Performance evaluation of different regression models: application in a breast cancer patient data.

This paper provides a comprehensive analysis of linear regression models, focusing on addressing multicollinearity challenges in breast cancer patient data. Linear regression methodologies, including GAM, Beta, GAM Beta, Ridge, and Beta Ridge, are compared using two statistical criteria. The study, conducted with R software, showcases the Beta regression model's exceptional performance, achieving a BIC of - 5520.416. Furthermore, the Ridge regression model demonstrates remarkable results with the best AIC at - 8002.647. The findings underscore the practical application of these models in real-world scenarios and emphasize the Beta regression model's superior ability to handle multicollinearity challenges. The preference for AIC over BIC in Generalized Additive Models (GAMs) is rooted in the AIC's calculation framework, highlighting its effectiveness in capturing the complexity and flexibility inherent in GAMs.

Platelet transfusion in patients with liver cirrhosis crosstalk with neutrophil: Prospective study

ABSTRACT Introduction: Immune dysfunction and thrombocytopenia are common features in liver cirrhosis. Platelet transfusion is the most widely used therapeutic approach for thrombocytopenia when indicated. The transfused platelets are prone to lesions during their storage that empower their interaction with the recipient leucocyte. These interactions modulate the host immune response. The impact of platelet transfusion on the immune system in cirrhotic patients is little understood. Therefore, this study aims to investigate the impact of platelet transfusion on neutrophil function in cirrhotic patients. Methods: This prospective cohort study was implemented on 30 cirrhotic patients receiving platelet transfusion and 30 healthy individuals as a control group. EDTA blood samples were collected from cirrhotic patients before and after an elective platelet transfusion. Flowcytometric analysis of neutrophil functions (CD11b expression and PCN formation) was performed. Results: There was a significant increase in expression of CD11b on neutrophils and Frequency of platelet-complexed neutrophils (PCN) in patients with cirrhosis compared with controls. Platelet transfusion increased level of CD11b and the frequency of PCN even more. There was a significant positive correlation between change in PCN Frequency pefore and after transfusion and the change in expression of CDllb among cirrhotic patients. Conclusions: Elective platelet transfusion appears to increase level of PCN in cirrhotic patients, moreover, exacerbate the expression of activation marker CDllb on both neutrophils and PCN. More research and studies are needed to corroborate our preliminary findings.

A lower prevalence of malignant lymphoma in Sjögren's syndrome patients: A cross-sectional study.

OBJECTIVE: This study aims to determine the prevalence and risk factors associated with lymphoma in primary Sjögren's syndrome (pSS). METHODS: We conducted a cross-sectional study on pSS patients who were registered into the Integrated Data Repository (IDR) at the University of Florida (UF) Health Shands Hospital. The parameters, such as age, sex, race, and smoking status, were included. Lymphoma types in pSS were categorized. The clinical and laboratory features were compared between pSS patients with and those without lymphoma by utilizing the items in the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). RESULTS: Among 1,211,343 patients, we found 6799 patients (0.56%) with lymphomas and 2562 patients (0.21%) with pSS. Out of the 2562 pSS patients, 67 patients (2.6%) were diagnosed with lymphoma. The difference in the clinical and laboratory features listed under the ESSDAI domains between pSS patients with lymphomas and pSS without it was significant (p < 0.05 or 0.01): fever, weight loss, lymphadenopathy, splenomegaly, lacrimal gland diseases, cough, shortness of breath, hematuria, cerebrovascular accident diseases, peripheral nerve involvement due to vasculitis, neutropenia, and thrombocytopenia. CONCLUSION: We report 2.6% of lymphoma prevalence in pSS, lower than previously reported in the literature.

A Bioinformatics Systems Biology Analysis of the Current Oral Proteomic Biomarkers and Implications for Diagnosis and Treatment of External Root Resorption.

