Treatment Strategies Research Articles

Multiomics Profiling Distinguishes Sebaceous Carcinoma from Benign Sebaceous Neoplasms and Provides Insight into the Genetic Evolution of Sebaceous Carcinogenesis.

Sebaceous carcinoma is the third most common nonkeratinocyte skin cancer in the United States with 1,000 cases per year. The clinicopathologic features of sebaceous carcinoma and benign sebaceous neoplasms (adenomas, sebaceomas) can overlap, highlighting the need for molecular biomarkers to improve classification. This study describes the genomic and transcriptomic landscape of sebaceous neoplasms in order to understand tumor etiology and biomarkers relevant for diagnosis and treatment. We performed whole-genome sequencing (WGS) and whole-transcriptome sequencing (WTS) of sebaceous neoplasms from six academic and two federal healthcare facilities in the United States diagnosed between January 1, 1999, and December 31, 2021. We evaluated 98 sebaceous neoplasms: 64 tumors (32 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 25 carcinomas) had sufficient material for WGS, 96 tumors (42 adenomas, 11 sebaceomas, 8 atypical sebaceous neoplasms, 35 carcinomas) had sufficient material for WTS, and 62 tumors (31 adenomas, 2 sebaceomas, 5 atypical sebaceous neoplasms, 24 carcinomas) had sufficient material for combined WGS and WTS. Overall, we found decreased cholesterol biosynthesis and increased TP53 mutations, copy number gains (chromosome 6, 8q, and/or 18), and tumor mutation burden-high (>10 mutations/MB) in carcinomas compared to adenomas. Although diminished compared to adenomas, most carcinomas still had higher cholesterol biosynthesis than nonmalignant skin. Multiomics profiling also supported a precancerous model of tumor evolution with sebaceomas and atypical sebaceous neoplasms being likely intermediate lesions. The study findings highlight key diagnostic biomarkers for sebaceous carcinoma and suggest that immunotherapy and modulation of cholesterol biosynthesis could be effective treatment strategies.

A Closer Look at Antipsychotic Adverse Effects: Investigating Anticholinergic Toxidrome Induced by Olanzapine Overdose

Background and Aims: Antipsychotic drugs are critical in managing psychosis but they also carry risks when misused, leading to toxicity. Case Presentation: A patient overdosed on olanzapine, resulting in anticholinergic toxidrome with symptoms like tachycardia and altered mental status. Immediate recognition and management of antipsychotic toxicity-induced toxidromes in emergency settings are crucial. Treatment strategy includes maintaining airway, breathing and circulation along with decontamination. There is no specific antidote. Conclusion: This case underscores the need for emergency physicians to remain vigilant and proactive in identifying and addressing such toxicity by identification of toxidromes to prevent complications and missed diagnosis in emergency department.

Comprehensive analysis of clinicopathological characteristics in oral squamous cell carcinoma arising from oral submucous fibrosis: a retrospective study

BackgroundOral squamous cell carcinoma arising from oral submucous fibrosis is recognized as a clinicopathologically distinct disease. This study aims to summarize and compare the population and clinicopathologic characteristics of OSCC-OSF with other OSCC in Hunan Province, China. The objective is to formulate treatment strategies more in line with regional characteristics.MethodsA retrospective review of OSCC cases recruited from the Second Xiangya Hospital from 2010 to 2020 was conducted. A total of 1,413 OSCC patients were selected, including 481 patients with OSCC-OSF and 932 were other OSCC. Population characteristics, risk factors and clinicopathological manifestations were explored in OSCC-OSF and other OSCC, as well as thinprep cytologic test and DNA quantification.ResultsWe found that OSCC-OSF patients were younger than those with other OSCC. Both types of disease were predominantly observed in males compared to females. Tumor biopsy analysis indicated that tumor cells within OSCC-OSF patients were more likely to be well differentiated and showed a higher frequency of lymph node metastases. Clinicopathological factors, such as the chewing betel nuts habit and smoking, were more prevalent in OSCC-OSF patients in contrast to other OSCC. DNA quantification revealed that the number of DNA aneuploid cells was higher in OSCC-OSF compared to other OSCCs.ConclusionIn this study, OSCC-OSF is considered a clinicopathologically distinct disease. Compared with other OSCC, OSCC-OSF patients have a higher incidence of nodal metastases, an early clinical TNM stage, and a lower three-year survival rate. Therefore, early diagnosis and treatment are crucial to improving the prognosis of OSCC-OSF.

