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Biofilm Jun 2024platforms capable of mimicking the hydrodynamic conditions prevailing in natural aquatic environments have been previously validated and used to predict the fouling...
platforms capable of mimicking the hydrodynamic conditions prevailing in natural aquatic environments have been previously validated and used to predict the fouling behavior on different surfaces. Computational Fluid Dynamics (CFD) has been used to predict the shear forces occurring in these platforms. In general, these predictions are made for the initial stages of biofilm formation, where the amount of biofilm does not affect the flow behavior, enabling the estimation of the shear forces that initial adhering organisms have to withstand. In this work, we go a step further in understanding the flow behavior when a mature biofilm is present in such platforms to better understand the shear rate distribution affecting marine biofilms. Using 3D images obtained by Optical Coherence Tomography, a mesh was produced and used in CFD simulations. Biofilms of two different marine cyanobacteria were developed in agitated microtiter plates incubated at two different shaking frequencies for 7 weeks. The biofilm-flow interactions were characterized in terms of the velocity field and shear rate distribution. Results show that global hydrodynamics imposed by the different shaking frequencies affect biofilm architecture and also that this architecture affects local hydrodynamics, causing a large heterogeneity in the shear rate field. Biofilm cells located in the streamers of the biofilm are subjected to much higher shear values than those located on the bottom of the streamers and this dispersion in shear rate values increases at lower bulk fluid velocities. This heterogeneity in the shear force field may be a contributing factor for the heterogeneous behavior in metabolic activity, growth status, gene expression pattern, and antibiotic resistance often associated with nutrient availability within the biofilm.
PubMed: 38948680
DOI: 10.1016/j.bioflm.2024.100204 -
Journal of Family Medicine and Primary... May 2024Polycystic ovary syndrome (PCOS) is a heterogeneous disorder and various phenotypes have been described. While most women with PCOS are obese, women who are lean also...
BACKGROUND
Polycystic ovary syndrome (PCOS) is a heterogeneous disorder and various phenotypes have been described. While most women with PCOS are obese, women who are lean also suffer from PCOS. Metabolic derangements often accompany this syndrome. Family physicians, being the first point of contact in the healthcare system, play a vital role in the early diagnosis and management of this condition through diet and lifestyle modifications. The present study was conducted at the Diet and Lifestyle Diseases Management Division of a Family Medicine Clinic.
METHODS
We conducted a retrospective analysis of the correlation between body mass index (BMI) and metabolic parameters in women diagnosed with PCOS. The case records of women with PCOS, diagnosed as per modified Rotterdam criteria and who attended the outpatient clinic from January 2020 to December 2022, were chosen. Data on BMI and metabolic parameters were retrieved and statistically analyzed.
RESULTS
Upon analysis of 51 case records, 25.49% of women were in the lean group and 74.51% were overweight or obese. Triglycerides/HDL ratio (1.91 ± 0.47 vs 3.97 ± 5.89) and Vitamin D levels (Median 14.12 vs 16.10 ng/ml) were abnormal in both the obese and the lean women groups. However, there was no significant difference between the groups. Other metabolic parameters were within normal ranges.
CONCLUSION
The present study indicates that metabolic derangements are associated with PCOS, irrespective of BMI. More robust studies in larger population samples are needed to elucidate the role of metabolic derangements and mainly insulin resistance in the pathophysiology of PCOS and its different phenotypes.
PubMed: 38948599
DOI: 10.4103/jfmpc.jfmpc_1425_23 -
Journal of Family Medicine and Primary... May 2024Oral lymphomas are rare and present a diagnostic challenge. Immunophenotyping is essential to decipher their biology and identify therapeutic targets. Histopathology can...
Oral lymphomas are rare and present a diagnostic challenge. Immunophenotyping is essential to decipher their biology and identify therapeutic targets. Histopathology can prove to be diagnostically difficult to type these lesions, and hence, immunohistochemistry (IHC) proves useful in deciphering their biology. Here, we present an evidence-based approach using a novel immunohistochemical marker panel to diagnose oral lymphomas by discussing four unique cases.