External root resorption (ERR) is a silent destructive phenomenon detrimental to dental health. ERR may have multiple etiologies such as infection, inflammation, traumatic injuries, pressure, mechanical stimulations, neoplastic conditions, systemic disorders, or idiopathic causes. Often, if undiagnosed and untreated, ERR can lead to the loss of the tooth or multiple teeth. Traditionally, clinicians have relied on radiographs and cone beam computed tomography (CBCT) images for the diagnosis of ERR; however, these techniques are not often precise or definitive and may require exposure of patients to more ionizing radiation than necessary. To overcome these shortcomings, there is an immense need to develop non-invasive approaches such as biomarker screening methods for rapid and precise diagnosis for ERR. In this review, we performed a literature survey for potential salivary or gingival crevicular fluid (GCF) proteomic biomarkers associated with ERR and analyzed the potential pathways leading to ERR. To the best of our knowledge, this is the first proteomics biomarker survey that connects ERR to body biofluids which represents a novel approach to diagnose and even monitor treatment progress for ERR.

Clinical usefulness of anti-muscarinic type 3 receptor autoantibodies in patients with primary Sjögren's syndrome.

OBJECTIVES: To elucidate the clinical values of anti-M3R in Sjögren's syndrome (SS) in the largest cohort for an anti-M3R study. METHODS: The plasma of 361 subjects (156 primary SS [pSS], 62 non-SS-sicca [SICCA], 40 systemic lupus erythematosus [SLE], 50 rheumatoid arthritis [RA], and 53 healthy controls [HC]) was screened using our modified On-Cell-Western assay. Saliva from pSS (n=37) compared to SICCA (n=26) was also analysed. The sensitivity and specificity of anti-M3R and its association with comprehensive clinical and laboratory features were determined. RESULTS: Plasma-anti-M3R was higher in pSS compared to other groups, differentiating pSS with good-to-excellent diagnostic power with a specificity of 85% and a sensitivity between 75% and 98%. pSS plasma-anti-M3R was positively correlated with ocular staining scores, anti-Ro/SSA, IgG, ß2-microglobulin, ESR, and ESSDAI. It was negatively correlated with WBC, C4, and salivary scintigraphic indices. Saliva-anti-M3R was 3.59 times higher in pSS than in SICCA. Interestingly, the agreement between the 2002 American European Consensus Group criteria and the criteria substituted with plasma-anti-M3R for the lip biopsy reached 92%, with a significant kappa of 0.824. CONCLUSIONS: Anti-M3R enhances sensitivity and specificity for SS diagnosis, correlating with ocular dryness and glandular hypofunction, and the haematological/biological domains of the ESSDAI. Our findings also highlight the clinical significance of anti-M3R in SS diagnosis, especially where clinical assessments, such as lip biopsy, sialometry, or ocular evaluation, by multi-disciplinary specialists are limited.

Secretome Analysis of Inductive Signals for BM-MSC Transdifferentiation into Salivary Gland Progenitors.

Severe dry mouth in patients with Sjögren's Syndrome, or radiation therapy for patients with head and neck cancer, significantly compromises their oral health and quality of life. The current clinical management of xerostomia is limited to palliative care as there are no clinically-proven treatments available. Previously, our studies demonstrated that mouse bone marrow-derived mesenchymal stem cells (mMSCs) can differentiate into salivary progenitors when co-cultured with primary salivary epithelial cells. Transcription factors that were upregulated in co-cultured mMSCs were identified concomitantly with morphological changes and the expression of acinar cell markers, such as α-amylase (AMY1), muscarinic-type-3-receptor(M3R), aquaporin-5(AQP5), and a ductal cell marker known as cytokeratin 19(CK19). In the present study, we further explored inductive molecules in the conditioned media that led to mMSC reprogramming by high-throughput liquid chromatography with tandem mass spectrometry and systems biology. Our approach identified ten differentially expressed proteins based on their putative roles in salivary gland embryogenesis and development. Additionally, systems biology analysis revealed six candidate proteins, namely insulin-like growth factor binding protein-7 (IGFBP7), cysteine-rich, angiogenetic inducer, 61(CYR61), agrin(AGRN), laminin, beta 2 (LAMB2), follistatin-like 1(FSTL1), and fibronectin 1(FN1), for their potential contribution to mMSC transdifferentiation during co-culture. To our knowledge, our study is the first in the field to identify soluble inductive molecules that drive mMSC into salivary progenitors, which crosses lineage boundaries.

