Improving the quality of care and patient safety in oncology, the contribution of simulation-based training: A scoping review.

Objective: Simulation-based training (SBT) is an effective educational method widely used in many clinical settings, including oncology. This study aimed to undertake a scoping review of research related to SBT in oncology to provide a comprehensive understanding of the role of SBT in enhancing the skills of healthcare professionals and thereby improving the quality of care and patient safety in oncology. Methods: We conducted a scoping review to map published studies in Medline, Scopus, and Web of Science databases. Peer-reviewed articles about data on the role of SBT in improving and enhancing the skills of healthcare professionals in oncology published in English and French from 2012 to 2022 were retrieved. Two researchers screened, extracted, and analyzed all identified studies independently. Results: Of the 1,013 publications identified in the initial phase, 29 studies were included in the analysis. Twenty-five of these studies focused on non-technical skills, such as decision-making, communication, teamwork, and cognitive abilities. Thirteen studies focused on technical skills. The results of all included studies showed significant improvement in the skills of oncology healthcare professionals through SBT programs. Fourteen studies subjectively assessed the role of this educational tool, while nine objectively evaluated it. Six studies used a combined subjective and objective evaluation method. Conclusions: SBT is a very effective tool for improving the skills of healthcare professionals in oncology. Supporting and promoting SBT is essential to providing high-quality care and ensuring patient safety in all areas of health care.

Rare images of an intense 18F-FDG PET-scan uptake in an incidentally discovered thyroid lesion: A case report.

Thyroid carcinoma is a type of cancer that starts in the cells of the thyroid gland, which plays a crucial role in regulating the body's metabolism. Thyroid cancer can manifest in various forms. We report the case of an 89 year-old patient presenting an incidental intense Fluorine-18-fluorodeoxyglucose (18F-FDG) PET-computed tomography (PET-CT) uptake within a thyroid lesion and the role of 18F-FDG PET-CT guiding the anatomopathological examination. The prevalence of FDG-avid thyroid incidentaloma ranges between 0.2% and 8.9%. Higher risks of cancer seems to be related to focal or unilateral uptake of 18F-FDG. Lesions with higher standardized uptake values or suspicious CT are more likely to be cancers. The diagnosis is clinically challenging. Nuclear and radiological images can guide practitioners.

Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial.

For patients with non-small-cell lung cancer (NSCLC) tumors without currently targetable molecular alterations, standard-of-care treatment is immunotherapy with anti-PD-(L)1 checkpoint inhibitors, alone or with platinum-doublet therapy. However, not all patients derive durable benefit and resistance to immune checkpoint blockade is common. Understanding mechanisms of resistance-which can include defects in DNA damage response and repair pathways, alterations or functional mutations in STK11/LKB1, alterations in antigen-presentation pathways, and immunosuppressive cellular subsets within the tumor microenvironment-and developing effective therapies to overcome them, remains an unmet need. Here the phase 2 umbrella HUDSON study evaluated rational combination regimens for advanced NSCLC following failure of anti-PD-(L)1-containing immunotherapy and platinum-doublet therapy. A total of 268 patients received durvalumab (anti-PD-L1 monoclonal antibody)-ceralasertib (ATR kinase inhibitor), durvalumab-olaparib (PARP inhibitor), durvalumab-danvatirsen (STAT3 antisense oligonucleotide) or durvalumab-oleclumab (anti-CD73 monoclonal antibody). Greatest clinical benefit was observed with durvalumab-ceralasertib; objective response rate (primary outcome) was 13.9% (11/79) versus 2.6% (5/189) with other regimens, pooled, median progression-free survival (secondary outcome) was 5.8 (80% confidence interval 4.6-7.4) versus 2.7 (1.8-2.8) months, and median overall survival (secondary outcome) was 17.4 (14.1-20.3) versus 9.4 (7.5-10.6) months. Benefit with durvalumab-ceralasertib was consistent across known immunotherapy-refractory subgroups. In ATM-altered patients hypothesized to harbor vulnerability to ATR inhibition, objective response rate was 26.1% (6/23) and median progression-free survival/median overall survival were 8.4/22.8 months. Durvalumab-ceralasertib safety/tolerability profile was manageable. Biomarker analyses suggested that anti-PD-L1/ATR inhibition induced immune changes that reinvigorated antitumor immunity. Durvalumab-ceralasertib is under further investigation in immunotherapy-refractory NSCLC.ClinicalTrials.gov identifier: NCT03334617.