Harmonizing Insights: LR-FFT Feature Extraction for Alzheimer’s and Autism Spectrum Disorder Detection in EEG Signals

Alzheimer’s Disease (AD) and Autism Spectrum Disorder (ASD) represent two distinct but equally impactful challenges in the field of neurology and cognitive health. AD is a degenerative neurological condition characterized by its progressive nature, typically affecting individuals in later stages of life. The hallmark features include cognitive impairment, mem- ory deterioration, and alterations in behavior. In contrast, ASD is a developmental disorder typically diagnosed in childhood, marked by difficulties in social interaction, communication, and repetitive behaviors. This paper explores the potential of the time-frequency feature extraction model known as the Left-Right Fast Fourier Transform (LR-FFT) in the context of these two disorders. While AD and ASD differ significantly in their onset, presentation, and demographic affected, both necessitate early and accurate diagnosis to enable timely intervention and tailored treatment strategies. Our research yields promising results, with classification accuracies reaching 88.26% for AD and 99.86% for ASD, demonstrating the LR-FFT’s potential to enhance diagnostic accuracy. By contributing to improved differentiation between these complex neurological conditions, this work aims to advance our understanding and management of AD and ASD, ultimately benefiting patients, their families, and healthcare practitioners.

Exogenous interactome analysis of bovine viral diarrhea virus-host using network based-approach and identification of hub genes and important pathways involved in virus pathogenesis

Bovine viral diarrhea (BVD) is one of the most important diseases in livestock, caused by BVD virus (BVDV). During the pathogenesis of the virus, many interactions occur between host and viral proteins. Studying these interactions can help better understand the pathogenesis of the virus, identify putative functional proteins, and find new treatment and prevention strategies. To this aim, a BVDV-host protein-protein interaction (PPI) network map was constructed using Cytoscape and analyzed with cytoHubba, Kyoto Encyclopedia of Genes and Genomics (KEGG), Gene Ontology (GO), and Protein Analysis Through Evolutionary Relationships (PANTHER). Npro with 125 connections had the greatest number of interactions with host proteins. CD46, EEF-2, and TXN genes were detected as hub genes using different ranking algorithms in cytoHubba. BVDV interactions with its host mainly focus on targeting translation, protein synthesis, and cellular metabolism pathways. Different classes of proteins including translational proteins, nucleic acid metabolism proteins, metabolite interconversion enzymes, and protein-modifying enzymes are affected by BVDV. These findings improve our understanding of the effects of the virus on the cell. Hub genes and key pathways identified in the present study can serve as targets for novel BVDV prevention or treatment strategies.

Are 19del and L858R really different disease entities?

Clinicians have recognized the similarities and differences between the two subtypes of common epidermal growth factor receptor (EGFR) mutations, but actual treatment strategies have not yet changed. The L858R mutation can be understood by considering the pharmacological conformational plasticity of the receptor protein and the presence of other co-occurring mutations, whether subtypes of EGFR or non-EGFR mutations and differences in downstream signaling pathways. As long as we know that molecular differences lead to biological differences, it is a challenge for all of us that our treatment strategies must change.