PubMed: 38948544
DOI: 10.4103/jfmpc.jfmpc_1570_23 -
Cancer Innovation Feb 2024In recent years, the three-dimensional (3D) culture system has emerged as a promising preclinical model for tumor research owing to its ability to replicate the tissue... (Review)
Review
In recent years, the three-dimensional (3D) culture system has emerged as a promising preclinical model for tumor research owing to its ability to replicate the tissue structure and molecular characteristics of solid tumors in vivo. This system offers several advantages, including high throughput, efficiency, and retention of tumor heterogeneity. Traditional Matrigel-submerged organoid cultures primarily support the long-term proliferation of epithelial cells. One solution for the exploration of the tumor microenvironment is a reconstitution approach involving the introduction of exogenous cell types, either in dual, triple or even multiple combinations. Another solution is a holistic approach including patient-derived tumor fragments, air-liquid interface, suspension 3D culture, and microfluidic tumor-on-chip models. Organoid co-culture models have also gained popularity for studying the tumor microenvironment, evaluating tumor immunotherapy, identifying predictive biomarkers, screening for effective drugs, and modeling infections. By leveraging these 3D culture systems, it is hoped to advance the clinical application of therapeutic approaches and improve patient outcomes.
PubMed: 38948532
DOI: 10.1002/cai2.101 -
Frontiers in Pharmacology 2024Neurodevelopmental disorders (NDDs) include a broad spectrum of pathological conditions that affect >4% of children worldwide, share common features and present a... (Review)
Review
Neurodevelopmental disorders (NDDs) include a broad spectrum of pathological conditions that affect >4% of children worldwide, share common features and present a variegated genetic origin. They include clinically defined diseases, such as autism spectrum disorders (ASD), attention-deficit/hyperactivity disorder (ADHD), motor disorders such as Tics and Tourette's syndromes, but also much more heterogeneous conditions like intellectual disability (ID) and epilepsy. Schizophrenia (SCZ) has also recently been proposed to belong to NDDs. Relatively common causes of NDDs are copy number variations (CNVs), characterised by the gain or the loss of a portion of a chromosome. In this review, we focus on deletions and duplications at the 16p11.2 chromosomal region, associated with NDDs, ID, ASD but also epilepsy and SCZ. Some of the core phenotypes presented by human carriers could be recapitulated in animal and cellular models, which also highlighted prominent neurophysiological and signalling alterations underpinning 16p11.2 CNVs-associated phenotypes. In this review, we also provide an overview of the genes within the 16p11.2 locus, including those with partially known or unknown function as well as non-coding RNAs. A particularly interesting interplay was observed between MVP and MAPK3 in modulating some of the pathological phenotypes associated with the 16p11.2 deletion. Elucidating their role in intracellular signalling and their functional links will be a key step to devise novel therapeutic strategies for 16p11.2 CNVs-related syndromes.
PubMed: 38948459
DOI: 10.3389/fphar.2024.1407865 -
Indian Journal of Orthopaedics Jul 2024Exosomes are the smallest extracellular vesicles (30-150 nm) secreted by all cell types, including synovial fluid. However, because biological fluids are complex,... (Review)
Review
BACKGROUND
Exosomes are the smallest extracellular vesicles (30-150 nm) secreted by all cell types, including synovial fluid. However, because biological fluids are complex, heterogeneous, and contain contaminants, their isolation is difficult and time-consuming. Furthermore, the pathophysiology of osteoarthritis (OA) involves exosomes carrying complex components that cause macrophages to release chemokines and proinflammatory cytokines. This narrative review aims to provide in-depth insights into exosome biology, isolation techniques, role in OA pathophysiology, and potential role in future OA therapeutics.
METHODS
A literature search was conducted using PubMed, Scopus, and Web of Science databases for studies involving exosomes in the osteoarthritis using keywords "Exosomes" and "Osteoarthritis". Relevant articles in the last 15 years involving both human and animal models were included. Studies involving exosomes in other inflammatory diseases were excluded.
RESULTS
Despite some progress, conventional techniques for isolating exosomes remain laborious and difficult, requiring intricate and time-consuming procedures across various body fluids and sample origins. Moreover, exosomes are involved in various physiological processes associated with OA, like cartilage calcification, degradation of osteoarthritic joints, and inflammation.
CONCLUSION
The process of achieving standardization, integration, and high throughput of exosome isolation equipment is challenging and time-consuming. The integration of various methodologies can be employed to effectively address specific issues by leveraging their complementary benefits. Exosomes have the potential to effectively repair damaged cartilage OA, reduce inflammation, and maintain a balance between the formation and breakdown of cartilage matrix, therefore showing promise as a therapeutic option for OA.