Rheumatoid Arthritis Associated With Anti-Signal Recognition Particle Immune-Mediated Necrotizing Myopathy: A Case Report.

Immune-mediated necrotizing myopathy (IMNM) is a rare subtype of idiopathic inflammatory myopathy that is characterized by severe subacute proximal weakness, myofiber necrosis, and significantly elevated serum creatine kinase. Anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme-A reductase autoantibodies have been found in about two-thirds of patients with IMNM. This myopathy is usually idiopathic and there is a scarce literature concerning its association with connective tissue diseases. Herein, we report an unusual case of a young woman who presented with both rheumatoid arthritis and severe anti-SRP IMNM. Thankfully to a therapeutic protocol combining rituximab and cyclophosphamide, an important improvement was achieved, and notably no serious side effect was observed.

Pathological investigation of high pathogenicity avian influenza H5N8 in captive houbara bustards (Chlamydotis undulata), the United Arab Emirates 2020.

At the end of 2020, an outbreak of HPAI H5N8 was registered in captive African houbara bustards (Chlamydotis undulata) in the United Arab Emirates. In order to better understand the pathobiology of this viral infection in bustards, a comprehensive pathological characterization was performed. A total of six birds were selected for necropsy, histopathology, immunohistochemistry, RNAscope in situ hybridization and RT-qPCR and nanopore sequencing on formalin-fixed and paraffin-embedded (FFPE) tissue blocks. Gross lesions included mottled and/or hemorrhagic pancreas, spleen and liver and fibrinous deposits on air sacs and intestine. Necrotizing pancreatitis, splenitis and concurrent vasculitis, hepatitis and fibrino-heterophilic peritonitis were identified, microscopically. Viral antigens (nucleoprotein) and RNAs (matrix gene) were both detected within necro-inflammatory foci, parenchymal cells, stromal cells and endothelial cells of affected organs, including the myenteric plexus. Molecular analysis of FFPE blocks successfully detected HPAI H5N8, further confirming its involvement in the lesions observed. In conclusion, HPAI H5N8 in African houbara bustards results in hyperacute/acute forms exhibiting marked pantropism, endotheliotropism and neurotropism. In addition, our findings support the use of FFPE tissues for molecular studies of poorly characterized pathogens in exotic and endangered species, when availability of samples is limited.

Novel hybrid kepler optimization algorithm for parameter estimation of photovoltaic modules.

The parameter identification problem of photovoltaic (PV) models is classified as a complex nonlinear optimization problem that cannot be accurately solved by traditional techniques. Therefore, metaheuristic algorithms have been recently used to solve this problem due to their potential to approximate the optimal solution for several complicated optimization problems. Despite that, the existing metaheuristic algorithms still suffer from sluggish convergence rates and stagnation in local optima when applied to tackle this problem. Therefore, this study presents a new parameter estimation technique, namely HKOA, based on integrating the recently published Kepler optimization algorithm (KOA) with the ranking-based update and exploitation improvement mechanisms to accurately estimate the unknown parameters of the third-, single-, and double-diode models. The former mechanism aims at promoting the KOA's exploration operator to diminish getting stuck in local optima, while the latter mechanism is used to strengthen its exploitation operator to faster converge to the approximate solution. Both KOA and HKOA are validated using the RTC France solar cell and five PV modules, including Photowatt-PWP201, Ultra 85-P, Ultra 85-P, STP6-120/36, and STM6-40/36, to show their efficiency and stability. In addition, they are extensively compared to several optimization techniques to show their effectiveness. According to the experimental findings, HKOA is a strong alternative method for estimating the unknown parameters of PV models because it can yield substantially different and superior findings for the third-, single-, and double-diode models.

The Gut Microbiome Controls Liver Tumors via the Vagus Nerve.

