Machine learning in predicting postoperative complications in Crohn's disease.

Crohn's disease (CD) is a chronic inflammatory bowel disease of unknown origin that can cause significant disability and morbidity with its progression. Due to the unique nature of CD, surgery is often necessary for many patients during their lifetime, and the incidence of postoperative complications is high, which can affect the prognosis of patients. Therefore, it is essential to identify and manage postoperative complications. Machine learning (ML) has become increasingly important in the medical field, and ML-based models can be used to predict postoperative complications of intestinal resection for CD. Recently, a valuable article titled "Predicting short-term major postoperative complications in intestinal resection for Crohn's disease: A machine learning-based study" was published by Wang et al. We appreciate the authors' creative work, and we are willing to share our views and discuss them with the authors.

Oocytes maintain low ROS levels to support the dormancy of primordial follicles.

Primordial follicles (PFs) function as the long-term reserve for female reproduction, remaining dormant in the ovaries and becoming progressively depleted with age. Oxidative stress plays an important role in promoting female reproductive senescence during aging, but the underlying mechanisms remain unclear. Here, we find that low levels of reactive oxygen species (ROS) are essential for sustaining PF dormancy. Compared to growing follicles, oocytes within PFs were shown to be more susceptible to ROS, which accumulates and damages PFs to promote reproductive senescence. Mechanistically, oocytes within PFs were shown to express high levels of the intracellular antioxidant enzyme superoxide dismutase 1 (SOD1), counteracting ROS accumulation. Decreased SOD1 expression, as a result of aging or through the experimental deletion of the Sod1 gene in oocytes, resulted in increased oxidative stress and triggered ferroptosis within PFs. In conclusion, this study identified antioxidant defense mechanisms protecting PFs in mouse ovaries and characterized cell death mechanisms of oxidative stress-induced PF death.

Paper-based colorimetric sensor using a single-atom nanozyme for the ultrasensitive detection of Cr(VI) in short-necked clams.

Single-atom nanozymes (SAzymes) as a class of highly active nanozymes with the advantages of high atom utilization, high catalytic activity and stability have attracted great attention. In this work, Fe-N-C SAzymes with exceptional oxidase (OXD)-like activity were achieved utilizing polyvinylpyrrolidone (PVP) as a template. The Fe-N-C SAzymes with remarkable OXD-like activity could oxidize TMB to blue oxTMB, but 8-hydroxyquinoline (8-HQ) as a metal chelator is capable of discoloring oxTMB. Thus, the addition of 8-HQ decolorized the solution. However, upon the introduction of Cr(VI) ions, 8-HQ preferentially chelated with the Cr(VI) ions, reversing the inhibition of the color reaction and restoring the blue color. Based on this phenomenon, we constructed a novel paper-based analytical device (PAD) that exhibited a linear range of 5-1000 µM and an LOD of 1.2 µM. Importantly, the PAD used in this study shows the merits of simplicity, low preparation costs, and rapid reaction times. When combined with smartphone RGB analysis, it enables the simultaneous analysis of eight different Cr(VI) concentrations without the need for large-scale instrumentation. Moreover, the proposed PAD displays high selectivity, accuracy and utility in testing actual short-necked clam samples. This work not only provides a simple and cost-effective method to detect Cr(VI) but also makes a contribution to rapid food testing.

Specific Cytokines Analysis Incorporating Latency-Associated Antigens Differentiates Mycobacterium tuberculosis Infection Status: An Exploratory Study.

