Gamma radiation assisted green synthesis of hesperidin-reduced graphene oxide nanocomposite targeted JNK/SMAD4/MMP2 signaling pathway.

In this study, a novel method for the fabrication of hesperidin/reduced graphene oxide nanocomposite (RGOH) with the assistance of gamma rays is reported. The different RGOHs were obtained by varying hesperidin concentrations (25, 50, 100, and 200 wt.%) in graphene oxide (GO) solution. Hesperidin concentrations (25, 50, 100, and 200 wt.%) in graphene oxide (GO) were varied to produce the various RGOHs. Upon irradiation with 80 kGy from γ-Ray, the successful reduction of GO occurred in the presence of hesperidin. The reduction process was confirmed by different characterization techniques such as FTIR, XRD, HRTEM, and Raman Spectroscopy. A cytotoxicity study using the MTT method was performed to evaluate the cytotoxic-anticancer effects of arbitrary RGOH on Wi38, CaCo2, and HepG2 cell lines. The assessment of RGOH's anti-inflammatory activity, including the monitoring of IL-1B and IL-6 activities as well as NF-kB gene expression was done. In addition, the anti-invasive and antimetastatic properties of RGOH, ICAM, and VCAM were assessed. Additionally, the expression of the MMP2-9 gene was quantified. The assessment of apoptotic activity was conducted by the detection of gene expressions related to BCl2 and P53. The documentation of the JNK/SMAD4/MMP2 signaling pathway was ultimately accomplished. The findings of our study indicate that RGOH therapy has significant inhibitory effects on the JNK/SMAD4/MMP2 pathway. This suggests that it could be a potential therapeutic option for cancer.

CYP2C8 rs11572080 and CYP3A4 rs2740574 risk genotypes in paclitaxel-treated premenopausal breast cancer patients.

Breast cancer (BC) is the most prevalent malignancy in women globally. At time of diagnosis, premenopausal BC is considered more aggressive and harder to treat than postmenopausal cases. Cytochrome P450 (CYP) enzymes are responsible for phase I of estrogen metabolism and thus, they are prominently involved in the pathogenesis of BC. Moreover, CYP subfamily 2C and 3A play a pivotal role in the metabolism of taxane anticancer agents. To understand genetic risk factors that may have a role in pre-menopausal BC we studied the genotypic variants of CYP2C8, rs11572080 and CYP3A4, rs2740574 in female BC patients on taxane-based therapy and their association with menopausal status. Our study comprised 105 female patients with histologically proven BC on paclitaxel-therapy. They were stratified into pre-menopausal (n = 52, 49.5%) and post-menopausal (n = 53, 50.5%) groups. Genotyping was done using TaqMan assays and employed on Quantstudio 12 K flex real-time platform. Significant increased frequencies of rs11572080 heterozygous CT genotype and variant T allele were established in pre-menopausal group compared to post-menopausal group (p = 0.023, 0.01, respectively). Moreover, logistic regression analysis revealed a significant association between rs11572080 CT genotype and premenopausal BC. However, regarding rs2740574, no significant differences in genotypes and allele frequencies between both groups were detected. We reported a significant association between CYP2C8 genotypic variants and premenopausal BC risk in Egyptian females. Further studies on larger sample sizes are still needed to evaluate its importance in early prediction of BC in young women and its effect on treatment outcome.

Clinical implications of seropositive and seronegative autoantibody status in rheumatoid arthritis patients: A comparative multicentre observational study.