Current Insights into Molecular Mechanisms and Potential Biomarkers for Treating Radiation-Induced Liver Damage

Highly conformal delivery of radiation therapy (RT) has revolutionized the treatment landscape for primary and metastatic liver cancers, yet concerns persist regarding radiation-induced liver disease (RILD). Despite advancements, RILD remains a major dose-limiting factor due to the potential damage to normal liver tissues by therapeutic radiation. The toxicity to normal liver tissues is associated with a multitude of physiological and pathological consequences. RILD unfolds as multifaceted processes, intricately linking various responses, such as DNA damage, oxidative stress, inflammation, cellular senescence, fibrosis, and immune reactions, through multiple signaling pathways. The DNA damage caused by ionizing radiation (IR) is a major contributor to the pathogenesis of RILD. Moreover, current treatment options for RILD are limited, with no established biomarker for early detection. RILD diagnosis often occurs at advanced stages, highlighting the critical need for early biomarkers to adjust treatment strategies and prevent liver failure. This review provides an outline of the diverse molecular and cellular mechanisms responsible for the development of RILD and points out all of the available biomarkers for early detection with the aim of helping clinicians decide on advance treatment strategies from a single literature recourse.

Helicobacter pylori induces GBA1 demethylation to inhibit ferroptosis in gastric cancer.

This research investigates potential therapeutic targets for gastric cancer, focusing on ferroptosis-related genes. Gastric cancer is known for its lower survival rates, necessitating new treatment strategies. This study employed Mendelian randomization to identify ferroptosis-related genes and methylation sites in gastric cancer, examining correlations between Helicobacter pylori infection, GBA1 gene expression, and promoter methylation with single-cell datasets and the TCGA-STAD database. We used Helicobacter pylori-infected gastric cancer cell models and used next-generation sequencing to monitor methylation changes pre- and post-infection. GBA1 expression levels were assessed via qRT-PCR and Western blot both before and after infection. The effect of Helicobacter pylori on GC cell proliferation was analyzed using CCK-8 and EdU assays after knocking down the GBA1 gene. The association between Helicobacter pylori infection and ferroptosis, including its reversibility after GBA1 knockdown, was evaluated using FerrOrange, GSH, MDA, and C11-BODIPY assays. Mass spectrometry measured the impact of Helicobacter pylori and GBA1 knockdown on lipid metabolism. An in vivo subcutaneous tumor-bearing model was also established to confirm these findings. Mendelian randomization analysis revealed that high GBA1 expression and reduced methylation levels of its promoter are risk factors for gastric cancer. Single-cell sequencing and TCGA-STAD datasets indicated a positive correlation between Helicobacter pylori infection and GBA1 expression, with a concurrent negative correlation between GBA1 promoter methylation and GBA1 expression. In gastric cancer cell lines, Helicobacter pylori infection was observed to enhance GBA1 expression and decrease methylation levels at its promoter. Additionally, Helicobacter pylori promoted GC cell proliferation, an effect mitigated by knocking down GBA1. Infection also reduced lipid peroxidation, increased glutathione levels, and impeded ferroptosis in GC cells; however, these effects were reversed following GBA1 knockdown. Changes in sphingolipid metabolism induced by I were detected in GC cell lines. In vivo experiments using a subcutaneous tumor-bearing model demonstrated that Helicobacter pylori infection fosters tumorigenesis in GC cells. Our study demonstrates that Helicobacter pylori infection triggers demethylation and upregulation of GBA1, subsequently inhibiting ferroptosis in gastric cancer cells. These findings suggest that targeting the GBA1 pathway may offer a novel therapeutic approach for managing gastric cancer.

Trem2-expressing multinucleated giant macrophages are a biomarker of good prognosis in head and neck squamous cell carcinoma.

Patients with head and neck squamous cell carcinomas (HNSCC) often have poor outcomes due to suboptimal risk-management and treatment strategies; yet integrating novel prognostic biomarkers into clinical practice is challenging. Here, we report the presence of multinucleated giant cells (MGC) - a type of macrophages - in tumors from patients with HNSCC, which are associated with a favorable prognosis in treatment-naive and preoperative-chemotherapy-treated patients. Importantly, MGC density increased in tumors following preoperative therapy, suggesting a role of these cells in the anti-tumoral response. To enable clinical translation of MGC density as a prognostic marker, we developed a deep-learning model to automate its quantification on routinely stained pathological whole slide images. Finally, we used spatial transcriptomic and proteomic approaches to describe the MGC-related tumor microenvironment and observed an increase in central memory CD4 T cells. We defined an MGC-specific signature resembling to TREM2-expressing mononuclear tumor associated macrophages, which co-localized in keratin tumor niches.

