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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]

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]

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]

In this paper, we hypothesize that it is possible to localize image regions of preclinical tumors in a Chest X-ray (CXR) image by a weakly-supervised training of a survival prediction model using a dataset containing CXR images of healthy patients and their time-to-death label. These visual explanations can empower clinicians in early lung cancer detection and increase patient awareness of their susceptibility to the disease. To test this hypothesis, we train a censor-aware multi-class survival prediction deep learning classifier that is robust to imbalanced training, where classes represent quantized number of days for time-to-death prediction. Such multi-class model allows us to use post-hoc interpretability methods, such as Grad-CAM, to localize image regions of preclinical tumors. For the experiments, we propose a new benchmark based on the National Lung Cancer Screening Trial (NLST) dataset to test weakly-supervised preclinical tumor localization and survival prediction models, and results suggest that our proposed method shows state-of-the-art C-index survival prediction and weakly-supervised preclinical tumor localization results. To our knowledge, this constitutes a pioneer approach in the field that is able to produce visual explanations of preclinical events associated with survival prediction results. • First weakly-supervised survival prediction method to localize preclinical tumors. • State-of-the-art survival time prediction results on the NLST dataset. • Innovative explainable censor-aware multi-class survival prediction. • Innovative survival prediction robust to imbalanced time-to-death distribution. • New benchmark for explainable preclinical survival prediction using the NLST dataset. [ABSTRACT FROM AUTHOR]

Background: The structure of age groups and social contacts of the total population influenced infection scales and hospital-bed requirements, especially influenced severe infections and deaths during the global prevalence of COVID-19. Before the end of the year 2022, Chinese government implemented the national vaccination and had built the herd immunity cross the country, and announced Twenty Measures (November 11) and Ten New Measures (December 7) for further modifications of dynamic zero-COVID polity on the Chinese mainland. With the nation-wide vaccination and modified measures background, Fuzhou COVID-19 large wave (November 19, 2022eFebruary 9, 2023) led by Omicron BA.5.2 variant was recorded and prevailed for three months in Fujian Province. Methods: A multi-age groups susceptible-exposed-infected-hospitalized-recovered (SEIHR) COVID-19 model with social contacts was proposed in this study. The main object was to evaluate the impacts of age groups and social contacts of the total population. The idea of Least Squares method was governed to perform the data fittings of four age groups against the surveillance data from Fujian Provincial Center for Disease Control and Prevention (Fujian CDC). The next generation matrix method was used to compute basic reproduction number for the total population and for the specific age group. The tendencies of effective reproduction number of four age groups were plotted by using the Epiestim R package and the SEIHR model for in-depth discussions. The sensitivity analysis by using sensitivity index and partial rank correlation coefficients values (PRCC values) were operated to reveal the differences of age groups against the main parameters. Results: The main epidemiological features such as basic reproduction number, effective reproduction number and sensitivity analysis were extensively discussed for multi-age groups SEIHR model in this study. Firstly, by using of the next generation matrix method, basic reproduction number R0 of the total population was estimated as 1.57 using parameter values of four age groups of Fuzhou COVID-19 large wave. Given age group k, the values of R0k (age group k to age group k), the values of Rk0 (an infected of age group k to the total population) and the values of Rk0 (an infected of the total population to age group k) were also estimated, in which the explorations of the impacts of age groups revealed that the relationship Rk0 > R0k > Rk0 was valid. Then, the fluctuating tendencies of effective reproduction number Rt were demonstrated by using two approaches (the surveillance data and the SEIHR model) for Fuzhou COVID-19 large wave, during which high-risk group (G4 group) mainly contributed the infection scale due to high susceptibility to infection and high risks to basic diseases. Further, the sensitivity analysis using two approaches (the sensitivity index and the PRCC values) revealed that susceptibility to infection of age groups played the vital roles, while the numerical simulation showed that infection scale varied with the changes of social contacts of age groups. The results of this study claimed that the high-risk group out of the total population was concerned by the local government with the highest susceptibility to infection against COVID-19. Conclusions: This study verified that the partition structure of age groups of the total population, the susceptibility to infection of age groups, the social contacts among age groups were the important contributors of infection scale. The less social contacts and adequate hospital beds for high-risk group were profitable to control the spread of COVID- 19. To avoid the emergence of medical runs against new variant in the future, the policymakers from local government were suggested to decline social contacts when hospital beds were limited. [ABSTRACT FROM AUTHOR]

The article offers a perspective on variants of unknown significance (VUS) in precision oncology and their impact on treatment choice. It presents clinical cases of patients with pancreatic cancer, a family history of cancer, and germline or somatic VUS, to illustrate the challenges of VUS in clinical practice. It considers pathogenic, germline mutations as loss-of-function mutations in tumor suppressors and presents data regarding pathogenic TET3 mutations and VUS.

The presence of heterogeneity in susceptibility, differences between hosts in their likelihood of becoming infected, can fundamentally alter disease dynamics and public health responses, for example, by changing the final epidemic size, the duration of an epidemic, and even the vaccination threshold required to achieve herd immunity. Yet, heterogeneity in susceptibility is notoriously difficult to detect and measure, especially early in an epidemic. Here we develop a method that can be used to detect and estimate heterogeneity in susceptibility given contact by using contact tracing data, which is typically collected early in the course of an outbreak. This approach provides the capability, given sufficient data, to estimate and account for the effects of this heterogeneity before they become apparent during an epidemic. It additionally provides the capability to analyze the wealth of contact tracing data available for previous epidemics and estimate heterogeneity in susceptibility for disease systems in which it has never been estimated previously. The premise of our approach is that highly susceptible individuals become infected more often than less susceptible individuals, and so individuals not infected after appearing in contact networks should be less susceptible than average. This change in susceptibility can be detected and quantified when individuals show up in a second contact network after not being infected in the first. To develop our method, we simulated contact tracing data from artificial populations with known levels of heterogeneity in susceptibility according to underlying discrete or continuous distributions of susceptibilities. We analyzed this data to determine the parameter space under which we are able to detect heterogeneity and the accuracy with which we are able to estimate it. We found that our power to detect heterogeneity increases with larger sample sizes, greater heterogeneity, and intermediate fractions of contacts becoming infected in the discrete case or greater fractions of contacts becoming infected in the continuous case. We also found that we are able to reliably estimate heterogeneity and disease dynamics. Ultimately, this means that contact tracing data alone is sufficient to detect and quantify heterogeneity in susceptibility. Author summary: Hosts often vary in their likelihood of contracting an infectious disease. This variation is referred to as heterogeneity in susceptibility, and it can have major public health consequences. However, heterogeneity in susceptibility is notoriously difficult to detect and quantify, and so, it has often been left out of mathematical models and ignored by decision makers. Here, we present a novel method that can be used to detect and quantify heterogeneity in susceptibility using only contact tracing data. The premise is that if heterogeneity is present, the average individual that did not become infected after appearing in a contact network would have lower susceptibility to infection than the average individual that has never appeared in a contact network. By measuring the difference in susceptibility between these two groups of individuals, which we assess with contact tracing data, it is possible to detect and quantify the level of heterogeneity. We demonstrate the application of this method and explore the method's power and accuracy using simulated contact tracing data. [ABSTRACT FROM AUTHOR]