Liver cancer ranks amongst the deadliest cancers. Nerves have emerged as an understudied regulator of tumor progression. The parasympathetic vagus nerve influences systemic immunity via acetylcholine (ACh). Whether cholinergic neuroimmune interactions influence hepatocellular carcinoma (HCC) remains uncertain. Liver denervation via hepatic vagotomy (HV) significantly reduced liver tumor burden, while pharmacological enhancement of parasympathetic tone promoted tumor growth. Cholinergic disruption in Rag1KO mice revealed that cholinergic regulation requires adaptive immunity. Further scRNA-seq and in vitro studies indicated that vagal ACh dampens CD8+ T cell activity via muscarinic ACh receptor (AChR) CHRM3. Depletion of CD8+ T cells abrogated HV outcomes and selective deletion of Chrm3 on CD8 + T cells inhibited liver tumor growth. Beyond tumor-specific outcomes, vagotomy improved cancer-associated fatigue and anxiety-like behavior. As microbiota transplantation from HCC donors was sufficient to impair behavior, we investigated putative microbiota-neuroimmune crosstalk. Tumor, rather than vagotomy, robustly altered fecal bacterial composition, increasing Desulfovibrionales and Clostridial taxa. Strikingly, in tumor-free mice, vagotomy permitted HCC-associated microbiota to activate hepatic CD8+ T cells. These findings reveal that gut bacteria influence behavior and liver anti-tumor immunity via a dynamic and pharmaceutically targetable, vagus-liver axis.

Non-alcoholic fatty liver disease in patients with morbid obesity: the gut microbiota axis as a potential pathophysiology mechanism.

BACKGROUND/AIM: Alterations in gut microbiota are associated with the pathogenesis of metabolic diseases, including metabolic-associated fatty liver disease (MAFLD). The aim of this study was to evaluate gut microbiota composition and functionality in patients with morbid obesity with different degrees of MAFLD, as assessed by biopsy. SUBJECTS/METHODS: 110 patients with morbid obesity were evaluated by biopsy obtained during bariatric surgery for MAFLD. Stool samples were collected prior to surgery for microbiota analysis. RESULTS: Gut microbiota from patients with steatosis and non-alcoholic steatohepatitis (NASH) were characterized by an enrichment in Enterobacteriaceae (an ethanol-producing bacteria), Acidaminococcus and Megasphaera and the depletion of Eggerthellaceae and Ruminococcaceae (SCFA-producing bacteria). MAFLD was also associated with enrichment of pathways related to proteinogenic amino acid degradation, succinate production, menaquinol-7 (K2-vitamin) biosynthesis, and saccharolytic and proteolytic fermentation. Basic histological hepatic alterations (steatosis, necroinflammatory activity, or fibrosis) were associated with specific changes in microbiota patterns. Overall, the core microbiome related to basic histological alterations in MAFLD showed an increase in Enterobacteriaceae and a decrease in Ruminococcaceae. Specifically, Escherichia coli was associated with steatosis and necroinflammatory activity, whilst Escherichia-shigella was associated with fibrosis and necroinflammatory activity. CONCLUSIONS: We established a link between gut microbiota alterations and histological injury in liver diagnosis using biopsy. Harmful products such as ethanol or succinate may be involved in the pathogenesis and progression of MAFLD. Thus, these alterations in gut microbiota patterns and their possible metabolic pathways could add information to the classical predictors of MAFLD severity and suggest novel metabolic targets.

Clinical and molecular features of acquired resistance to immunotherapy in non-small cell lung cancer.

Although immunotherapy with PD-(L)1 blockade is routine for lung cancer, little is known about acquired resistance. Among 1,201 patients with non-small cell lung cancer (NSCLC) treated with PD-(L)1 blockade, acquired resistance is common, occurring in >60% of initial responders. Acquired resistance shows differential expression of inflammation and interferon (IFN) signaling. Relapsed tumors can be separated by upregulated or stable expression of IFNγ response genes. Upregulation of IFNγ response genes is associated with putative routes of resistance characterized by signatures of persistent IFN signaling, immune dysfunction, and mutations in antigen presentation genes which can be recapitulated in multiple murine models of acquired resistance to PD-(L)1 blockade after in vitro IFNγ treatment. Acquired resistance to PD-(L)1 blockade in NSCLC is associated with an ongoing, but altered IFN response. The persistently inflamed, rather than excluded or deserted, tumor microenvironment of acquired resistance may inform therapeutic strategies to effectively reprogram and reverse acquired resistance.