Detection methods and prognosis implications of measurable residual disease in acute myeloid leukemia.

Measurable residual disease (MRD) in acute myeloid leukemia (AML) refers to the quantity of residual leukemic cells in a patient after treatment.According to the latest agreements, MRD in AML offering essential prognostic insights. However, there is ongoing debate regarding MRD-based monitoring and treatment strategies. There are multiple platforms for detecting MRD, each varying in sensitivity and suitability for different patients. MRD not only predicts treatment outcomes but also serves as an indicator of treatment effectiveness and a prognostic biomarker. In AML, most retrospective studies indicate that patients who are MRD-positive or show increasing MRD levels at specific time points during remission have significantly higher risks of relapse and mortality compared to MRD-negative patients. Although achieving MRD-negative status can improve patient prognosis, the possibility of relapse remains. Despite the correlation between MRD and clinical outcomes, MRD assessment methods are not yet standardized, leading to discrepancies in results across different techniques. To provide reliable MRD results, it is essential to optimize and standardize MRD detection methods. Methods for assessing MRD include multiparameter flow cytometry (MFC) and molecular assays, chosen based on disease characteristics. This review focuses on currently available MRD detection methods and discusses how the prognostic value of MRD test results informs personalized treatment strategies for AML patients.

Vascular cognitive impairment and dementia: Mechanisms, treatment, and future directions.

Worldwide, around 50 million people live with dementia, and this number is projected to triple by 2050. It has been estimated that 20% of all dementia cases have a predominant cerebrovascular pathology, while perhaps another 20% of vascular diseases contribute to a mixed dementia picture. Therefore, the vascular contribution to dementia affects 20 million people currently and will increase markedly in the next few decades, particularly in lower- and middle-income countries.In this review, we discuss the mechanisms of vascular cognitive impairment (VCI) and review management. VCI refers to the spectrum of cerebrovascular pathologies that contribute to any degree of cognitive impairment, ranging from subjective cognitive decline, to mild cognitive impairment, to dementia. While acute cognitive decline occurring soon after a stroke is the most recognized form of VCI, chronic cerebrovascular disease, in particular cerebral small-vessel disease, can cause insidious cognitive decline in the absence of stroke. Moreover, cerebrovascular disease not only commonly co-occurs with Alzheimer's disease (AD) and increases the probability that AD pathology will result in clinical dementia, but may also contribute etiologically to the development of AD pathologies.Despite its enormous health and economic impact, VCI has been a neglected research area, with few adequately powered trials of therapies, resulting in few proven treatments. Current management of VCI emphasizes prevention and treatment of stroke and vascular risk factors, with most evidence for intensive hypertension control. Reperfusion therapies in acute stroke may attenuate the risk of VCI. Associated behavioral symptoms such as apathy and poststroke emotionalism are common. We also highlight novel treatment strategies that will hopefully lead to new disease course-modifying therapies. Finally, we highlight the importance of including cognitive endpoints in large cardiovascular prevention trials and the need for an increased research focus and funding for this important area.

Dynamics of hemostasis system parameters in assessing the risk of complications in the patients with acute myocardial infarction receiving antiplatelet therapy

