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T-cell-redirecting therapies are promising new therapeutic options in the field of cancer immunotherapy, but the development of these modalities is challenging. A commonly observed adverse event in patients treated with T-cell-redirecting therapies is cytokine release syndrome (CRS). Its clinical manifestation is a burden on patients, and continues to be a big hurdle in the clinical development of this class of therapeutics. We review different T-cell-redirecting therapies, discuss key factors related to cytokine release and potentially leading to CRS, and present clinical mitigation strategies applied for those modalities. We propose to dissect those risk factors into drug-target-disease-related factors and individual patient risk factors. Aiming to optimize the therapeutic intervention of these modalities, we illustrate how the knowledge on drug-target-disease-related factors, such as target expression, binding affinity, and target accessibility, can be leveraged in a model-based framework and highlight with case examples how modeling and simulation is applied to guide drug discovery and development. We draw attention to the current gaps in predicting the individual patient's risk towards a high-grade CRS, which requires further considerations of risk factors related, but not limited to, the patient's demographics, genetics, underlying pathologies, treatment history, and environmental exposures. The drug-target-disease-related factors together with the individual patient's risk factors can be regarded as the patient's propensity for developing CRS in response to therapy. As an outlook, we suggest implementing a risk scoring system combined with mechanistic modeling to enable the prediction of an individual patient's risk of CRS for a given therapeutic intervention., (©2021 American Association for Cancer Research.)

Preterm birth is a major clinical and public health challenge, with a prevalence of 11% worldwide. It is the leading cause of death in children younger than 5 years old and represents 70% of neonatal deaths and 75% of neonatal morbidity. Despite the clinical and public health significance, this condition's etiology is still unclear, and most of the cases are spontaneous. There are several known preterm birth risk factors, including inflammatory diseases and the genetic background, although the underlying molecular mechanisms are far from understood. The present review highlights the research advances on the association between inflammatory-related genes and the increased risk for preterm delivery. The most associated genetic variants are the TNFα rs1800629, the IL1α rs17561, and the IL1RN rs2234663. Moreover, many of the genes discussed in this review are also implicated in pathologies involving inflammatory or autoimmune systems, such as periodontal disease, bowel inflammatory disease, and autoimmune rheumatic diseases. This review presents evidence suggesting a common genetic background to preterm birth, autoimmune and inflammatory diseases susceptibility., (© 2021 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.)

Simple Summary: The journey of discovering melanoma—the most dangerous type of skin cancer—biomarkers is never-ending. Under that assumption, this study attempts to partially fill a gap in that journey by identifying melanoma-related biomarkers. This research paper studied the genetic and molecular profiling of melanoma. A transcriptome-wide association study (TWAS) was conducted to reveal the significant biomarkers associated with melanoma. A molecular network was constructed to represent the significant interactions between genes and microRNAs (miRNAs). The related biological processes, the enriched pathways, and the associated diseases were identified. The hotspot biomarkers were discovered to elucidate further the mechanism of these genes and miRNAs in melanoma pathogenesis. This work reveals the pathogenesis and biologically important molecular interactions of melanoma and provides new insights into the molecular mechanisms of melanoma. A transcriptome-wide association study (TWAS) was conducted on genome-wide association study (GWAS) summary statistics of malignant melanoma of skin (UK Biobank dataset) and The Cancer Genome Atlas-Skin Cutaneous Melanoma (TCGA-SKCM) gene expression weights to identify melanoma susceptibility genes. The GWAS included 2465 cases and 449,799 controls, while the gene expression testing was conducted on 103 cases. Afterward, a gene enrichment analysis was applied to identify significant TWAS associations. The melanoma's gene–microRNA (miRNA) regulatory network was constructed from the TWAS genes and their corresponding miRNAs. At last, a disease enrichment analysis was conducted on the corresponding miRNAs. The TWAS detected 27 genes associated with melanoma with p-values less than 0.05 (the top three genes are LOC389458 (RBAK), C16orf73 (MEIOB), and EIF3CL). After the joint/conditional test, one gene (AMIGO1) was dropped, resulting in 26 significant genes. The Gene Ontology (GO) biological process associated the extended gene set (76 genes) with protein K11-linked ubiquitination and regulation of cell cycle phase transition. K11-linked ubiquitin chains regulate cell division. Interestingly, the extended gene set was related to different skin cancer subtypes. Moreover, the enriched pathways were nsp1 from SARS-CoV-2 that inhibit translation initiation in the host cell, cell cycle, translation factors, and DNA repair pathways full network. The gene-miRNA regulatory network identified 10 hotspot genes with the top three: TP53, BRCA1, and MDM2; and four hotspot miRNAs: mir-16, mir-15a, mir-125b, and mir-146a. Melanoma was among the top ten diseases associated with the corresponding (106) miRNAs. Our results shed light on melanoma pathogenesis and biologically significant molecular interactions. [ABSTRACT FROM AUTHOR]

The entorhinal cortex (EC) stands out as a critical brain region affected in the early phases of Alzheimer's disease (AD), with some of the disease's pathological processes originating from this area, making it one of the most crucial brain regions in AD. Recent research highlights disruptions in the brain's network activity, characterized by heightened excitability and irregular oscillations, may contribute to cognitive impairment. These disruptions are proposed not only as potential therapeutic targets but also as early biomarkers for AD. In this paper, we will begin with a review of the anatomy and function of EC, highlighting its selective vulnerability in AD. Subsequently, we will discuss the disruption of EC network activity, exploring changes in excitability and neuronal oscillations in this region during AD and hypothesize that, considering the advancements in neuromodulation techniques, addressing the disturbances in the network activity of the EC could offer fresh insights for both the diagnosis and treatment of AD. [ABSTRACT FROM AUTHOR]

This paper discusses the use of biomarkers in clinical practice and biomedical research. Biomarkers are measurable characteristics that can be used to indicate the presence or absence of a disease or to track the progression of a disease. They can also be used to predict how a patient will respond to a particular treatment. Biomarkers have enriched clinical practice and disease prognosis by providing measurable characteristics that indicate biological processes. They offer valuable insights into disease susceptibility, progression, and treatment response, aiding drug development and personalized medicine. However, developing and implementing biomarkers come with challenges that must be addressed. Rigorous testing, standardization of assays, and consideration of ethical factors are crucial in ensuring the reliability and validity of biomarkers. Reliability is vital in biomarker research. It ensures accurate measurements by preventing biases and facilitating robust correlations with outcomes. Conversely, validation examines which and how many biomarkers correspond to theoretical constructs and external criteria, establishing their predictive value. Multiple biomarkers are sometimes necessary to represent the complex relationship between exposure and disease outcomes accurately. Susceptibility factors are pivotal in disease states' complex interaction among genetic and environmental factors. Gaining a comprehensive understanding of these factors is essential for effectively interpreting biomarker data and maximizing their clinical usefulness. Using well-validated biomarkers can improve diagnoses, more effective treatment evaluations, and enhanced disease prediction. This, in turn, will contribute to better patient outcomes and drive progress in medicine. [ABSTRACT FROM AUTHOR]