The role of chamomile oil against ochratoxin A in quail breeders: productive and reproductive performances, egg quality, and blood metabolites.

This study aimed to evaluate the beneficial role of chamomile essential oil in improving productive and reproductive performances, egg quality, and blood metabolites and reducing the toxic effect of Ochratoxin A (OTA) in quail breeder's diets. A total of 144 mature quails, 8 wk old, were divided into 6 groups. The treatments were: G1 (the control), G2 (supplemented with OTA 1 mg/kg diet), G3 (supplemented with chamomile oil 0.5 g/kg diet), G4 (supplemented with chamomile oil 1 G/kg diet), G5 (supplemented with OTA 1 mg/kg diet + chamomile oil 0.5 g/kg diet), and G6 (supplemented with OTA 1 mg/kg diet + chamomile oil 1 g/kg diet). The OTA administration alone significantly decreased egg production and mass in quail breeders (P < 0.0001). Moreover, poor feed conversion ratio (FCR), fertility percentage (P < 0.0001), and hatchability percentage (P < 0.0009) were recorded. A significant decline (P < 0.05) in the levels of serum protein (total protein and globulin) was also recorded in OTA-contaminated groups, along with elevated serum levels of liver enzymes such as alanine transaminase (ALT) and Aspartate transaminase (AST) and kidney function test as urea and creatinine levels (P < 0.05). Ochratoxin A-contaminated feed resulted in a significant elevation (P < 0.05) in total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL), along with a significant reduction (P < 0.05) in antioxidant status and immunological response. The supplementation of chamomile essential oil, either 0.5 g/kg or 1g/kg, to the basal diet or OTA-supplemented feed, revealed a significant increase in hatchability %, fertility, egg mass, and egg production and better FCR, egg quality, and immunological status when compared to OTA only. Moreover, chamomile essential oil supplementation improves liver and kidney function markers, decreases LDL, VLDL), TG, and TC. Along with a significant increase (P < 0.05) in terms of antioxidant status as glutathione peroxidase enzyme (GPX), total antioxidant capacity (TAC), and superoxide dismutase (SOD) and significantly (P < 0.05) improves immunological response as IgM, IgG, lysozyme and complement 3. In summary, chamomile oil supplementation, either separate or combined with OTA, reduced the adverse effects of OTA and led to improved productive and reproductive performance, egg quality, and blood metabolites in Japanese quail breeders.

Adenosine A2a receptor inhibition increases the anti-tumor efficacy of anti-PD1 treatment in murine hepatobiliary cancers.

Backgrounds & Aims: The efficacy of immune checkpoint inhibitor (ICI) therapy for liver cancer remains limited. As the hypoxic liver environment regulates adenosine signaling, we tested the efficacy of adenosine A2a receptor (A2aR) inhibition in combination with ICI treatment in murine models of liver cancer. Methods: RNA expression related to the adenosine pathway was analyzed from public databases. Peripheral blood mononuclear cells of 13 patients with hepatocellular carcinoma (HCC) were examined by flow cytometry. The following murine cell lines were used: SB-1, RIL175, and Hep55.1c (liver cancer), CT26 (colon cancer), and B16-F10 (melanoma). C57BL/6 and BALB/c mice were used for orthotopic tumor models and were treated with SCH58261, an A2aR inhibitor, in combination with anti-PD1 therapy. Results: RNA expression of ADORA2A in tumor tissues derived from patients with HCC was higher than in tissues from other cancer types. A2aR+ T cells in peripheral blood from patients with HCC were highly proliferative after immunotherapy. Likewise, in an orthotopic murine model, A2aR expression on T cells increased following anti-PD1 treatment, and the expression of A2aR on T cells increased more in tumor-bearing mice compared with tumor-free mice. The combination of SCH58261 and anti-PD1 led to activation of T cells and reductions in tumor size in orthotopic liver cancer models. In contrast, SCH58261 monotherapy was ineffective in orthotopic liver cancer models and the combination was ineffective in the subcutaneous tumor models tested. CD4+ T-cell depletion attenuated the efficacy of the combination therapy. Conclusion: A2aR inhibition and anti-PD1 therapy had a synergistic anti-tumor effect in murine liver cancer models. Impact and implications: Adenosine A2a receptor (A2aR)-expressing T cells in the liver increased in tumor-bearing mice and after anti-PD1 treatment. The combination of an A2aR inhibitor and anti-PD1 treatment had potent anti-tumor effects in two murine models of orthotopic liver cancer. Adenosine A2a receptor blockade promotes immunotherapy efficacy in murine models, highlighting putative clinical benefits for advanced stage liver cancer patients.