Introduction: Current immunologic methods cannot distinguish Mycobacterium tuberculosis (Mtb) infection statuses, especially to discriminate active tuberculosis (ATB) from latent tuberculosis infection (LTBI). This study explored the potential of latency-associated antigens (Rv1733cSLP and Rv2028c) and multifactorial cytokine detection to distinguish tuberculosis infection states. Methods: ATB patients (20), LTBI healthcare workers (25), fever patients (11), and healthy controls (10) were enrolled. Cytokine levels (IFN-γ, TNF-α, IL-2, IL-6, IP-10, IL-1Ra, CXCL-1, and MCP-1) were measured using Luminex with/without MTB-specific virulence factor and latency-associated antigens stimulation. Results: Without antigen stimulation, IL-6, IP-10, MCP-1, and IL-1Ra were higher in the ATB group than in the LTBI group (p<0.05), but no significant differences between the ATB group and the fever group. Stimulated with the four antigens, respectively, the cytokines, including IP-10Esat-6, IP-10CFP-10, IFN-γRv1733cSLP, IFN-γRv2028c, IL-6Esat-6, IL-6Rv1733cSLP, IL-6Rv2028c, IL-2Rv1733cSLP, IL-2 Rv2028c, IL-1RaEsat-6, IL-1RaCFP-10, IL-1RaRv2028c, CXCL-1Esat-6, CXCL-1CFP-10, CXCL-1Rv1733cSLP, CXCL-1Rv2028c, MCP-1Esat-6 and MCP-1CFP-10, demonstrated accurate discrimination between ATB and LTBI (p<0.05). Additive concentrations demonstrated significant secretion differences of IFN-γ, IP-10 and IL-2, primarily by virulence factors in ATB and latency-associated antigens in LTBI. Latency-associated antigens synergized with virulence factors, enhancing TH1-type cytokine diagnostic efficacy for discriminating ATB from LTBI, the AUC for TNF-α increased from 0.696 to 0.820 (p=0.038), IFN-γ increased from 0.806 to 0.962 (p=0.025), and IL-2 increased from 0.565 to 0.868 (p=0.007). Model selected by forward likelihood method indicated combined detection of IFN-γCFP-10, IFN-γRv1733cSLP, IP-10Rv1733cSLP, and CXCL-1Rv1733cSLP achieved ATB diagnosis (AUC=0.996) and ATB-LTBI differentiation (AUC=0.992). Combined detection of IFN-γCFP-10 and IFN-γRv1733cSLP achieved tuberculosis infection diagnosis (AUC=0.943). Conclusion: Latency-associated antigens enhance multiple cytokine discriminatory ability, particularly TH1-type cytokines, for differentiating Mtb infection statuses.

Knowledge and Attitudes About Screening and Preventive Treatment of Latent Tuberculosis Infection Among Patients with Rheumatic Diseases in Beijing, China.

Objective: Tuberculosis preventive treatment (TPT) is an important strategy for tuberculosis (TB) control. Rheumatic diseases (RD) patients are at high risk for active TB development. More researches are needed in terms of patient compliance in clinical practice. This study aims to explore the potential difficulties and obstacles in latent tuberculosis infection (LTBI) screening and TPT in RD patients. Methods: Convenience sampling was used to recruit RD outpatients who had indications for LTBI screening and TPT. All participants were given questionnaires on knowledge and attitudes regarding screening and preventive treatment of LTBI. Results: Of the 200 RD patients, most people were aware that they were at increased risk of ATB due to their rheumatic disease and knew that TB was curable. The main association with willingness to have screening for LTBI was tertiary education (P = 0.013). The main association with willingness to take treatment for LTBI was a sense of personal risk and belief that the treatment would reduce risk of ATB (P < 0.001). More than half of the people surveyed could not accept taking 6 or more pills per day, while more than half of the patients could tolerate a treatment course of 9 months or longer. Most (65.4%) preferred their own rheumatologists to initiate treatment. Conclusion: Educating RD patients about their individual risks of TB and the side effects of treatment, and educating/empowering rheumatologists to discuss these aspects with their patients and to offer LTBI screening and treatment, may help improve patients' compliance with LTBI screening and TPT.

Differential expression of ADRB1 causes different responses to norepinephrine in adipocytes of Duroc-Landrace-Yorkshire pigs and min pigs.

