving clinical relevance and utility.MethodsA systematic review was conducted by a multidisciplinary team of researchers and clinicians (Prospero CRD42023402382). PubMed and Web of Science databases were searched using relevant keywords and inclusion/exclusion criteria.ResultsA total of 657 articles were initially identified, and after the selection process, 76 records were included for analysis comprising a total of 1293 patients with cerebral palsy. The quality assessment of the reviewed studies revealed a moderate overall quality, with deficiencies in sample size justification and participant information. Optoelectronic motion capture systems were predominantly used in the studies (N = 57/76). The population mainly consisted of individuals with spastic cerebral palsy (834/1293) with unilateral impairment (N = 1092/1293). Patients with severe functional impairment (MACS IV and V) were underrepresented with 3.4% of the 754 patients for whom the information was provided. Thirty-nine tasks were used across the articles. Most articles focused on unimanual activities (N = 66/76) and reach or reach and grasp (N = 51/76). Bimanual cooperative tasks only represented 3 tasks present in 4 articles. A total of 140 different parameters were identified across articles. Task duration was the most frequently used parameter and 23% of the parameters were used in only one article.ConclusionFurther research is necessary before incorporating quantified motion analysis into clinical practice. Existing protocols focus on extensively studied populations and rely on costly equipment, limiting their practicality. Standardized unimanual tasks provide limited insights into everyday arm use. Balancing methodological requirements and performance evaluation flexibility is a challenge. Exploring the correlation between outcome parameters and therapeutic guidance could facilitate the integration of quantified movement assessment into treatment pathways.
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Project description:Suicidal behaviors (SBs), which range from suicidal ideation to suicide attempts and completed suicide, represent a fatal dimension of mental ill-health. The involvement of genetic risk factors in SB is supported by family, twin, and adoption studies. The aim of this paper is to review recent genetic association studies in SBs including (i) case-control studies, (ii) family-based association studies, and (iii) genome-wide association studies (GWAS). Various studies on genetic associations have tended to suggest that a number of genes [e.g., tryptophan hydroxylase, serotonin receptors and transporters, or brain-derived neurotrophic factors (BDNFs)] are linked to SBs, but these findings are not consistently supported by the results obtained. Although the candidate-gene approach is useful, it is hampered by the present state of knowledge concerning the pathophysiology of diseases. Interpretations of GWAS results are mostly hindered by a lack of annotation describing the functions of most variation throughout the genome. Association studies have addressed a wide range of single-nucleotide polymorphisms in numerous genes. We have included 104 such studies, of which 10 are family-based association studies and 11 are GWAS. Numerous meta-analyses of case-control studies have shown significant associations of SB with variants in the serotonin transporter gene (5-HTT or SLC6A4) and the tryptophan hydroxylase 1 gene (TPH1), but others report contradictory results. The gene encoding BDNF and its receptor (NTRK2) are also promising candidates. Only two of the GWAS showed any significant associations. Several pathways are mentioned in an attempt to understand the lack of reproducibility and the disappointing results. Consequently, we review and discuss here the following aspects: (i) sample characteristics and confounding factors; (ii) statistical limits; (iii) gene-gene interactions; (iv) gene, environment, and by time interactions; and (v) technological and theoretical limits.
| S-EPMC5034008 | biostudies-literature