This paper explores the dynamics of COVID-19 transmission, particularly focusing on super-spreaders, through the lens of the SIR model. The model comprises six compartments representing susceptible, exposed, symptomatic infected, super-spreader, asymptomatic infected, and recovered individuals. Utilizing a set of non-linear, interdependent differential equations, we numerically solve for model parameters to examine the influence of super-spreaders on infection spread within the population. We calculate the basic reproduction number (R0) and discuss the stability of disease-free equilibrium. Our findings underscore the significant role played by super-spreaders and asymptomatic individuals in disease dissemination. Drawing on the epidemiological concept of the iceberg phenomenon, we offer insights into super-spreader events (SSEs) in India and their ramifications. [ABSTRACT FROM AUTHOR]

Mitochondrial DNA (mtDNA) exhibits distinct characteristics distinguishing it from the nuclear genome, necessitating specific analytical methods in genetic studies. This comprehensive review explores the complex role of mtDNA in a variety of genetic studies, including genome-wide, epigenome-wide, and phenome-wide association studies, with a focus on its implications for human traits and diseases. Here, we discuss the structure and gene-encoding properties of mtDNA, along with the influence of environmental factors and epigenetic modifications on its function and variability. Particularly significant are the challenges posed by mtDNA's high mutation rate, heteroplasmy, and copy number variations, and their impact on disease susceptibility and population genetic analyses. The review also highlights recent advances in methodological approaches that enhance our understanding of mtDNA associations, advocating for refined genetic research techniques that accommodate its complexities. By providing a comprehensive overview of the intricacies of mtDNA, this paper underscores the need for an integrated approach to genetic studies that considers the unique properties of mitochondrial genetics. Our findings aim to inform future research and encourage the development of innovative methodologies to better interpret the broad implications of mtDNA in human health and disease. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a rare autoimmune connective tissue disorder characterized by massive fibrosis, vascular damage, and immune imbalance. Advances in rheumatology and immunology over the past two decades have led to a redefinition of systemic sclerosis, shifting from its initial perception as primarily a "hyperfibrotic" state towards a recognition of systemic sclerosis as an immune-mediated disease. Consequently, the search for genetic markers has transitioned from focusing on fibrotic mechanisms to exploring immune regulatory pathways. Immunogenetics, an emerging field at the intersection of immunology, molecular biology, and genetics has provided valuable insights into inherited factors that influence immunity. Data from genetic studies conducted thus far indicate that alterations in genetic messages can significantly impact disease risk and progression. While certain genetic variations may confer protective effects, others may exacerbate disease susceptibility. This paper presents a comprehensive review of the most relevant genetic changes that influence both the risk and course of systemic sclerosis. Special emphasis is placed on factors regulating the immune response, recognizing their pivotal role in the pathogenesis of the disease. [ABSTRACT FROM AUTHOR]

Background: Motor neuron disease (MND) (also known as amyotrophic lateral sclerosis) is a life‐limiting neurodegenerative condition. In up to 20% of people with MND, a pathogenic variant associated with autosomal dominant inheritance can be identified. Children of people carrying a pathogenic variant have a 50% chance of inheriting this and a higher, although harder to predict, chance of developing the disease compared to the general adult population. This paper explores the experience of living with the genetic risk of MND. Methods: We undertook a UK‐based interview study with 35 individuals, including: 7 people living with genetically‐mediated forms of MND; 24 asymptomatic relatives, the majority of whom had an increased risk of developing the disease; and 4 unrelated partners. Results: We explore how individuals make sense of genetic risk, unpacking the interplay between genetic knowledge, personal perception, experiences of the disease in the family, age and life stage and the implications that living with risk has for different aspects of their lives. We balance an emphasis on the emotional and psychological impact described by participants, with a recognition that the salience of risk fluctuates over time. Furthermore, we highlight the diverse strategies and approaches people employ to live well in the face of uncertainty and the complex ways they engage with the possibility of developing symptoms in the future. Finally, we outline the need for open‐ended, tailored support and information provision. Conclusions: Drawing on wider literature on genetic risk, we foreground how knowledge of MND risk can disrupt individuals' taken‐for‐granted assumptions on life and perceptions of the future, but also its contextuality, whereby its relevance becomes more prominent at critical junctures. This research has been used in the development of a public‐facing resource on the healthtalk.org website. Patient or Public Contribution: People with experience of living with genetic risk were involved throughout the design and conduct of the study and advised on aspects including the topic guide, sampling and recruitment and the developing analysis. Two patient and public involvement contributors joined a formal advisory panel. [ABSTRACT FROM AUTHOR]

Cotton, a crucial cash crop in Pakistan, faces persistent threats from diseases, notably the Cotton Leaf Curl Virus (CLCuV). Detecting these diseases accurately and early is vital for effective management. This paper offers a comprehensive account of the process involved in collecting, preprocessing, and analyzing an extensive dataset of cotton leaf images. The primary aim of this dataset is to support automated disease detection systems. We delve into the data collection procedure, distribution of the dataset, preprocessing stages, feature extraction methods, and potential applications. Furthermore, we present the preliminary findings of our analyses and emphasize the significance of such datasets in advancing agricultural technology. The impact of these factors on plant growth is significant, but the intrusion of plant diseases, such as Cotton Leaf Curl Disease (CLCuD) caused by the Cotton Leaf Curl Gemini Virus (CLCuV), poses a substantial threat to cotton yield. Identifying CLCuD promptly, especially in areas lacking critical infrastructure, remains a formidable challenge. Despite the substantial research dedicated to cotton leaf diseases in agriculture, deep learning technology continues to play a vital role across various sectors. In this study, we harness the power of two deep learning models, specifically the Convolutional Neural Network (CNN). We evaluate these models using two distinct datasets: one from the publicly available Kaggle dataset and the other from our proprietary collection, encompassing a total of 1349 images capturing both healthy and disease-affected cotton leaves. Our meticulously curated dataset is categorized into five groups: Healthy, Fully Susceptible, Partially Susceptible, Fully Resistant, and Partially Resistant. Agricultural experts annotated our dataset based on their expertise in identifying abnormal growth patterns and appearances. Data augmentation enhances the precision of model performance, with deep features extracted to support both training and testing efforts. Notably, the CNN model outperforms other models, achieving an impressive accuracy rate of 99% when tested against our proprietary dataset. [ABSTRACT FROM AUTHOR]

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This paper provides a comprehensive review of the current understanding of non-alcoholic fatty liver disease (NAFLD) and its progression to non-alcoholic steatohepatitis (NASH), focusing on key factors influencing its pathogenesis and emerging therapeutic strategies. This review highlights the growing prevalence of NAFLD and NASH, emphasizing their multifactorial nature. The manuscript identifies various contributors to NAFLD development, including genetic, dietary, and environmental factors, while examining the intricate interplay between these factors and their impact on hepatic lipid metabolism, inflammation, and insulin resistance. Genetic predisposition, dietary fat intake, and excessive fructose consumption are discussed as significant contributors to NAFLD progression. The article emphasizes the lack of a single therapeutic approach and underscores the need for combination strategies. Lifestyle interventions, particularly weight loss through diet and exercise, remain crucial, while pharmacological options like GLP-1 receptor agonists, obeticholic acid, lanifibranor, and resmetirom show promise but require further validation. Bariatric surgery and emerging endoscopic procedures offer potential in eligible patients. In sum, this article underscores the complexity of NAFLD and NASH, addresses key factors influencing pathogenesis, and discusses emerging therapies advocating for a multifaceted approach to this increasingly prevalent and clinically relevant condition. [ABSTRACT FROM AUTHOR]

