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Scientific Reports Jul 2024In recent times, the pathogenesis of generalized anxiety disorder (GAD) and the influence of pro- and anti-inflammatory cytokines on it have garnered considerable...
In recent times, the pathogenesis of generalized anxiety disorder (GAD) and the influence of pro- and anti-inflammatory cytokines on it have garnered considerable interest. Cytokine research, especially Th-17 cytokine research on GAD patients, is limited. Here, we aim to assess the role of interleukin-17A (IL-17A) and interleukin-23A (IL-23A) in the pathophysiology and development of GAD. This investigation included 50 GAD patients and 38 age-sex-matched healthy controls (HCs). A psychiatrist diagnosed patients with GAD and assessed symptom severity using the DSM-5 and the GAD-7 scales. The serum concentrations of IL-17A and IL-23A were determined using commercially available ELISA kits. GAD patients exhibited elevated levels of IL-17A (77.14 ± 58.30 pg/ml) and IL-23A (644.90 ± 296.70 pg/ml) compared to HCs (43.50 ± 25.54 pg/ml and 334.40 ± 176.0 pg/ml). We observed a positive correlation between disease severity and cytokine changes (IL-23A: r = 0.359, p = 0.039; IL-17A: r = 0.397, p = 0.032). These findings indicate that IL-17A and IL-23A may be associated with the pathophysiology of GAD. ROC analysis revealed moderately higher AUC values (IL-23A: 0.824 and IL-17A: 0.710), demonstrating their potential to discriminate between patients and HCs. Also, the sensitivity values of both cytokines were relatively higher (IL-23A: 80.49% and IL-17A: 77.27%). According to the present findings, there may be an association between peripheral serum levels of IL-17A and IL-23A and the pathophysiology and development of GAD. These altered serum IL-17A and IL-23A levels may play a role in directing the early risk of developing GAD. We recommend further research to ascertain their exact role in the pathophysiology and their performance as risk assessment markers of GAD.
Topics: Humans; Interleukin-17; Male; Female; Anxiety Disorders; Adult; Interleukin-23 Subunit p19; Case-Control Studies; Biomarkers; Middle Aged; Severity of Illness Index
PubMed: 38956309
DOI: 10.1038/s41598-024-66131-9 -
Scientific Reports Jul 2024This study evaluated the level of risk practices and awareness of leptospirosis among residents of Zaria, Nigeria. A pre-tested questionnaires were administered via...
This study evaluated the level of risk practices and awareness of leptospirosis among residents of Zaria, Nigeria. A pre-tested questionnaires were administered via face-to-face interview to 100 residents. The data was analyzed using chi-square and multivariate analysis to identify risk factors for leptospirosis. The demography showed that the majority of the respondents were male, aged 21-40 years, and majorly crop farmers. The risk factors identified showed that males were 4.14 times more likely to be affected by leptospirosis (OR 4.14, 95% CI [1.93-5.37], p = 0.02) and the source of animal's water was 5.56 times more likely to be contaminated by Leptospira spp. (OR 4.14, 95% CI [2.88-8.03], p = 0.01) and these relationships were significant. The majority of respondents were not aware of the disease (OR 1.87, 95% CI [1.22-4.57], p = 0.01) with 78% of the respondents not sure of which of the animal species leptospirosis affected (OR 1.67, 95% CI [1.07-2.62], p = 0.02). This study has demonstrated the existence of risk behaviors, and paucity of knowledge about leptospirosis in the study area. It is therefore recommended to organize an enlightenment program and the need for protective clothing for individuals occupationally at risk of infection by Leptospira spp.
Topics: Humans; Leptospirosis; Male; Nigeria; Adult; Female; Health Knowledge, Attitudes, Practice; Young Adult; Risk Factors; Surveys and Questionnaires; Middle Aged; Leptospira; Animals; Adolescent
PubMed: 38956307
DOI: 10.1038/s41598-024-66361-x -
Scientific Reports Jul 2024Pan-Immune-Inflammation Value (PIV) has recently received more attention as a novel indicator of inflammation. We aimed to evaluate the association between PIV and...