Research has shown that pigs from different regions exhibit varying responses to cold stimuli. Typically, cold stimuli induce browning of white adipose tissue mediated by adrenaline, promoting non-shivering thermogenesis. However, the molecular mechanisms underlying differential response of pig breeds to norepinephrine are unclear. The aim of this study was to investigate the differences and molecular mechanisms of the effects of norepinephrine (NE) treatment on adipocytes of Min pigs (a cold-resistant pig breed) and Duroc-Landrace-Yorkshire (DLY) pigs. Real time-qPCR, western blot, and immunofluorescence were performed following NE treatment on cell cultures of adipocytes originating from Min pigs (n = 3) and DLY pigs (n = 3) to assess the expressions of adipogenesis markers, beige fat markers, and mitochondrial biogenesis markers. The results showed that NE did not affect browning of adipocytes in DLY pigs, whereas promoted browning of adipocytes in Min pigs. Further, the expression of ADRB1 (Adrenoceptor Beta 1, ADRB1) was higher in subcutaneous adipose tissue and adipocytes of Min pigs than those of DLY pigs. Overexpression of ADRB1 in DLY pig adipocytes enhanced sensitivity to NE, exhibiting decreased adipogenesis markers, upregulated beige fat markers, and increased mitochondrial biogenesis. Conversely, adipocytes treated with ADRB1 antagonist in Min pigs resulted in decreased cellular sensitivity to NE. Further studies revealed differential CpG island methylation in ADRB1 promoter region, with lower methylation levels in Min pigs compared to DLY pigs. In conclusion, differential methylation of the ADRB1 promoter region leads to different ADRB1 expression, resulting in varying responsiveness to NE in adipocytes of two pig breeds. Our results provide new insights for further analysis of the differential cold responsiveness in pig breeds from different regions.

Cytomegalovirus antigen-specific multi-cytokine immune responses in patients with rheumatic diseases under different cytomegalovirus infection status: A case-control study.

OBJECTIVE: To explore Cytomegalovirus (CMV) antigen-specific multi-cytokine immune responses in patients with rheumatic disease (RD) under different CMV infection status. METHODS: A total of 60 RD patients in our center from March 2023 to August 2023 were enrolled. The patients were divided into latent CMV infection and active CMV infection, the latter was classified as subclinical CMV infection or CMV disease based on presence or absence of symptoms related to CMV. Whole blood was collected and stimulated with QuantiFERON-CMV antigen. The levels of IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, IL-17 and CXCL-2 in supernatant were measured by Luminex Assays. The receiver operating characteristic curve was used to evaluate the diagnostic accuracy of cytokine for distinguishing different CMV infection status. RESULTS: The proportion of patients with severe lymphopenia was lowest in the latent CMV infection group, while there were no significant differences in medication usage in different CMV infection status. After stimulation with QF-CMV antigens, the levels of IFN-γ, TNF-α and IL-2 in the CMV disease group were significantly lower than those in the latent CMV infection group. CMV antigen-specific IFN-γ, TNF-α levels and severe lymphopenia together provided the best discriminatory performance for distinguishing between latent and either active CMV infection patients (AUC = 0.854) or CMV disease patients (AUC = 0.935). CONCLUSION: Noninvasive peripheral blood biomarkers (the combination of CMV antigen-specific IFN-γ, TNF-α levels and severe lymphopenia) may have the potential to diferentiate different status of CMV infection in RD population.

The myokine CCL5 recruits subcutaneous preadipocytes and promotes intramuscular fat deposition in obese mice.