Hackathons are collaborative events that bring together diverse groups to solve predefined challenges. The COVID-19 pandemic caused by SARS-CoV-2 has emphasized the need for portable and reproducible genomics analysis pipelines to study the genetic susceptibility of the human host and investigate human-SARS-CoV-2 protein interactions. To build and strengthen institutional capacities in OMICS data analysis applied to host-pathogen interaction (HPI), the PHINDaccess project organized two hackathons in 2020 and 2021. These hackathons are aimed at developing bioinformatics pipelines related to the SARS-CoV-2 viral genome, its phylodynamic transmission, and the identification of human genome host variants, with a focus on addressing global health challenges, particularly in low- and middle-income countries (LMIC). This paper outlines the preparation, proceedings, and lessons learned from these hackathons, including the challenges faced by participants and our recommendations based on our experience for organizing hackathons in LMIC and beyond. [ABSTRACT FROM AUTHOR]

In this paper, a reaction-diffusion SIRS epidemic model with nonlinear incidence rate and partial immunity in a spatially heterogeneous environment is proposed. The wellposedness of the solution is firstly established. Then the basic reproduction number R0 is defined and a threshold dynamics is obtained. That is, when R0 < 1, the disease-free steady state is locally stable, which implies that the disease is extinct, when R0 > 1, the disease is permanent, and there exists at least one positive steady state solution. Finally, the asymptotic profiles of the positive steady state solution as individuals disperse at small and large rates are investigated. Furthermore, as an application of theoretical analysis, a numerical example involving the spread of influenza is discussed. Based on the numerical simulations, we find that the increase of transmission rate and spatial heterogeneity can enhance the risk of influenza propagation, and the increase of diffusion rate, saturation incidence for susceptible and recovery rate can reduce the risk of influenza propagation. Therefore, we propose to reduce the flow of people to lower the effect of spatial heterogeneity, increase the transfer of infected individuals to hospitals in surrounding areas to increase the diffusion rate, and increase the construction of public medical resources to increase the recovery rate for controlling influenza propagation. [ABSTRACT FROM AUTHOR]

Fusarium oxysporum f. sp. cubense Tropical Race 4 (Foc TR4) (Syn. Fusarium odoratissimum) is a devastating soil-borne pathogen that infects the roots of banana plants and causes Fusarium wilt disease. Colombia is one of the world's leading banana producers; therefore, new uncontrolled outbreaks could have serious consequences. Despite this, little is known about the susceptibility of Musaceae lands in Colombia to Foc TR4. This work presents a pioneering study on the susceptibility of Colombian soils to Foc TR4. For this, a study was carried out to characterize climatic, edaphic, and density factors of Musaceae productive systems at the Colombian level, articulated with expert criteria to map and define areas with different levels of susceptibility to Foc R4T. These criteria are typically selected based on the existing scientific literature, consultation with domain experts, and consideration of established methods for assessing soil health and disease susceptibility in Musaceae plantations. By joining the analyzed susceptibility factors, differentiated areas were generated that imply a greater or lesser predisposition to the disease. Subsequently, a validation of the classification was made with Random Forest. The results indicate that at the level of climate, soil, and farm density as a fit factor, practically 50% of the cultivated territory of Musaceae are areas high and very highly susceptible to the pathogen (572,000 km2). The results showed that from the total Musaceae area, Antioquia, Bolívar, Chocó, and Santander turned out to be the departments with the highest proportion of very high susceptibility class of the production farms. The analysis of Random Forest classification performance shows that the model has a relatively low out-of-bag (OOB) error rate (0.023). The study on the susceptibility is highly novel and original, as it represents the first systematic investigation of Foc TR4 susceptibility in Colombian soils. This paper provides important insights into the susceptibility of Musaceae lands in Colombia to Foc TR4. The study highlights the need for ongoing monitoring, containment, and control measures to prevent the spread of this deadly pathogen and protect Colombia's important banana industry. [ABSTRACT FROM AUTHOR]

Background: Genetic studies previously reported that variants in TERT-CLPTM1L genes were related to susceptibility of cancer and non-cancer diseases. However, conclusions were not always concordant. Methods: We performed meta-analyses to assess correlations between 23 variants within TERT-CLPTM1L region and susceptibility to 12 cancers and 1 non-cancer disease based on data in 109 papers (involving 139,510 cases and 208,530 controls). Two approaches (false-positive report probability test and Venice criteria) were adopted for assessing the cumulative evidence of significant associations. Current study evaluated the potential role of these variants based on data in Encyclopedia of DNA Elements (ENCODE) Project. Results: Thirteen variants were statistically associated with susceptibility to 11 cancers and 1 non-cancer disease (p < 0.05). Besides, 12 variants with eight cancers and one non-cancer disease were rated as strong evidence (rs2736098, rs401681, and rs402710 in bladder cancer; rs2736100, rs2853691, and rs401681 in esophageal cancer; rs10069690 in gastric cancer; rs2736100 and rs2853676 in glioma; rs2242652, rs2736098, rs2736100, rs2853677, rs31489, rs401681, rs402710, rs465498, and rs4975616 in lung cancer; rs2736100 in idiopathic pulmonary fibrosis and myeloproliferative neoplasms; and rs401681 in pancreatic and skin cancer). According to data from ENCODE and other public databases, 12 variants with strong evidence might fall within putative functional regions. Conclusions: This paper demonstrated that common variants of TERT-CLPTM1L genes were related to susceptibility to bladder, esophageal, gastric, lung, pancreatic, and skin cancer, as well as to glioma, myeloproliferative neoplasms, and idiopathic pulmonary fibrosis, and, besides, the crucial function of the TERT-CLPTM1L region in the genetic predisposition to human diseases is elucidated. [ABSTRACT FROM AUTHOR]

Structural variation (SV) is an important type of genome variation and confers susceptibility to human cancer diseases. Systematic analysis of SVs has become a crucial step for the exploration of mechanisms and precision diagnosis of cancers. The central point is how to accurately detect SV breakpoints by using next-generation sequencing (NGS) data. Due to the cooccurrence of multiple types of SVs in the human genome and the intrinsic complexity of SVs, the discrimination of SV breakpoint types is a challenging task. In this paper, we propose a convolutional neural network- (CNN-) based approach, called svBreak, for the detection and discrimination of common types of SV breakpoints. The principle of svBreak is that it extracts a set of SV-related features for each genome site from the sequencing reads aligned to the reference genome and establishes a data matrix where each row represents one site and each column represents one feature and then adopts a CNN model to analyze such data matrix for the prediction of SV breakpoints. The performance of the proposed approach is tested via simulation studies and application to a real sequencing sample. The experimental results demonstrate the merits of the proposed approach when compared with existing methods. Thus, svBreak can be expected to be a supplementary approach in the field of SV analysis in human tumor genomes. [ABSTRACT FROM AUTHOR]