Background and Objectives: Rheumatoid factor (RF) and anti-cyclic citrullinated protein (anti-CCP) have been used to improve the diagnosis and prognosis of rheumatoid arthritis (RA). However, their association with RA disease phenotypes, individually and in combination, is not well studied. The aim of the study was to compare patients' and disease characteristics, activity and severity in double seronegative (DNRA), single seropositive RF, single seropositive anti-CCP and double seropositive (DPRA) patients. Methods: Adults subjects with RA from Egyptian College of Rheumatology (ECR) database who had RF and anti-CCP results available were included. Demographic, clinical features, disease activity score 28 (DAS28), Health Assessment Questionnaire (HAQ) and laboratory data were collected and compared among different RA groups. Results: 5268 RA patients with mean age of 44.9±11.6 years, and 4477 (85%) were females. 2900 (55%) had DPRA, 892 (16.9%) had single positive RF, 597 (11.3%) had single positive anti-CCP while 879 (16.7%) had DNRA. Patients with DPRA had significantly high percentage of metabolic syndrome (19.3%, P < 0.001), and functional impairment using HAQ (P = 0.01). Older age (RRR [relative risk ratio]: 1.03, 95%CI: 1.0, 1.0, P = 0.029), greater DAS28 (RRR: 1.51, 95%CI: 1.2, 1.9, P < 0.001), higher steroid use (RRR: 2.4, 95%CI: 1.36, 4.25, P = 0.002) were at higher risk of DPRA while longer disease duration (RRR: 1.08, 95%CI: 1.01, 1.16, P = 0.017) and fibromyalgia syndrome (RRR: 2.54, 95%CI: 1.10, 5.88, P = 0.028) were associated with higher odds of single positive RF status. Conclusion: Dual antibody-positive status has higher disease activity and severity, and higher chance of development of metabolic syndrome; highlighting the implicated role of inflammation, atherogenesis and cardiovascular disease risk in RA.

Prevalence of extended-spectrum beta-lactamase and molecular detection of blaTEM, blaSHV, and blaCTX-M genotypes among gram-negative Bacilli isolates from hospital acquired infections in pediatrics, one institutional study.

BACKGROUND: Gram-negative bacilli represents an important pathogen in hospital-acquired infections (HAIs) worldwide. The emergence of antibiotic resistance in these pathogens warrants attention for the proper management of infections. Extended-spectrum beta-lactamase (ESBL) resistance represents a major therapeutic problem in infections due to Gram-negative bacilli. The present study aimed to study the extended-spectrum beta-lactamase genes blaTEM, blaSHV, and blaCTX-M by multiplex polymerase reaction in isolated Gram-negative bacilli from HAIs in pediatric patients. METHODS: The study included one hundred-five isolates of Gram-negative bacilli from pediatric patients with different types of HAIs. The isolates were subjected to full microbiological identification, antibiotics susceptibility by disc diffusion method, the phenotypic study of ESBL, and the genetic study of ESBL genes by multiplex PCR. RESULTS: Fifty isolates of Gram-Negative bacilli showed ESBL activity by a phenotypic study by double disc diffusion method (50/105). All ESBL producers' isolates were positive by PCR for ESBL genes. The most frequent gene was blaTEM (64%), followed by blaSHV (30%) and CTX-M (22%). Mixed genes were found in 4 isolates (8%) for blaTEM and blaSHV, blaTEM and CTX-M. There was a significant association between PCR for ESBL genes and phenotypic ESBL detection (P = 0.001). There was significant detection of ESBL genes in E. coli (28%), followed by Enterobacter spp. (26%), Klebsiella spp. (24%), Serratia (14%), Pseudomonas spp. (6%) and Proteus (2%), P = 0.01. There Seventy percent of isolates positive for ESBL production had an insignificant association between MDR and PCR for ESBL genes (P = 0.23). CONCLUSION: The present study highlights the prevalence of ESBL activity among clinical isolates of Gram-negative bacilli isolated from hospital-acquired infections in pediatric patients. The most common gene responsible for this activity was blaTEM gee followed by blaSHV and blaCTX-M. There was a high prevalence of multiple antibiotic resistance among isolates with ESBL activity. The finding of the present study denotes the importance of screening extended beta-lactamase among Gram-negative bacilli associated with HAIs in pediatric patients.

Modeling of the Statistical Distribution of Tracheids in Conifer Rings: Finding Universal Criterion for Earlywood-Latewood Distinction.