Pressure-induced left ventricular hypertrophy in canine model of aortic stenosis using nylon tie

The aim of this study was to develop an experimentally-induced canine model of left ventricular hypertrophy through banding of the ascending aorta using nylon ties. Seven clinically normal dogs free of cardiovascular disease were used. Nylon tie was used in banding the mid-ascending aorta. Clinical, radiographic and echocardiographic evaluations were done at 1.5, 3 and 6 months. Dogs were euthanized at 6 months for post mortem and histopathological evaluation. Clinically, dogs did not exhibit any signs of cardiovascular disease at 1.5 or 3 months, while at 6 months two dogs (28.6 %) exhibited mild weight loss, exercise intolerance and heart murmurs. Radiographic evaluation revealed significant increase in cardiac size only at 6 months based on measurement of the cardiothoracic area evaluation. Echocardiography revealed increased left ventricular wall thickness starting from 1.5 month, although this increase was statistically significant at 3 and 6 months (p > 0.05). Left ventricular hypertrophy was confirmed by post mortem examination. Histopathological sections of left ventricle in all dogs demonstrated myocyte hypertrophy and interstitial fibrosis. This model simulates the naturally occurring ventricular hypertrophy using a rapid and economic technique. Such models are required to understand pathogenesis of heart disease and to develop effective treatment strategy.

MIST1, an Inductive Signal for Salivary Amylase in Mesenchymal Stem Cells.

Sjögren's syndrome (SjS) is an autoimmune disease that destroys the salivary glands and results in severe dry mouth. Mesenchymal stem cell (MSC) transplantation has been recently proposed as a promising therapy for restoring cells in multiple degenerative diseases. We have recently utilized advanced proteomics biochemical assays to identify the key molecules involved in the mesenchymal-epithelial transition (MET) of co-cultured mouse bone-marrow-derived MSCs mMSCs with primary salivary gland cells. Among the multiple transcription factors (TFs) that were differentially expressed, two major TFs were selected: muscle, intestine, and stomach expression-1 (MIST1) and transcription factor E2a (TCF3). These factors were assessed in the current study for their ability to drive the expression of acinar cell marker, alpha-salivary amylase 1 (AMY1), and ductal cell marker, cytokeratin19 (CK19), in vitro. Overexpression of MIST1-induced AMY1 expression while it had little effect on CK19 expression. In contrast, TCF3 induced neither of those cellular markers. Furthermore, we have identified that mMSCs express muscarinic-type 3 receptor (M3R) mainly in the cytoplasm and aquaporin 5 (AQP5) in the nucleus. While MIST1 did not alter M3R levels in mMSCs, a TCF3 overexpression downregulated M3R expressions in mMSCs. The mechanisms for such differential regulation of glandular markers by these TFs warrant further investigation.

Cryptochrome-1 Gene Expression is a Reliable Prognostic Indicator in Egyptian Patients with Chronic Lymphocytic Leukemia: A Prospective Cohort Study