Background: Social Frailty is a significant public health concern affecting the elderly, particularly with the global population aging rapidly. Older adults with social frailty are at significantly higher risk of adverse outcomes such as disability, cognitive impairment, depression, and even death. In recent years, there have been more and more studies on social frailty, but no bibliometrics has been used to analyze and understand the general situation in this field. Therefore, by using CiteSpace, VOSviewer, and Bilioshiny software programs, this study aims to analyze the general situation of the research on social frailties of the older adults and determine the research trends and hot spots. Methods: A bibliometric analysis was conducted by searching relevant literature on the social frailty of the older adults from 2003 to 2022 in the Web of Science core database, using visualization software to map publication volume, country and author cooperation networks, keyword co-occurrences, and word emergence. Results: We analyzed 415 articles from 2003 to 2022. Brazil has the highest number of articles in the field of social frailty of the older adults, and the United States has the highest number of cooperative publications. Andrew MK, from Canada, is the most published and co-cited author, with primary research interests in geriatric assessment, epidemiology, and public health. "Social Vulnerability," "Health," "Frailty," "Mortality," and "Older Adult" are among the research hotspots in this field. "Dementia," "Alzheimer's disease," "Population," and "Covid-19" are emerging research trends in social frailty among the older adults. Conclusion: This scientometric study maps the research hotspots and trends for the past 20 years in social frailty among the older adults. Our findings will enable researchers to better understand trends in this field and find suitable directions and partners for future research. [ABSTRACT FROM AUTHOR]

Objective: The Samoan community has a disproportionately higher incidence of gestational diabetes mellitus (GDM). We explored consumer and healthcare providers' insight into perceptions of risk, attitudes to lifestyle behaviour change and experiences of GDM among Australian Samoan women in South Western Sydney. Methods: Semi-structured interviews and a focus group with Samoan women recruited through three churches, a diabetes and pregnancy clinic in South Western Sydney and via social media were conducted. Semi-structured interviews with healthcare providers' were also conducted. Main themes were thematically analysed to identify recurring patterns using Quirkos software. Identified themes were framed against the constructs of the Health Belief Model. Results: One focus group (n=4) and 12 one-to-one interviews were conducted among Samoan women. Eighteen semi-structured interviews with healthcare providers' were also conducted. There was a high concordance between Samoan women and healthcare providers' regarding perception of risk and barriers to maintaining a healthy lifestyle. However, Samoan women reported negative interactions with healthcare providers' that hindered their behaviour change, while healthcare providers' reported that normalisation of diabetes, confusion of GDM with type 2 diabetes and spiritual health beliefs were deterrents to behaviour change among Samoan women. Conclusion: Cross-cultural factors can influence the uptake of a healthy lifestyle. Future research should consider use of culturally tailored strategies when developing educational resources targeting Samoan women. Implications for research, policy and practice: The participants' viewpoints expressed in this study suggest a critical need for the development of culturally-tailored health promotion strategies for Samoan women and cultural training for healthcare providers', to improve GDM care and subsequent pregnancy outcomes. What is already known about the topic? * There is limited data and research on GDM particularly among the Australian-Samoan community though the available data highlight the significant morbidity and mortality due to diabetes in this population. * Samoan women are at an increased risk of gestational diabetes mellitus. What this paper adds: * This paper provides knowledge and understanding on ways to prevent and manage GDM by investigating the perception of risk and experiences of GDM among Australian Samoan women and healthcare professionals in Sydney. * It provides current evidence base for policy makers and researchers to develop health promotion strategies and interventions that are relevant to the Samoan and other culturally and linguistically diverse (CALD) communities in Australia. [ABSTRACT FROM AUTHOR]

Despite well-documented evidence that structurally disadvantaged populations are disproportionately affected by infectious diseases, our understanding of the pathways that connect structural disadvantage to the burden of infectious diseases is limited. We propose a conceptual framework to facilitate more rigorous examination and testing of hypothesized mechanisms through which social and environmental factors shape the burden of infectious diseases and lead to persistent inequities. Drawing upon the principles laid out by Link and Phelan in their landmark paper on social conditions (J Health Soc Behav. 1995;(spec no.):80–94), we offer an explication of potential pathways through which structural disadvantage (e.g. racism, sexism, and economic deprivation) operates to produce infectious disease inequities. Specifically, we describe how the social environment affects an individual's risk of infectious disease by 1) increasing exposure to infectious pathogens and 2) increasing susceptibility to infection. This framework will facilitate both the systematic examination of the ways in which structural disadvantage shapes the burden of infectious disease and the design of interventions that can disrupt these pathways. [ABSTRACT FROM AUTHOR]

Background: Osteoarthritis of the knee is an irreversible disease that causes great pain, and genetic factors play an important role in its occurrence and development. There have been many studies on the correlation between ADAM12 polymorphisms and genetic susceptibility to osteoarthritis, but the results remain inconclusive. Methods: Papers from PubMed, Web of Science, EMbase, Springer, SCOPUS, Google Scholar and other databases were systematically retrieved with a cut-off of January 2022. All case–control studies on ADAM12 rs3740199, rs1871054, rs1044122, and rs1278279 polymorphisms and osteoarthritis were searched. Fixed or random effects models were used for pooled analysis with OR values and 95% confidence intervals (CI), and publication bias was assessed. In addition, the false-positive reporting probability test was used to assess the confidence of a statistically significant association. Results: Eleven articles were included, which included 3332 patients with osteoarthritis and 5108 healthy controls. Meta-analysis showed that the rs1871054 polymorphism of ADAM12 was associated with osteoarthritis in dominant, recessive, allelic, and homozygote genetic models [C vs. T: OR = 1.34 95% CI (1.05, 1.71), P < 0.001]. Our subgroup analysis revealed an association between the ADAM12 polymorphism rs1871054 in Asians and osteoarthritis [C vs. T: OR = 1.61, 95% CI (1.25, 2.08), P < 0.001], albeit this was only for three studies. In addition, the ADAM12 polymorphism rs1871054 is associated with osteoarthritis in patients younger than 60 years of age [C vs. T: OR = 1.39, 95% CI (1.01, 1.92), P = 0.289]; however, the ADAM12 gene rs3740199, rs1044122, and rs1278279 site polymorphisms were not significantly. Furthermore, when assessing the confidence of the positive results, the positive results were found to be credible (except for Age < 60). Conclusion: Polymorphism at the rs1871054 site of ADAM12 is associated with genetic susceptibility to osteoarthritis, but rs3740199, rs1044122, and rs1278279 site polymorphisms are not. [ABSTRACT FROM AUTHOR]

Genetic studies of disease progression can be used to identify factors that may influence survival or prognosis, which may differ from factors that influence on disease susceptibility. Studies of disease progression feed directly into therapeutics for disease, whereas studies of incidence inform prevention strategies. However, studies of disease progression are known to be affected by collider (also known as "index event") bias since the disease progression phenotype can only be observed for individuals who have the disease. This applies equally to observational and genetic studies, including genome-wide association studies and Mendelian randomisation (MR) analyses. In this paper, our aim is to review several statistical methods that can be used to detect and adjust for index event bias in studies of disease progression, and how they apply to genetic and MR studies using both individual- and summary-level data. Methods to detect the presence of index event bias include the use of negative controls, a comparison of associations between risk factors for incidence in individuals with and without the disease, and an inspection of Miami plots. Methods to adjust for the bias include inverse probability weighting (with individual-level data), or Slope-Hunter and Dudbridge et al.'s index event bias adjustment (when only summary-level data are available). We also outline two approaches for sensitivity analysis. We then illustrate how three methods to minimise bias can be used in practice with two applied examples. Our first example investigates the effects of blood lipid traits on mortality from coronary heart disease, while our second example investigates genetic associations with breast cancer mortality. [ABSTRACT FROM AUTHOR]

