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Molecular and Clinical Oncology Jul 2024Breast cancer (BC) is one of the most prevalent types of malignancy and a major cause of cancer-related death. The purpose of the present study was to identify...
Breast cancer (BC) is one of the most prevalent types of malignancy and a major cause of cancer-related death. The purpose of the present study was to identify prognostic models of necroptosis-related genes (NRGs) in BC at the single-cell RNA-sequencing level and reveal the role of NRGs in tumour immune microenvironment (TIME). A risk model was constructed based on Cox regression and LASSO methods. Next, high-scoring cell populations were searched through AUCell scores, and cell subtypes were then analyzed by pseudotime analysis. Finally, the expression level of the model genes was verified by reverse transcription-quantitative (RT-qPCR). A new prognostic model was constructed and validated based on five NRGs (BCL2, BIRC3, AIFM1, IFNG and VDAC1), which could effectively predict the prognosis of patients with BC. NRGs were found to be highly active in CD4 T cells and differentially expressed in their developmental trajectories. Finally, the RT-qPCR results showed that most of the model genes were significantly overexpressed in MDA-MB-231 and MCF-7 cells (P<0.05). In conclusion, an NRG signature with excellent predictive properties in prognosis and TIME was successfully established. Moreover, NRGs were involved in the differentiation and development of CD4 T cells in TIME. These findings provide potential therapeutic strategies for BC.
PubMed: 38872949
DOI: 10.3892/mco.2024.2747 -
Annals of Occupational and... 2024Perfluoroalkyl substances (PFASs) are non-aromatic organic compounds, whose hydrogen atoms in the carbon chain substituted by fluorine atoms. PFASs exhibit developmental...
BACKGROUND
Perfluoroalkyl substances (PFASs) are non-aromatic organic compounds, whose hydrogen atoms in the carbon chain substituted by fluorine atoms. PFASs exhibit developmental toxicity, carcinogenicity, hepatotoxicity, reproductive toxicity, immunotoxicity, and hormone toxicity. PFASs are used in the production of disposable food packages, aircraft and automobile devices, cooking utensils, outdoor gear, furniture and carpets, aqueous film forming foam (AFFF), cables and wires, electronics, and semiconductors. This study aimed to determine the association between crustacean consumption and serum PFASs.
METHODS
Adult participants (2,993) aged ≥ 19 years were extracted from the 4th cycle data of the Korean National Environmental Health Survey (KoNEHS). Based on the 50th percentile concentrations of serum PFASs, participants were divided into the low-concentration group (LC) and the high-concentration group (HC). General characteristics, dietary factors, coated product usage, and personal care product usage, an independent t-test and χ test were analyzed. The odds ratio (OR) of serum PFAS concentration against crustacean consumption was estimated via logistic regression analysis adjusting for general characteristics, dietary factors, coated product usage, and personal care product usage.
RESULTS
The OR for the HC of serum PFASs was higher in individuals with ≥once a week crustacean consumption than in those with < once a week crustacean consumption. Estimated ORs were perfluorohexanesulfonic acid 2.15 (95% confidence interval [CI]: 1.53-3.02), perfluorononanoic acid (PFNA) 1.23 (95% CI: 1.07-1.41), and perfluorodecanoic acid (PFDeA) 1.42 (95% CI: 1.17-1.74) in males, and perfluorooctanoic acid 1.48 (95% CI: 1.19-1.84), perfluorooctanesulfonic acid 1.39 (95% CI: 1.27-1.52), PFNA 1.70 (95% CI: 1.29-2.26) and PFDeA 1.43 (95% CI: 1.32-1.54) in females.
CONCLUSIONS
This study revealed the association between the crustacean consumption and concentrations of serum PFASs in general Korean population.
PubMed: 38872633
DOI: 10.35371/aoem.2024.36.e12 -
BMC Plant Biology Jun 2024Bracts are important for ornamental plants, and their developmental regulation process is complex; however, relatively little research has been conducted on bracts. In...
BACKGROUND
Bracts are important for ornamental plants, and their developmental regulation process is complex; however, relatively little research has been conducted on bracts. In this study, physiological, biochemical and morphological changes in Bougainvillea glabra leaves, leaf buds and bracts during seven developmental periods were systematically investigated. Moreover, transcriptomic data of B. glabra bracts were obtained using PacBio and Illumina sequencing technologies, and key genes regulating their development were screened.
