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Journal of Medical Internet Research May 2024Due to their accessibility and anonymity, web-based counseling services are expanding at an unprecedented rate. One of the most prominent challenges such services face... (Observational Study)
Observational Study
BACKGROUND
Due to their accessibility and anonymity, web-based counseling services are expanding at an unprecedented rate. One of the most prominent challenges such services face is repeated users, who represent a small fraction of total users but consume significant resources by continually returning to the system and reiterating the same narrative and issues. A deeper understanding of repeated users and tailoring interventions may help improve service efficiency and effectiveness. Previous studies on repeated users were mainly on telephone counseling, and the classification of repeated users tended to be arbitrary and failed to capture the heterogeneity in this group of users.
OBJECTIVE
In this study, we aimed to develop a systematic method to profile repeated users and to understand what drives their use of the service. By doing so, we aimed to provide insight and practical implications that can inform the provision of service catering to different types of users and improve service effectiveness.
METHODS
We extracted session data from 29,400 users from a free 24/7 web-based counseling service from 2018 to 2021. To systematically investigate the heterogeneity of repeated users, hierarchical clustering was used to classify the users based on 3 indicators of service use behaviors, including the duration of their user journey, use frequency, and intensity. We then compared the psychological profile of the identified subgroups including their suicide risks and primary concerns to gain insights into the factors driving their patterns of service use.
RESULTS
Three clusters of repeated users with clear psychological profiles were detected: episodic, intermittent, and persistent-intensive users. Generally, compared with one-time users, repeated users showed higher suicide risks and more complicated backgrounds, including more severe presenting issues such as suicide or self-harm, bullying, and addictive behaviors. Higher frequency and intensity of service use were also associated with elevated suicide risk levels and a higher proportion of users citing mental disorders as their primary concerns.
CONCLUSIONS
This study presents a systematic method of identifying and classifying repeated users in web-based counseling services. The proposed bottom-up clustering method identified 3 subgroups of repeated users with distinct service behaviors and psychological profiles. The findings can facilitate frontline personnel in delivering more efficient interventions and the proposed method can also be meaningful to a wider range of services in improving service provision, resource allocation, and service effectiveness.
Topics: Humans; Longitudinal Studies; Cluster Analysis; Female; Adult; Male; Counseling; Middle Aged; Text Messaging; Young Adult
PubMed: 38815258
DOI: 10.2196/50976 -
PLoS Genetics May 2024Whether single-cell RNA-sequencing (scRNA-seq) captures the same biological information as single-nucleus RNA-sequencing (snRNA-seq) remains uncertain and likely to be...
Whether single-cell RNA-sequencing (scRNA-seq) captures the same biological information as single-nucleus RNA-sequencing (snRNA-seq) remains uncertain and likely to be context-dependent. Herein, a head-to-head comparison was performed in matched normal-adenocarcinoma human lung samples to assess biological insights derived from scRNA-seq versus snRNA-seq and better understand the cellular transition that occurs from normal to tumoral tissue. Here, the transcriptome of 160,621 cells/nuclei was obtained. In non-tumor lung, cell type proportions varied widely between scRNA-seq and snRNA-seq with a predominance of immune cells in the former (81.5%) and epithelial cells (69.9%) in the later. Similar results were observed in adenocarcinomas, in addition to an overall increase in cell type heterogeneity and a greater prevalence of copy number variants in cells of epithelial origin, which suggests malignant assignment. The cell type transition that occurs from normal lung tissue to adenocarcinoma was not always concordant whether cells or nuclei were examined. As expected, large differential expression of the whole-cell and nuclear transcriptome was observed, but cell-type specific changes of paired normal and tumor lung samples revealed a set of common genes in the cells and nuclei involved in cancer-related pathways. In addition, we showed that the ligand-receptor interactome landscape of lung adenocarcinoma was largely different whether cells or nuclei were evaluated. Immune cell depletion in fresh specimens partly mitigated the difference in cell type composition observed between cells and nuclei. However, the extra manipulations affected cell viability and amplified the transcriptional signatures associated with stress responses. In conclusion, research applications focussing on mapping the immune landscape of lung adenocarcinoma benefit from scRNA-seq in fresh samples, whereas snRNA-seq of frozen samples provide a low-cost alternative to profile more epithelial and cancer cells, and yield cell type proportions that more closely match tissue content.
