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Medicine Jun 2024As chronic autoimmune inflammatory diseases, rheumatoid arthritis (RA) and Crohn disease (CD) are closely associated and display a significant positive correlation....
As chronic autoimmune inflammatory diseases, rheumatoid arthritis (RA) and Crohn disease (CD) are closely associated and display a significant positive correlation. However, the underlying mechanisms and disease markers responsible for their cooccurrence remain unknown and have not been systematically studied. Therefore, this study aimed to identify key molecules and pathways commonly involved in both RA and CD through bioinformatic analysis of public sequencing databases. Datasets for RA and CD were downloaded from the GEO database. Overlapping genes were identified using weighted gene co-expression network analysis and differential analysis crossover, and enrichment analysis was conducted for these genes. Protein-protein interaction networks were then constructed using these overlapping genes to identify hub genes. Expression validation and receiver operating characteristic curve validation were performed for these hub genes using different datasets. Additionally, the immune cell correlation, single-cell expression cluster, and the immune cell expression cluster of the core gene were analyzed. Furthermore, upstream shared microRNAs (miRNA) were predicted and a miRNA-gene network was constructed. Finally, drug candidates were analyzed and predicted. These core genes were found to be positively correlated with multiple immune cells that are infiltrated by the disease. Analysis of gene expression clusters revealed that these genes were mostly associated with inflammatory and immune responses. The miRNA-genes network analysis suggested that hsa-miR-31-5p may play an important role in the common mechanism of RA and CD. Finally, tamibarotene, retinoic acid, and benzo[a]pyrene were identified as potential treatment options for patients with both RA and CD. This bioinformatics study has identified ITGB2, LCP2, and PLEK as key diagnostic genes in patients with both RA and CD. The study has further confirmed that inflammation and immune response play a central role in the development of both RA and CD. Interestingly, the study has highlighted hsa-miR-31-5p as a potential key player in the common mechanism of both diseases, representing a new direction in research and a potential therapeutic target. These shared genes, potential mechanisms, and regulatory networks offer new opportunities for further research and may provide hope for future treatment of patients with both RA and CD.
Topics: Humans; Crohn Disease; Arthritis, Rheumatoid; Computational Biology; MicroRNAs; Protein Interaction Maps; Gene Regulatory Networks; Biomarkers; Gene Expression Profiling
PubMed: 38941374
DOI: 10.1097/MD.0000000000038690 -
Medicine Jun 2024NHHR (non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio) is a novel lipid parameter. However, the association between NHHR and sleep...
NHHR (non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio) is a novel lipid parameter. However, the association between NHHR and sleep disorders remains unknown.; A cross-sectional analysis was conducted using data from the National Health and Nutrition Examination Survey (NHANES) 2005 to 2016. The association between NHHR and sleep disorders was explored using weighted multivariate logistic regression and generalized summation models. Subgroup analyses were employed to verify the robustness of this association. The prevalence of sleep disorders was 25.83% in a total of 22,221 participants. Compared to the lowest quartile of NHHR, participants in the top quartile had a 14% higher odds of sleep disorders prevalence in fully adjusted model (OR: 1.14, 95% CI: 1.06-1.23). After subgroup analyses and interaction tests, sex, race, marital status, education level, body mass index (BMI), person income ratio (PIR), alcohol consumption, smoking status, hypertension, and diabetes mellitus were not significantly associated with this positive association (P for interaction > 0.05). The NHHR is positively associated with sleep disorders in US adults. The management and monitoring of NHHR may have a potential role in improving sleep disorders.
Topics: Humans; Male; Female; Nutrition Surveys; United States; Cross-Sectional Studies; Sleep Wake Disorders; Middle Aged; Adult; Cholesterol, HDL; Prevalence; Risk Factors; Aged
PubMed: 38941362
DOI: 10.1097/MD.0000000000038748 -
PLoS Neglected Tropical Diseases Jun 2024Histoplasmosis is a frequent cause of infections in people living with HIV/AIDS (PLWHA). This study introduces the application of a Histoplasma capsulatum urine antigen...