Intramuscular fat (IMF) refers to the lipid stored in skeletal muscle tissue. The number and size of intramuscular adipocytes are the primary factors that regulate IMF content. Intramuscular adipocytes can be derived from either in situ or ectopic migration. In this study, it was discovered that the regulation of IMF levels is achieved through the chemokine (C-C motif) ligand 5 (CCL5)/chemokine (C-C motif) receptor 5 (CCR5) pathway by modulating adipocyte migration. In coculture experiments, C2C12 myotubes were more effective in promoting the migration of 3T3-L1 preadipocytes than C2C12 myoblasts, along with increasing CCL5. Correspondingly, overexpressing the CCR5, one of the receptors of CCL5, in 3T3-L1 preadipocytes facilitated their migration. Conversely, the application of the CCL5/CCR5 inhibitor, MARAVIROC (MVC), reduced this migration. In vivo, transplanted experiments of subcutaneous adipose tissue (SCAT) from transgenic mice expressing green fluorescent protein (GFP) provided evidence that injecting recombinant CCL5 (rCCL5) into skeletal muscle promotes the migration of subcutaneous adipocytes to the skeletal muscle. The level of CCL5 in skeletal muscle increased with obesity. Blocking the CCL5/CCR5 axis by MVC inhibited IMF deposition, whereas elevated skeletal muscle CCL5 promoted IMF deposition in obese mice. These results establish a link between the IMF and the CCL5/CCR5 pathway, which could have a potential application for modulating IMF through adipocyte migration.NEW & NOTEWORTHY C2C12 myotubes attract 3T3-L1 preadipocyte migration regulated by the chemokine (C-C motif) ligand 5 (CCL5)/ chemokine (C-C motif) receptor 5 (CCR5) axis. High levels of skeletal muscle-specific CCL5 promote the migration of subcutaneous adipocytes to skeletal muscle and induce the intramuscular fat (IMF) content.

Dynamic transcriptome analysis provides molecular insights into underground floral differentiation in Adonis Amurensis Regel & Radde.

Understanding flower developmental processes is a prerequisite for improving flowering 'plants' production. Adonis amurensis is a fascinating spring ephemeral plant that develops its flower organs underground. Nevertheless, knowledge of the molecular mechanisms driving this particular process is scarce. Herein, we examined transcriptional changes during underground flower differentiation in A. amurensis and unveiled key differently regulated genes and pathways. High-throughput RNA sequencing of meristems at different flower developmental stages, including flower primordium (FP), sepal stage (SE), perianth primordium (PE), stamen stage (ST), and pistil stage (PI), identified 303,234 unigenes that showed 44.79% similarity with sequences in Aquilegia coerulea. Correlations, principal component, and differentially expressed genes (DEGs) analyses revealed that few molecular changes occurred during the transition from PE to ST. Many DEGs exhibited stage-specific regulations. Transcription factor (TF) and phytohormone family genes are critical regulators of the floral differentiation process in A. amurensis. The most differentially regulated TFs were MADS, FAR1, MYBs, AP2/ERF, B3, C2H2, and LOBs. We filtered out 186 candidate genes for future functional studies, including 18 flowering/circadian-related, 32 phytohormone-related, and TF family genes. Our findings deepen our understanding of the underground flower differentiation process and offer critical resources to dissect its regulatory network in A. amurensis. These findings establish a foundational platform for researchers dedicated to exploring the unique phenotypic characteristics of this specific flowering modality and delving into the intricate molecular mechanisms underpinning its regulation and expression.

Incidence and Risk Factors of Active Tuberculosis Among Hospitalized Patients with Latent Tuberculosis Infection in China: A Cohort Study.