Background. Current treatment of patients with myocardial infarction is based on the strategy of early invasive coronary intervention in combination with dual antiplatelet therapy - with acetylsalicylic acid and a P2Y12 blocker of platelet adenosine diphosphate receptors. In patients with thrombosis of the infarct-related artery, the phenomenon of “slow/ no reflow” (slowing of blood flow due to distal embolization of the artery), inhibitors of glycoprotein IIb/IIIa platelet receptors are administered as additional disaggregant therapy. In patients undergoing standard antiplatelet therapy in combination with glycoprotein IIb/IIIa inhibitors, there is a risk of hemorrhagic complications, therefore, monitoring of hemostasis parameters is necessary. Currently, there are no standard approaches to monitor the antiplatelet therapy.Objective. To study the dynamics of hemostatic system parameters in patients with acute myocardial infarction during antiplatelet therapy.Material and methods. We assessed platelet aggregation with 10 µmol of adenosine phosphate as an inducer in patients with ST-segment elevation myocardial infarction with different options of standard antiplatelet therapy in combination with GPIIb/IIIa inhibitors. Group 1 included 20 patients on dual antiplatelet therapy (clopidogrel 75 mg + acetylsalicylic acid 100 mg) + GPIIb/IIIa inhibitor (tirofiban). Group 2 included 15 patients on dual antiplatelet therapy (ticagrelor 180 mg + acetylsalicylic acid 100 mg) + GPIIb/IIIa inhibitor.Results. While on antiplatelet therapy the patients in both groups 1 and 2 demonstrated a decrease in platelet aggregation ability under the impact of adenosine phosphate, relative to the norm: 38 (21;43) % and 14 (11;15) %, respectively, the norm being 79 (73;84) % (p<0.05). Meantime, no thrombotic events in the form of stent thrombosis were noted, which indicated antiplatelet therapy efficacy. In an intragroup comparison, the decrease in the platelet aggregation ability was most pronounced in group 2 (p<0.05). By the 7th day of myocardial infarction, the platelet aggregation had continued to decrease to 26 (17;43) % in group 1, to 10 (7;11) % in group 2. The most pronounced effect of antiplatelet therapy was observed in group 2 (p<0.05), which was manifested by a statistically significant decrease in platelet aggregation ability under the impact of 10 µmol of adenosine phosphate.Conclusions. While studying the hemostasis system changes over time in patients with myocardial infarction receiving antiplatelet therapy, we have found that making the platelet aggregation ability assessment with 10 µmol of adenosine phosphate as an inducer is possible to identify the effect of medications. However, further studies including larger patient groups are needed to determine the target values of platelet aggregation with 10 µmol of adenosine phosphate and assess the therapy efficacy.

Deciphering Internal Regulatory Patterns within the p53 Core Tetramer: Insights from Community Network Analysis.

Gene therapy is one of the most effective strategies for cancer treatment. The p53 protein, commonly known as the "guardian of the genome", plays a critical role in gene activation and tumor suppression. Tetramerization of the p53 core domain is an essential allosteric process that supports its suppression functions. This letter presents a framework to analyze the structure, function, and dynamic connectivity of the p53 tetramer, using community network analysis based on all-atom molecular dynamics simulations. The communities within the p53 monomer exhibit distinct functional roles, while interactions between molecules establish a symmetrical network structure. We identified direct evidence of single, double, and multiple pathway regulations within the p53 tetramer and crucial residue pairs involved in these connections. Our study provides a comprehensive framework to understand the community network of the p53 tetramer, offering new insights into the stable formation of the p53 core tetramer.

A strategy for treatment of low-grade ore: Efficient separation and purification of iron

The gradual depletion of mineral resources has led to the emergence of a new engineering challenge in the field of mineral processing: the effective treatment of low-grade ores. In this study, the low-grade titanium ore leaching solution was employed as the raw material. The extraction ability of a series of hydroxyl extractants for the most common metal iron in minerals was investigated. As a result, a new high-quality processing system for low-grade ore with branched-chain octanol as the core component was constructed. In the treatment of mineral leaching solution, branched-chain octanol has high selectivity and large capacity (111.7 g/L) for iron. It was capable of efficiently removing a significant quantity of iron ions in low-grade ores that were not anticipated to be present. By employing quantum chemical (QC) methodologies, the mechanism for the high selectivity of branched-chain octanol for Fe(Ⅲ) has been elucidated by analyzing the frontier molecular orbital (FMO) energy of acid salts of common metals in minerals. Combined with spectral analysis and slope method, the structure of the extracted complex was confirmed to be [n-R8-OH]2·H·FeCl4. On the basis of system optimization, a three-stage countercurrent extraction and three-stage countercurrent stripping was employed to remove all the Fe(Ⅲ) in the mineral leaching solution. And after detecting, the purity of the obtained Fe(III) solution was greater than 99.5 %. In the treatment of low-grade minerals, especially those containing key metals, the branched-chain octanol extraction system demonstrates high selectivity and reliability, which is a effective means to improve the quality of mineral leaching solution.