The quantitative description of growth rings is yet incomplete, including the functional division into earlywood and latewood. Methods developed to date, such as the Mork criterion for conifers, can be biased and arbitrary depending on species and growth conditions. We proposed the use of modeling of the statistical distribution of tracheids to determine a universal criterion applicable to all conifer species. Thisstudy was based on 50-year anatomical measurements of Pinus sylvestris L., Pinus sibirica Du Tour, and Picea obovata Ledeb. near the upper tree line in the Western Sayan Mountains (South Siberia). Statistical distributions of the cell wall thickness (CWT)-to-radial-diameter (D) ratio and its slope were investigated for raw and standardized data (divided by the mean). The bimodal distribution of the slope for standardized CWT and D was modeled with beta distributions for earlywood and latewood tracheids and a generalized normal distribution for transition wood to account for the gradual shift in cell traits. The modelcan describe with high accuracy the growth ring structure for species characterized by various proportions of latewood, histometric traits, and gradual or abrupt transition. The proportion of two (or three, including transition wood) zones in the modeled distribution is proposed as a desired criterion.

Multidisciplinary Checklist for Safe Transitions to Home Total Parenteral Nutrition From Hospital-Based Palliative Care: A Case Study From Al Ain, Abu Dhabi.

We present a complex case of a multimorbid elderly patient admitted with septic shock, suspected to be secondary to aspiration pneumonia, who subsequently developed an intestinal obstruction due to an ileocecal junction mass. Despite conservative management, the patient's clinical status deteriorated and required comprehensive palliative care. This case highlights the challenges in managing patients with multimorbidities, the importance of a multidisciplinary approach, and the central role of palliative care in the setting of advanced disease. We demonstrate the effectiveness of the above method to safely transit an elderly male with a recent diagnosis of colon cancer with malignant intestinal obstruction, initiated on total parenteral nutrition (TPN). This study emphasizes the successful implementation of an innovative, multidisciplinary checklist for managing elderly palliative care patients on home total parenteral nutrition (HTPN) in Al Ain, Abu Dhabi. The collaborative approach adopted by the multidisciplinary team (MDT), coupled with comprehensive staff training, patient and caregiver education, and ongoing monitoring and support, facilitated the seamless integration of HTPN into the patient's care plan. The positive outcomes observed in this case underscore the potential of such tailored interventions to bridge the existing gap in HTPN implementation within the region, thus improving the quality of life and overall well-being of elderly patients requiring specialized nutrition support.

Implementation and Feasibility of Clinical Genome Sequencing Embedded Into the Outpatient Nephrology Care for Patients With Proteinuric Kidney Disease.

Introduction: The diagnosis and management of proteinuric kidney diseases such as focal segmental glomerulosclerosis (FSGS) are challenging. Genetics holds the promise to improve clinical decision making for these diseases; however, it is often performed too late to enable timely clinical action and it is not implemented within routine outpatient nephrology visits. Methods: We sought to test the implementation and feasibility of clinical rapid genome sequencing (GS) in guiding decision making in patients with proteinuric kidney disease in real-time and embedded in the outpatient nephrology setting. Results: We enrolled 10 children or young adults with biopsy-proven FSGS (9 cases) or minimal change disease (1 case). The mean age at enrollment was 16.2 years (range 2-30). The workflow did not require referral to external genetics clinics but was conducted entirely during the nephrology standard-of-care appointments. The total turn-around-time from enrollment to return-of-results and clinical decision averaged 21.8 days (12.4 for GS), which is well within a time frame that allows clinically relevant treatment decisions. A monogenic or APOL1-related form of kidney disease was diagnosed in 5 of 10 patients. The genetic findings resulted in a rectified diagnosis in 6 patients. Both positive and negative GS findings determined a change in pharmacological treatment. In 3 patients, the results were instrumental for transplant evaluation, donor selection, and the immunosuppressive treatment. All patients and families received genetic counseling. Conclusion: Clinical GS is feasible and can be implemented in real-time in the outpatient care to help guiding clinical management. Additional studies are needed to confirm the cost-effectiveness and broader utility of clinical GS across the phenotypic and demographic spectrum of kidney diseases.