Rare complications of infective endocarditis in marfan-like morphotype: diagnosis of multiple mitral valve aneurysms and aortic root abscess using three-dimensional transesophageal echocardiography.

Mitral valve aneurysm (MVA) is characterized by a saccular outpouching of the mitral leaflet, and it represents a rare condition typically associated with aortic valve endocarditis. Three-Dimensional Transesophageal Echocardiography (3D-TEE) serves as an effective tool for detecting the presence of MVA and its potential complications. In this report, we present a case involving a young man with striking images of bicuspid aortic valve endocarditis complicated by an aortic root abscess and multiple perforated mitral valve aneurysms, diagnosed using 3D TEE. This case suggests the uncommon coexistence of Marfan like morphotype, bicuspid aortic valve, and infective endocarditis as a triple mechanism in the occurrence of MVA. It underscores the significance of early and accurate imaging diagnosis for facilitating prompt surgical intervention.

Immunosuppressive CD29+ Treg accumulation in the liver in mice on checkpoint inhibitor therapy.

OBJECTIVE: Liver metastases are often resistant to immune checkpoint inhibitor therapy (ICI) and portend a worse prognosis compared with metastases to other locations. Regulatory T cells (Tregs) are one of several immunosuppressive cells implicated in ICI resistance of liver tumours, but the role played by Tregs residing within the liver surrounding a tumour is unknown. DESIGN: Flow cytometry and single-cell RNA sequencing were used to characterise hepatic Tregs before and after ICI therapy. RESULTS: We found that the murine liver houses a Treg population that, unlike those found in other organs, is both highly proliferative and apoptotic at baseline. On administration of αPD-1, αPD-L1 or αCTLA4, the liver Treg population doubled regardless of the presence of an intrahepatic tumour. Remarkably, this change was not due to the preferential expansion of the subpopulation of Tregs that express PD-1. Instead, a subpopulation of CD29+ (Itgb1, integrin ß1) Tregs, that were highly proliferative at baseline, doubled its size in response to αPD-1. Partial and full depletion of Tregs identified CD29+ Tregs as the prominent niche-filling subpopulation in the liver, and CD29+ Tregs demonstrated enhanced suppression in vitro when derived from the liver but not the spleen. We identified IL2 as a critical modulator of both CD29+ and CD29- hepatic Tregs, but expansion of the liver Treg population with αPD-1 driven by CD29+ Tregs was in part IL2-independent. CONCLUSION: We propose that CD29+ Tregs constitute a unique subpopulation of hepatic Tregs that are primed to respond to ICI agents and mediate resistance.

Chronic kidney disease's impact on revascularization and subsequent major adverse cardiovascular events in patients with chronic coronary syndrome.

OBJECTIVE: To determine the impact of CKD on the completeness of revascularization and major adverse cardiovascular events (MACE) in patients with chronic coronary syndrome (CCS). PATIENTS AND METHODS: The study enrolled 400 CCS patients who underwent revascularization by PCI. They were separated into two categories according to their eGFR levels: the control group: 200 patients with eGFR ≥60mL/min/1.73m2, and the CKD Group: 200 patients with eGFR< 60ml/min/1.73m.2 Patients were reclassified according to revascularization into complete and incomplete revascularization groups with one-year follow-up to assess the MACE. RESULTS: CKD patients were significantly older (65.78 ± 6.41 vs. 56.70 ± 9.20 years, P=<0.001). They had higher syntax scores (P = 0.005), CIN (P = 0.001), all-cause mortality (P = 0.02), MACE (P = 0.037), and heart failure (P = 0.014). After reclassification according to revascularization. GFR was significantly reduced among patients with incomplete revascularization (51.08 ± 28.15 vs. 65.67 ± 26.62, respectively, P =<0.001). Repeated revascularization (P < 0.001), STEMI (P = 0.003), stent thrombosis (P = 0.015), MACE (P < 0.001), stroke (P < 0.001), and all-cause mortality (P < 0.001) were more prevalent among patients with incomplete revascularization. Multivariate regression analysis revealed eGFR (P = 0.001) and Syntax score (SS) (P=<0.001) as independent predictors of incomplete revascularization. The optimal eGFR cutoff value for predicting partial revascularization is 49.50mL/min/1.73m2, with 58.8% sensitivity and 69.3 % specificity. CONCLUSION: Chronic kidney disease is associated with a higher syntax score and incomplete revascularization prevalence in CCS patients. Additionally, incomplete revascularization is associated with an increased incidence of major adverse cardiac events. In patients with CCS, CKD predicts partial revascularization and subsequent MACE.

