Circular RNAs: Epigenetic regulators of PTEN expression and function in cancer.

Epigenetic regulation of gene expression, without altering the DNA sequence, is involved in many normal cellular growth and division events, as well as diseases such as cancer. Epigenetics is no longer limited to DNA methylation, and histone modification, but regulatory non-coding RNAs (ncRNAs) also play an important role in epigenetics. Circular RNAs (circRNAs), single-stranded RNAs without 3' and 5' ends, have recently emerged as a class of ncRNAs that regulate gene expression. CircRNAs regulate phosphatase and tensin homolog (PTEN) expression at various levels of transcription, post-transcription, translation, and post-translation under their own regulation. Given the importance of PTEN as a tumor suppressor in cancer that inhibits one of the most important cancer pathways PI3K/AKT involved in tumor cell proliferation and survival, significant studies have been conducted on the regulatory role of circRNAs in relation to PTEN. These studies will be reviewed in this paper to better understand the function of this protein in cancer and explore new therapeutic approaches.

Effectiveness of oral levamisole as an adjuvant to hepatitis B vaccination in healthcare workers non-responsive to previous vaccination: A randomized controlled trial.

Background: Healthcare workers are at risk for HBV infection through percutaneous or mucosal contact with infected blood, body secretions, or blood products or via sharps injury. Hepatitis B vaccination, despite immunogenicity, may not induce a proper immune response in 5-10% of the general adult population. Increased immune response in healthcare providers that do not respond properly to conventional hepatitis B vaccination is an important health challenge. Therefore, the aim of the present study was to evaluate the effectiveness of hepatitis B vaccination plus oral levamisole as adjuvant in healthcare providers non-responsive to routine vaccination. Materials and methods: The healthcare workers that were non-responsive to previous hepatitis B vaccination were enrolled in a double-blind randomized placebo-controlled clinical trial. The participants were then randomized to two groups including hepatitis B vaccination (as a three-dose series on a 0, 1, and 2-month schedule in the deltoid muscle) plus levamisole (levamisole group) and hepatitis B vaccination plus placebo (placebo group) at a 1:1 ratio. The outcome measure was the HBs antibody titer one month after receiving each dose as well as the seroprotection ratio. The side effects were also evaluated in all participants. Results: In total, 22 subjects finished the trial (11 individual in per group). The median antibody titer one month after receiving the first and third doses increased more in the levamisole group compared to the placebo group but the difference was not significant (p â€‹= â€‹0.34, p â€‹= â€‹0.66, respectively).The seroprotection ratio after three doses was similarly high in both groups (90.9% in per group). Furthermore, the seroprotection ratio and median antibody titer had no significant correlation with age, sex, BMI, and history of smoking in intervention and control groups (p>0.05). No serious side effects were noted in both groups. Conclusions: Re-vaccination can boost the immune response in healthcare professionals that were non-responsive to previous vaccination although the mean antibody titer was higher in the levamisole group.

A Mixture Method for Robust Detection HCV Early Diagnosis Biomarker with ML Approach and Molecular Docking.

Given the substantial correlation between early diagnosis and prolonged patient survival in HCV patients, it is vital to identify a reliable and accessible biomarker. The purpose of this research was to identify accurate miRNA biomarkers to aid in the early diagnosis of HCV and to identify key target genes for anti-hepatic fibrosis therapeutics. The expression of 188 miRNAs in 42 HCV liver patients with different functional states and 23 normal livers were determined using RT-qPCR. After screening out differentially expressed miRNA (DEmiRNAs), the target genes were predicted. To validate target genes, an HCV microarray dataset was subjected to five machine learning algorithms (Random Forest, Adaboost, Bagging, Boosting, XGBoost) and then, based on the best model, importance features were selected. After identification of hub target genes, to evaluate the potency of compounds that might hit key hub target genes, molecular docking was performed. According to our data, eight DEmiRNAs are associated with early stage and eight DEmiRNAs are linked to a deterioration in liver function and an increase in HCV severity. In the validation phase of target genes, model evaluation revealed that XGBoost (AUC = 0.978) outperformed the other machine learning algorithms. The results of the maximal clique centrality algorithm determined that CDK1 is a hub target gene, which can be hinted at by hsa-miR-335, hsa-miR-140, hsa-miR-152, and hsa-miR-195. Because viral proteins boost CDK1 activation for cell mitosis, pharmacological inhibition may have anti-HCV therapeutic promise. The strong affinity binding of paeoniflorin (-6.32 kcal/mol) and diosmin (-6.01 kcal/mol) with CDK1 was demonstrated by molecular docking, which may result in attractive anti-HCV compounds. The findings of this study may provide significant evidence, in the context of the miRNA biomarkers, for early-stage HCV diagnosis. In addition, recognized hub target genes and small molecules with high binding affinity may constitute a novel set of therapeutic targets for HCV.