Introduction: Migraine, as a complex neurological disease, brings heavy burden to patients and society. Despite the availability of established therapies, existing medications have limited efficacy. Thus, we aimed to find the drug targets that improve the prognosis of migraine. Method: We used Mendelian Randomization (MR) and Summary-data-based MR (SMR) analyses to study possible drug targets of migraine by summary statistics from FinnGen cohorts (nCase = 44,616, nControl = 367,565), with further replication in UK Biobank (nCase = 26,052, nControl = 487,214). Genetic instruments were obtained from eQTLGen and UKB-PPP to verify the drug targets at the gene expression and protein levels. The additional analyses including Bayesian co-localization, the heterogeneity in dependent instruments(HEIDI), Linkage Disequilibrium Score(LDSC), bidirectional MR, multivariate MR(MVMR), heterogeneity test, horizontal pleiotropy test, and Steiger filtering were implemented to consolidate the findings further. Lastly, drug prediction analysis and phenome-wide association study(PheWAS) were employed to imply the possibility of drug targets for future clinical applications. Result: The MR analysis of eQTL data showed that four drug targets (PROCR, GSTM4, SLC4A1, and TNFRSF10A) were significantly associated with migraine risk in both the FinnGen and UK Biobank cohorts. However, only GSTM4 exhibited consistent effect directions across the two outcomes(Discovery cohort: OR(95%CI) = 0.94(0.93–0.96); p = 2.70e − 10; Replication cohort: OR(95%CI) = 0.93(0.91–0.94); p = 4.21e − 17). Furthermore, GSTM4 passed the SMR at p < 0.05 and HEIDI test at p > 0.05 at both the gene expression and protein levels. The protein-level MR analysis revealed a strong correlation between genetically predicted GSTM4 with a lower incidence of migraine and its subtypes(Overall migraine: OR(95%CI) = 0.91(0.87–0.95); p = 6.98e-05; Migraine with aura(MA): OR(95%CI) = 0.90(0.85–0.96); p = 2.54e-03; Migraine without aura(MO): OR(95%CI) = 0.90(0.83–0.96); p = 2.87e-03), indicating a strong co-localization relationship (PPH4 = 0.86). Further analyses provided additional validation for the possibility of GSTM4 as a migraine treatment target. Conclusion: This study identifies GSTM4 as a potential druggable gene and promising therapeutic target for migraine. [ABSTRACT FROM AUTHOR]

Studying the influence of the host plant genotype on the spectral reflectance of crops infected by a pathogen is one of the key directions in the development of precision methods for monitoring the phytosanitary state of wheat agrocenoses. The purpose of this research was to study the influence of varietal factors and disease development on the spectral characteristics of winter wheat varieties of different susceptibility to diseases during the growing seasons of 2021, 2022 and 2023. The studied winter wheat crops were represented by three varieties differing in susceptibility to phytopathogens: Grom, Svarog and Bezostaya 100. Over three years of research, a clear and pronounced influence of the varietal factor on the spectral characteristics of winter wheat crops was observed, which in most cases manifested itself as an immunological reaction of specific varieties to the influence of pathogen development. The nature of the influence of the pathogenic background and the spectral characteristics of winter wheat crops were determined by the complex interaction of the development of individual diseases under the conditions of a particular year of research. A uniform and clear division of the spectral characteristics of winter wheat according to the intensity of the disease was recorded only at a level of pathogen development of more than 5%. Moreover, this gradation was most clearly manifested in the spectral channels of the near-infrared range and at a wavelength of 720 nm. [ABSTRACT FROM AUTHOR]

Background: Auriculocondylar syndrome (ARCND) is an extremely rare autosomal dominant or recessive condition that typically manifests as question mark ears (QMEs), mandibular condyle hypoplasia, and micrognathia. Severe dental and maxillofacial malformations present considerable challenges in patients' lives and clinical treatment. Currently, only a few ARCND cases have been reported worldwide, but most of them are related to genetic mutations, clinical symptoms, and ear correction; there are few reports concerning the treatment of dentofacial deformities. Case presentation: Here, we report a rare case of ARCND in a Chinese family. A novel insertional mutation in the guanine nucleotide-binding protein alpha-inhibiting activity polypeptide 3 (GNAI3) was identified in the patient and their brother using whole-exome sequencing. After a multidisciplinary consultation and examination, sequential orthodontic treatment and craniofacial surgery, including distraction osteogenesis and orthognathic surgery, were performed using three-dimensional (3D) digital technology to treat the patient's dentofacial deformity. A good prognosis was achieved at the 5-year follow-up, and the patient returned to normal life. Conclusions: ARCND is a monogenic and rare condition that can be diagnosed based on its clinical triad of core features. Molecular diagnosis plays a crucial role in the diagnosis of patients with inconspicuous clinical features. We present a novel insertion variation in GNAI3, which was identified in exon 2 of chromosome 110116384 in a Chinese family. Sequential therapy with preoperative orthodontic treatment combined with distraction osteogenesis and orthognathic surgery guided by 3D digital technology may be a practical and effective method for treating ARCND. [ABSTRACT FROM AUTHOR]

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This study aimed to evaluate the growth, wood properties, disease susceptibility, and sex traits of 1122 Populus deltoides clones to reveal the trait variability and correlations, providing a basis for genetic improvement and breeding. The measurements included the diameter at breast height (DBH), leaf area, basic wood density (BWD), content of cellulose, hemicellulose, lignin, and disease susceptibility index (DSI). The coefficients of variation ranged 6.91%–41.96%, with the BWD showing the lowest variability. Significant sexual dimorphism was observed, with male clones exhibiting higher DBH and hemicellulose content, and female clones displaying larger leaf areas and greater phenotypic variability. Correlation analysis revealed that the leaf area was positively correlated with the BWD and hemicellulose, and it was negatively correlated with the DBH and lignin; lignin was negatively correlated with cellulose. PCA confirmed these relationships and additionally highlighted a positive correlation between the DSI and DBH. These findings established links between the growth traits and wood properties, enhancing our understanding of trait diversity in P. deltoides and providing insights for breeding strategies to develop high-quality, high-yielding cultivars. [ABSTRACT FROM AUTHOR]