Post-mortem 'soft flesh' in three commercial fish species from off Atlantic Morocco associated with the myxosporean parasites Kudoa thyrsites and K. encrasicoli (Myxozoa).

Small pelagic fishes represent one of the most important food resources off the Northwest coast of Africa. Despite their economic significance, little is known about the infections with flesh invading myxosporean parasites of genus Kudoa (Cnidaria, Myxozoa). Heavy infections in the flesh may be associated with post-mortem myoliquefaction, commonly known as 'soft flesh'. This condition may reduce the quality and marketability of the fish fillet, resulting in both economic losses to the fishing industry and loss of consumer confidence. In this study, we investigated Kudoa-induced 'soft flesh' occurrence in European anchovy Engraulis encrasicolus, European pilchard Sardina pilchardus, and Atlantic chub mackerel Scomber colias caught in 2019 off the Moroccan Atlantic coast. Five hundred specimens of each fish species were examined for 'soft flesh' by texture testing and visual inspection 48 h post-catch. 'Soft flesh' occurred in 0.2 % of the European anchovies, 1.4 % of the European pilchard, and in 4.4 % of the Atlantic chub mackerel. Microscopic examination of muscle samples revealed that 'soft flesh'-affected fish were infected with myxospores of K. thyrsites-like morphotype. Analysis of the kudoid SSU rDNA sequence obtained from European pilchard and the Atlantic chub mackerel identified these as K. thyrsites (100 % identity), whereas analysis of the sequence from European anchovy identified the presence of K. encrasicoli (100 % identity). Even if there are no known human health consequences associated with the ingestion of these Kudoa species, the unsightly appearance of some infected fillets is a food quality issue, that can eventually lead to reduced marketability and value.

Erratum to 'Pancreas divisum causing recurrent pancreatitis in a young patient: A case report' [Radiology Case Reports 18 (2023) 3535-3538].

[This corrects the article DOI: 10.1016/j.radcr.2023.07.028.].

Medical students' perceptions, experiences, and barriers towards research implementation at the faculty of medicine, Tanta university.

BACKGROUND: Research is essential for advancing medical knowledge and improving patient care. However, research capacity and output are low in low- and middle-income countries due to various challenges, including a lack of research training among medical students. Integrating research training into undergraduate medical curricula can help address this issue. METHODS: A cross-sectional study was conducted between December 2022 and March 2023 among 462 undergraduate medical students at Tanta University, Egypt to assess their knowledge, attitudes, and perceived barriers toward conducting research. Data were collected using a self-administered questionnaire and analyzed using SPSS. RESULTS: Nearly half (49.8%) of the students had an acceptable level of knowledge about research concepts while over two-thirds (66.2%) had a positive attitude. The most common barriers were lack of funding, time, and training in research methods. Previous research training was reported by 66.7% of students, but less than half had participated in or presented research. Students in the competency-based program had significantly higher knowledge and more positive attitudes than those in the mainstream program. Knowledge level was positively correlated with attitude. CONCLUSION: While attitudes were generally positive, improvements are needed in research training and opportunities among undergraduate medical students at Tanta University to help address low research capacity challenges in low- and middle-income countries. Integration of formal research training into the curriculum may help increase knowledge and participation in research.

BRCA1 Promoter Hypermethylation in Malignant Breast Tumors and in the Histologically Normal Adjacent Tissues to the Tumors: Exploring Its Potential as a Biomarker and Its Clinical Significance in a Translational Approach.