Detection of key mRNAs in liver tissue of hepatocellular carcinoma patients based on machine learning and bioinformatics analysis.

One methodology extensively used to develop biomarkers is the precise detection of highly responsive genes that can distinguish cancer samples from healthy samples. The purpose of this study was to screen for potential hepatocellular carcinoma (HCC) biomarkers based on non-fusion integrative multi-platform meta-analysis method. The gene expression profiles of liver tissue samples from two microarray platforms were initially analyzed using a meta-analysis based on an empirical Bayesian method to robust discover differentially expressed genes in HCC and non-tumor tissues. Then, using the bioinformatics technique of weighted correlation network analysis, the highly associated prioritized Differentially Expressed Genes (DEGs) were clustered. Co-expression network and topological analysis were utilized to identify sub-clusters and confirm candidate genes. Next, a diagnostic model was developed and validated using a machine learning algorithm. To construct a prognostic model, the Cox proportional hazard regression analysis was applied and validated. We identified three genes as specific biomarkers for the diagnosis of HCC based on accuracy and feasibility. The diagnostic model's area under the curve was 0.931 with confidence interval of 0.923-0.952.•Non-fusion integrative multi-platform meta-analysis method.•Classification methods and biomarkers recognition via machine learning method.•Biomarker validation models.

Minimally invasive and invasive liver surgery based on augmented reality training: a review of the literature.

A liver surgeon's knowledge of anatomy is critical. Due to the patient's small field of vision, patient specific, complex nerve system, and other factors, even a minor loss can result in irreversible damage. Surgeons could benefit from the use of augmented reality (AR) technology, which would bring three-dimensional image data into the operating room. AR visualization can improve surgical procedures, facilitate intraoperative planning, and enhance surgical guidance for the anatomy of interest, all of which contribute to the application's minimal invasiveness. This literature review on image guidance in liver surgery provides the reader with information about AR techniques. To ascertain the current state of Augmented reality technology's application in liver surgery, a PubMed and Embase search were conducted using the following keywords: < (Augmented reality) AND (liver surgery) > and < 'Augmented reality' AND 'liver surgery' > (publication date from January 1991 until Jun 2022). The query yielded a total of 205 publications-excluded papers in other languages, virtual reality (VR), and reviews leaving 135 studies for review. After removing duplication, the titles and abstracts of those studies were manually reviewed. Finally, 31 pertinent studies were determined to be pertinent to the subject. Generally, augmented reality technology includes preoperative planning and three-dimensional reconstruction, intraoperative three-dimensional navigation, and registration. Visualization may be aided by virtual three-dimensional reconstruction models of the liver from Computed Tomography/Magnetic Resonance Imaging scans. The results demonstrate that by utilizing augmented reality technology, blood vessels and tumor structures in the liver can be visualized during surgery, allowing for precise navigation during complicated surgical procedures. Augmented reality has been demonstrated to be safe and effective in both minimally invasive and invasive liver surgery. With recent advancements and significant effort by liver surgeons, augmented reality technologies have the potential to increase hepatobiliary surgical procedures dramatically. However, further clinical trials will be necessary to evaluate augmented reality as a tool for reducing post-operative morbidity and mortality. The impact of these cutting-edge computerized image guidance techniques on clinically relevant outcome parameters should be assessed in the future.

Distribution of injury in inflatable jumping amusements in the U.S. over the last 20 years.