PubMed: 38948378
DOI: 10.1007/s43465-024-01175-7 -
Pleura and Peritoneum Jun 2024Malignant pleural effusion (MPE) is a common and debilitating condition seen in advanced cancer disease, and life-expectancy is short. Symptoms include pain and severe... (Review)
Review
BACKGROUND
Malignant pleural effusion (MPE) is a common and debilitating condition seen in advanced cancer disease, and life-expectancy is short. Symptoms include pain and severe shortness of breath. Current first-line treatment options include pleural drainage using catheters as well as pleurodesis. However, these treatment modalities are often inefficient and patients need repeated procedures. Pressurized IntraThoracic Aerosol Chemotherapy (PITAC) is a minimally invasive procedure, where antineoplastic agents are nebulized under pressure into the pleural space.
CONTENT
We present the preliminary safety, feasibility, and response assessment data for PITAC based on a comprehensive literature review.
SUMMARY
Five retrospective studies reported data on 38 PITACs in 21 patients. Data were heterogeneous and incomplete on several important aspects such as procedure, safety, local effect and long-term outcomes. PITAC seems technically feasible with a low risk of complications and may provide some reduction in MPE in selected cases.
OUTLOOK
PITAC seems feasible, but prospective phase I and II studies are needed to define safety, indications, and efficacy.
PubMed: 38948327
DOI: 10.1515/pp-2023-0048 -
PNAS Nexus Jun 2024Large language models (LLMs) demonstrate increasingly human-like abilities across a wide variety of tasks. In this paper, we investigate whether LLMs like ChatGPT can...
Large language models (LLMs) demonstrate increasingly human-like abilities across a wide variety of tasks. In this paper, we investigate whether LLMs like ChatGPT can accurately infer the psychological dispositions of social media users and whether their ability to do so varies across socio-demographic groups. Specifically, we test whether GPT-3.5 and GPT-4 can derive the Big Five personality traits from users' Facebook status updates in a zero-shot learning scenario. Our results show an average correlation of ( ) between LLM-inferred and self-reported trait scores-a level of accuracy that is similar to that of supervised machine learning models specifically trained to infer personality. Our findings also highlight heterogeneity in the accuracy of personality inferences across different age groups and gender categories: predictions were found to be more accurate for women and younger individuals on several traits, suggesting a potential bias stemming from the underlying training data or differences in online self-expression. The ability of LLMs to infer psychological dispositions from user-generated text has the potential to democratize access to cheap and scalable psychometric assessments for both researchers and practitioners. On the one hand, this democratization might facilitate large-scale research of high ecological validity and spark innovation in personalized services. On the other hand, it also raises ethical concerns regarding user privacy and self-determination, highlighting the need for stringent ethical frameworks and regulation.
PubMed: 38948324
DOI: 10.1093/pnasnexus/pgae231 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024Atrial fibrillation (AF) is a disease of high heterogeneity, and the association between AF phenotypes and the outcome of different catheter ablation strategies remains...
OBJECTIVE
Atrial fibrillation (AF) is a disease of high heterogeneity, and the association between AF phenotypes and the outcome of different catheter ablation strategies remains unclear. Conventional classification of AF (e.g. according to duration, atrial size, and thromboembolism risk) fails to provide reference for the optimal stratification of the prognostic risks or to guide individualized treatment plan. In recent years, research on machine learning has found that cluster analysis, an unsupervised data-driven approach, can uncover the intrinsic structure of data and identify clusters of patients with pathophysiological similarity. It has been demonstrated that cluster analysis helps improve the characterization of AF phenotypes and provide valuable prognostic information. In our cohort of AF inpatients undergoing radiofrequency catheter ablation, we used unsupervised cluster analysis to identify patient subgroups, to compare them with previous studies, and to evaluate their association with different suitable ablation patterns and outcomes.