For many applications of agent-based models (ABMs), an agent’s age influences important decisions (e.g. their contribution to/withdrawal from pension funds, their level of risk aversion in decision-making, etc.) and outcomes in their life cycle (e.g. their susceptibility to disease). These considerations make it crucial to accurately capture the age distribution of the population being considered. Often, empirical survival probabilities cannot be used in ABMs to generate the observed age structure. This may be due to discrepancies between samples (e.g. when empirical survival probabilities are calculated across the whole population, but only a subpopulation is being modelled) or models (between the survival model underpinning the ABM and the statistical model used to produce empirical survival probabilities). In these cases, imputing empirical survival probabilities will not generate the observed age structure of the population, and assumptions such as exogenous agent inflows are required (but not necessarily empirically valid). In this paper, we propose a method that allows for the preservation of agent age-structure without the exogenous influx of agents, even when only a subset of the population is being modelled. We demonstrate the flexibility and accuracy of our methodology by performing simulations of several real-world age distributions. This method is a useful tool for those developing ABMs across a broad range of applications. [ABSTRACT FROM AUTHOR]

Mathematical models have wide applications in studying COVID-19 epidemic transmission dynamics, however, most mathematical models do not take into account the heterogeneity of susceptible populations and the non-exponential distribution infectious period. This paper attempts to investigate whether non-exponentially distributed infectious period can better characterize the transmission process in heterogeneous susceptible populations and how it impacts the control strategies. For this purpose, we establish two COVID-19 epidemic models with heterogeneous susceptible populations based on different assumptions for infectious period: the first one is an exponential distribution model (EDM), and the other one is a gamma distribution model (GDM); explicit formula of peak time of the EDM is presented via our analytical approach. By data fitting with the COVID-19 (Omicron) epidemic in Spain and Norway, it seems that Spain is more suitable for EDM while Norway is more suitable for GDM. Finally, we use EDM and GDM to evaluate the impaction of control strategies such as reduction of transmission rates, and increase of primary course rate (PCR) and booster dose rate (BDR). [ABSTRACT FROM AUTHOR]

Simple Summary: The coronavirus disease (COVID-19) pandemic has increased morbidity and mortality in the general population. Patients with cancer have immune dysfunction due to the use of immunosuppressive agents, poor nutritional status, or the direct effects of the tumor on the reactivity of the immune system, making oncological patients more susceptible to severe disease and death. In this systematic review and meta-analysis, we evaluated whether lung cancer increases the risk of severe COVID-19 and the risk of dying from the disease. We found that mortality in patients with lung cancer was significantly higher than that in control patients (HR = 2.00 [95%CI 1.52, 2.63], p < 0.01) or with other malignancies (HR = 1.91 [95%CI 1.53, 2.39], p < 0.01). In addition, we also observed a higher risk of severe infection in patients with lung cancer (HR = 1.47 [95%CI 1.06, 2.03], p = 0.02). We suggest that, in this setting, vaccine use may be considered a useful and mandatory measure to save lives. Introduction: The outbreak of COVID-19 poses an unprecedented challenge to global public health. Patients with cancer are at a higher risk during the SARS-CoV-2 pandemic. Patients with lung cancer and COVID-19 were compared to those without cancer and those with other malignancies for the main outcome of this study. The aim of this study was to evaluate the differences in susceptibility, disease severity, and mortality between lung cancer patients and the general population. Methods: Using PRISMA reporting guidelines, we conducted a systematic review and meta-analysis of the published literature. The Cochrane Library database, PubMed, EMBASE, and PubMed Central were comprehensively searched for published papers until 31 May 2022. A pooled risk ratio (OR) with 95% CI was presented as the result of this meta-analysis. Results: We included 29 studies involved 21,257 patients with lung cancer and SARS-CoV-2 infection. Analysis data showed that mortality in patients with lung cancer was significantly higher than that in patients without cancer (HR = 2.00 [95%CI 1.52, 2.63], p < 0.01) or with other malignancies (HR = 1.91 [95%CI 1.53, 2.39], p < 0.01). In addition, we also observed a higher risk of severe infection in terms of life-threatening or required ICU admission/mechanical ventilation for lung cancer patients (HR = 1.47 [95%CI 1.06, 2.03], p = 0.02) than for patients with no cancer or other malignancies. Regarding lung cancer as a risk factor for acquiring SARS-CoV-2 infection, we could not reach statistical significance (hazard ratio [HR] =2.73 [95%CI 0.84, 8.94], p = 0.1). Conclusion: Lung cancer represents an important comorbidity and modifies COVID-19 prognosis in terms of disease severity and mortality. More patients experience severe or even fatal events. Considering their inherent fragility, patients with lung cancer, and generally all oncological populations, should be treated more carefully during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Introduction: Several studies have reported alterations in gut microbiota composition of Alzheimer's disease (AD) patients. However, the observed differences are not consistent across studies. We aimed to investigate associations between gut microbiota composition and AD biomarkers using machine learning models in patients with AD dementia, mild cognitive impairment (MCI) and subjective cognitive decline (SCD)., Materials and Methods: We included 170 patients from the Amsterdam Dementia Cohort, comprising 33 with AD dementia (66 ± 8 years, 46%F, mini-mental state examination (MMSE) 21[19-24]), 21 with MCI (64 ± 8 years, 43%F, MMSE 27[25-29]) and 116 with SCD (62 ± 8 years, 44%F, MMSE 29[28-30]). Fecal samples were collected and gut microbiome composition was determined using 16S rRNA sequencing. Biomarkers of AD included cerebrospinal fluid (CSF) amyloid-beta 1-42 (amyloid) and phosphorylated tau (p-tau), and MRI visual scores (medial temporal atrophy, global cortical atrophy, white matter hyperintensities). Associations between gut microbiota composition and dichotomized AD biomarkers were assessed with machine learning classification models. The two models with the highest area under the curve (AUC) were selected for logistic regression, to assess associations between the 20 best predicting microbes and the outcome measures from these machine learning models while adjusting for age, sex, BMI, diabetes, medication use, and MMSE., Results: The machine learning prediction for amyloid and p-tau from microbiota composition performed best with AUCs of 0.64 and 0.63. Highest ranked microbes included several short chain fatty acid (SCFA)-producing species. Higher abundance of [Clostridium] leptum and lower abundance of [Eubacterium] ventriosum group spp., Lachnospiraceae spp., Marvinbryantia spp., Monoglobus spp., [Ruminococcus] torques group spp., Roseburia hominis , and Christensenellaceae R-7 spp., was associated with higher odds of amyloid positivity. We found associations between lower abundance of Lachnospiraceae spp., Lachnoclostridium spp., Roseburia hominis and Bilophila wadsworthia and higher odds of positive p-tau status., Conclusions: Gut microbiota composition was associated with amyloid and p-tau status. We extend on recent studies that observed associations between SCFA levels and AD CSF biomarkers by showing that lower abundances of SCFA-producing microbes were associated with higher odds of positive amyloid and p-tau status., Competing Interests: CT received grants from the European Commission, the Dutch Research Council (ZonMW), Association of Frontotemporal Dementia/Alzheimer’s Drug Discovery Foundation, The Weston Brain Institute, Alzheimer Netherlands. CT has a collaboration contract with ADx Neurosciences, performed contract research or received grants from Probiodrug, Biogen, Esai, Toyama, Janssen prevention center, Boehringer, AxonNeurosciences, Fujirebio, EIP farma, PeopleBio, and Roche. FB is a consultant for Biogen-Idec, Bayer-Schering, Merck-Serono, Roche, Combinostics and IXICO; has received sponsorship from European Commission–Horizon 2020, National Institute for Health Research–University College London Hospitals Biomedical Research Centre, Novartis, and Merck; and serves on the editorial boards of Radiology, Neuroradiology, Multiple Sclerosis Journal, and Neurology. PS has received consultancy/speaker fees from Lilly, GE Healthcare, Novartis, Sanofi, Nutricia, Probiodrug, Biogen, Roche, Avraham, and EIP Pharma. PS has acquired grant support from GE Healthcare, Danone Research, Piramal, and MERCK. All funding was paid to the institution. MN is part of the Scientific Advisory Board of Caelus Health, The Netherlands and Kaleido Biosciences, USA. However, none of these are directly relevant to the current paper. WF received research funding from ZonMW, NWO, EU-FP7, EU-JPND, Alzheimer Nederland, CardioVascular Onderzoek Nederland, Health~Holland, Topsector Life Sciences & Health, stichting Dioraphte, Gieskes-Strijbis fonds, stichting Equilibrio, Pasman stichting, Biogen MA Inc, Boehringer Ingelheim, Life-MI, AVID, Roche BV, Fujifilm, Combinostics. WF holds the Pasman chair. WF is recipient of ABOARD, which is a public-private partnership receiving funding from ZonMW (#73305095007) and Health~Holland, Topsector Life Sciences & Health (PPP-allowance; #LSHM20106). She has performed contract research for Biogen MA Inc, and Boehringer Ingelheim. She has been an invited speaker at Boehringer Ingelheim, Biogen MA Inc, Danone, Eisai, WebMD Neurology (Medscape). WF is consultant to Oxford Health Policy Forum CIC, Roche, and Biogen MA Inc. WF participated in an advisory board of Biogen MA Inc and Roche. WF was associate editor of Alzheimer, Research & Therapy in 2020/2021. WF is associate editor at Brain. All funding was paid to the institution. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Verhaar, Hendriksen, de Leeuw, Doorduijn, van Leeuwenstijn, Teunissen, Barkhof, Scheltens, Kraaij, van Duijn, Nieuwdorp, Muller and van der Flier.)