Simple Summary: An urgent demand exists to identify inherited genetic risk variants for prostate cancer (PrCa), particularly in DNA damage repair genes targetable with precision medicine-based strategies. Though the most heritable common cancer, discovery of rare germline PrCa risk variants is hampered by their low frequency, even in sizeable population datasets. Through utilising two large, independent, familial PrCa resources and their likely enrichment of rare causative variants, we provide robust evidence for several novel risk variants in DNA damage repair genes. Rare, inherited variants in DNA damage repair (DDR) genes have a recognised role in prostate cancer (PrCa) susceptibility. In addition, these genes are therapeutically targetable. While rare variants are informing clinical management in other common cancers, defining the rare disease-associated variants in PrCa has been challenging. Here, whole-genome and -exome sequencing data from two independent, high-risk Australian and North American familial PrCa datasets were interrogated for novel DDR risk variants. Rare DDR gene variants (predicted to be damaging and present in two or more family members) were identified and subsequently genotyped in 1963 individuals (700 familial and 459 sporadic PrCa cases, 482 unaffected relatives, and 322 screened controls), and association analyses accounting for relatedness (MQLS) undertaken. In the combined datasets, rare ERCC3 (rs145201970, p = 2.57 × 10−4) and BRIP1 (rs4988345, p = 0.025) variants were significantly associated with PrCa risk. A PARP2 (rs200603922, p = 0.028) variant in the Australian dataset and a MUTYH (rs36053993, p = 0.031) variant in the North American dataset were also associated with risk. Evaluation of clinicopathological characteristics provided no evidence for a younger age or higher-grade disease at diagnosis in variant carriers, which should be taken into consideration when determining genetic screening eligibility criteria for targeted, gene-based treatments in the future. This study adds valuable knowledge to our understanding of PrCa-associated DDR genes, which will underpin effective clinical screening and treatment strategies. [ABSTRACT FROM AUTHOR]

To address high rates of malnutrition among children from vulnerable households in Rwanda, the government initiated a national food supplementation programme. A before and after evaluation, using repeat cross‐sectional surveys in randomly selected villages was conducted; aimed at assessing the effectiveness of providing fortified blended food (FBF) to children 18–23 months of age, pregnant and lactating women in the lowest tier of Rwanda's social support system. Data were collected in 2017, 2018 and 2021 through interviews with caregivers; anthropometric measurements and a capillary blood sample were obtained from children. The primary statistical analysis compared the nutritional status of children before and after the introduction of FBF. We enroled 724 children during each survey. The prevalence of stunting declined from 47% to 35% between 2017 and 2021; in 2018, the prevalence of stunting was 43%. Children had a 42% reduction in the odds of being stunted (adjusted odds ratio [AOR]: 0.58, 95% confidence interval [CI]: 0.47–0.74, p < 0.001) from 2017 to 2021 even after adjusting for inherent, distal, proximal, and intermediate covariates. The reduction in stunting observed within the first year of the programme was not statistically significant (AOR: 0.83, 95% CI: 0.67–1.03, p < 0.091). We observed meaningful reductions in the prevalence of stunting among children which coincided with the introduction of Government‐led initiative to reduce malnutrition. The Rwandan Government has committed to improving the living conditions of vulnerable households and has made strong investments in reducing malnutrition. The impact of these investments can be seen in the overall trend towards improved nutritional status highlighted in this evaluation. Key messages: The national distribution of fortified blended food (FBF) to pregnant and lactating women and 6‐ to 23‐month‐old children living in the most vulnerable households was associated with a meaningful reduction in stunted linear growth, iron deficiency and anaemia among young children after 5 years.This study indicates that stunted linear growth, in early childhood, can be reduced over 5 years when the government is committed to and invests in improving the living conditions of vulnerable households, including the national food supplementation programme.It was attainable to distribute FBF to vulnerable pregnant and lactating women and 6‐ to 23‐month‐old children, in a national programme, over the 5‐year evaluation period, including during the COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

Grape cultivation is important globally, contributing to the agricultural economy and providing diverse grape-based products. However, the susceptibility of grapes to disease poses a significant threat to yield and quality. Traditional disease identification methods demand expert knowledge, which limits scalability and efficiency. To address these limitations our research aims to design an automated deep learning approach for grape leaf disease detection. This research introduces a novel dual-track network for classifying grape leaf diseases, employing a combination of the Swin Transformer and Group Shuffle Residual DeformNet (GSRDN) tracks. The Swin Transformer track exploits shifted window techniques to construct hierarchical feature maps, enhancing global feature extraction. Simultaneously, the GSRDN track combines Group Shuffle Depthwise Residual block and Deformable Convolution block to extract local features with reduced computational complexity. The features from both tracks are concatenated and processed through Triplet Attention for cross-dimensional interaction. The proposed model achieved an accuracy of 98.6%, the precision, recall, and F1-score are recorded as 98.7%, 98.59%, and 98.64%, respectively as validated on a dataset containing grape leaf disease information from the PlantVillage dataset, demonstrating its potential for efficient grape disease classification. [ABSTRACT FROM AUTHOR]

Genetic support for a drug target has been shown to increase the probability of success in drug development, with the potential to reduce attrition in the pharmaceutical industry alongside discovering novel therapeutic targets. It is therefore important to maximise the detection of genetic associations that affect disease susceptibility. Conventional statistical methods such as genome-wide association studies (GWAS) only identify some of the genetic contribution to disease, so novel analytical approaches are required to extract additional insights. C4X Discovery has developed Taxonomy3, a unique method for analysing genetic datasets based on mathematics that is novel in drug discovery. When applied to a previously published rheumatoid arthritis GWAS dataset, Taxonomy3 identified many additional novel genetic signals associated with this autoimmune disease. Follow-up studies using tool compounds support the utility of the method in identifying novel biology and tractable drug targets with genetic support for further investigation. [ABSTRACT FROM AUTHOR]