PubMed: 38814983
DOI: 10.1371/journal.pgen.1011301 -
PloS One 2024To explore the causal relationship between ulcerative colitis (UC) and male infertility using Mendelian randomization method with single nucleotide polymorphism (SNP) as...
AIMS
To explore the causal relationship between ulcerative colitis (UC) and male infertility using Mendelian randomization method with single nucleotide polymorphism (SNP) as the instrumental variables.
METHODS
Genetic loci closely associated with UC were extracted as instrumental variables and male infertility was the outcome variable in pooled data from the gene-wide association study (GWAS),which was derived from European ethnic groups. The UC data(ebi-a-GCST003045) contained a total sample size of 27432 individuals and 110944 SNPs, and the male infertility data(finn-b-N14_MALEINFERT) contained a total sample size of 73479 individuals and 16377329 SNPs. The SNPs highly correlated with UC were screened from ebi-a-GCST003045(P<5×10-8 as the screening condition, the linkage disequilibrium coefficient was 0.001,and the width of the linkage disequilibrium area was 10000 kb).SNPs related to male infertility from finn-b-N14_MALEINFERT (the minimum r2>0.8,replacing the missing SNPs with SNPs with high linkage, and deleting SNPs without substitution sites) were extracted. MR analysis was performed using MR-Egger regression, the weighted median and the inverse-variance weighted (IVW) respectively, and the causal relationship between UC and male infertility was evaluated by OR and 95% CI, and the Egger-intercept method was used to test for horizontal multiplicity, and the sensitivity analysis was performed using "leave-one-out method". Finally, we used Bayesian Weighted Mendelian Randomization (BWMR) approach to test the results of MR study.
RESULTS
A total of 86 SNPs were included as IVs, with OR and 95% CI of 1.095(0.820~1.462)、1.059(0.899~1.248)、1.125(1.002~1.264) for MR-Egger, the weighted median and IVW results respectively, and P value of less than 0.05 for IVW, indicating that a causal relationship between UC and male infertility was causally related. The results of MR analysis combined with BWMR analysis also showed positive genetic causal relationship between UC and male infertility.MR-Egger regression showed an intercept of -2.21×10-3 with a standard error of 0.006 and P = 0.751, there was no horizontal pleiotropy for the IVs of exposure factors. Heterogeneity tests showed no heterogeneity and the results of the "leave-one-out" sensitivity analysis were stable.
CONCLUSION
There is a causal association between UC and male infertility, which increases the risk of developing male infertility.
Topics: Humans; Male; Colitis, Ulcerative; Polymorphism, Single Nucleotide; Mendelian Randomization Analysis; Infertility, Male; Genome-Wide Association Study; Linkage Disequilibrium; Genetic Predisposition to Disease
PubMed: 38814907
DOI: 10.1371/journal.pone.0303827 -
PLoS Biology May 2024Glioblastoma, the most aggressive and prevalent form of primary brain tumor, is characterized by rapid growth, diffuse infiltration, and resistance to therapies.... (Review)
Review
Glioblastoma, the most aggressive and prevalent form of primary brain tumor, is characterized by rapid growth, diffuse infiltration, and resistance to therapies. Intrinsic heterogeneity and cellular plasticity contribute to its rapid progression under therapy; therefore, there is a need to fully understand these tumors at a single-cell level. Over the past decade, single-cell transcriptomics has enabled the molecular characterization of individual cells within glioblastomas, providing previously unattainable insights into the genetic and molecular features that drive tumorigenesis, disease progression, and therapy resistance. However, despite advances in single-cell technologies, challenges such as high costs, complex data analysis and interpretation, and difficulties in translating findings into clinical practice persist. As single-cell technologies are developed further, more insights into the cellular and molecular heterogeneity of glioblastomas are expected, which will help guide the development of personalized and effective therapies, thereby improving prognosis and quality of life for patients.