Background: The population with latent tuberculosis infection (LTBI) represents a potential pool of patients with active tuberculosis (ATB). T-SPOT.TB is an important test tool for screening LTBI. Owing to the large population of LTBI patients in China, it is necessary to identify a high-risk group for LTBI and enlarge tuberculosis preventive treatment (TPT) to reduce the incidence of ATB. Methods: Hospitalized patients with positive T-SPOT.TB results were recruited from January 2013 to December 2016. Patients with ATB were excluded. Basic information was collected and the development of ATBs was examined during follow-up. The life-table method was used to calculate cumulative incidence rates. Potential risk factors were analyzed through Cox regression analysis. Results: A total of 1680 patients with LTBI were recruited in the follow-up cohort, and 377 (22.44%) patients dropped out. With a median follow-up time of 81 months [interquartile range (IQR):61-93], 19 of 1303 patients with LTBI developed ATB. The 1-year incidence of ATB was 614 per 100,000 individuals [95%confidence interval (95% CI):584-644]. Over 5-year period, the cumulative incidence of ATB was 1496 per 100,000 [95% CI:1430-1570], and the incidence density was 240 per 100,000 person-years[95% CI:144-375]. In the Cox regression model, exposure of pulmonary tuberculosis (PTB) [adjusted hazard ratio (aHR)=10.557, 95% CI:2.273-49.031], maximum daily dosage of glucocorticoids (GCs)≥ 50 mg/d (aHR=2.948, 95% CI:1.122-7.748), leflunomide (LEF) treatment (aHR=8.572, 95% CI:2.222 -33.070), anemia (aHR=2.565, 95% CI:1.015-6.479) and T-SPOT.TB level≥300SFCs/106 PBMCs (aHR=4.195, 95% CI:1.365-12.892) were independent risk factors for ATB development in LTBI patients. Conclusion: The incidence of ATB is significantly higher in hospitalized patients with LTBI than in the general population. The exposure history of PTB, maximum daily dosage of GCs≥ 50 mg/day, LEF treatment, anemia, and T-SPOT.TB level≥300SFCs/106PBMCs, were the risk factors of tuberculosis reactivation. Hospitalized LTBI patients with the above factors may need TPT.

Clinical features and prognosis of systemic lupus erythematosus complicated by active cytomegalovirus infection: a retrospective cohort study.

Objective: The aim of this study was to investigate the clinical traits and consequences of systemic lupus erythematosus (SLE) complicated by active cytomegalovirus (CMV) infection. Methods: This retrospective review involved the examination of medical records for patients diagnosed with SLE who had an active CMV infection at the time of their discharge from Peking Union Medical College Hospital between June 2016 and December 2022. The consistency between plasma CMV deoxyribonucleic acid (DNA) viral load and pp65 antigenemia was analyzed using the chi-square test. Related factors for CMV disease in SLE complicated by active CMV infection patients were analyzed by univariate analysis and multivariable stepwise logistic regression. Cox hazards regression analysis was used to determine predictors for all-cause mortality and CMV recurrence within 3 months. Results: A total of 206 patients were enrolled in this study. Of the 123 patients who were detected with both plasma CMV DNA viral load and pp65 antigenemia within an interval not exceeding 72 h, the consistency between plasma CMV DNA viral load and pp65 antigenemia was not good (Kappa = -0.304, p < 0.001). Plasma CMV DNA viral load ≥ 1,600 copies/mL [odds ratio (OR) 4.411, 95% CI 1.871-10.402, p = 0.001], current glucocorticoids dose (equivalent to prednisolone) ≥60 mg/d (OR 2.155, 95% CI 1.071-4.334, p = 0.031), and elevated alanine transaminase (OR 3.409, 95% CI 1.563-7.435, p = 0.002) were significant clinical clues indicating CMV disease in SLE. Multivariable Cox hazards regression analysis showed that CMV organ involvement [hazard ratio (HR) 47.222, 95% CI 5.621-396.689, p < 0.001], SLE multi-system involvement (HR 1.794, 95% CI 1.029-3.128, p = 0.039), and elevated hypersensitive C-reactive protein (hsCRP) (HR 5.767, 95% CI 1.190-27.943, p = 0.030) were independent risk factors for 3-month all-cause mortality. CMV organ involvement (HR 3.404, 95% CI 1.074-10.793, p = 0.037) was an independent risk factor for CMV recurrence within 3 months. Conclusion: In SLE patients, plasma CMV DNA viral load seemed to have a higher value in the diagnosis of CMV disease; patients with CMV organ involvement, SLE multi-system involvement, and elevated hsCRP might have a higher risk of 3-month all-cause mortality; and patients with CMV organ involvement might have a higher risk of CMV recurrence within 3 months.

Perceived stress of COVID-19 pandemic and problematic mobile phone use during quarantine conditions among Chinese adolescents: a mediated moderation model.