Simple Summary: The efficacy of killing human cancer cells with a modified herpes simplex virus thymidine kinase TK.007/ganciclovir (GCV) system was investigated in malignant cells of different histogenetic origin. The aim was to determine whether different histogenetic origins of cancer cells in themselves influence their reaction towards an approach of synthetic lethality, which theoretically should be toxic in a similar range independently of the cell type. Fifteen malignant human cell lines were transduced with a lentiviral vector to stably express the TK.007 gene and cell proliferation assays under GCV. Among TK.007-expressing cell lines, lymphoma and leukemia cells were more susceptible to killing than solid cancer cells, while osteosarcoma and melanoma cells exhibited an intermediate susceptibility. This study highlights that the histogenetic origin of malignant cells strongly influences their susceptibility towards cytotoxic agents, with leukemias and lymphomas being more sensitive than solid cancer cells. Background: Remarkable differences exist in the outcome of systemic cancer therapies. Lymphomas and leukemias generally respond well to systemic chemotherapies, while solid cancers often fail. We engineered different human cancer cells lines to uniformly express a modified herpes simplex virus thymidine kinase TK.007 as a suicide gene when ganciclovir (GCV) is applied, thus in theory achieving a similar response in all cell lines. Methods: Fifteen different cell lines were engineered to express the TK.007 gene. XTT-cell proliferation assays were performed and the IC50-values were calculated. Functional kinome profiling, mRNA sequencing, and bottom-up proteomics analysis with Ingenuity pathway analysis were performed. Results: GCV potency varied among cell lines, with lymphoma and leukemia cells showing higher susceptibility than solid cancer cells. Functional kinome profiling implies a contribution of the SRC family kinases and decreased overall kinase activity. mRNA sequencing highlighted alterations in the MAPK pathways and bottom-up proteomics showed differences in apoptotic and epithelial junction signaling proteins. Conclusions: The histogenetic origin of cells influenced the susceptibility of human malignant cells towards cytotoxic agents with leukemias and lymphomas being more sensitive than solid cancer cells. [ABSTRACT FROM AUTHOR]

Background: Congenital talipes equinovarus (CTEV) is a prevalent pediatric deformity with a multifactorial etiology. The objective of this meta-analysis was to explore the association between genetic variations in COL9A1 and the susceptibility to CTEV. Methods: A comprehensive analysis of pertinent literature released before November 15, 2023, in electronic bibliographic databases was carried out. The importance of the connection was clarified through odds ratios (ORs) with 95% confidence intervals (CIs), utilizing random or fixed-effects models depending on study heterogeneity. Statistical analysis was executed using Comprehensive Meta-Analysis software (Version 4.0). Results: A total of eight case-control studies involving 833 CTEV patients and 1280 healthy individuals were included in the analysis. Among these, four studies investigated the rs1135056 variant, encompassing 432 CTEV cases and 603 controls; two studies examined the rs35470562 variant, with 189 CTEV cases and 378 controls; and two studies explored the rs592121 variant, including 212 CTEV cases and 299 controls. The results revealed a significant association between the rs1135056 and rs35470562 polymorphisms in the COL9A1 gene, suggesting an increased risk of CTEV in the overall population. Conversely, no such association was found for the rs592121 variant. Conclusion: Our findings reveal a substantial association between the genetic variants COL9A1 rs1135056 and rs35470562 and susceptibility to CTEV. Conversely, the variant rs592121 did not exhibit any corresponding link. However, the limitations imposed by the small study population have compromised the statistical reliability and generalizability of the results. [ABSTRACT FROM AUTHOR]

The use of electronic cigarettes (ECs) is a major problem globally. Susceptibility and curiosity are important factors that develop prior to the onset of substance use, such as ECs, and are therefore considered as predictors. Both factors are used to obtain an extended index of susceptibility (ESIe-c), which allows the identification of adolescents who are at risk of starting to use these devices. The aim of this study was to determine the prevalence of EC consumption and to assess the association of possible predictors with susceptibility to use and experimentation with ECs among adolescents. A cross-sectional study was carried out in 377 adolescents (53.0% female). Participants were compared according to their experimentation with ECs. A total of 45.9% had already used electronic cigarettes, and 20.8% were current users. Among those who had not tried electronic cigarettes, 43.3% had a medium-high susceptibility to EC initiation. Consumption among close friends, receiving offers of consumption and alcohol consumption were associated with initiation. There was an inverse association between a medium susceptibility index electronic cigarette score and the consumption of cigarettes and positive affect; on the other hand, the lack of premeditation was associated with a higher susceptibility index score. Intrapersonal factors and social factors seem to influence the ESIe-c and onset of EC use, respectively. The main conclusion in this study is that susceptibility is influenced by intrapersonal factors such as affectivity and impulsivity through the lack of premeditation, and by social factors such as EC consumption by best friends. [ABSTRACT FROM AUTHOR]

To develop and validate the Insomnia in Response to Sports‐related Stress Test (IRSST) questionnaire, a new specific instrument with the goal of sensitively measuring vulnerability to sport‐specific stressful situations among elite athletes. Five hundred and thirty‐one competitive elite athletes (mean age = 17.6 ± 4.4 years) completed the Ford Insomnia Response to Stress Test (FIRST) questionnaire and the IRSST, a six‐item questionnaire developed to assess the level of sleep disturbance in response to the commonly experienced sport‐specific stressful situations. A development and validation process including substantive, structural, and external stages was used in the present study. One eigenvalue of the exploratory factor analyses was greater than 1.0 (i.e., 2.91, 48.52% of explained variance) whereas the scree test provided evidence for a one‐factor solution, with all the six items achieving a loading of 0.40 or higher on the factor. Cronbach alpha was 0.77 and provided evidence for the reliability of the IRSST score. The correlation between IRSST and FIRST scores was 0.47 (p < 0.001, moderate effect size). These results provide strong evidence for construct validity, indicating that the IRSST is a promising scale for assessing the likelihood of sleep disruption due to sports‐related stressful situations. The results of reliability and correlational analyses provided further evidence of the promising psychometric properties of the IRSST. We believe that the IRSST could provide to the sport and sleep science communities a sleep screening tool for use in this unique population. Highlights: The Insomnia in Response to Sports‐related Stress Test (IRSST) questionnaire is a promising new specific instrument for assessing the likelihood of sleep disruption due to sports‐related stressful situationsThe IRSST could provide to the sport and sleep science communities a sleep screening tool for use in the unique population of competitive elite athletesThe IRSST can be used to identify athletes with sleep difficulties related to sports‐specific stressful situations (e.g., training, competition, injury) [ABSTRACT FROM AUTHOR]

The incidence of thyroid cancer, one of the most common forms of endocrine cancer, is increasing rapidly worldwide in developed and developing countries. Various risk factors can increase susceptibility to thyroid cancer, but particular emphasis is put on the role of DNA repair genes, which have a significant impact on genome stability. Polymorphisms of these genes can increase the risk of developing thyroid cancer by affecting their function. In this article, we present a concise review on the most common polymorphisms of selected DNA repair genes that may influence the risk of thyroid cancer. We point out significant differences in the frequency of these polymorphisms between various populations and their potential relationship with susceptibility to the disease. A more complete understanding of these differences may lead to the development of effective prevention strategies and targeted therapies for thyroid cancer. Simultaneously, there is a need for further research on the role of polymorphisms of previously uninvestigated DNA repair genes in the context of thyroid cancer, which may contribute to filling the knowledge gaps on this subject. [ABSTRACT FROM AUTHOR]