Pan-Immune-Inflammation Value (PIV) has recently received more attention as a novel indicator of inflammation. We aimed to evaluate the association between PIV and prognosis in septic patients. Data were extracted from the Medical Information Mart for Intensive Care IV database. The primary and secondary outcomes were 28-day and 90-day mortality. The association between PIV and outcomes was assessed by Kaplan-Meier curves, Cox regression analysis, restricted cubic spline curves and subgroup analysis. A total of 11,331 septic patients were included. Kaplan-Meier curves showed that septic patients with higher PIV had lower 28-day survival rate. In multivariable Cox regression analysis, log2-PIV was positively associated with the risk of 28-day mortality [HR (95% CI) 1.06 (1.03, 1.09), P < 0.001]. The relationship between log2-PIV and 28-day mortality was non-linear with a predicted inflection point at 8. To the right of the inflection point, high log2-PIV was associated with an increased 28-day mortality risk [HR (95% CI) 1.13 (1.09, 1.18), P < 0.001]. However, to the left of this point, this association was non-significant [HR (95% CI) 1.01 (0.94, 1.08), P = 0.791]. Similar results were found for 90-day mortality. Our study showed a non-linear relationship between PIV and 28-day and 90-day mortality risk in septic patients.
Topics: Humans; Sepsis; Male; Female; Retrospective Studies; Middle Aged; Aged; Prognosis; Inflammation; Kaplan-Meier Estimate; Biomarkers; Intensive Care Units; Proportional Hazards Models
PubMed: 38956306
DOI: 10.1038/s41598-024-66142-6 -
Communications Biology Jul 2024In this paper, we propose a fluorescence-lifetime imaging microscopy (FLIM) multiplexing system based on the fluorogen-activating protein FAST. This genetically encoded...
In this paper, we propose a fluorescence-lifetime imaging microscopy (FLIM) multiplexing system based on the fluorogen-activating protein FAST. This genetically encoded fluorescent labeling platform employs FAST mutants that activate the same fluorogen but provide different fluorescence lifetimes for each specific protein-dye pair. All the proposed probes with varying lifetimes possess nearly identical and the smallest-in-class size, along with quite similar steady-state optical properties. In live mammalian cells, we target these chemogenetic tags to two intracellular structures simultaneously, where their fluorescence signals are clearly distinguished by FLIM. Due to the unique structure of certain fluorogens under study, their complexes with FAST mutants display a monophasic fluorescence decay, which may facilitate enhanced multiplexing efficiency by reducing signal cross-talks and providing optimal prerequisites for signal separation upon co-localized and/or spatially overlapped labeling.
Topics: Microscopy, Fluorescence; Fluorescent Dyes; Humans; Animals; Fluorescence; Mutation
PubMed: 38956304
DOI: 10.1038/s42003-024-06501-1 -
Scientific Reports Jul 2024Recent studies show declining trends in hysterectomy rates in several countries. The objective of this study was to analyse hysterectomy time trends in Germany over a...
Recent studies show declining trends in hysterectomy rates in several countries. The objective of this study was to analyse hysterectomy time trends in Germany over a fifteen-year period using an age-period-cohort approach. Using an ecological study design, inpatient data from Diagnoses Related Group on hysterectomies by subtype performed in Germany from 2005 to 2019 were retrieved from the German Statistical Office. Descriptive time trends and age-period-cohort analyses were then performed. A total of 1,974,836 hysterectomies were performed over the study period. The absolute number of hysterectomies reduced progressively from 155,680 (365 procedures/100,000 women) in 2005 to 101,046 (257 procedures/100,000 women) in 2019. Total and radical hysterectomy decreased by 49.7% and 44.2%, respectively, whilst subtotal hysterectomy increased five-fold. The age-period-cohort analysis revealed highest hysterectomy rates in women aged 45-49 for total and subtotal hysterectomy with 608.63 procedures/100,000 women (95% CI 565.70, 654.82) and 151.30 procedures/100,000 women (95% CI 138.38, 165.44) respectively. Radical hysterectomy peaked later at 65-69 years with a rate of 40.63 procedures/100,000 women (95% CI 38.84, 42.52). The risk of undergoing total or radical hysterectomy decreased over the study period but increased for subtotal hysterectomy. Although, overall hysterectomy rates have declined, subtotal hysterectomy rates have increased; reflecting changes in clinical practice largely influenced by the availability of uterus-sparing options, evolving guidelines and introduction of newer surgical approaches.
Topics: Humans; Hysterectomy; Female; Germany; Middle Aged; Aged; Adult; Cohort Studies; Incidence; Age Factors; Aged, 80 and over; Young Adult
PubMed: 38956303
DOI: 10.1038/s41598-024-66019-8 -
Communications Biology Jul 2024G protein-coupled receptors (GPCRs) are mainly regulated by GPCR kinase (GRK) phosphorylation and subsequent β-arrestin recruitment. The ubiquitously expressed GRKs are...