The relation between perceived general stress and problematic mobile phone use (PMPU) has been well established. With the outbreak of the coronavirus disease (COVID-19), the present study was designed to examine the association between perceived stress of COVID-19 as a kind of event-related stress and PMPU, and the mechanisms underlying this relation. Participants were 724 adolescents ranging from 12 to 16 years old (M = 13.28, SD = 1.05) who completed four online questionnaires addressing perceived stress of COVID-19, search for meaning in life, escapism motivation, and PMPU. The results revealed that escapism motivation mediated the relationship between perceived stress of COVID-19 and PMPU. In addition, search for meaning in life played a moderating role between perceived stress of COVID-19 and escapism motivation. These findings extend the literature by addressing how and under what conditions perceived stress of COVID-19 can contribute to PMPU. We discussed the implications for developing targeted intervention programs aimed at reducing PMPU among adolescents.

Multiple cytokine analysis based on QuantiFERON-TB gold plus in different tuberculosis infection status: an exploratory study.

BACKGROUND: More efficient and convenient diagnostic method is a desperate need to reduce the burden of tuberculosis (TB). This study explores the multiple cytokines secretion based on QuantiFERON-TB Gold Plus (QFT-Plus), and screens for optimal cytokines with diagnostic potential to differentiate TB infection status. METHODS: Twenty active tuberculosis (ATB) patients, fifteen patients with latent TB infection (LTBI), ten patients with previous TB and ten healthy controls (HC) were enrolled. Whole blood samples were collected and stimulated by QFT-Plus TB1 and TB2 antigens. The levels of IFN-γ, TNF-α, IL-2, IL-6, IL-5, IL-10, IP-10, IL-1Ra, CXCL-1 and MCP-1 in supernatant were measured by Luminex bead-based multiplex assays. The receiver operating characteristic curve was used to evaluate the diagnostic accuracy of cytokine for distinguishing different TB infection status. RESULTS: After stimulation with QFT-Plus TB1 and TB2 antigens, the levels of all cytokines, except IL-5 in TB2 tube, in ATB group were significantly higher than that in HC group. The levels of IL-1Ra concurrently showed the equally highest AUC for distinguishing TB infection from HC, followed by the levels of IP-10 in both TB1 tube and TB2 tube. Moreover, IP-10 levels displayed the largest AUC for distinguishing ATB patients from non-ATB patients. Meanwhile, the levels of IP-10 also demonstrated the largest AUC in both TB1 tube and TB2 tube for distinguishing ATB patients from LTBI. CONCLUSIONS: In addition to conventional detection of IFN-γ, measuring IP-10 and IL-1Ra based on QFT-Plus may have the more tremendous potential to discriminate different TB infection status.

High Serum Albumin Levels were Associated with Acute Kidney Injury in Pediatric Surgical Intensive Care Units.

INTRODUCTION: There are limited studies revealing the association between serum albumin concentrations and acute kidney injury (AKI) in critically ill children. METHODS: This was a multicenter retrospective study. Children consecutively admitted to four pediatric surgical intensive care units (PSICUs) between January 2016 and December 2020 were screened for analysis. Patients without recorded albumin values during the PSICU stay were excluded. Data were extracted from the electronic medical records systems of the hospitals. AKI was defined according to the Kidney Disease Improving Global Outcome (KDIGO) guidelines. The associations between serum albumin levels and AKI were assessed by using logistic regression models. RESULTS: A total of 7802 children were included in the analysis. The median age of the children was 1.0 (interquartile range (IQR), 0.0-4.0) years. There were 3214 (41.2 %) children who developed AKI. In the univariate logistic regression model, serum albumin levels were associated with AKI (odds ratio (OR) = 1.04, 95 % confidence interval (CI) 1.04-1.05). After adjusting for covariates, serum albumin showed an independent association with AKI (OR = 1.04, 95 % CI 1.03-1.05). Albumin levels above 39.43 g/L (OR = 1.036, 95 % CI 1.002-1.070) were associated with AKI in the unadjusted cubic spline. In the adjusted cubic spline, albumin levels above 40.41 g/L (OR = 1.061, 95 % CI 1.003-1.122) were associated with AKI. CONCLUSION: High serum albumin was associated with AKI in critically ill children in the PSICU. Further studies are needed to validate our findings. TYPE OF STUDY: Prognostic Study. LEVEL OF EVIDENCE: LEVEL II.