Histoplasmosis is a frequent cause of infections in people living with HIV/AIDS (PLWHA). This study introduces the application of a Histoplasma capsulatum urine antigen lateral flow assay (LFA) for diagnosing disseminated histoplasmosis in PLWHA in Suriname. The LFA's diagnostic accuracy was compared with the current diagnostic approach, aiming to assess whether this test resulted in improved early detection and management. Additionally, the prevalence of histoplasmosis among advanced stage HIV patients without clinical suspicion of infection was evaluated using the same LFA. In total, 98 patients were included in the study, of which 58 were classified as "possible disseminated histoplasmosis (DH)" based on clinical criteria and 40 as 'controls". Of these possible DH cases, only 19 (32.7%) had a positive LFA. During the study, decisions for treatment were made without the treating physician being aware of the LFA result. Only 55% of the patients who started treatment for histoplasmosis based on clinical criteria had a positive LFA, and 21% of untreated patients had a positive LFA. This study shows that combining clinical signs with LFA results enhances diagnostic accuracy and is cost effective, resulting in better treatment decisions.
PubMed: 38941354
DOI: 10.1371/journal.pntd.0012272 -
PloS One 2024Pain changes how we move, but it is often confounded by other factors due to disease or injury. Experimental pain offers an opportunity to isolate the independent effect...
Pain changes how we move, but it is often confounded by other factors due to disease or injury. Experimental pain offers an opportunity to isolate the independent effect of pain on movement. We used cutaneous electrical stimulation to induce experimental knee pain during locomotion to study the short-term motor adaptions to pain. While other models of experimental pain have been used in locomotion, they lack the ability to modulate pain in real-time. Twelve healthy adults completed the single data collection session where they experienced six pain intensity conditions (0.5, 1, 2, 3, 4, 5 out of 10) and two pain delivery modes (tonic and phasic). Electrodes were placed over the lateral infrapatellar fat pad and medial tibial condyle to deliver the 10 Hz pure sinusoid via a constant current electrical stimulator. Pain intensity was calibrated prior to each walking bout based on the target intensity and was recorded using an 11-point numerical rating scale. Knee joint angles and moments were recorded over the walking bouts and summarized in waveform and discrete outcomes to be compared with baseline walking. Knee joint angles changed during the swing phase of gait, with higher pain intensities resulting in greater knee flexion angles. Minimal changes in joint moments were observed but there was a consistent pattern of decreasing joint stiffness with increasing pain intensity. Habituation was limited across the 30-90 second walking bouts and the electrical current needed to deliver the target pain intensities showed a positive linear relationship. Experimental knee pain shows subtle biomechanical changes and favourable habituation patterns over short walking bouts. Further exploration of this model is needed in real-world walking conditions and over longer timeframes to quantify motor adaptations.
Topics: Humans; Male; Adult; Biomechanical Phenomena; Female; Knee Joint; Pain; Gait; Locomotion; Walking; Young Adult; Electric Stimulation; Range of Motion, Articular
PubMed: 38941337
DOI: 10.1371/journal.pone.0302752 -
PloS One 2024Many newborn screening programs worldwide have introduced screening for diseases using DNA extracted from dried blood spots (DBS). In Germany, DNA-based assays are...
BACKGROUND
Many newborn screening programs worldwide have introduced screening for diseases using DNA extracted from dried blood spots (DBS). In Germany, DNA-based assays are currently used to screen for severe combined immunodeficiency (SCID), spinal muscular atrophy (SMA), and sickle cell disease (SCD).
METHODS
This study analysed the impact of pre-analytic DNA carry-over in sample preparation on the outcome of DNA-based newborn screening for SCID and SMA and compared the efficacy of rapid extraction versus automated protocols. Additionally, the distribution of T cell receptor excision circles (TREC) on DBS cards, commonly used for routine newborn screening, was determined.
RESULTS
Contaminations from the punching procedure were detected in the SCID and SMA assays in all experimental setups tested. However, a careful evaluation of a cut-off allowed for a clear separation of true positive polymerase chain reaction (PCR) amplifications. Our rapid in-house extraction protocol produced similar amounts compared to automated commercial systems. Therefore, it can be used for reliable DNA-based screening. Additionally, the amount of extracted DNA significantly differs depending on the location of punching within a DBS.