PURPOSE: To describe the distribution of injuries attributed to inflatable bounce house devices in children 2-18 years old in the United States from 2000 to 2019. METHODS: The National Electronic Injury Surveillance System (NEISS) was used to identify patients <18 years of age with injuries from activities classified as amusements (NEISS Code 1293 and 3219) during the period from 2000 to 2019. RESULTS: A weighted estimate of 159,569 injuries was obtained using NEISS statistical weights. Injury estimates and rate of estimated injury per year showed a continued linear increase from 2000-2019 (p<0.0001). Bounce house-related injuries were more common in males (53.9%) than in females (46.1%). The injuries reported most commonly were fracture (25.8%), muscle strain (25.7%), and contusion (14.5%). The factors associated with bounce house-related injury were compared between "younger" patients ≤6 years of age and "older" patients >6 years of age. In both age groups, the patient's residence was the most prevalent location of injury (≤6 yr, 95.6%; >6 yr, 97.2%), and the lower extremity was the most prevalent anatomic site of injury (≤6 yr, 34.6%, >6 yr 35.3%). Concussion was rare in both groups (≤6 yr, 1.6%; >6 yr, 2.9%); however, concussion was 86% more prevalent in those >6 years of age (p<0.0001). CONCLUSIONS: The frequency and rate of pediatric bounce house injuries has increased steadily since 2000. The most severe injuries occur disproportionately in children > 6 years old.

Evaluation of High-Efficiency Image Coding algorithm for dermatology images in teledermatology.

BACKGROUND: Currently, teledermatology assumes a progressively greater role in the modern healthcare system, especially in consultation, diagnosis, or examining lesions and skin cancers. One of the major challenges facing teledermatology systems is determining the optimal image compression method to efficiently reduce the space needed for electronic storage and data transmission. OBJECTIVE: To the objective and subjective assessment of HEIC compression method on dermatological color images and benchmarking the performance of High-Efficiency Image Coding (HEIC) with different algorithms to a feasibility study of the method for teledermatology. METHODS: Twenty-five clinical and five skin histopathology images were taken in department of dermatology, Imam Reza Hospital, Mashhad, Iran. For each image, a set of 24 compressed images with different compression rates, which is composed of eight JPEG, eight JPEG2000, and eight HEIC images, has been prepared. Compressed and original images were shown simultaneously to three dermatologists and one dermatopathologist with different experiences. Each dermatologist scored quality and suitability of compressed images for diagnostic, as well as educational/scientific purposes. An objective evaluation was performed by calculating the mean "distance" of pixel colors and peak signal-to-noise ratio (PSNR). RESULTS: All compression rates for HEIC were objectively better than JPEG and JPEG2000, particularly at PSNR. Moreover, mean "color distance" per pixel for compressed images using HEIC was lower than others. The subjective image quality assessment also confirms the results of objective evaluation. In both educational and clinical diagnostic applications, HEIC compressed images have the highest score. CONCLUSION: In consideration of objective and subjective evaluation, the HEIC algorithm represents an optimal performance in dermatology images compression compared with JPEG and JPEG2000.

Identifying Differentially Expressed MicroRNAs, Target Genes, and Key Pathways Deregulated in Patients with Liver Diseases.

Liver diseases are important causes of morbidity and mortality worldwide. The aim of this study was to identify differentially expressed microRNAs (miRNAs), target genes, and key pathways as innovative diagnostic biomarkers in liver patients with different pathology and functional state. We determined, using RT-qPCR, the expression of 472 miRNAs in 125 explanted livers from subjects with six different liver pathologies and from control livers. ANOVA was employed to obtain differentially expressed miRNAs (DEMs), and miRDB (MicroRNA target prediction database) was used to predict target genes. A miRNA-gene differential regulatory (MGDR) network was constructed for each condition. Key miRNAs were detected using topological analysis. Enrichment analysis for DEMs was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). We identified important DEMs common and specific to the different patient groups and disease progression stages. hsa-miR-1275 was universally downregulated regardless the disease etiology and stage, while hsa-let-7a*, hsa-miR-195, hsa-miR-374, and hsa-miR-378 were deregulated. The most significantly enriched pathways of target genes controlled by these miRNAs comprise p53 tumor suppressor protein (TP53)-regulated metabolic genes, and those involved in regulation of methyl-CpG-binding protein 2 (MECP2) expression, phosphatase and tensin homolog (PTEN) messenger RNA (mRNA) translation and copper homeostasis. Our findings show a novel panel of deregulated miRNAs in the liver tissue from patients with different liver pathologies. These miRNAs hold potential as biomarkers for diagnosis and staging of liver diseases.