Whole Genome Resequencing Revealed the Genetic Relationship and Selected Regions among Baicheng-You, Beijing-You, and European-Origin Broilers.

As the only two You-chicken breeds in China, Baicheng-You (BCY) and Beijing-You (BJY) chickens are famous for their good meat quality. However, so far, the molecular basis of germplasm of the two You-chicken breeds is not yet clear. The genetic relationship among BCY, BJY, and European-origin broilers (BRs) was analyzed using whole genome resequencing data to contribute to this issue. A total of 18,852,372 single nucleotide polymorphisms (SNPs) were obtained in this study. After quality control, 8,207,242 SNPs were applied to subsequent analysis. The data indicated that BJY chickens possessed distant distance with BRs (genetic differentiation coefficient (FST) = 0.1681) and BCY (FST = 0.1231), respectively, while BCY and BRs had a closer relationship (FST = 0.0946). In addition, by using FST, cross-population extended haplotype homozygosity (XP-EHH), and cross-population composite likelihood ratio (XP-CLR) methods, we found 374 selected genes between BJY and BRs chickens and 279 selected genes between BCY and BJY chickens, respectively, which contained a number of important candidates or genetic variations associated with feather growth and fat deposition of BJY chickens and potential disease resistance of BCY chickens. Our study demonstrates a genome-wide view of genetic diversity and differentiation among BCY, BJY, and BRs. These results may provide useful information on a molecular basis related to the special characteristics of these broiler breeds, thus enabling us to better understand the formation mechanism of Chinese-You chickens.

Identification and validation of a pyroptosis-related signature in identifying active tuberculosis via a deep learning algorithm.

Introduction: Active tuberculosis (ATB), instigated by Mycobacterium tuberculosis (M.tb), rises as a primary instigator of morbidity and mortality within the realm of infectious illnesses. A significant portion of M.tb infections maintain an asymptomatic nature, recognizably termed as latent tuberculosis infections (LTBI). The complexities inherent to its diagnosis significantly hamper the initiatives aimed at its control and eventual eradication. Methodology: Utilizing the Gene Expression Omnibus (GEO), we procured two dedicated microarray datasets, labeled GSE39940 and GSE37250. The technique of weighted correlation network analysis was employed to discern the co-expression modules from the differentially expressed genes derived from the first dataset, GSE39940. Consequently, a pyroptosis-related module was garnered, facilitating the identification of a pyroptosis-related signature (PRS) diagnostic model through the application of a neural network algorithm. With the aid of Single Sample Gene Set Enrichment Analysis (ssGSEA), we further examined the immune cells engaged in the pyroptosis process in the context of active ATB. Lastly, dataset GSE37250 played a crucial role as a validating cohort, aimed at evaluating the diagnostic prowess of our model. Results: In executing the Weighted Gene Co-expression Network Analysis (WGCNA), a total of nine discrete co-expression modules were lucidly elucidated. Module 1 demonstrated a potent correlation with pyroptosis. A predictive diagnostic paradigm comprising three pyroptosis-related signatures, specifically AIM2, CASP8, and NAIP, was devised accordingly. The established PRS model exhibited outstanding accuracy across both cohorts, with the area under the curve (AUC) being respectively articulated as 0.946 and 0.787. Conclusion: The present research succeeded in identifying the pyroptosis-related signature within the pathogenetic framework of ATB. Furthermore, we developed a diagnostic model which exuded a remarkable potential for efficient and accurate diagnosis.