CONCLUSIONS
Newborn screening for SMA and SCID can be performed reliably. It is crucial to ensure that affected newborns are not overlooked. Therefore a carefully consideration of potential contaminating factors and the definition of appropriate cut-offs to minimise the risk of false results are of special concern. It is also important to note that the location of punching plays a pivotal role, and therefore an exact quantification of TREC numbers per μl may not be reliable and should therefore be avoided.
Topics: Humans; Neonatal Screening; Infant, Newborn; Muscular Atrophy, Spinal; Severe Combined Immunodeficiency; DNA; Dried Blood Spot Testing; High-Throughput Screening Assays; Polymerase Chain Reaction
PubMed: 38941330
DOI: 10.1371/journal.pone.0306329 -
PloS One 2024A growing increase in the number of serious infections caused by multidrug resistant bacteria (MDR) is challenging our society. Despite efforts to discover novel...
A growing increase in the number of serious infections caused by multidrug resistant bacteria (MDR) is challenging our society. Despite efforts to discover novel therapeutic options, few antibiotics targeting MDR have been approved by the Food and Drug Administration (FDA). Lactic acid bacteria have emerged as a promising therapeutic alternative due to their demonstrated ability to combat MDR pathogens in vitro. Our previous co-culture studies showed Lacticaseibacillus rhamnosus CRL 2244 as having a potent killing effect against carbapenem-resistant Acinetobacter baumannii (CRAB) strains. Here we report that cell-free conditioned media (CFCM) samples obtained from Lcb. rhamnosus CRL 2244 cultures incubated at different times display antimicrobial activity against 43 different pathogens, including CRAB, methicillin-resistant Staphylococcus aureus (MRSA) and carbapenemase Klebsiella pneumoniae (KPC)-positive strains. Furthermore, transwell and ultrafiltration analyses together with physical and chemical/biochemical tests showed that Lcb. rhamnosus CRL 2244 secretes a <3 kDa metabolite(s) whose antimicrobial activity is not significantly impaired by mild changes in pH, temperature and various enzymatic treatments. Furthermore, sensitivity and time-kill assays showed that the bactericidal activity of the Lcb. rhamnosus CRL 2244 metabolite(s) enhances the activity of some current FDA approved antibiotics. We hypothesize that this observation could be due to the effects of Lcb. rhamnosus CRL 2244 metabolite(s) on cell morphology and the enhanced transcriptional expression of genes coding for the phenylacetate (PAA) and histidine catabolic Hut pathways, metal acquisition and biofilm formation, all of which are associated with bacterial virulence. Interestingly, the extracellular presence of Lcb. rhamnosus CRL 2244 induced the transcription of the gene coding for the CidA/LgrA protein, which is involved in programmed cell death in some bacteria. Overall, the findings presented in this report underscore the promising potential of the compound(s) released by Lcb. rhamnosus CRL2244 as an alternative and/or complementary option to treat infections caused by A. baumannii as well as other MDR bacterial pathogens.
Topics: Lacticaseibacillus rhamnosus; Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Microbial Sensitivity Tests; Acinetobacter baumannii; Drug Synergism; Methicillin-Resistant Staphylococcus aureus; Culture Media, Conditioned; Bacterial Proteins
PubMed: 38941324
DOI: 10.1371/journal.pone.0306273 -
PloS One 2024This study develops a "Skill Talent Ecological Evaluation Model" across cultivation, potential energy, kinetic energy, innovation, and service and support ecologies....
This study develops a "Skill Talent Ecological Evaluation Model" across cultivation, potential energy, kinetic energy, innovation, and service and support ecologies. AHP-entropy determines indicator weights, Hopfield neural network assesses talent ecology levels, and the PVAR model analyzes digital transformation effects. Findings reveal: Cultivation ecology rates A, potential ecology rates B+, kinetic ecology rates B-, service and support ecology rates B-, and innovation ecology rates C. Digital transformation spurs skill demand, impacting talent and economic contributions. Kinetic ecology sees increased demand, potentially impacting traditional industries positively. Innovation ecology necessitates continuous skill learning. Service and support ecology witnesses growth in digital entrepreneurship, requiring policy incentives and incubation center support.