Deconstructing paradigms: the contribution of women to science

In recent times, academic research has focused on how the concept of the "social" permeates notions of science and knowledge, in the methodologies employed, the results discussed and the relationship between theory and practice. Against this backdrop, feminist epistemology has gained prominence, criticizing the traditional model of science and advocating an interdisciplinary methodology that incorporates individuals from different fields into dialogues, contextualizing knowledge in context and examining the influence of gender on the generation of knowledge. This theoretical article seeks to investigate the link between female representation and knowledge creation, shedding light on the persistent gender gap in academic institutions and research establishments. Furthermore, it aims to contemplate how a more feminist perspective can impact research efforts and social intervention strategies, recognizing the value of women's perspectives in the theoretical discourse on social and gender equality. By highlighting the importance of including different perspectives in science, the article emphasizes the need to promote an inclusive and equitable approach to human progress.

Assessing personal PM2.5 exposure using a novel neck-mounted monitoring device in rural Rwanda

There is growing global concern regarding the detrimental health impacts of PM2.5 emissions from traditional stoves that utilize polluting fuels. Conventional methods for estimating daily personal PM2.5 exposure involve personal air samplers and measuring devices placed in a waist pouch, but these instruments are cumbersome and inconvenient. To address this issue, we developed a novel neck-mounted PM2.5 monitoring device (Pocket PM2.5 Logger) that is compact, lightweight, and can operate continuously for 1 week without recharging. Twelve participants who utilized charcoal, firewood, or propane gas for cooking in rural regions of Rwanda wore the Pocket PM2.5 Logger continuously for 1 week, and time-series variations in personal PM2.5 exposure were recorded at 5-min intervals. Individual daily exposure concentrations during cooking differed significantly among users of the different fuel types, and PM2.5 exposure was at least 2.6 and 3.4 times higher for charcoal and firewood users, respectively, than for propane gas users. Therefore, switching from biomass fuels to propane gas would reduce daily individual exposure by at least one-third. An analysis of cooking times showed that the median cooking time per meal was 30 min; however, half the participants cooked for 1.5 h per meal, and one-third cooked for over 4.5 h per meal. Reducing these extremely long cooking times would reduce exposure with all fuel types. The Pocket PM2.5 Logger facilitates the comprehensive assessment of personal PM2.5 exposure dynamics and is beneficial for the development of intervention strategies targeting household air pollution.

Deciphering the Protective Role of HIF-1α Downregulation on HIBD through the MALAT1/miR-140-5p/TGFBR1/NF-κB Signaling Pathway.

Hypoxic-ischemic brain damage (HIBD) in neonates is a substantial cause of mortality and neurodevelopmental impairment, with the exact molecular mechanisms still being elucidated. The involvement of HIF-1α, MALAT1, miR-140-5p, TGFBR1, and the NF-κB signaling pathway in such injury cascades is of increasing research interest due to their pivotal roles in cellular and pathological processes. This study aimed to explore how HIF-1α regulates the MALAT1/miR-140-5p/TGFBR1/NF-κB signaling axis to participate in the molecular mechanisms of HIBD in neonatal rats. Utilizing bioinformatic analyses and a suite of experimental approaches, the study delineated interactions and regulatory relationships among the molecules. Knockdown of HIF-1α was shown to mitigate brain tissue damage in a neonatal HIBD rat model through the MALAT1/miR-140-5p/TGFBR1/NF-κB signaling axis, revealing a protective effect achieved by inhibiting hippocampal neuron apoptosis and potentially guiding the way toward therapeutic interventions in HIBD. This study implicates the HIF-1α mediated regulation of the MALAT1/miR-140-5p/TGFBR1/NF-κB signaling axis in the pathological development of HIBD, offering insights into novel potential interventional strategies.