Background: Healthcare and support workers play a pivotal role in delivering quality services and support to people seeking sanctuary who have experienced poor physical and mental health linked to previous trauma, relocation and loss of freedoms. However, they often encounter various challenges in their daily work, ranging from communication barriers to resource constraints. This qualitative study seeks to delve into the perspectives of healthcare and support workers' experience of workarounds, employed to overcome barriers to providing care. Aim: This study aims to describe healthcare providers', practitioners' and health and third sector support workers' views on barriers and workarounds to providing care for people seeking sanctuary, to inform policy and practice. Design: A qualitative study was carried out using semi‐structured telephone interviews. Setting: This study focused on primary, secondary, community and specialist National Health Service (NHS) support services for people seeking sanctuary in Wales, United Kingdom (2018). Method: We interviewed 32 healthcare providers, practitioners and support workers employed by primary care and third sector organisations. Our approach involved obtaining verbal informed consent before digitally recording and transcribing all interviews. To analyse the data, we used the Four Levels of Change for Improving Quality model as a guiding framework for interpretation. Results: Our study findings reveal that certain respondents expressed challenges in meeting the needs of people seeking sanctuary; notably, their experience of delivering care differed by care settings. Specifically, those involved in providing specialist NHS care believed that there was room for improvement. Mainstream primary, secondary and community health practitioners faced limitations due to resource constraints and lacked tailored information to address the unique circumstances and needs of sanctuary seekers. To address these gaps, workarounds emerged at both individual and local levels (team/departmental and organisational level). These included establishing informal communication channels between providers, fostering cross service collaboration to fill gaps and adapting existing services to enhance accessibility. Conclusion: Understanding healthcare providers', practitioners' and support workers' perspectives offers invaluable insights into ways to enhance healthcare delivery to sanctuary seekers. Acknowledging challenges and harnessing innovative workarounds can foster a more effective and compassionate service for this vulnerable population. Patient or Public Contribution: The HEAR study actively involved public contributors in the design, delivery and dissemination of the research. Two public contributors (S. M. and G. R.) who had personal experience of seeking asylum served as study co‐applicants. They played pivotal roles in shaping the research by participating in its development and securing funding. Alongside other co‐applicants, S. M. and G. R. formed the Research Management Group, overseeing study delivery. Their contributions extended to strategic decision‐making and specific feedback at critical junctures, including participant recruitment, data collection, analysis and reporting. Additionally, S. M. and G. R. were instrumental in recruiting and supporting a team of peer researchers, enhancing respondent participation among people seeking sanctuary. To facilitate effective public involvement, we provided named contacts for support (A. K. and R. F.), research training, honoraria, reimbursement of expenses and accessible information in line with best practice. [ABSTRACT FROM AUTHOR]

Background: We conducted this systematic review and meta-analysis to better understand the association between rs1799762 PAI-1 gene polymorphism and the risk of RPL. Methods: A systematic search for studies that assessed the association between PAI-1 4G/5G polymorphism and RPL risk published in search sources, PubMed/Medline, ISI Web of Knowledge, Scopus, and Google Scholar till January 2024 was conducted. Results: There were 23 case-control studies in total, with a high degree of statistical heterogeneity among them which indicated the need for subgroup analysis. We found a significant positive association between the risk of RPL and 4G/4G PAI-1 (OR: 2.57; 95% CI: 1.69-3.90), likewise 4G/5G (OR: 2/02 95% CI: 1.39-2.92) and mixed genotype (4G/4G+4G/5G) (OR: 2.31 95% CI: 1.81-2.93). Considering the ethnicity, the 4G/4G polymorphism is significantly associated with Asian descent (OR: 2.10; CI: 1.65-2.69) while the strong association (OR: 6.47; CI: 3.23-12.97) observed in the Greater Middle East descent is not statistically significant (P=0.16). PAI-1 4G/5G polymorphism association with RPL was only significant in Greater Middle East descent (OR: 2.93; CI: 2.41-3.56), and mixed genotype was significantly associated with RPL in Asian (OR: 2.37; CI: 1.55-3.61), Greater Middle East (OR: 3.01; CI: 2.16-4.19), and European populations (OR: 1.38; CI: 0.91-2.10). The association between RPL and PAI-1 4G/4G was significant for RPLs both under 12 weeks (OR: 1.82; 95% CI: 1.34-2.47), and under 24 weeks (OR: 1.46; 95% CI: 1.11-1.92), while considering heterozygote form the association was only significant for RPLs under 24 weeks (OR: 1.91; 95% CI: 1.58-2.31). Regarding the mixed genotype, there is a significant positive association between PAI-1 and RPL for RPLs under 12 weeks (OR: 2.09; 95% CI: 1.49-2.93), and under 24 weeks (OR: 2.10; 95% CI: 1.52-2.92). Conclusions: Our findings indicate a significant association between the rs1799762 PAI-1 polymorphism and the risk of RPL. [ABSTRACT FROM AUTHOR]

In recent years, the utility of polygenic risk scores (PRS) in forecasting disease susceptibility from genome-wide association studies (GWAS) results has been widely recognised. Yet, these models face limitations due to overfitting and the potential overestimation of effect sizes in correlated variants. To surmount these obstacles, we devised the Stacked Neural Network Polygenic Risk Score (SNPRS). This novel approach synthesises outputs from multiple neural network models, each calibrated using genetic variants chosen based on diverse p-value thresholds. By doing so, SNPRS captures a broader array of genetic variants, enabling a more nuanced interpretation of the combined effects of these variants. We assessed the efficacy of SNPRS using the UK Biobank data, focusing on the genetic risks associated with breast and prostate cancers, as well as quantitative traits like height and BMI. We also extended our analysis to the Korea Genome and Epidemiology Study (KoGES) dataset. Impressively, our results indicate that SNPRS surpasses traditional PRS models and an isolated deep neural network in terms of accuracy, highlighting its promise in refining the efficacy and relevance of PRS in genetic studies. [ABSTRACT FROM AUTHOR]

Activated phosphoinositide 3-kinase (PI3Kδ) Syndrome (APDS) is an inborn error of immunity (IEI) with a variable clinical presentation, characterized by infection susceptibility and immune dysregulation that may overlaps with other Primary Immune Regulatory Disorders (PIRDs). The rarity of the disease, its recent discovery, and the multiform /multifaced clinical presentation make it difficult to establish a correct diagnosis, especially at an early stage. As a result, the true prevalence of the pathology remains unknown. There is no treatment protocol for APDS, and drug therapy is primarily focused on treating symptoms. The most common therapies include immunoglobulin replacement therapy, antimicrobial prophylaxis, and immunosuppressive drugs. Hematopoietic stem cell transplantation (HSCT) has been used in some cases, but the risk-benefit balance remains unclear. With the upcoming introduction of specific medications, such as selective inhibitors for PI3Kδ, clinicians are shifting their attention towards target therapy. This review provides a comprehensive overview of APDS with a focus on diagnostic and treatments procedures available. This review may be useful in implementing strategies for a more efficient patients' management and therapeutic interventions. Main Text. [ABSTRACT FROM AUTHOR]