Objective: Traditional prognostic factors have proved insufficient to account for heterogeneity in the clinical behavior of chronic lymphocytic leukemia (CLL). Cryptochrome-1 (CRY-1) is a circadian clock gene essential in maintaining the circadian rhythm and regulating cell proliferation. We evaluated CRY-1 gene expression in CLL and addressed its putative role as a prognostic indicator for the clinical course of CLL. Materials and Methods: A total of 100 CLL patients at diagnosis were studied for CRY-1 gene expression by real-time reverse-transcription polymerase chain reaction and were followed for assessment of time to first treatment (TFT). Results: CRY-1 was expressed in 94% of the CLL patients at diagnosis. The median CRY-1 relative gene expression level (0.006) stratified patients into high and low expression groups. Forty of 100 (40%) CLL patients showed high CRY-1, 54/100 (54%) showed low CRY-1, and 6/100 (6%) had undetectable CRY-1 gene expression. High CRY-1 gene expression was concordant with CD38+, Zap-70+, and double CD38+Zap-70+ expression; unfavorable/intermediate cytogenetics; unmutated immunoglobulin heavy-chain variable-region gene; and diffuse marrow infiltration. The high CRY-1 gene expression patient group exhibited shorter TFT than the patients with low CRY-1 gene expression. A Cox proportional hazard regression model identified CRY-1 gene expression to be independently predictive for TFT. Conclusion: CRY-1 is differentially expressed among CLL patients, stratifying them into low-risk and high-risk groups. CRY-1 gene expression could constitute a reliable prognostic indicator for CLL progression, complementing the role of standard well-established prognostic factors. CRY-1 gene expression could be employed as a prognostic indicator for disease progression during the initial prognostic work-up and follow-up for CLL patients.

Exploiting bilosomes for delivering bioactive polysaccharide isolated from Enteromorpha intestinalis for hacking hepatocellular carcinoma.

Bile salts containing vesicles (bilosomes) represent a portentous vesicular carrier that showed prosperous results in delivering active moieties in the gastrointestinal tract (GIT). In this study, bilosomes were exploited to deliver sulfated polysaccharide-protein complexes of Enteromorpha intestinalis (EHEM) and enhance its activity against hepatocellular carcinoma as well as resist harsh GIT conditions. Bilosomes were prepared using the sodium salt of three different bile acids (cholic, deoxycholic, taurodeoxycholic) and two different nonionic surfactants (Span 40 and 65). The effects of experimental variables were thoroughly studied to obtain an optimum formulation loading EHEM. The selected formulation (EH-Bilo-2) prepared with sodium cholate and Span 65 displayed nano-sized (181.1 ± 16.80 nm) spherical vesicles with reasonable entrapment efficiency (71.60 ± 0.25%) and controlled release properties; and thus was investigated as anti-hepatocarcinogenic candidate for in vivo studies. Treatment of hepatocellular carcinoma (HCC) bearing rats with EH-Bilo-2 experienced significant decrease in serum α-fetoprotein, endoglin, lipocalin-2, and heat shock protein 70 levels vs. the untreated counterparts. Furthermore, the photomicrographs of their liver tissue sections showed focal area of degenerated pleomorphic hepatocytes with fine fibrosis originating from the portal area. Thus, the optimized bilosomal formulation is a promising delegate for tackling hepatocellular carcinoma owing to its powerful anti-cancer and anti-angiogenic activity.

Myxoma virus sensitizes cancer cells to gemcitabine and is an effective oncolytic virotherapeutic in models of disseminated pancreatic cancer.

Myxoma virus (MYXV) is a novel oncolytic virus that has been shown to replicate in pancreatic cancer cells, but its efficacy in animal models of pancreatic cancer has not been determined. The efficacy of MYXV as monotherapy or in combination with gemcitabine was evaluated in intraperitoneal dissemination (IPD) models of pancreatic cancer. The effects of an intact immune system on the efficacy of MYXV therapy was tested by comparing immunodeficient versus immunocompetent murine models and combination therapy with gemcitabine was also evaluated. In cell culture, MYXV replication was robust in a broad range of pancreatic cancer cells and also showed increased oncolysis in combination with gemcitabine. In animal models, MYXV treatment conferred survival benefits over control or gemcitabine-treated cohorts regardless of the cell line or animal model used. MYXV monotherapy was most effective in an immunocompetent IPD model, and resulted in 60% long-term survivors. In Pan02 engrafted immunocompetent IPD models, sequential treatment in which MYXV was administered first, followed by gemcitabine, was the most effective and resulted in 100% long-term survivors. MYXV is an effective oncolytic virus for pancreatic cancer and can be combined with gemcitabine to enhance survival, particularly in the presence of an intact host immune system.