G protein-coupled receptors (GPCRs) are mainly regulated by GPCR kinase (GRK) phosphorylation and subsequent β-arrestin recruitment. The ubiquitously expressed GRKs are classified into cytosolic GRK2/3 and membrane-tethered GRK5/6 subfamilies. GRK2/3 interact with activated G protein βγ-subunits to translocate to the membrane. Yet, this need was not linked as a factor for bias, influencing the effectiveness of β-arrestin-biased agonist creation. Using multiple approaches such as GRK2/3 mutants unable to interact with Gβγ, membrane-tethered GRKs and G protein inhibitors in GRK2/3/5/6 knockout cells, we show that G protein activation will precede GRK2/3-mediated β-arrestin2 recruitment to activated receptors. This was independent of the source of free Gβγ and observable for Gs-, Gi- and Gq-coupled GPCRs. Thus, β-arrestin interaction for GRK2/3-regulated receptors is inseparably connected with G protein activation. We outline a theoretical framework of how GRK dependence on free Gβγ can determine a GPCR's potential for biased agonism. Due to this inherent cellular mechanism for GRK2/3 recruitment and receptor phosphorylation, we anticipate generation of β-arrestin-biased ligands to be mechanistically challenging for the subgroup of GPCRs exclusively regulated by GRK2/3, but achievable for GRK5/6-regulated receptors, that do not demand liberated Gβγ. Accordingly, GRK specificity of any GPCR is foundational for developing arrestin-biased ligands.
Topics: Humans; GTP-Binding Protein gamma Subunits; HEK293 Cells; GTP-Binding Protein beta Subunits; G-Protein-Coupled Receptor Kinases; Receptors, G-Protein-Coupled; Phosphorylation; Animals; Signal Transduction
PubMed: 38956302
DOI: 10.1038/s42003-024-06490-1 -
Scientific Reports Jul 2024Historically, the analysis of stimulus-dependent time-frequency patterns has been the cornerstone of most electroencephalography (EEG) studies. The abnormal oscillations...
Historically, the analysis of stimulus-dependent time-frequency patterns has been the cornerstone of most electroencephalography (EEG) studies. The abnormal oscillations in high-frequency waves associated with psychotic disorders during sensory and cognitive tasks have been studied many times. However, any significant dissimilarity in the resting-state low-frequency bands is yet to be established. Spectral analysis of the alpha and delta band waves shows the effectiveness of stimulus-independent EEG in identifying the abnormal activity patterns of pathological brains. A generalized model incorporating multiple frequency bands should be more efficient in associating potential EEG biomarkers with first-episode psychosis (FEP), leading to an accurate diagnosis. We explore multiple machine-learning methods, including random-forest, support vector machine, and Gaussian process classifier (GPC), to demonstrate the practicality of resting-state power spectral density (PSD) to distinguish patients of FEP from healthy controls. A comprehensive discussion of our preprocessing methods for PSD analysis and a detailed comparison of different models are included in this paper. The GPC model outperforms the other models with a specificity of 95.78% to show that PSD can be used as an effective feature extraction technique for analyzing and classifying resting-state EEG signals of psychiatric disorders.
Topics: Humans; Psychotic Disorders; Electroencephalography; Female; Male; Adult; Support Vector Machine; Young Adult; Rest; Machine Learning; Brain; Adolescent; Signal Processing, Computer-Assisted
PubMed: 38956297
DOI: 10.1038/s41598-024-66110-0 -
Scientific Reports Jul 2024Human norovirus (HuNoV) is an enteric infectious pathogen belonging to the Caliciviridae family that causes occasional epidemics. Circulating alcohol-tolerant viral...
Human norovirus (HuNoV) is an enteric infectious pathogen belonging to the Caliciviridae family that causes occasional epidemics. Circulating alcohol-tolerant viral particles that are readily transmitted via food-borne routes significantly contribute to the global burden of HuNoV-induced gastroenteritis. Moreover, contact with enzymes secreted by other microorganisms in the environment can impact the infectivity of viruses. Hence, understanding the circulation dynamics of Caliciviridae is critical to mitigating epidemics. Accordingly, in this study, we screened whether environmentally abundant secretase components, particularly proteases, affect Caliciviridae infectivity. Results showed that combining Bacillaceae serine proteases with epsilon-poly-L-lysine (EPL) produced by Streptomyces-a natural antimicrobial-elicited anti-Caliciviridae properties, including against the epidemic HuNoV GII.4_Sydney_2012 strain. In vitro and in vivo biochemical and virological analyses revealed that EPL has two unique synergistic viral inactivation functions. First, it maintains an optimal pH to promote viral surface conformational changes to the protease-sensitive structure. Subsequently, it inhibits viral RNA genome release via partial protease digestion at the P2 and S domains in the VP1 capsid. This study provides new insights regarding the high-dimensional environmental interactions between bacteria and Caliciviridae, while promoting the development of protease-based anti-viral disinfectants.