Climate change has emerged as a significant occurrence that adversely affects broiler production, especially in tropical climates. Broiler chickens, bred for rapid growth and high meat production, rely heavily on optimal environmental conditions to achieve their genetic potential. However, climate change disrupts these conditions and poses numerous challenges for broiler production. One of the primary impacts of climate change on broiler production is the decreased ability of birds to attain their genetic potential for faster growth. Broilers are bred to possess specific genetic traits that enable them to grow rapidly and efficiently convert feed into meat. However, in tropical climates affected by climate change, the consequent rise in daily temperatures, increased humidity and altered precipitation patterns create an unfavourable environment for broilers. These conditions impede their growth and development, preventing them from reaching their maximum genetic influence, which is crucial for achieving desirable production outcomes. Furthermore, climate change exacerbates the existing challenges faced by broiler production systems. Higher feed costs impact the industry's economic viability and limit the availability of quality nutrition for the birds, further hampering their growth potential. In addition to feed scarcity, climate change also predisposes broiler chickens to thermal stress. This review collates existing information on climate change and its impact on broiler production, including nutrition, immune function, health and disease susceptibility. It also summarizes the challenges of broiler production under hot and humid climate conditions with different approaches to ameliorating the effects of harsh climatic conditions in poultry. [ABSTRACT FROM AUTHOR]

Simple Summary: Hypertrophic cardiomyopathy (HCM) is the most common feline heart pathology, which is characterized by thickening of the ventricular walls. This disease is genetic in nature and often occurs in cats of certain breeds such as Maine Coon, Persian, Ragdoll, and Norwegian Forest. In this study, we attempted to identify the significance of determining genetic predisposition to this disease using DNA tests. We found that in homozygous cats, the disease manifests itself earlier and its progression is more severe than in heterozygous cats. Since the disease is often asymptomatic, we compared the quality of various diagnostic methods and clinical aspects for identifying HCM at an early stage. Hypertrophic cardiomyopathy (HCM), which is associated with thickening of the left ventricular wall, is one of the most common heart pathologies in cats. This disease has a hereditary etiology and is primarily related to mutations in the MYBPC3 and MYH7 genes. This study aims to determine the effect of the presence of heterozygosity or homozygosity for the p. A31P mutation (c.91G>C) in the MYBPC3 gene in cats (Maine Coon) of different ages referring to the HCM severity and development, and to compare echocardiographic data and various clinical aspects for the most objective detection of disease in cats of different breeds. The incidence of HCM was 59% of the 103 cases of heart disease in cats in this study. In 23 cats diagnosed with HCM, cats heterozygous for the mutation accounted for 34%, and homozygous cats accounted for 26%. Cats homozygous for this mutation had moderate to severe HCM, suggesting an association with high penetrance of HCM and a significant risk of cardiac death in this group. The penetrance of the heterozygous type was lower than that of the homozygous genotype. This study also indicates that HCM has some age-related penetrance. The disease did not occur in the study group of cats aged up to 1 year, whereas at the age of 7 and older, the percentage of animals diagnosed with HCM was the highest and amounted to 44.3% of the total number of studied cats with HCM. [ABSTRACT FROM AUTHOR]

Asthma, a prevalent chronic respiratory condition affecting millions of children globally, presents a significant health challenge. This review critically examines the developmental pathways of asthma in children, focusing on genetic, environmental, and early-life determinants. Specifically, we explore the impact of prenatal and postnatal factors such as maternal smoking, nutrition, respiratory infections, and allergen exposure on asthma development. Our analysis highlights the intricate interplay of these influences and their contribution to childhood asthma. Moreover, we emphasize targeted strategies and interventions to mitigate its burden, including genetic counseling for at-risk families, environmental modifications to reduce triggers, and early-life immunomodulation. By delving into these preventive measures and interventions, our review aims to provide actionable insights for healthcare professionals in developing tailored strategies to address the complexities of childhood asthma. In summary, this article offers a detailed examination of asthma development in children, aiming to enhance understanding and inform efforts to reduce its burden through targeted interventions. [ABSTRACT FROM AUTHOR]

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Vitamin D is a lipid soluble steroid hormone, which plays a critical role in the calcium homeostasis, neuronal development, cellular differentiation, and growth by binding to vitamin D receptor (VDR). Associations between VDR gene polymorphism and Alzheimer's disease (AD), Parkinson's disease (PD), and mild cognitive impairment (MCI) risk has been investigated extensively, but the results remain ambiguous. The aim of this study was to comprehensively assess the correlations between four VDR polymorphisms (FokI, BsmI, TaqI, and ApaI) and susceptibility to AD, PD, and MCI. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to determine the relationship of interest. Pooled analyses suggested that the ApaI polymorphism decreased the overall AD risk, and the TaqI increased the overall PD susceptibility. In addition, the BsmI and ApaI polymorphisms were significantly correlated with the overall MCI risk. Stratified analysis by ethnicity further showed that the TaqI and ApaI genotypes reduced the AD predisposition among Caucasians, while the TaqI polymorphism enhanced the PD risk among Asians. Intriguingly, carriers with the BB genotype significantly decreased the MCI risk in Asian descents, and the ApaI variant elevated the predisposition to MCI in Caucasians and Asians. Further studies are need to identify the role of VDR polymorphisms in AD, PD, and MCI susceptibility. [ABSTRACT FROM AUTHOR]