METHODS
The participants were AF patients undergoing radiofrequency catheter ablation at West China Hospital between October 2015 and December 2017. All participants were aged 18 years or older. They underwent radiofrequency catheter ablation during their hospitalization. They completed the follow-up process under explicit informed consent. Patients with AF of a reversible cause, severe mitral stenosis or prosthetic heart valve, congenital heart disease, new-onset acute coronary syndrome within three months prior to the surgery, or a life expectancy less than 12 months were excluded according to the exclusion criteria. The cohort consisted of 1102 participants with paroxysmal or persistent/long-standing persistent AF. Data on 59 variables representing demographics, AF type, comorbidities, therapeutic history, vital signs, electrocardiographic and echocardiographic findings, and laboratory findings were collected. Overall, data for the variables were rarely missing (<5%), and multiple imputation was used for correction of missing data. Follow-up surveys were conducted through outpatient clinic visits or by telephone. Patients were scheduled for follow-up with 12-lead resting electrocardiography and 24-hours Holter monitoring at 3 months and 6 months after the ablation procedure. Early ablation success was defined as the absence of documented AF, atrial flutter, or atrial tachycardia >30 seconds at 6-month follow-up. Hierarchical clustering was performed on the 59 baseline variables. All characteristic variables were standardized to have a mean of zero and a standard deviation of one. Initially, each patient was regarded as a separate cluster, and the distance between these clusters was calculated. Then, the Ward minimum variance method of clustering was used to merge the pair of clusters with the minimum total variance. This process continued until all patients formed one whole cluster. The "NbClust" package in R software, capable of calculating various statistical indices, including pseudo t index, cubic clustering criterion, silhouette index etc, was applied to determine the optimal number of clusters. The most frequently chosen number of clusters by these indices was selected. A heatmap was generated to illustrate the clinical features of clusters, while a tree diagram was used to depict the clustering process and the heterogeneity among clusters. Ablation strategies were compared within each cluster regarding ablation efficacy.
RESULTS
Five statistically driven clusters were identified: 1) the younger age cluster (=404), characterized by the lowest prevalence of cardiovascular and cerebrovascular comorbidities but the highest prevalence of obstructive sleep apnea syndrome (14.4%); 2) a cluster of elderly adults with chronic diseases (=438), the largest cluster, showing relatively higher rates of hypertension, diabetes, stroke, and chronic obstructive pulmonary disease; 3) a cluster with high prevalence of sinus node dysfunction (=160), with patients showing the highest prevalence of sick sinus syndrome and pacemaker implantation; 4) the heart failure cluster (=80), with the highest prevalence of heart failure (58.8%) and persistent/long-standing persistent AF (73.7%); 5) prior coronary artery revascularization cluster (=20), with patients of the most advanced age (median: 69.0 years old) and predominantly male patients, all of whom had prior myocardial infarction and coronary artery revascularization. Patients in cluster 2 achieved higher early ablation success with pulmonary veins isolation alone compared to extensive ablation strategies (79.6% vs. 66.5%; odds ratio [OR]=1.97, 95% confidence interval [CI]: 1.28-3.03). Although extensive ablation strategies had a slightly higher success rate in the heart failure group, the difference was not statistically significant.
CONCLUSIONS
This study provided a unique classification of AF patients undergoing catheter ablation by cluster analysis. Age, chronic disease, sinus node dysfunction, heart failure and history of coronary artery revascularization contributed to the formation of the five clinically relevant subtypes. These subtypes showed differences in ablation success rates, highlighting the potential of cluster analysis in guiding individualized risk stratification and treatment decisions for AF patients.
PubMed: 38948279
DOI: 10.12182/20240560101 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024Some epidemiological studies have shown that pregnant women who develop preeclampsia (PE) have elevated levels of testosterone in their maternal plasma compared to women...
OBJECTIVE
Some epidemiological studies have shown that pregnant women who develop preeclampsia (PE) have elevated levels of testosterone in their maternal plasma compared to women with normal blood pressure during pregnancy, revealing a potential association between hyperandrogenism in women and PE. To explore the causal relationship between hyperandrogenism and PE, this study selected total testosterone (TT), bioavailable testosterone (BIOT), and sex hormone binding globulin (SHBG) as exposure factors and PE and chronic hypertension with superimposed PE as disease outcomes. Two-sample Mendelian randomization (MR) analyses were used to genetically dissect the causal relationships between the three exposure factors (TT, BIOT, and SHBG) and the outcomes of PE and chronic hypertension with superimposed PE.