Topics: Streptomyces; Polylysine; Serine Proteases; Bacillaceae; RNA, Viral; Humans; Genome, Viral; Animals; Norovirus; Virus Inactivation; Caliciviridae; Antiviral Agents
PubMed: 38956295
DOI: 10.1038/s41598-024-65963-9 -
Scientific Reports Jul 2024The prenatal diagnosis of fetal heart disease potentially influences parental decision-making regarding pregnancy termination. Existing literature indicates that the...
The prenatal diagnosis of fetal heart disease potentially influences parental decision-making regarding pregnancy termination. Existing literature indicates that the severity, whether in complexity or lethality, significantly influences parental decisions concerning abortion. However, questions remain as to how fetal heart disease severity impacts parental decisions, given recent advancements in postsurgical outcomes. Therefore, we investigated risk factors associated with parents' decision-making regarding abortion following a prenatal diagnosis of fetal heart disease. Our analysis included 73 (terminated: n = 37; continued: n = 36) pregnancies with a fetal heart disease diagnosed before 22 weeks of gestation. Increased gestational age at diagnosis reduced the likelihood of parents' decision on termination (Model 1: adjusted odds ratio, 0.94; 95% confidence interval 0.89-0.99; Model 2: 0.95 0.90-0.997). Critical disease (5.25; 1.09-25.19) and concurrent extracardiac or genetic abnormalities (Model 1: 4.19, 1.21-14.53; Model 2: 5.47, 1.50-19.96) increased the likelihood of choosing abortion. Notably, complex disease did not significantly influence parental decisions (0.56; 0.14-2.20). These results suggest that parental decision-making regarding abortion may be influenced by earlier gestational age at diagnosis, the lethality of heart disease, and extracardiac or genetic abnormalities, but not its complexity if prenatal diagnosis and parental counseling are provided at a cardiovascular-specialized facility.
Topics: Humans; Female; Pregnancy; Abortion, Induced; Decision Making; Adult; Parents; Prenatal Diagnosis; Gestational Age; Heart Defects, Congenital; Heart Diseases; Risk Factors; Fetal Diseases; Male; Severity of Illness Index
PubMed: 38956291
DOI: 10.1038/s41598-024-66027-8 -
Scientific Reports Jul 2024Anoikis, a distinct form of programmed cell death, is crucial for both organismal development and maintaining tissue equilibrium. Its role extends to the proliferation...
Anoikis, a distinct form of programmed cell death, is crucial for both organismal development and maintaining tissue equilibrium. Its role extends to the proliferation and progression of cancer cells. This study aimed to establish an anoikis-related prognostic model to predict the prognosis of pancreatic cancer (PC) patients. Gene expression data and patient clinical profiles were sourced from The Cancer Genome Atlas (TCGA-PAAD: Pancreatic Adenocarcinoma) and the International Cancer Genome Consortium (ICGC-PACA: Pancreatic Ductal Adenocarcinoma). Non-cancerous pancreatic tissue gene expression data were obtained from the Genotype-Tissue Expression (GTEx) project. The R package was used to construct anoikis-related PC prognostic models, which were later validated with the ICGC-PACA database. Survival analyses demonstrated a poorer prognosis for patients in the high-risk group, consistent across both TCGA-PAAD and ICGC-PACA datasets. A nomogram was designed as a predictive tool to estimate patient mortality. The study also analyzed tumor mutations and immune infiltration across various risk groups, uncovering notable differences in tumor mutation patterns and immune landscapes between high- and low-risk groups. In conclusion, this research successfully developed a prognostic model centered on anoikis-related genes, offering a novel tool for predicting the clinical trajectory of PC patients.
Topics: Anoikis; Humans; Pancreatic Neoplasms; Prognosis; Gene Expression Regulation, Neoplastic; Carcinoma, Pancreatic Ductal; Nomograms; Biomarkers, Tumor; Mutation; Female; Male; Survival Analysis; Gene Expression Profiling
PubMed: 38956290
DOI: 10.1038/s41598-024-65981-7