Topics: Humans; Glioblastoma; Single-Cell Analysis; Brain Neoplasms; Transcriptome; Animals
PubMed: 38814900
DOI: 10.1371/journal.pbio.3002640 -
Blood Transfusion = Trasfusione Del... May 2024Elderly populations face an increased risk of anemia, leading to elevated transfusion requirements during surgery, especially major orthopedic procedures. Anemia itself... (Review)
Review
BACKGROUND
Elderly populations face an increased risk of anemia, leading to elevated transfusion requirements during surgery, especially major orthopedic procedures. Anemia itself increases the risk of thromboembolic events, thus compounding complications in elderly individuals. Polypharmacy and the prevalent use of oral anticoagulants (OAC), particularly for atrial fibrillation, contribute to bleeding risks in this population. Data available in the literature on the peri-operative management of anemia in patients taking OAC is limited and often heterogeneous.
MATERIALS AND METHODS
This narrative case-based review focuses on the peri-operative management of elderly patients on OAC undergoing major orthopedic surgery. PubMed/Medline was used to search for relevant literature.
RESULTS
With reference to two cases, we critically evaluate the literature, and focus on risk factors, and preventive and therapeutic strategies as fundamental tools to reduce bleeding and correct anemia as soon as possible in elderly patients undergoing major orthopedic surgery.
DISCUSSION
Peri-operative management of these patients, especially those on OAC, requires a balanced approach considering bleeding and thrombotic risks. Intravenous iron therapy and tranexamic acid emerge as valuable strategies in minimizing transfusion requirements and optimizing patients' outcomes.
PubMed: 38814879
DOI: 10.2450/BloodTransfus.640 -
Translational Vision Science &... May 2024We aimed to determine the causal effects of physical activities with different frequencies, durations, and intensities on the risk of senile cataracts using Mendelian...
PURPOSE
We aimed to determine the causal effects of physical activities with different frequencies, durations, and intensities on the risk of senile cataracts using Mendelian randomization (MR).
METHODS
A bidirectional two-sample MR approach was used to determine the association between physical activity and senile cataract risk. Our primary analysis used the inverse variance weighted method, and secondary analyses included MR-Egger regression, MR-PRESSO, and Cochran's Q statistic to evaluate heterogeneity and pleiotropy. Causal estimates were presented as odds ratios (ORs) with 95% confidence intervals (95% CIs).
RESULTS
Genetically predicted moderate physical activity ≥ 10 min/wk (OR = 0.765, 95% CI = 0.627-0.936, P = 8.73E-03), vigorous physical activity ≥ 10 min/wk (OR = 0.691, 95% CI = 0.521-0.917, P = 1.04E-02), moderate-to-vigorous physical activity levels (OR = 0.552, 95% CI = 0.369-0.823, P = 3.75E-03), and overall acceleration average (OR = 0.952, 95% CI = 0.926-0.978, P = 3.80E-04) were associated with a decreased risk of senile cataract while walking ≥ 10 min/wk (OR = 0.972, 95% CI = 0.741-1.275, P = 8.36E-01) had no significant correlation. The reverse MR analysis showed no reversal causality from senile cataract to physical activity except for walking ≥ 10 min/wk (OR = 0.951, 95% CI = 0.923-0.979, P = 7.30E-04).
CONCLUSIONS
Our findings suggest that moderate to vigorous physical activity with higher frequency and longer duration will causally reduce the risk of senile cataracts, and there is no reverse causal relationship.
TRANSLATIONAL RELEVANCE
These findings underscore the potential of incorporating physical activity into preventive health strategies for senile cataracts.
Topics: Humans; Cataract; Mendelian Randomization Analysis; Exercise; Risk Factors; Aged; Polymorphism, Single Nucleotide; Odds Ratio; Time Factors
PubMed: 38814746
DOI: 10.1167/tvst.13.5.26 -
The Turkish Journal of Pediatrics May 2024We aimed to delineate the genotype and phenotype of patients with KCNQ2 mutations from South China.