One of the most interesting biological models is that of snail-trematode interactions, many of which ultimately result in the transmission of several important diseases, particularly in the tropics. Herein, we review the scientific advances on a trematode-snail system in which certain populations of Pseudosuccinea columella (a common host species for trematodes) have been demonstrated naturally-resistant to Fasciola hepatica , in association with an effective encapsulation of the parasite by innate immune cells of the host, the hemocytes. Emphasis is made on the molecular and immunological features characterizing each P. columella phenotype in relation to their anti-parasitic competence, their distinctive ecological patterns and the existence of a significant cost of resistance. An integrative overview of the resistance to F. hepatica through comparative immunobiology, genetics and ecology is presented to hypothesize on the possible origins and evolution of this phenomenon and to postulate significant roles for parasite mediated-selection and environmental factors in shaping and maintaining the resistant phenotype in the field. Lastly, clues into future experimental perspectives to deeply characterize the interplay between P. columella and F. hepatica and the immunobiology of the resistance are also included. The advances revised in the present paper are only beginning to unravel mechanisms of anti-parasite innate defense responses and their evolutionary bases, and can facilitate the development of prospective approaches towards practical applications of P. columella resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Alba, Vázquez, Sánchez and Gourbal.)

Gastropods (class Gastropoda) form the largest of the classes in the phylum Mollusca and inhabit terrestrial, fresh water and marine environments. A large number of these species are of major conservation importance and are an essential component of ecosystems. Gastropods may be deemed as pests, having a negative impact in horticulture and agriculture, whereas others may be used as a food source for human consumption and therefore are beneficial. Gastropods are susceptible to primary diseases and also act as intermediate hosts for diseases which affect other animals, including humans. The diseases described include two that are notifiable to the World Organisation for Animal Health (OIE): Xenohaliotis californiensis and Abalone viral ganglioneuritis caused by Haliotid herpesvirus-1 (HaHV-1). Research into the diseases of gastropods has often focused on those species that act as intermediate disease hosts, those that are used in research or those cultured for food. In this paper we review the viral, bacterial, fungal, parasitic and miscellaneous conditions that have been reported in gastropods and mention some of the factors that appear to predispose them to disease. The pathogenicity of a number of these conditions has not been fully ascertained and more research is needed into specifying both the etiological agent and significance in some of the diseases reported., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 O’Brien and Pellett.)

The tumor microenvironment is essential for the formation and development of tumors. Cytokines in the microenvironment may affect the growth, metastasis and prognosis of tumors, and play different roles in different stages of tumors, of which transforming growth factor β (TGF-β) and tumor necrosis factor α (TNF-α) are critical. The two have synergistic and antagonistic effect on tumor regulation. The inhibition of TGF-β can promote the formation rate of tumor, while TGF-β can promote the malignancy of tumor. TNF-α was initially determined to be a natural immune serum mediator that can induce tumor hemorrhagic necrosis, it has a wide range of biological activities and can be used clinically as a target to immune diseases as well as tumors. However, there are few reports on the interaction between the two in the tumor microenvironment. This paper combs the biological effect of the two in different aspects of different tumors. We summarized the changes and clinical medication rules of the two in different tissue cells, hoping to provide a new idea for the clinical application of the two cytokines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Liu, Zhang, Zhang, Zhou, Li, Zhou, Miao, Shang, He, Ding and Liu.)