Topics: Neural Networks, Computer; China; Ecosystem; Humans; Ecology; Aptitude; Models, Theoretical
PubMed: 38941320
DOI: 10.1371/journal.pone.0302909 -
PloS One 2024Agricultural non-point source pollution control (ANSPC) is a complex, long-term and dynamic environmental protection process. In order to motivate multiple subjects to...
Agricultural non-point source pollution control (ANSPC) is a complex, long-term and dynamic environmental protection process. In order to motivate multiple subjects to participate in ANSPC, this paper constructs a tripartite evolutionary game model of local government, village collectives and farmers, which explores the strategic choices and influencing factors of different subjects through simulation analysis. The results indicate that: There are five stable strategy points in the ANSPC game system, which can be divided into four stages based on subject interactions. Village collectives should play an intermediary role in ANSPC and try to coordinate the behaviour of different subjects. The ideal and stable evolution state is "weak supervise, positive response, and active participate", but it cannot be realized at present. The strategy selection of subjects is determined by relative net income. Providing penalties requires considering the heterogeneity of subjects, but incentives are beneficial for achieving tripartite governance. This study provides new evidence for understanding the role of multi-agency participation in agricultural non-point source pollution control, and provides theoretical guidance for the government to formulate differentiated intervention mechanisms, which is an important reference for achieving sustainable development goals.
Topics: Agriculture; Humans; Game Theory; Environmental Pollution; Computer Simulation; Farmers; Models, Theoretical
PubMed: 38941318
DOI: 10.1371/journal.pone.0305191 -
PloS One 2024Based on 908 consumer questionnaire data from 15 urban areas in Shanghai, we use the binary logit model to empirically analyze the impact of traceability label trust on...
Based on 908 consumer questionnaire data from 15 urban areas in Shanghai, we use the binary logit model to empirically analyze the impact of traceability label trust on consumers' traceable pork purchase behavior and the moderating effect of food safety identification. After constructing the theoretical analysis framework, this paper verifies it from the two aspects of statistical analysis and econometric analysis and tests the robustness of the final results. The results show that: first, traceability label trust has a significant positive impact on consumers' traceability pork behavior. Second, food safety identification can significantly strengthen and promote this process. Third, consumers' purchasing behavior is significantly positively affected by traceable pork consumption scenarios and price labels, but the permanent elderly in the composition of family members significantly negative impact on it. Therefore, we put forward relevant policy suggestions, such as strengthening the knowledge popularization and publicity based on the advantageous commodity attributes of traceable pork, carrying out food safety knowledge popularization education, and enhancing consumers' risk perception and food safety identification ability.
Topics: Humans; Consumer Behavior; Food Safety; Male; Female; Food Labeling; Middle Aged; Adult; Trust; Surveys and Questionnaires; Animals; Swine; China; Young Adult; Aged
PubMed: 38941301
DOI: 10.1371/journal.pone.0306041 -
PloS One 2024Application essays are a commonly used admission instrument for students entering higher education. The quality of the essay is usually scored, but this score is often...
Application essays are a commonly used admission instrument for students entering higher education. The quality of the essay is usually scored, but this score is often subjective and has poor interrater reliability due to the unstructured format of the essays. This results in mixed findings on the validity of application essays as an admission instrument. We propose a more objective method of using application essays, using Latent Dirichlet Allocation (LDA), a text mining method, to distinguish seven moves occurring in application essays written by students who apply to a master degree program. We use the probability that these moves occur in the essay to predict study success in the master. Thereby we answer the following research question: What is the effect of discussing different moves in students' application essays on the student grades in a master program? From the seven different moves (functional unit of text) we distinguished, five of which have a significant effect on student grades. The moves we labeled as 'master specific' and 'interest to learn' have a positive effect on student grades, and the moves we labeled as 'research skills', 'societal impact' and 'city and university' have a negative effect. Our interpretation of this finding is that topics related to intrinsic motivation and specific knowledge, as opposed to generic knowledge, are positively related with study success. We thereby demonstrate that application essays can be a valid predictor of study success. This contributes to justifying their use as admission instruments.
Topics: Humans; Students; School Admission Criteria; Universities; Educational Measurement
PubMed: 38941298
DOI: 10.1371/journal.pone.0304394