METHODS
Two independent genome-wide association study (GWAS) databases were used for the two-sample MR analysis. In the GWAS data of female participants from the UK Biobank cohort, single nucleotide polymorphisms (SNPs) associated with TT, BIOT, and SHBG were analyzed, involving 230454, 188507, and 188908 samples, respectively. GWAS data on PE and chronic hypertension with superimposed PE from the Finnish database were used to calculate SNP, involving 3556 PE cases and 114735 controls, as well as 38 cases of chronic hypertension with superimposed PE and 114735 controls. To meet the assumptions of instrumental relevance and independence in MR analysis, SNPs associated with exposure were identified at the genome-wide level (<5.0×10), and those in linkage disequilibrium interference were excluded based on clustering thresholds of <0.001 and an allele distance greater than 10000 kb. Known confounding factors, including previous PE, chronic kidney disease, chronic hypertension, diabetes, systemic lupus erythematosus, or antiphospholipid syndrome, were also identified and the relevant SNPs were removed. Finally, we extracted the outcome data based on the exposure-related SNPs in the outcome GWAS, integrating exposure and outcome data, and removing palindromic sequences. Five genetic causal analysis methods, including inverse variance-weighted method (IVW), MR-Egger regression, weighted median method, simple mode method, and weighted mode method, were used to infer causal relationships. In the IVW, it was assumed that the selected SNPs satisfied the three assumptions and provided the most ideal estimate of the effect. IVW was consequently used as the primary analysis method in this study. Considering the potential heterogeneity among the instrumental variables, random-effects IVW was used for MR analysis. The results were interpreted using odds ratios (OR) and the corresponding 95% confidence interval (CI) to explain the impact of exposure factors on PE and chronic hypertension with superimposed PE. If the CI did not include 1 and had a value less than 0.05, the difference was considered statistically significant. Sensitivity analysis was conducted to assess heterogeneity and pleiotropy. Heterogeneity was examined using Cochran's test, and pleiotropy was assessed using MR-Egger intercept analysis. Additionally, leave-one-out analysis was conducted to examine whether individual SNPs were driving the causal associations. To further validate the findings, MR analyses were performed using the same methods and outcome variables, but with different exposure factors, including waist-to-hip ratio adjusted for BMI (WHRadjBMI) and 25-hydroxyvitamin D levels, with MR results for WHRadjBMI and PE serving as the positive controls and MR results for 25-hydroxyvitamin D levels and PE as the negative controls.
RESULTS
According to the criteria for selecting genetic instrumental variables, 186, 127, and 262 SNPs were identified as genetic instrumental variables significantly associated with testosterone indicators TT, BIOT, and SHBG. MR analysis did not find a causal relationship between the TT, BIOT, and SHBG levels and the risk of developing PE and chronic hypertension with superimposed PE. The IVW method predicted that genetically predicted TT (OR [95% CI]=1.018 [0.897-1.156], =0.78), BIOT (OR [95% CI]=1.11 [0.874-1.408], =0.392), and SHBG (OR [95% CI]=0.855 [0.659-1.109], =0.239) were not associated with PE. Similarly, genetically predicted TT (OR [95% CI]=1.222 [0.548-2.722], =0.624), BIOT (OR [95% CI]=1.066 [0.242-4.695], =0.933), and SHBG (OR [95% CI]=0.529 [0.119-2.343], =0.402) were not significantly associated with chronic hypertension with superimposed PE. Additionally, MR analysis using the MR-Egger method, weighted median method, simple mode method, and weighted mode method yielded consistent results, indicating no significant causal relationship between elevated testosterone levels and PE or chronic hypertension with superimposed PE. Heterogeneity was observed for SHBG in the analysis with PE (Cochran's test, =0.01), and pleiotropy was detected for BIOT in the analysis with PE (MR-Egger intercept analysis, =0.014), suggesting that the instrumental variables did not affect PE through BIOT. Other instrumental variables did not show significant heterogeneity or pleiotropy. Leave-one-out analysis confirmed that the results of the MR analysis were not driven by individual instrumental variables. Consistent with previous MR studies, the results of the control MR analyses using WHRadjBMI and 25-hydroxyvitamin D levels supported the accuracy of the MR analysis approach and the methods used in this study.
CONCLUSION
The MR analysis results suggest that current genetic evidence does not support a causal relationship between TT, BIOT, and SHBG levels and the development of PE and chronic hypertension with superimposed PE. This study suggests that elevated testosterone may be a risk factor for PE but not a direct cause.
PubMed: 38948277
DOI: 10.12182/20240560106