Prediction of 7-Day Readmission Risk for Pediatric Trauma Patients.

BACKGROUND: Pediatric patients admitted for trauma may have unique risk factors of unplanned readmission and require condition-specific models to maximize accuracy of prediction. We used a multicenter data set on trauma admissions to study risk factors and predict unplanned 7-day readmissions with comparison to the 30-day metric. METHODS: Data from 28 hospitals in the United States consisting of 82,532 patients (95,158 encounters) were retrieved, and 75% of the data were used for building a random intercept, mixed-effects regression model, whereas the remaining were used for evaluating model performance. The variables included were demographics, payer, current and past health care utilization, trauma-related and other diagnoses, medications, and surgical procedures. RESULTS: Certain conditions such as poisoning and medical/surgical complications during treatment of traumatic injuries are associated with increased odds of unplanned readmission. Conversely, trauma-related conditions, such as trauma to the thorax, knee, lower leg, hip/thigh, elbow/forearm, and shoulder/upper arm, are associated with reduced odds of readmission. Additional predictors include the current and past health care utilization and the number of medications. The corresponding 7-day model achieved an area under the receiver operator characteristic curve of 0.737 (0.716, 0.757) on an independent test set and shared similar risk factors with the 30-day version. CONCLUSIONS: Patients with trauma-related conditions have risk of readmission modified by the type of trauma. As a result, additional quality of care measures may be required for patients with trauma-related conditions that elevate their risk of readmission.

Reconstruction and Analysis of Cattle Metabolic Networks in Normal and Acidosis Rumen Tissue.

The objective of this study was to develop a system-level understanding of acidosis biology. Therefore, the genes expression differences between the normal and acidosis rumen epithelial tissues were first examined using the RNA-seq data in order to understand the molecular mechanisms involved in the disease and then their corresponding metabolic networks constructed. A number of 1074 genes, 978 isoforms, 1049 transcription start sites (TSS), 998 coding DNA sequence (CDS) and 2 promoters were identified being differentially expressed in the rumen tissue between the normal and acidosis samples (p < 0.05). The functional analysis of 627 up-regulated genes revealed their involvement in ion transmembrane transport, filament organization, regulation of cell adhesion, regulation of the actin cytoskeleton, ATP binding, glucose transmembrane transporter activity, carbohydrate binding, growth factor binding and cAMP metabolic process. Additionally, 111 differentially expressed enzymes were identified between the rumen epithelial tissue of the normal and acidosis steers with 46 up-regulated and 65 down-regulated ones in the acidosis group. The pathways and reactions analyses associated with the up-regulated enzymes indicate that most of these enzymes are involved in the fatty acid metabolism, biosynthesis of amino acids, pyruvate and carbon metabolism while most of the down-regulated ones are involved in purine and pyrimidine, vitamin B6 and antibiotics metabolisms. The degree distribution of both metabolic networks follows a power-law one, hence displaying a scale-free property. The top 15 hub metabolites were determined in the acidosis metabolic network with most of them involved in the fatty acid oxidation, VFA biosynthesis, amino acid biogenesis and glutathione metabolism which plays an important role in the stress condition. The limitations of this study were low number of animals and using only epithelial tissue (ventral sac) for RNA-seq.

Prevalence of ectoparasites in free-range backyard chickens, domestic pigeons (Columba livia domestica) and turkeys of Kermanshah province, west of Iran.