RESULTS
Scanning electron microscopy revealed that the bracts develop via a process involving regression of hairs and a color change from green to white. Transcriptome sequencing revealed 79,130,973 bp of transcript sequences and 45,788 transcripts. Differential gene expression analysis revealed 50 expression patterns across seven developmental periods, with significant variability in transcription factors such as BgAP1, BgFULL, BgCMB1, BgSPL16, BgSPL8, BgDEFA, BgEIL1, and BgBH305. KEGG and GO analyses of growth and development showed the involvement of chlorophyll metabolism and hormone-related metabolic pathways. The chlorophyll metabolism genes included BgPORA, BgSGR, BgPPH, BgPAO and BgRCCR. The growth hormone and abscisic acid signaling pathways involved 44 and 23 homologous genes, and coexpression network analyses revealed that the screened genes BgAPRR5 and BgEXLA1 are involved in the regulation of bract development.
CONCLUSIONS
These findings improve the understanding of the molecular mechanism of plant bract development and provide important guidance for the molecular regulation and genetic improvement of the growth and development of ornamental plants, mainly ornamental bracts.
Topics: Gene Expression Profiling; Nyctaginaceae; Gene Regulatory Networks; Gene Expression Regulation, Plant; Transcriptome; Plant Leaves; Genes, Plant; Plant Proteins; Flowers
PubMed: 38872082
DOI: 10.1186/s12870-024-05246-7 -
Molecular Autism Jun 2024An intense and precocious interest in written material, together with a discrepancy between decoding and reading comprehension skills are defining criteria for...
BACKGROUND
An intense and precocious interest in written material, together with a discrepancy between decoding and reading comprehension skills are defining criteria for hyperlexia, which is found in up to 20% of autistic individuals. It may represent the extreme end of a broader interest in written material in autism. This study examines the magnitude and nature of the interest in written material in a large population of autistic and non-autistic children.
METHODS
All 701 children (391 autistic, 310 non-autistic) under the age of 7 referred to an autism assessment clinic over a span of 4 years were included. Ordinal logistic regressions assessed the association between diagnosis and the level of interest in letters and numbers. A nested sample of parents of 138 autistic, 99 non-autistic clinical, and 76 typically developing (TD) children completed a detailed questionnaire. Cox proportional hazards models analyzed the age of emergence of these interests. Linear regressions evaluated the association between diagnosis and interest level. The frequency of each behaviour showing interest and competence with letters and numbers were compared.
RESULTS
In the two studies, 22 to 37% of autistic children had an intense or exclusive interest in letters. The odds of having a greater interest in letters was 2.78 times higher for autistic children than for non-autistic clinical children of the same age, and 3.49 times higher for the interest in numbers, even if 76% of autistic children were minimally or non-verbal. The age of emergence of these interests did not differ between autistic and TD children and did not depend on their level of oral language. Non-autistic children showed more interest in letters within a social context.
LIMITATIONS
The study holds limitations inherent to the use of a phone questionnaire with caregivers and missing sociodemographic information.
CONCLUSIONS
The emergence of the interest of autistic children toward written language is contemporaneous to the moment in their development where they display a strong deficit in oral language. Together with recent demonstrations of non-social development of oral language in some autistic children, precocious and intense interest in written material suggests that language acquisition in autism may follow an alternative developmental pathway.
Topics: Humans; Male; Female; Autistic Disorder; Child, Preschool; Child; Reading; Surveys and Questionnaires
PubMed: 38867240
DOI: 10.1186/s13229-024-00606-4 -
Frontiers in Psychology 2024Older sexual minority people meet a double stigma in our society related to their sexual identity and chronological age. The present study explores how experiences of...
INTRODUCTION
Older sexual minority people meet a double stigma in our society related to their sexual identity and chronological age. The present study explores how experiences of discrimination and prejudice, coming out, and personal resiliency influence physical health of older lesbian, gay, and bisexual (LGB) adults.
METHODS
Respondents were recruited through online advertisements and an online-based survey. The sample included 82 Italian cisgender LGB adults over 65 years: young older adults (65-70 years; 78%) and old-old adults (over 71 years; 22%). Regarding sexual orientation, the sample was composed of sexual minority women ( = 30; 37%) and sexual minority men ( = 52; 63%).
RESULTS
ANOVAs' findings showed that sexual minority women described lower levels of physical health compared to sexual minority men. At the same time, old-old adults reported higher experiences of discrimination and prejudice compared to young older adults. Moreover, findings from hierarchical multiple regression analysis described that coming out, higher levels of personal resiliency, and fewer experiences of discrimination were predictors of physical health, regardless of age and sexual minority categories.
CONCLUSION
These findings seem to align with previous studies that underline the relevance of investigating aging well in sexual minority people. Knowledge and awareness of LGBTQ+ issues are necessary for recognizing the unique needs and resources of older LGB people for promoting a healthy aging process.
PubMed: 38860050
DOI: 10.3389/fpsyg.2024.1369021 -
JAMA Network Open Jun 2024Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18...