Coping With Interstitial Cystitis/Bladder Pain Syndrome.

Compensatory coping, or maladaptive alterations in behavior with the intention of preventing or managing symptoms, is increasingly being explored as a key factor in how people respond to bladder conditions. Preliminary investigations have identified relations between coping behaviors and psychological distress in urologic conditions, including interstitial cystitis/bladder pain syndrome (IC/BPS). However, previous explorations of coping have not accounted for heterogeneity in coping behaviors or addressed the likelihood that some coping behaviors may be more adaptive than others. This study sought to examine how two specific types of coping behaviors, primary control coping and disengaged coping, are related to distress and symptoms in IC/BPS, and to explore the potential role of pain phenotype in this relationship. A secondary data analysis was conducted with a large community data set (N = 677 women with IC/BPS) and employed descriptive and inferential statistics to characterize coping patterns and explore novel predictors of distress. Results indicated that almost all participants engaged in at least one compensatory coping behavior within the last week. Both types of coping behaviors correlated with psychological symptoms, and when controlling for relevant clinical variables (i.e., age and severity of urinary symptoms), disengaged coping behaviors were significantly associated with psychological distress. Further, the addition of pain phenotype to multiple regression models resulted in a more effective predictive model when considering the relation between coping behaviors and depression. By investigating more deeply the relationship between coping and distress, understanding of potential risk factors and mechanisms is increased, offering valuable insights for intervention strategies for IC/BPS patients.

Analysis of high school students' awareness of the psychosocial effects of internet addiction

The present study aims to determine secondary school students' awareness of the psychosocial consequences of Internet addiction and to investigate differences in the level of awareness based on students' sociodemographic characteristics (Sex, grade level, number of family members, parent's marital status, education and occupation of the parents, and the family's monthly income). A cross-sectional descriptive study was conducted from December 10, 2022, to December 30, 2023. The sample included (765) secondary school students were (375 males and 390 females). The population was composed of 10th and 12th grade students withdrawn from ten high schools located in the Babylon Governorate in Iraq. The results of the study revealed a variation in participants’ awareness of their knowledge of the psychosocial effects of Internet addiction, as more than half of them (57.5%) recorded a fair level of awareness, while (40.1%) of them recorded a good level, and only (2.4%) exhibited a waek level of awareness. Furthermore, the data revealed notable gender and grade-level differences in psychosocial awareness. Females exhibited a higher level of awareness (51.5%) compared to males. Additionally, students in the 10-grade showed a relatively higher rate of good psychosocial awareness (44.9%). It is necessary to understand the demographic factors in shaping awareness of the effects of Internet addiction, which helps in developing targeted intervention strategies to enhance awareness and improve students' control behaviors.

Proteomic Mendelian randomization to identify protein biomarkers of telomere length

Shortening of telomere length (TL) is correlated with many age-related disorders and is a hallmark of biological aging. This study used proteome-wide Mendelian randomization to identify the protein biomarkers associated with telomere length. Protein quantitative trait loci (pQTL) were derived from two studies, the deCODE Health study (4907 plasma proteins) and the UK Biobank Pharma Proteomics Project (2923 plasma proteins). Summary data from genome-wide association studies (GWAS) for TL were obtained from the UK Biobank (472,174 cases) and GWAS Catalog (418,401 cases). The association between proteins and TL was further assessed using colocalization and summary data-based Mendelian randomization (SMR) analyses. The protein–protein network, druggability assessment, and phenome-wide MR were used to further evaluate the potential biological effects, druggability, and safety of the target proteins. Proteome-wide MR analysis identified 22 plasma proteins that were causally associated with telomere length. Five of these proteins (APOE, SPRED2, MAX, RALY, and PSMB1) had the highest evidence of association with TL and should be prioritized. This study revealed telomere length-related protein biomarkers, providing new insights into the development of new treatment targets for chronic diseases and anti-aging intervention strategies.