Erythropoietin Suppresses the Hepatic Fibrosis Caused by Thioacetamide: Role of the PI3K/Akt and TLR4 Signaling Pathways.

Erythropoietin (EPO) is recognized for its function in erythropoiesis; however, its potential antifibrotic effect against liver fibrosis remains unknown. This study examined whether EPO affects thioacetamide (TAA)-induced liver fibrosis by concentrating on the Toll-like receptor 4 (TLR4) cascade and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway as possible pathways. Male Wistar rats were randomized into four groups, which included: the negative control group, the TAA group (intraperitoneal; TAA 100 mg/kg three times per week for 2 weeks), and EPO-treated groups (150 and 300 IU/kg, i.p.) for 2 weeks after TAA injections. EPO attenuated hepatic fibrosis in a dosage-dependent way, as manifested by the diminution in serum alanine aminotransferase and aspartate aminotransferase activities, as well as the increase in albumin level. EPO inhibited the increase in tissue levels of tumor necrosis factors-α, interleukin-1ß, transforming growth factor-ß1, and TLR4 and raised tissue levels of PI3K and p-PI3K. EPO antioxidant properties were demonstrated by restoring hepatic glutathione and superoxide dismutase by preventing the accumulation of hepatic malondialdehyde. Further, EPO increased the protein expression of PI3K and Akt and decreased TLR4 protein expression. Immunohistochemically, EPO treatment altered tissue histology and downregulated mitogen-activated protein kinase protein expression. Overall, the research suggested that EPO could prevent TAA-induced hepatic fibrosis through upregulating the PI3K/Akt signaling cascade and downregulation the TLR4 downstream axis.

Luteolin/ZnO nanoparticles attenuate neuroinflammation associated with diabetes via regulating MicroRNA-124 by targeting C/EBPA.

OBJECTIVE: The most prevalent brain-specific microRNA, MicroRNA-124, exhibits anti-inflammatory properties. Luteolin nano-formulation with Zn oxide in the form of L/ZnO NPs may boost anti-diabetic properties; however, its beneficial effect on miRNAs is yet unknown in diabetes. The effectiveness of L/ZnONPs supplements in preventing diabetic neurodegeneration by modulating inflammatory responses in a diabetic model was investigated. METHODS: A diabetic rat model was induced by a high-fat diet and streptozotocin (30 mg/kg I.P.). Plasma glucose, insulin, and HOMR-IR levels, as well as cytokines, lipid peroxidation, GSH/GSSG, and glucose transporter 1, were determined along with the tight junction proteins occludin (OCLN) and zona occludens 1 (ZO-1). Moreover, the expressions of brain CCAAT/enhancer-binding protein (C/EBPA mRNA), miR-124, glial fibrillary acidic protein (GFAP), and NF-kBp65 were measured alongside the histological investigation. RESULTS: The results revealed that L/ZnO NPs were able to diminish lipid peroxidation, increase the activity of antioxidant enzymes, and reduce inflammation under oxidative stress. Consequently, it was able to reduce hyperglycemia, elevate insulin levels, and improve insulin resistance. Besides, L/ZnO NPs upregulate miR-124, reduce C/EBPA mRNA, increase BCl-2, and inhibit apoptosis. The results indicate that diabetes raises BBB permeability via tight junction protein decline, which is restored following L/ZnO NPs treatment. Luteolin/ZnO NPs regulate miR-124 and microglia polarization by targeting C/EBPA and are expected to alleviate inflammatory injury via modulation of the redox-sensitive signal transduction pathways. Luteolin/ZnO NPs have a novel target for the protection of the BBB and the prevention of neurological complications in diabetes.