BACKGROUND
We aimed to delineate the genotype and phenotype of patients with KCNQ2 mutations from South China.
METHODS
Clinical manifestations and characteristics of KCNQ2 mutations of patients from South China were analyzed. Previous patients with mutations detected in this study were reviewed.
RESULTS
Eighteen epilepsy patients with KCNQ2 mutations, including seven self-limited neonatal epilepsy (SeLNE), two self-limited infantile epilepsy (SeLIE) and nine developmental and epileptic encephalopathy (DEE) were enrolled. The age of onset (p=0.006), mutation types (p=0.029), hypertonia (p=0.000), and seizure offset (p=0.029) were different in self-limited epilepsy (SeLE) and DEE. De novo mutations were mainly detected in DEE patients (p=0.026). The mutation position, EEG or the age of onset were not predictive for the seizure or ID/DD outcome in DEE, while the development of patients free of seizures was better than that of patients with seizures (p=0.008). Sodium channel blockers were the most effective anti-seizure medication, while the age of starting sodium channel blockers did not affect the seizure or development offset. We first discovered the seizure recurrence ratio in SeLNE/SeLIE was 23.1% in South China. Four novel mutations (c.790T>C, c.355_363delGAGAAGAG, c.296+2T>G, 20q13.33del) were discovered. Each of eight mutations (c.1918delC, c.1678C>T, c.683A>G, c.833T>C, c.868G>A, c.638G>A, c.997C>T, c.830C>T) only resulted in SeLE or DEE, while heterogeneity was also found. Six patients in this study have enriched the known phenotype caused by the mutations (c.365C>T, c.1A>G, c.683A>G, c.833T>C, c.830C>T, c.1678C>T).
CONCLUSION
This research has expanded known phenotype and genotype of KCNQ2-related epilepsy, and the different clinical features of SeLE and DEE from South China.
Topics: Humans; KCNQ2 Potassium Channel; China; Female; Male; Mutation; Infant; Phenotype; Child, Preschool; Genotype; Child; Infant, Newborn; Epilepsy; Genetic Testing
PubMed: 38814296
DOI: 10.24953/turkjpediatr.2024.4593 -
Aging May 2024Osteoarthritis (OA), a degenerative joint disease, involves synovial inflammation, subchondral bone erosion, and cartilage degeneration. Ferroptosis, a regulated...
Osteoarthritis (OA), a degenerative joint disease, involves synovial inflammation, subchondral bone erosion, and cartilage degeneration. Ferroptosis, a regulated non-apoptotic programmed cell death, is associated with various diseases. This study investigates ferroptosis-related molecular subtypes in OA to comprehend underlying mechanisms. The Gene Expression Omnibus datasets GSE206848, GSE55457, GSE55235, GSE77298 and GSE82107 were used utilized. Unsupervised clustering identified the ferroptosis-related gene (FRG) subtypes, and their immune characteristics were assessed. FRG signatures were derived using LASSO and SVM-RFE algorithms, forming models to evaluate OA's ferroptosis-related immune features. Three FRG clusters were found to be immunologically heterogeneous, with cluster 1 displaying robust immune response. Models identified nine key signature genes via algorithms, demonstrating strong diagnostic and prognostic performance. Finally, qRT-PCR and Western blot validated these genes, offering consistent results. In addition, some of these genes may have implications as new therapeutic targets and can be used to guide clinical applications.
PubMed: 38814177
DOI: 10.18632/aging.205875 -
Microbiology Spectrum May 2024Assessing the bacterial community composition across cacao crops is important to understand its potential role as a modulator of cadmium (Cd) translocation to plant...