IMPORTANCE
Neurological manifestations during acute SARS-CoV-2-related multisystem inflammatory syndrome in children (MIS-C) are common in hospitalized patients younger than 18 years and may increase risk of new neurocognitive or functional morbidity.
OBJECTIVE
To assess the association of severe neurological manifestations during a SARS-CoV-2-related hospital admission with new neurocognitive or functional morbidities at discharge.
DESIGN, SETTING, AND PARTICIPANTS
This prospective cohort study from 46 centers in 10 countries included patients younger than 18 years who were hospitalized for acute SARS-CoV-2 or MIS-C between January 2, 2020, and July 31, 2021.
EXPOSURE
Severe neurological manifestations, which included acute encephalopathy, seizures or status epilepticus, meningitis or encephalitis, sympathetic storming or dysautonomia, cardiac arrest, coma, delirium, and stroke.
MAIN OUTCOMES AND MEASURES
The primary outcome was new neurocognitive (based on the Pediatric Cerebral Performance Category scale) and/or functional (based on the Functional Status Scale) morbidity at hospital discharge. Multivariable logistic regression analyses were performed to examine the association of severe neurological manifestations with new morbidity in each SARS-CoV-2-related condition.
RESULTS
Overall, 3568 patients younger than 18 years (median age, 8 years [IQR, 1-14 years]; 54.3% male) were included in this study. Most (2980 [83.5%]) had acute SARS-CoV-2; the remainder (588 [16.5%]) had MIS-C. Among the patients with acute SARS-CoV-2, 536 (18.0%) had a severe neurological manifestation during hospitalization, as did 146 patients with MIS-C (24.8%). Among survivors with acute SARS-CoV-2, those with severe neurological manifestations were more likely to have new neurocognitive or functional morbidity at hospital discharge compared with those without severe neurological manifestations (27.7% [n = 142] vs 14.6% [n = 356]; P < .001). For survivors with MIS-C, 28.0% (n = 39) with severe neurological manifestations had new neurocognitive and/or functional morbidity at hospital discharge compared with 15.5% (n = 68) of those without severe neurological manifestations (P = .002). When adjusting for risk factors in those with severe neurological manifestations, both patients with acute SARS-CoV-2 (odds ratio, 1.85 [95% CI, 1.27-2.70]; P = .001) and those with MIS-C (odds ratio, 2.18 [95% CI, 1.22-3.89]; P = .009) had higher odds of having new neurocognitive and/or functional morbidity at hospital discharge.
CONCLUSIONS AND RELEVANCE
The results of this study suggest that children and adolescents with acute SARS-CoV-2 or MIS-C and severe neurological manifestations may be at high risk for long-term impairment and may benefit from screening and early intervention to assist recovery.
Topics: Humans; COVID-19; Child; Female; Male; Child, Preschool; Hospitalization; Adolescent; Prospective Studies; SARS-CoV-2; Systemic Inflammatory Response Syndrome; Nervous System Diseases; Infant; Severity of Illness Index
PubMed: 38857050
DOI: 10.1001/jamanetworkopen.2024.14122 -
BMC Public Health Jun 2024Risky sexual behaviour (RSB), particularly multiple sexual partnerships (MSP) continues to be a major public health concern and has been linked to the increasing STIs,...
BACKGROUND
Risky sexual behaviour (RSB), particularly multiple sexual partnerships (MSP) continues to be a major public health concern and has been linked to the increasing STIs, including HIV/AIDS in many parts of sub-Saharan Africa (SSA), suggesting that there is an association between contextual factors and multiple sexual partnering. However, in South Africa, this association is not well established in recent literature. Hence, this study examined the contextual factors contributing to multiple sexual partnerships among young people in South Africa.
MATERIALS AND METHODS
Data was extracted from the 2016 South Africa Demographics and Health Survey (2016 SADHS). A cross-sectional study of 3889 never-married young people. Descriptive and inferential statistics as well as multilevel logistic regression were used to analyse the data on never-married young people aged 15 to 24 years.
RESULTS
The results indicated that at the individual level, young males (61.7%) were significantly more likely than their female counterparts (56.1%) to engage in multiple sexual partners, although, the difference was not as significant as expected. At the community level clustering, the likelihood of exposure to multiple sexual partnerships significantly increased among females (OR = 1.47; 95% CI: 1.25-1.73) but decreased among their male counterparts (OR = 0.73; 95% CI: 0.58-0.92), in particular, family disruption, residential instability, and ethnic diversity led young people to engage in multiple sexual partnerships.
CONCLUSIONS
There is a need to intensify programmes aimed at considering appropriate policy options to reduce the prevalence of multiple sexual partnerships. Adopting the implications of these findings is essential for a developmental strategy towards achieving the sustainable development goal of ending STIs among young people in South Africa.