Simple Summary: Ovarian cancer is the leading cause of death due to gynecologic malignancies. Peritoneal metastases represent the most common pathway for the spread of OC, both at the time of initial diagnosis and at recurrence. Accurate mapping of peritoneal metastases helps in planning the appropriate therapeutic strategy, predicting the likelihood of optimal cytoreduction, and identifying potentially unresectable or difficult disease sites that may require surgical technique modifications. Preoperative diagnostic work-up with multidetector CT (MDCT), MRI, including diffusion-weighted imaging (DWI), or FDG PET/CT plays a vital role in the accurate assessment of the extent of peritoneal carcinomatosis. In this article, the aim was to update the role of MDCT, MRI, including DWI, and FDG PET/CT in the detection of peritoneal metastases in ovarian cancer by conducting a systematic review and meta-analysis of the existing literature. This review aims to compare the diagnostic performance of multidetector CT (MDCT), MRI, including diffusion-weighted imaging, and FDG PET/CT in the detection of peritoneal metastases (PMs) in ovarian cancer (OC). A comprehensive search was performed for articles published from 2000 to February 2023. The inclusion criteria were the following: diagnosis/suspicion of PMs in patients with ovarian/fallopian/primary peritoneal cancer; initial staging or suspicion of recurrence; MDCT, MRI and/or FDG PET/CT performed for the detection of PMs; population of at least 10 patients; surgical results, histopathologic analysis, and/or radiologic follow-up, used as reference standard; and per-patient and per-region data and data for calculating sensitivity and specificity reported. In total, 33 studies were assessed, including 487 women with OC and PMs. On a per-patient basis, MRI (p = 0.03) and FDG PET/CT (p < 0.01) had higher sensitivity compared to MDCT. MRI and PET/CT had comparable sensitivities (p = 0.84). On a per-lesion analysis, no differences in sensitivity estimates were noted between MDCT and MRI (p = 0.25), MDCT and FDG PET/CT (p = 0.68), and MRI and FDG PET/CT (p = 0.35). Based on our results, FDG PET/CT and MRI are the preferred imaging modalities for the detection of PMs in OC. However, the value of FDG PET/CT and MRI compared to MDCT needs to be determined. Future research to address the limitations of the existing studies and the need for standardization and to explore the cost-effectiveness of the three imaging modalities is required. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to investigate the relationship between attachment styles and Separation Anxiety Disorder (SAD) through the internalized symptoms and stress coping strategies in badly-cared and orphan adolescent girls living in Tehran in 2022. Method: This was a correlational study of a Structural Equation Modeling (SEM) type. The statistical population included all adolescent girls aged between 12 and 18 under the direct or indirect supervision of Tehran's welfare center, of whom 200 were selected by the convenience sampling method. The participants answered the questionnaires of Collins and Reed's attachment styles, Billings and Moss's coping strategies, Achenbach and Rascorella's adolescent self-report, and Morris et al.'s SAD. Results: The findings of SEM demonstrated that the hypothesized model of this study has a good fit in the studied sample. The findings reveal that the secure attachment style is related to separation anxiety both directly (T=-4.18 and b=-.22) and indirectly through problem-oriented coping style (P<.01 and Z=-10.83) and emotion-oriented coping style (P<.01 and Z=-7.23). Avoidant attachment style is directly (T=4.98 and b=.25) and indirectly related to separation anxiety through problem-oriented coping style (P<.01 and Z=4.33) and emotion-oriented coping style (P<.01 and Z=8.79) and internalized symptoms (P<.01 and Z=2.61). Finally, ambivalent attachment style had no significant correlation (P>.05) with separation anxiety. Conclusion: These results emphasize the importance of attachment patterns formed under the influence of adverse conditions of the vulnerable group, and the lifelong effects of these patterns in the mental health of them. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) has left a devasting effect on various regions globally. Africa has exceptionally high rates of other infectious diseases, such as tuberculosis (TB), human immunodeficiency virus (HIV), and malaria, and was not impacted by COVID-19 to the extent of other continents Globally, COVID-19 has caused approximately 7 million deaths and 700 million infections thus far. COVID-19 disease severity and susceptibility vary among individuals and populations, which could be attributed to various factors, including the viral strain, host genetics, environment, lifespan, and co-existing conditions. Host genetics play a substantial part in COVID-19 disease severity among individuals. Human leukocyte antigen (HLA) was previously been shown to be very important across host immune responses against viruses. HLA has been a widely studied gene region for various disease associations that have been identified. HLA proteins present peptides to the cytotoxic lymphocytes, which causes an immune response to kill infected cells. The HLA molecule serves as the central region for infectious disease association; therefore, we expect HLA disease association with COVID-19. Therefore, in this narrative review, we look at the HLA gene region, particularly, HLA class I, to understand its role in COVID-19 disease. [ABSTRACT FROM AUTHOR]

Aims: Motor abnormalities have been identified as one common symptom in patients with generalized tonic–clonic seizures (GTCS) inspiring us to explore the disease in a motor execution condition, which might provide novel insight into the pathomechanism. Methods: Resting‐state and motor‐task fMRI data were collected from 50 patients with GTCS, including 18 patients newly diagnosed without antiepileptic drugs (ND_GTCS) and 32 patients receiving antiepileptic drugs (AEDs_GTCS). Motor activation and its association with head motion and cerebral gradients were assessed. Whole‐brain network connectivity across resting and motor states was further calculated and compared between groups. Results: All patients showed over‐activation in the postcentral gyrus and the ND_GTCS showed decreased activation in putamen. Specifically, activation maps of ND_GTCS showed an abnormal correlation with head motion and cerebral gradient. Moreover, we detected altered functional network connectivity in patients within states and across resting and motor states by using repeated‐measures analysis of variance. Patients did not show abnormal connectivity in the resting state, while distributed abnormal connectivity in the motor‐task state. Decreased across‐state network connectivity was also found in all patients. Conclusion: Convergent findings suggested the over‐response of activation and connection of the brain to motor execution in GTCS, providing new clues to uncover motor susceptibility underlying the disease. [ABSTRACT FROM AUTHOR]

Introduction: When examining health literacy and disease specific knowledge levels across ethnicities and communities, ethnic minority groups are known to be at a higher risk of being below the average health literacy threshold which is a factor linked to poor health status and higher mortality rates. This study examined disease specific knowledge levels, perceived severity, and perceived susceptibility surrounding anal cancer and HPV-related screening behaviors. Methods: The following research questions were explored: (1) "What are the common themes and/or beliefs when asked about anal cancer, HPV, and preventive screening?" and (2) "What are the common themes and beliefs surrounding the severity and susceptibility of contracting anal cancer?". This study utilized a cross-sectional design to survey 26 individuals regarding their knowledge level and perspectives regarding anal cancer and HPV. An 8-question survey was developed de novo based on an application of the Health Belief Model (HBM) elements. This study employed thematic analysis to explore critical themes to construct a model to understand knowledge levels, attitudes, and risk perceptions regarding anal cancer and intention to participate in preventive screenings. The fundamental attitudes and themes related to anal cancer risk and intention to participate in preventative screenings were elicited using a qualitative descriptive technique. Coded data was utilized to analyze themes based on (1) knowledge and (2) perceived risk, both severity and susceptibility. Results: Overall, the findings indicate very low levels of knowledge regarding screening, anal cancer, and HPV across all genders. The low levels of anal cancer and HPV knowledge were seen in 13 coded segments (50% of surveys) which showed no familiarity with or comprehension of HPV, and 4 coded segments indicated no familiarity with anal cancer. In addition, 15 respondents (57%) had low or no preventive or screening-related knowledge. While some respondents (46%) illustrated high perceived severity for anal cancer, only 23% indicated high perceived susceptibility for anal cancer. Conclusion: The results from this study may be used to inform practitioners, providers, and policymakers in developing interventions addressing low levels of understanding and disease specific knowledge surrounding anal cancer in support of creating a standardized health screening procedure. [ABSTRACT FROM AUTHOR]