The hypermethylation status of the promoter region of the breast cancer 1 (BRCA1), a well-known tumor suppressor gene, has been extensively investigated in the last two decades as a potential biomarker for breast cancer. In this retrospective study, we investigated the prevalence of BRCA1 promoter methylation in 84 human breast tissues, and we correlated this epigenetic silencing with the clinical and histopathological parameters of breast cancer. We used methylation-specific PCR (MSP) to analyze BRCA1 promoter hypermethylation in 48 malignant breast tumors (MBTs), 15 normal adjacent tissues (NATs), and 21 benign breast lesions (BBLs). The results showed that BRCA1 promoter hypermethylation was higher in MBTs (20/48; 41.67%) and NATs (7/15; 46.67%) compared to BBLs (4/21; 19.05%). The high percentage of BRCA1 hypermethylation in the histologically normal adjacent tissues to the tumors (NATs) suggests the involvement of this epigenetic silencing as a potential biomarker of the early genomic instability in NATs surrounding the tumors. The detection of BRCA1 promoter hypermethylation in BBLs reinforces this suggestion, knowing that a non-negligible rate of benign breast lesions was reported to evolve into cancer. Moreover, our results indicated that the BRCA1 promoter hypermethylated group of MBTs exhibited higher rates of aggressive features, as indicated by the SBR III grade (14/19; 73.68%), elevated Ki67 levels (13/16; 81.25%), and Her2 receptor overexpression (5/20; 25%). Finally, we observed a concordance (60%) in BRCA1 promoter hypermethylation status between malignant breast tumors and their paired histologically normal adjacent tissues. This study highlights the role of BRCA1 promoter hypermethylation as a potential useful biomarker of aggressiveness in MBTs and as an early marker of genomic instability in both histological NATs and BBLs.

The X-linked histone demethylases KDM5C and KDM6A as regulators of T cell-driven autoimmunity in the central nervous system.

T cell-driven autoimmune responses are subject to striking sex-dependent effects. While the contributions of sex hormones are well-understood, those of sex chromosomes are meeting with increased appreciation. Here, we outline what is known about the contribution of sex chromosome-linked factors to experimental autoimmune encephalomyelitis (EAE), a mouse model that recapitulates many of the T cell-driven mechanisms of multiple sclerosis (MS) pathology. Particular attention is paid to the KDM family of histone demethylases, several of which - KDM5C, KDM5D and KDM6A - are sex chromosome encoded. Finally, we provide evidence that functional inhibition of KDM5 molecules can suppress interferon (IFN)γ production from murine male effector T cells, and that an increased ratio of inflammatory Kdm6a to immunomodulatory Kdm5c transcript is observed in T helper 17 (Th17) cells from women with the autoimmune disorder ankylosing spondylitis (AS). Histone lysine demethlyases thus represent intriguing targets for the treatment of T cell-driven autoimmune disorders.

Support Matrix Machine via Joint l2,1 and Nuclear Norm Minimization Under Matrix Completion Framework for Classification of Corrupted Data.

Traditional support vector machines (SVMs) are fragile in the presence of outliers; even a single corrupt data point can arbitrarily alter the quality of the approximation. If even a small fraction of columns is corrupted, then classification performance will inevitably deteriorate. This article considers the problem of high-dimensional data classification, where a number of the columns are arbitrarily corrupted. An efficient Support Matrix Machine that simultaneously performs matrix Recovery (SSMRe) is proposed, i.e. feature selection and classification through joint minimization of l2,1 (the nuclear norm of L ). The data are assumed to consist of a low-rank clean matrix plus a sparse noisy matrix. SSMRe works under incoherence and ambiguity conditions and is able to recover an intrinsic matrix of higher rank in the presence of data densely corrupted. The objective function is a spectral extension of the conventional elastic net; it combines the property of matrix recovery along with low rank and joint sparsity to deal with complex high-dimensional noisy data. Furthermore, SSMRe leverages structural information, as well as the intrinsic structure of data, avoiding the inevitable upper bound. Experimental results on different real-time applications, supported by the theoretical analysis and statistical testing, show significant gain for BCI, face recognition, and person identification datasets, especially in the presence of outliers, while preserving a reasonable number of support vectors.