Topics: Humans; South Africa; Male; Adolescent; Female; Young Adult; Cross-Sectional Studies; Multilevel Analysis; Sexual Partners; Sexual Behavior; Risk-Taking; Health Surveys
PubMed: 38849818
DOI: 10.1186/s12889-024-18872-5 -
Annals of Medicine and Surgery (2012) Jun 2024Cytochrome C oxidase (COX) deficiency is an uncommon inherited metabolic disorder. It is identified by a lack of the COX, also known as Complex IV. This enzyme plays a...
INTRODUCTION AND IMPORTANCE
Cytochrome C oxidase (COX) deficiency is an uncommon inherited metabolic disorder. It is identified by a lack of the COX, also known as Complex IV. This enzyme plays a crucial role in the rate-limiting and oxygen-accepting step of the respiratory chain within the subcellular structures called mitochondria. The deficiency of COX can either be restricted to skeletal muscle tissues or can impact multiple tissues throughout the body.
CASE PRESENTATION
A 3-year-old girl was admitted due to muscle weakness and a decline in developmental milestones 7 days after a significant stressor. Leukodystrophy was observed in the brain magnetic resonance imaging, and genome sequencing identified a homozygous mutation in exon 1 and 7 of chromosome 17. This mutation led to a deficiency in COX10, which is a component of mitochondrial complex IV.
CLINICAL DISCUSSION
In the medical field, inherited metabolic disorders can be complex to diagnose due to overlapping symptoms with other conditions. Mitochondria's oxidative phosphorylation system, including the COX enzyme complex, plays a crucial role in energy production. Mitochondrial disorders, including COX deficiency, can present at various stages of life with diverse symptoms. Treatment options focus on supportive care and potential benefits from supplements like coenzyme-Q10 and small-molecule therapies targeting mitochondrial function. Identifying genetic mutations is key for advancing treatments in this area.
CONCLUSION
This report presents a unique case of developmental regression and muscle weakness in a paediatric patient, which can be attributed to a rare occurrence of type 3 nuclear mitochondrial complex IV deficiency.
PubMed: 38846886
DOI: 10.1097/MS9.0000000000002096 -
Frontiers in Neuroscience 2024Deep-learning-based brain age estimation using magnetic resonance imaging data has been proposed to identify abnormalities in brain development and the risk of adverse...
BACKGROUND
Deep-learning-based brain age estimation using magnetic resonance imaging data has been proposed to identify abnormalities in brain development and the risk of adverse developmental outcomes in the fetal brain. Although saliency and attention activation maps have been used to understand the contribution of different brain regions in determining brain age, there has been no attempt to explain the influence of shape-related cortical structural features on the variance of predicted fetal brain age.
METHODS
We examined the association between the predicted brain age difference (PAD: predicted brain age-chronological age) from our convolution neural networks-based model and global and regional cortical structural measures, such as cortical volume, surface area, curvature, gyrification index, and folding depth, using regression analysis.
RESULTS
Our results showed that global brain volume and surface area were positively correlated with PAD. Additionally, higher cortical surface curvature and folding depth led to a significant increase in PAD in specific regions, including the perisylvian areas, where dramatic agerelated changes in folding structures were observed in the late second trimester. Furthermore, PAD decreased with disorganized sulcal area patterns, suggesting that the interrelated arrangement and areal patterning of the sulcal folds also significantly affected the prediction of fetal brain age.
CONCLUSION
These results allow us to better understand the variance in deep learning-based fetal brain age and provide insight into the mechanism of the fetal brain age prediction model.
PubMed: 38846713
DOI: 10.3389/fnins.2024.1411334 -
Sleep Science (Sao Paulo, Brazil) Jun 2024Insomnia is highly prevalent among individuals with Attention-Deficit/Hyperactivity Disorder (ADHD). However, the biological mechanisms shared between both...
Insomnia is highly prevalent among individuals with Attention-Deficit/Hyperactivity Disorder (ADHD). However, the biological mechanisms shared between both conditions is still elusive. We aimed to investigate whether insomnia's genomic component is able to predict ADHD in childhood and adolescence. A Brazilian sample of 259 ADHD probands and their biological parents were included in the study. Their genomic DNA genotypes were used to construct the polygenic risk score for insomnia (Insomnia PRS), using the largest GWAS summary statistics as a discovery sample. The association was tested using logistic regression, under a case-pseudocontrol design. Insomnia PRS was nominally associated with ADHD (OR = 1.228, = 0.022), showing that the alleles that increase the risk for insomnia also increase the risk for ADHD. Our results suggest that genetic factors associated with insomnia may play a role in the ADHD genetic etiology, with both phenotypes likely to have a shared genetic mechanism.
PubMed: 38846582
DOI: 10.1055/s-0043-1777787