Background: Genetic variation underly inter-individual variation in host immune responses to infectious diseases, and may affect susceptibility or the course of signs and symptoms. Methods: We performed genome-wide association studies in a prospective cohort of 1138 patients with physician-confirmed Lyme borreliosis (LB), the most common tick-borne disease in the Northern hemisphere caused by the bacterium Borrelia burgdorferi sensu lato. Genome-wide variants in LB patients—divided into a discovery and validation cohort—were compared to two healthy cohorts. Additionally, ex vivo monocyte-derived cytokine responses of peripheral blood mononuclear cells to several stimuli including Borrelia burgdorferi were performed in both LB patient and healthy control samples, as were stimulation experiments using mechanistic/mammalian target of rapamycin (mTOR) inhibitors. In addition, for LB patients, anti-Borrelia antibody responses were measured. Finally, in a subset of LB patients, gene expression was analysed using RNA-sequencing data from the ex vivo stimulation experiments. Results: We identified a previously unknown genetic variant, rs1061632, that was associated with enhanced LB susceptibility. This polymorphism was an eQTL for KCTD20 and ETV7 genes, and its major risk allele was associated with upregulation of the mTOR pathway and cytokine responses, and lower anti-Borrelia antibody production. In addition, we replicated the recently reported SCGB1D2 locus that was suggested to have a protective effect on B. burgdorferi infection, and associated this locus with higher Borrelia burgdorferi antibody indexes and lower IL-10 responses. Conclusions: Susceptibility for LB was associated with higher anti-inflammatory responses and reduced anti-Borrelia antibody production, which in turn may negatively impact bacterial clearance. These findings provide important insights into the immunogenetic susceptibility for LB and may guide future studies on development of preventive or therapeutic measures. Trial registration: The LymeProspect study was registered with the International Clinical Trials Registry Platform (NTR4998, registration date 2015–02-13). [ABSTRACT FROM AUTHOR]

The hospital at home concept integrates key digital medicine technologies and concepts in a single platform approach, with telemedicine, wearables, and sensors. It could bring benefits to patients, who face lower risks from hospital infections and who want to be at home with their loved ones. Moreover, it may lead to efficiency savings, through its seamless integration of data flows, and therefore is likely to be an increasingly implemented model. But what happens when the platform succumbs to exploited platform/infrastructure vulnerabilities or cyber attacks like ransomware that have been weaponized to bring networked systems crashing down? Exploring the attack modes and their consequences could help prioritize adequate safeguards. [ABSTRACT FROM AUTHOR]

Modern plant breeding relies heavily on the deployment of susceptibility and resistance genes to defend crops against diseases. The expression of these genes is usually regulated by transcription factors including members of the AP2/ERF family. While these factors are a vital component of the plant immune response, little is known of their specific roles in defense against Fusarium oxysporum f. sp. cubense tropical race 4 (Foc TR4) in banana plants. In this study, we discovered that MaERF12, a pathogen-induced ERF in bananas, acts as a resistance gene against Foc TR4. The yeast two-hybrid assays and protein-protein docking analyses verified the interaction between this gene and MaSMG7, which plays a role in nonsense-mediated RNA decay. The transient expression of MaERF12 in Nicotiana benthamiana was found to induce strong cell death, which could be inhibited by MaSMG7 during co-expression. Furthermore, the immunoblot analyses have revealed the potential degradation of MaERF12 by MaSMG7 through the 26S proteasome pathway. These findings demonstrate that MaSMG7 acts as a susceptibility factor and interferes with MaERF12 to facilitate Foc TR4 infection in banana plants. Our study provides novel insights into the biological functions of the MaERF12 as a resistance gene and MaSMG7 as a susceptibility gene in banana plants. Furthermore, the first discovery of interactions between MaERF12 and MaSMG7 could facilitate future research on disease resistance or susceptibility genes for the genetic improvement of bananas. [ABSTRACT FROM AUTHOR]

The Greater Athens Area (GAA), situated in the southern part of the European continent (in Greece), has a Mediterranean climate characterized by hot, dry summers and mild, wet winters. As a result of increased sunshine and high temperatures, exceedances in ozone concentrations are often recorded during the hot period. In the present study, the monthly as well as daily variations of O3 concentrations at thirteen stations in the GAA were investigated for the period 1987–2019. Moreover, the impact of O3 on the people's health in Greece was examined by using data from the Global Burden of Disease (GBD) study with the socio-economic conditions of the country. Ozone concentrations were found to be particularly high during the summer months, especially in suburban stations. Values ranged from 65 μg/m3 to 90 μg/m3 during the night, in contrast to urban areas and remain high for several hours. Comparing estimates from GBD, it was found that exposure to ozone can impair respiratory function, leading to death or susceptibility to respiratory diseases that reduce quality of life, especially for people over 55 years of age. Finally, since 2009, when the economic crisis began in Greece, an upward trend was observed for deaths and disability adjusted life years. [ABSTRACT FROM AUTHOR]

Introduction: COVID-19, caused by SARS-CoV-2, has resulted in significant mortality and morbidity worldwide. Patients of chronic kidney disease who are on maintenance hemodialysis represent a vulnerable population cohort that is susceptible to severe disease. Hence, it is of utmost importance to prioritize vaccination in this population and to assess their response to said vaccination. Methods: This prospective analytical study was conducted at the Institute of Nephrology, Madras Medical College, between August 2021 and February 2022. Patients of chronic kidney disease stage 5 dialysis (CKD5D) who were on maintenance hemodialysis and who consented to receive COVID-19 vaccine were studied. Serum samples were obtained before vaccination, ≥28 days after receiving the first dose of the vaccine, and ≥28 days after receiving the second dose. Antibody titers against the spike protein were estimated using the Roche chemiluminescent immunosorbent assay. Patients were grouped into non-responders/seronegative (<0.8 U/ml) and responders/seropositive (≥0.8 U/ml), with a value ≥250 U/ml considered as robust response. Results: A total of 96 patients were included. The mean age was 36.70 (±11.53) years and 77.1% of them were male. The median dialysis vintage was 2 (IQR: 0.95-5) years. Twelve patients (9.9%) had a prior COVID-19 infection. Sixty-seven (69.8%) patients had received Covaxin and 29 (30.2%) had received Covishield vaccines. Among the 17 patients who were seronegative at baseline, 4 (23.52%) became seropositive after the first dose of the vaccine, and 11 (64.7%) were seropositive after the second dose, with high titers ("robust response") achieved in two patients (11.76%). No antibody response, despite two doses of the vaccine, was noted in six patients (35.29%). Conclusion: Our study showed a high baseline seropositivity rate, even prior to vaccination, which indicated a high rate of subclinical COVID infection. Among those who were seronegative at baseline, the seroconversion rate after two doses of Covaxin or Covishield was 64.70%. [ABSTRACT FROM AUTHOR]