Hepatoprotective role of myricitrin isolated from Mimusops elengi Linn. leaves extract on γ-radiation-induced liver damage in rats: Phyto-biochemical investigations.

The hepatoprotective effects of methanol extract of Mimusops elengi Linn. (M. elengi L.) leaves and isolated pure myricitrin (3-, 4-, 5-, 5, 7-five hydroxyflavone-3-O-α-l-rhamnoside) (Myr) were evaluated in male rats exposed to γ-irradiation. The extraction of M. elengi L. leaves was performed using ethyl acetate (EtOAC). Seven groups of rats were used: control group, irradiated (IRR) group (6 Gy of γ-rays in a single dose), vehicle group (oral administration of 0.5% carboxymethyl cellulose for 10 days), EtOAC extract group (100 mg/kg body weight of extract, orally for 10 days), EtOAC + IRR group (administration of extract and exposure to γ-rays on Day 7), Myr group (50 mg/kg body weight Myr, orally for 10 days), and Myr + IRR group (administration of Myr and exposure to γ-rays on Day 7). High-performance liquid chromatography and 1H-nuclear magnetic resonance were used to isolate and characterize the compounds from M. elengi L. leaves. Enzyme-linked immunosorbent assay was used for biochemical analyses. Identified compounds were Myr, myricetin 3-O-galactoside, myricetin 3-O-rahmnopyranoside (1 → 6) glucopyranoside, quercetin, quercitol, gallic acid, α-,ß-amyrin, ursolic acid, and lupeol. Serum aspartate transaminase and alanine transaminase activities were significantly increased, while serum protein and albumin levels were significantly decreased after irradiation. Hepatic levels of tumor necrosis factor-α, prostaglandin 2, inducible nitric oxide synthase, interleukin-6 (IL-6), and IL-12 were increased following irradiation. Improvements were observed in most serological parameters after treatment with extract or pure Myr, with histological analyses confirming decreased liver injury in treated rats. Our study demonstrates that pure Myr has a greater hepatoprotective effect than M. elengi leaf extracts against irradiation-induced hepatic inflammation.

Application of Chlorella vulgaris Beijerinck as a Biostimulant for Growing Cucumber Seedlings in Hydroponics.

Hydroponics is a promising method for growing agricultural plants and is especially relevant in the context of global climate change. Microscopic algae, including Chlorella vulgaris, has great potential for use in hydroponic systems as natural growth stimulators. The effect of the suspension of an authentic strain of Chlorella vulgaris Beijerinck on the length of cucumber shoots and roots, as well as its dry biomass, was studied. During cultivation in a Knop medium with the addition of Chlorella suspension, the length of the shoots was shortened from 11.30 to 8.15 cm, while the length of the roots also decreased from 16.41 to 10.59 cm. At the same time, the biomass of the roots increased from 0.04 to 0.05 g. The data obtained indicate the positive effect of the suspension of the Chlorella vulgaris authentic strain on the dry biomass of cucumber plants in hydroponic conditions and make it possible to recommend this strain for use when growing plants in hydroponic systems.

Factors Limiting Radial Growth of Conifers on Their Semiarid Borders across Kazakhstan.

The forests of Central Asia are biodiversity hotspots at risk from rapid climate change, but they are understudied in terms of the climate-growth relationships of trees. This classical dendroclimatic case study was performed for six conifer forest stands near their semiarid boundaries across Kazakhstan: (1-3) Pinus sylvestris L., temperate forest steppes; (4-5) Picea schrenkiana Fisch. & C.A. Mey, foothills, the Western Tien Shan, southeast; (6) Juniperus seravschanica Kom., montane zone, the Western Tien Shan, southern subtropics. Due to large distances, correlations between local tree-ring width (TRW) chronologies are significant only within species (pine, 0.19-0.50; spruce, 0.55). The most stable climatic response is negative correlations of TRW with maximum temperatures of the previous (from -0.37 to -0.50) and current (from -0.17 to -0.44) growing season. The strength of the positive response to annual precipitation (0.10-0.48) and Standardized Precipitation Evapotranspiration Index (0.15-0.49) depends on local aridity. The timeframe of climatic responses shifts to earlier months north-to-south. For years with maximum and minimum TRW, differences in seasonal maximal temperatures (by ~1-3 °C) and precipitation (by ~12-83%) were also found. Heat stress being the primary factor limiting conifer growth across Kazakhstan, we suggest experiments there on heat protection measures in plantations and for urban trees, alongside broadening the coverage of the dendroclimatic net with accents on the impact of habitat conditions and climate-induced long-term growth dynamics.