UNLABELLED
Assessing the bacterial community composition across cacao crops is important to understand its potential role as a modulator of cadmium (Cd) translocation to plant tissues under field conditions; Cd mobility between soil and plants is a complex and multifactorial problem that cannot be captured only by experimentation. Although microbes have been shown to metabolize and drive the speciation of Cd under controlled conditions, regardless of the link between soil bacterial community (SBC) dynamics and Cd mobilization in the rhizosphere, only a few studies have addressed the relationship between soil bacterial community composition (SBCC) and Cd content in cacao seeds (Cd). Therefore, this study aimed to explore the association between SBCC and different factors influencing the distribution of Cd across cacao crop systems. This study comprised 225 samples collected across five farms, where we used an amplicon sequencing approach to characterize the bacterial community composition. The soil Cd concentration alone (Cd) was a poor predictor of Cd. Still, we found that this relationship was more apparent when the variation within farms was controlled, suggesting a role of heterogeneity within farms in modulating Cd translocation and, thus, seed Cd content. Our results provide evidence of the link between soil bacterial communities and the distribution of Cd across Colombian cacao crops, and highlight the importance of incorporating fine-spatial-scale studies to advance the understanding of factors driving Cd uptake and accumulation in cacao plants.
IMPORTANCE
Cadmium (Cd) content in cacao crops is an issue that generates interest due to the commercialization of chocolate for human consumption. Several studies provided evidence about the non-biological factors involved in its translocation into the cacao plant. However, factors related to this process, including soil bacterial community composition (SBCC), still need to be addressed. It is well known that soil microbiome could impact compounds' chemical transformation, including Cd, on the field. Here, we found the first evidence of the link between soil bacterial community composition and Cd concentration in cacao soils and seeds. It highlights the importance of including the variation of bacterial communities to assess the factors driving the Cd translocation into cacao seeds. Moreover, the results highlight the relevance of the spatial heterogeneity within and across cacao farms, influencing the variability of Cd concentrations.
PubMed: 38814085
DOI: 10.1128/spectrum.03363-23 -
Saudi Journal of Gastroenterology :... May 2024Colorectal cancer (CRC) ranks third in both the incidence and mortality rates among male and female cancers, and it is the leading digestive system cancer. Due to the...
BACKGROUND
Colorectal cancer (CRC) ranks third in both the incidence and mortality rates among male and female cancers, and it is the leading digestive system cancer. Due to the inter- and intratumor heterogeneity of cancer, the TNM system is insufficient for predicting prognosis, necessitating the use of molecular biomarkers for prognostic prediction. Toll-like receptors (TLRs) have been associated with CRC survival rates. This study focused on the investigation of the role and potential value of TLRs in CRC genotyping to aid in immunotherapy for CRC patients.
METHODS
Differential gene expression analysis was performed on CRC transcriptomic data from The Cancer Genome Atlas database. TLRs were referred from the literature, and their intersection with differentially expressed genes (DEGs) in CRC yielded TLR-DEGs. The expression patterns of TLR-DEGs were predicted using the STRING website, and copy number variations of TLR-DEGs were analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on TLR-DEGs. ConsensusClusterPlus R package was used for clustering CRC patients, and ESTIMATE and GSEAbase were employed to analyze immune characteristics of different subtypes. Immune phenotyping scores and tumor immune dysfunction and exclusion scores were evaluated. DEGs of different subtypes were analyzed, followed by GO and KEGG enrichment analyses, the protein-protein interaction (PPI) network analysis, and further selection of hub genes. The sensitivity of drugs was assessed using the identified hub genes.
RESULTS
We identified 37 TLR-DEGs, and the PPI analysis revealed their coexpression, although they were distributed on different chromosomes. Enrichment analyses indicated that the 37 TLR-DEGs were linked to cancer cell immune response. Based on these TLR-DEGs, CRC patients were classified into three subtypes. Cluster2 exhibited lower survival rates and higher immune infiltration levels and predicted poorer response to immune checkpoint inhibitor therapy. The intersection of DEGs from cluster2 and cluster1 with DEGs from cluster2 and cluster3 yielded a set of 426 commonly shared DEGs. Enrichment analyses revealed that these shared DEGs might regulate immune cell viability. Eight common hub genes for different subtypes were further identified to predict drug-related correlations.
CONCLUSION
The developed TLR genotyping was used to predict the survival status and tumor microenvironment of CRC, providing a foundation for understanding the molecular mechanisms of TLR signaling and deepening its clinical significance.
PubMed: 38813725
DOI: 10.4103/sjg.sjg_424_23