Background: Strong participant recruitment practices are critical to public health research but are difficult to achieve. Traditional recruitment practices are often time consuming, costly, and fail to adequately target difficult-to-reach populations. Social media platforms such as Facebook are well-positioned to address this area of need, enabling researchers to leverage existing social networks and deliver targeted information. The MAGENTA (Making Genetic Testing Accessible) study aimed to improve the availability of genetic testing for hereditary cancer susceptibility in at-risk individuals through the use of a web-based communication system along with social media advertisements to improve reach. Objective: This paper is aimed to evaluate the effectiveness of Facebook as an outreach tool for targeting women aged ≥30 years for recruitment in the MAGENTA study. Methods: We designed and implemented paid and unpaid social media posts with ongoing assessment as a primary means of research participant recruitment in collaboration with patient advocates. Facebook analytics were used to assess the effectiveness of paid and unpaid outreach efforts. Results: Over the course of the reported recruitment period, Facebook materials had a reach of 407,769 people and 57,248 (14.04%) instances of engagement, indicating that approximately 14.04% of people who saw information about the study on Facebook engaged with the content. Paid advertisements had a total reach of 373,682. Among those reached, just <15% (54,117/373,682, 14.48%) engaged with the page content. Unpaid posts published on the MAGENTA Facebook page resulted in a total of 34,087 reach and 3131 instances of engagement, indicating that around 9.19% (3131/34,087) of people who saw unpaid posts engaged. Women aged ≥65 years reported the best response rate, with approximately 43.95% (15,124/34,410) of reaches translating to engagement. Among the participants who completed the eligibility questionnaire, 27.44% (3837/13,983) had heard about the study through social media or another webpage. Conclusions: Facebook is a useful way of enhancing clinical trial recruitment of women aged ≥30 years who have a potentially increased risk for ovarian cancer by promoting news stories over social media, collaborating with patient advocacy groups, and running paid and unpaid campaigns. [ABSTRACT FROM AUTHOR]

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hematopoietic stem cell genetic mutation disease that causes defective erythrocyte membrane hemolysis. Its pathologic basis is the mutation of the PIG-A gene, whose product is necessary for the synthesis of glycosylphosphatidylinositol (GPI) anchors; the mutation of PIG-A gene results in the reduction or deletion of the GPI anchor, which leads to the deficiency of GPI-anchored proteins (GPI-APs), such as CD55 and CD59, which are complement inhibitors. The deficiency of complement inhibitors causes chronic complement-mediated intravascular hemolysis of GPI-anchor-deficient erythrocyte. PIG-A gene mutation could also be found in bone marrow hematopoietic stem cells (HSCs) of healthy people, but they have no growth advantage; only the HSCs with PIG-A gene mutation in PNH patients have this advantage and expand. Besides, HSCs from PIG-A -knockout mice do not show clonal expansion in bone marrow, so PIG-A mutation cannot explain the clonal advantage of the PNH clone and some additional factors are needed; thus, in recent years, many scholars have put forward the theories of the second hit, and immune escape theory is one of them. In this paper, we focus on how T lymphocytes are involved in immune escape hypothesis in the pathogenesis of PNH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Li, Dong, Wang and Shao.)

Macrophages are important immune cells in innate immunity, and have remarkable heterogeneity and polarization. Under pathological conditions, in addition to the resident macrophages, other macrophages are also recruited to the diseased tissues, and polarize to various phenotypes (mainly M1 and M2) under the stimulation of various factors in the microenvironment, thus playing different roles and functions. Liver diseases are hepatic pathological changes caused by a variety of pathogenic factors (viruses, alcohol, drugs, etc.), including acute liver injury, viral hepatitis, alcoholic liver disease, metabolic-associated fatty liver disease, liver fibrosis, and hepatocellular carcinoma. Recent studies have shown that macrophage polarization plays an important role in the initiation and development of liver diseases. However, because both macrophage polarization and the pathogenesis of liver diseases are complex, the role and mechanism of macrophage polarization in liver diseases need to be further clarified. Therefore, the origin of hepatic macrophages, and the phenotypes and mechanisms of macrophage polarization are reviewed first in this paper. It is found that macrophage polarization involves several molecular mechanisms, mainly including TLR4/NF-κB, JAK/STATs, TGF-β/Smads, PPARγ, Notch, and miRNA signaling pathways. In addition, this paper also expounds the role and mechanism of macrophage polarization in various liver diseases, which aims to provide references for further research of macrophage polarization in liver diseases, contributing to the therapeutic strategy of ameliorating liver diseases by modulating macrophage polarization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wang, Ma, Gong, Guo, Fu, Zhang, Zhou and Li.)

Motivation: Assessment of genetic mutations is an essential element in the modern era of personalized cancer treatment. Our strategy is focused on 'multiple network analysis' in which we try to improve cancer diagnostics by using biological networks. Genetic alterations in some important hubs or in driver genes such as BRAF and TP53 play a critical role in regulating many important molecular processes. Most of the studies are focused on the analysis of the effects of single mutations, while tumors often carry mutations of multiple driver genes. The aim of this work is to define an innovative bioinformatics pipeline focused on the design and analysis of networks (such as biomedical and molecular networks), in order to: (1) improve the disease diagnosis; (2) identify the patients that could better respond to a given drug treatment; and (3) predict what are the primary and secondary effects of gene mutations involved in human diseases., Results: By using our pipeline based on a multiple network approach, it has been possible to demonstrate and validate what are the joint effects and changes of the molecular profile that occur in patients with metastatic colorectal carcinoma (mCRC) carrying mutations in multiple genes. In this way, we can identify the most suitable drugs for the therapy for the individual patient. This information is useful to improve precision medicine in cancer patients. As an application of our pipeline, the clinically significant case studies of a cohort of mCRC patients with the BRAF V600E-TP53 I195N missense combined mutation were considered., Availability: The procedures used in this paper are part of the Cytoscape Core, available at (www.cytoscape.org). Data used here on mCRC patients have been published in [55]., Supplementary Information: A supplementary file containing a more detailed discussion of this case study and other cases is available at the journal site as Supplementary Data., (© The Author(s) 2021. Published by Oxford University Press.)

INTRODUCTION The Health Belief Model comprises two constructs influencing changed behaviors impacting on health, namely perceived severity and susceptibility. The aim of this study was to identify the impact of the combination of, or interactions between, these two constructs on quitting smoking in smokers with a diagnosis of a non-communicable disease (NCD). METHODS From the large insurance claims database maintained by JMDC database (JMDC, Tokyo), we extracted data on 13284 participants who smoked. All participants were stratified according to their NCD diagnosis based on perceived severity and susceptibility as follows: Category I (high severity and high susceptibility) -- acute myocardial infarction, and lung cancer; Category II (high severity and low susceptibility) -- colorectal cancer, and stomach cancer; Category III (low severity and high susceptibility) -- asthma, and transient ischemic attack; Category IV (low severity and low susceptibility) -- appendicitis, and glaucoma. We performed multi-variable logistic regression analysis and calculated the proportion of those who were smoking at the first health check-up after the diagnosis and every three years thereafter. RESULTS Using glaucoma as the reference, the adjusted odds ratios for smoking cessation were 14.2 (95% CI: 11.4-17.8) to 14.8 (95% CI: 12.5-17.4) in Category I; 4.5 (95% CI: 3.8-5.4) to 6.6 (95% CI: 5.4-8.0) in Category II; and 1.9 (95% CI: 1.7-2.1) to 2.8 (95% CI: 2.2-3.7) in Category III. In Categories I and II, the proportion of smokers rapidly decreased after diagnosis and mostly remained low thereafter. Smoking cessation rates for Categories I and II were not associated with readiness to improve lifestyles prior to NCD diagnosis. CONCLUSIONS Our study confirms the significant impact of perceived severity of and susceptibility to the diagnosed disease on smoking cessation. The multiplicative effect of these two constructs at NCD diagnosis represents a 'teachable moment', a window of opportunity, for encouraging successful long-term smoking cessation. [ABSTRACT FROM AUTHOR]