This study was carried out on free-range backyard chickens, domestic pigeons (Columba livia domestica) and turkeys from May 2012 to April 2013 to determine the prevalence and identify the species of ectoparasites in Kermanshah province, west of Iran. Of the total of 600 free-range backyard chickens (185 ♂ and 415 ♀), 700 domestic pigeons (278 ♂ and 422 ♀) and 150 turkeys (53 ♂ and 97 ♀), 389 (64.83 %), 608 (86.85 %) and 54 (36 %) were infected with one or more parasites respectively. Eleven ectoparasites species including five of lice (50.16 % Menacanthus stramineus, 13.66 % Menopon gallinae, 4.83 % Cuclotogaster heterographus, 5.16 % Goniocotes gallinae, 2.33 % Goniodes gigas), three of mites (26.33 % Dermanyssus gallinae, 8.5 % Ornithonyssus bursa, 7 % Cnemidocoptes mutans), one of tick (78.66 % Argas persicus) and two of flea (12.33 % Echidnophaga gallinacea, 2 % Pulex irritans) were found in the backyard chickens. The domestic pigeons were infected with six species of parasites including: Columbicola columbae (61.7 %), M. gallinae (10.43 %), M. stramineus (9 %), D. gallinae (8.28 %), Argas reflexus (74.14 %) and Pseudolynchia canariensis (27.7 %). The ectoparasites species recorded in turkeys were M. gallinae (14 %), M. stramineus (8 %), D. gallinae (12.66 %), C. mutans (6 %), A. persicus (24.66 %) and E. gallinacean (6 %). This is the first survey to determine the prevalence and identify the species of ectoparasites among free-range backyard chicken, domestic pigeons and turkeys in Kermanshah province. The high prevalence rate of ectoparasites in free-range backyard chickens and domestic pigeons indicates that parasitic infection is a common problem in this area.

Hepatic metastasectomy in children.

BACKGROUND: There are little data regarding the safety and efficacy of hepatic metastasectomy for solid tumors in childhood. We reviewed our institutional experience to assess operative mortality and morbidity, technique of resection, local control, and survival in pediatric patients undergoing liver resection for metastases. METHODS: All pediatric patients who underwent hepatic resection for metastatic disease from August 1988 to July 2005 were retrospectively identified and clinical data were collected. RESULTS: Fifteen patients were identified during this period and primary malignancies included neuroblastoma (7), Wilms tumor (3), osteogenic sarcoma (2), malignant gastric epithelial tumor (1), and desmoplastic small round cell tumor (2). Twelve patients underwent anatomical hepatic resections and 3 had wedge resections. There were no intraoperative or postoperative deaths. The 2 postoperative complications included 1 wound infection and 1 bile collection. The median follow-up after hepatic resection was 1.6 years (0.2-7 years). Three patients remain alive. Eleven patients died of progressive disease; 4 patients suffered local recurrence. One patient died from enterocolitis and sepsis and was without evidence of malignancy at the time of death. CONCLUSIONS: Hepatic metastasectomy in children is feasible and is associated with a low operative mortality and morbidity. In this small group of patients anatomic hepatectomy was associated with better local control compared with wedge resection. Overall prognosis in these patients remains poor and the decision to perform hepatic metastasectomy should be highly selective.

Surgical management and outcome of osteosarcoma patients with unilateral pulmonary metastases.

PURPOSE: The surgical management of osteosarcoma patients with unilateral pulmonary nodules is controversial. The authors reviewed their institutional experience to evaluate the incidence of occult contralateral metastases. METHODS: Data were obtained retrospectively on all consecutive osteosarcoma patients from 1980 to 2002. Eighty-four patients with pulmonary nodules were identified. Forty-one had bilateral disease, and 43 had unilateral involvement by computed tomography (CT) scan. RESULTS: All 43 patients with unilateral nodules underwent ipsilateral thoracotomies. Fifteen patients had negative exploration findings, and only 1 had pulmonary relapse. Of the 28 patients with metastases confirmed at initial thoracotomies, 14 had extensive pleural or extrapulmonary disease at initial thoracotomy followed by disease progression. The other 14 are separated into early versus late metastases, using 2 years from diagnosis as the cutoff point. Seven of the 9 (78%) patients with early metastases had or subsequently had contralateral disease; 6 were identified at staged contralateral thoracotomy and 1 had relapsed in the unexplored lung a year later. Only 1 of the 5 patients with late unilateral metastases had relapse in the contralateral side. CONCLUSIONS: Our data indicate that there is a high rate of contralateral involvement in osteosarcoma patients with unilateral nodules diagnosed by CT scan. Staged bilateral thoracotomies should be considered in osteosarcoma patients presenting with unilateral pulmonary disease on imaging studies within 2 years of diagnosis.