Background: This paper aims to assess the presence of gender differences in medication use and mortality in a cohort of patients affected exclusively by hypertension, in 193 municipalities in the Lombardy Region (Northern Italy), including Milan's metropolitan area. Methods: A retrospective cohort study was conducted (N = 232,507) querying administrative healthcare data and the Register of Causes of Death. Hypertensive patients (55.4% women; 44.6% men) in 2017 were identified; gender differences in medication use (treatment, 80% compliance) and deaths (from all causes and CVDs) were assessed at two-year follow-ups in logistic regression models adjusted for age class, census-based deprivation index, nationality, and pre-existing health conditions. Models stratified by age, deprivation index, and therapeutic compliance were also tested. Results: Overall, women had higher odds of being treated, but lower odds of therapeutic compliance, death from all causes, and death from CVDs. All the outcomes had clear sex differences across age classes, though not between different levels of deprivation. Comparing patients with medication adherence, women had lower odds of death from all causes than men (with a narrowing protective effect as age increased), while no gender differences emerged in non-compliant patients. Conclusions: Among hypertensive patients, gender differences in medication consumption and mortality have been found, but the extent to which these are attributable to a female socio-cultural disadvantage is questionable. The findings reached, with marked age-dependent effects in the outcomes investigated, suggest a prominent role for innate sex differences in biological susceptibility to the disease, whereby women would take advantage of the protective effects of their innate physiological characteristics, especially prior to the beginning of menopause. [ABSTRACT FROM AUTHOR]

Arterial hypertension (AH) is a major risk factor for the development of cardiovascular diseases. It is estimated that the disease affects between 10% and 20% of the adult population and is responsible for 5.8% of all deaths worldwide. Several pathophysiologic factors are crucial in AH, including inappropriate activation of the renin-angiotensin-aldosterone system, oxidative stress and inflammation. The heart, kidney, brain, retina and arterial blood vessels are prime targets of hypertensive damage. Uncontrolled and untreated AH accelerates the damage to these organs and could cause their failure. Damage to these organs could also manifest as coronary heart disease, cognitive impairment, retinopathy or optic neuropathy. For better understanding, it is important to analyze molecular factors which take part in pathogenesis of AH and hypertension-related target organ damage. In our paper, we would like to focus on molecular interactions of AH in the heart, blood vessels, brain and kidneys. We focus on matrix metalloproteinases, the role of immune system, the renin-angiotensin-aldosterone system and oxidative stress in hypertensive induced organ damage.

Background: As the vector-borne diseases tick-borne encephalitis (TBE) and Lyme borreliosis (LB) are common in Germany and transmitted by tick bites, the aim of this study was to assess differences in the number of tick bites in various professions and regions across southern Germany to evaluate the differences in tick-associated risk.Materials and Methods: The analysis is based on three cross-sectional studies that were conducted in 2016 and 2017 in two real-life settings and in one medical setting in Bavaria. All participants filled in a paper-based questionnaire about their history with tick bites. Only adult participants (≥ 18 years) were included in this study.Results: Overall, 3503 individuals (mean age 50.8 ± 15.2 years, median age 53.0 ± 12.2 years, 54.0% female) were included. Of these, 50% worked in an outdoor profession and 56% lived in environs. Around 70% of participants reported at least one previous tick bite. In comparison to indoor workers, forestry workers (OR = 2.50; 95% CI: 1.10-5.68) had the highest risk for a tick bite followed by farmers (OR = 1.22; 95% CI: 1.01-1.47). Furthermore, people living in rural areas (OR = 1.97, 95% CI:1.49-2.59) and environs (OR = 1.98, 95% CI: 1.54-2.55) were twice as likely to have a previous tick bite than people living in urban areas. In general, slightly more tick bites were reported by people living in eastern Bavaria.Conclusion: Rising numbers of TBE and LB indicate the need for further prevention strategies, which should focus on outdoor professions with a higher risk and people living in environs and rural areas. [ABSTRACT FROM AUTHOR]

Obesity and metabolic disorders have become a worldwide pandemic affecting millions of people. Although obesity is a multifaceted disease, there is growing evidence supporting the obesogen hypothesis, which proposes that exposure to a subset of endocrine disrupting chemicals (EDCs), known as obesogens, promotes obesity. While these effects can be observed in vitro using cell models , in vivo and human epidemiological studies have strengthened this hypothesis. Evidence from animal models showed that the effects of obesogen exposure can be inherited transgenerationally through at least the F4 generation. Transgenerational effects of EDC exposure predispose future generations to undesirable phenotypic traits and diseases, including obesity and related metabolic disorders. The exact mechanisms through which phenotypic traits are passed from an exposed organism to their offspring, without altering the primary DNA sequence, remain largely unknown. Recent research has provided strong evidence suggesting that a variety of epigenetic mechanisms may underlie transgenerational inheritance. These include differential DNA methylation, histone methylation, histone retention, the expression and/or deposition of non-coding RNAs and large-scale alterations in chromatin structure and organization. This review highlights the most recent advances in the field of epigenetics with respect to the transgenerational effects of environmental obesogens. We highlight throughout the paper the strengths and weaknesses of the evidence for proposed mechanisms underlying transgenerational inheritance and why none of these is sufficient to fully explain the phenomenon. We propose that changes in higher order chromatin organization and structure may be a plausible explanation for how some disease predispositions are heritable through multiple generations, including those that were not exposed. A solid understanding of these possible mechanisms is essential to fully understanding how environmental exposures can lead to inherited susceptibility to diseases such as obesity. [ABSTRACT FROM AUTHOR]

The diagnosis and management of periodontal diseases can be enhanced by the identification of biomolecules which can predict disease susceptibility, indicate current disease activity, and monitor response to therapy. Salivary proteomics is a major avenue in the ongoing search for a biomarker in periodontal research. Saliva is a valuable diagnostic vehicle which "mirrors" oral and systemic health and disease. Standardized methods of saliva sampling and processing will increase diagnostic test accuracy and decrease bias in measurements. Prominent databases such as PubMed/Medline, PMC, Scopus, and Google Scholar were searched and literature evidence from January 2000 till September 2022 were studied to identify the methodological considerations employed in salivary proteomics for periodontal research. Evidence and recommendations in this regard were collated into this narrative review. The methods of saliva collection and processing presented in this review will help researchers conduct salivary proteomic studies with standardized protocols. [ABSTRACT FROM AUTHOR]

Asthma is a chronic inflammatory disease of the respiratory tract that has become a public health problem in various countries. Referring to the Global Initiative for Asthma, the prevalence of asthma continues to increase especially in children. Coronavirus Disease 2019 (COVID-19) is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) that has declared a pandemic by the world health organization on March 2020. For many years, it has been known that people with asthma have a worse impact on respiratory viral infections. Asthma has been listed by the centers for disease control and prevention as one of the risk factors for COVID-19, although several studies have different results. SARS-CoV-2 utilizes angiotensin-converting enzyme 2 (ACE2) as its cellular receptor, and it has been known that the expression of the ACE2 receptor is reduced in asthma patients. This reduced expression could also be accounted from the therapy of asthma. This paper aims to discuss the pathophysiology of asthma and COVID-19 and the susceptibility of asthma patients in contracting COVID-19. [ABSTRACT FROM AUTHOR]