Multi-population genome-wide association study implicates immune and non-immune factors in pediatric steroid-sensitive nephrotic syndrome.

Pediatric steroid-sensitive nephrotic syndrome (pSSNS) is the most common childhood glomerular disease. Previous genome-wide association studies (GWAS) identified a risk locus in the HLA Class II region and three additional independent risk loci. But the genetic architecture of pSSNS, and its genetically driven pathobiology, is largely unknown. Here, we conduct a multi-population GWAS meta-analysis in 38,463 participants (2440 cases). We then conduct conditional analyses and population specific GWAS. We discover twelve significant associations-eight from the multi-population meta-analysis (four novel), two from the multi-population conditional analysis (one novel), and two additional novel loci from the European meta-analysis. Fine-mapping implicates specific amino acid haplotypes in HLA-DQA1 and HLA-DQB1 driving the HLA Class II risk locus. Non-HLA loci colocalize with eQTLs of monocytes and numerous T-cell subsets in independent datasets. Colocalization with kidney eQTLs is lacking but overlap with kidney cell open chromatin suggests an uncharacterized disease mechanism in kidney cells. A polygenic risk score (PRS) associates with earlier disease onset. Altogether, these discoveries expand our knowledge of pSSNS genetic architecture across populations and provide cell-specific insights into its molecular drivers. Evaluating these associations in additional cohorts will refine our understanding of population specificity, heterogeneity, and clinical and molecular associations.

Review on Biomedical Advances of Hybrid Nanocomposite Biopolymeric Materials.

Hybrid materials are classified as one of the most highly important topics that have been of great interest to many researchers in recent decades. There are many species that can fall under this category, one of the most important of which contain biopolymeric materials as a matrix and are additionally reinforced by different types of carbon sources. Such materials are characterized by many diverse properties in a variety industrial and applied fields but especially in the field of biomedical applications. The biopolymeric materials that fall under this label are divided into natural biopolymers, which include chitosan, cellulose, and gelatin, and industrial or synthetic polymers, which include polycaprolactone, polyurethane, and conducting polymers of variable chemical structures. Furthermore, there are many types of carbon nanomaterials that are used as enhancers in the chemical synthesis of these materials as reinforcement agents, which include carbon nanotubes, graphene, and fullerene. This research investigates natural biopolymers, which can be composed of carbon materials, and the educational and medical applications that have been developed for them in recent years. These applications include tissue engineering, scaffold bones, and drug delivery systems.

Recent Biomedical Applications of Coupling Nanocomposite Polymeric Materials Reinforced with Variable Carbon Nanofillers.

The hybridization between polymers and carbon materials is one of the most recent and crucial study areas which abstracted more concern from scientists in the past few years. Polymers could be classified into two classes according to the source materials synthetic and natural. Synthetic polymeric materials have been applied over a floppy zone of industrial fields including the field of biomedicine. Carbon nanomaterials including (fullerene, carbon nanotubes, and graphene) classified as one of the most significant sources of hybrid materials. Nanocarbons are improving significantly mechanical properties of polymers in nanocomposites in addition to physical and chemical properties of the new materials. In all varieties of proposed bio-nanocomposites, a considerable improvement in the microbiological performance of the materials has been explored. Various polymeric materials and carbon-course nanofillers were present, along with antibacterial, antifungal, and anticancer products. This review spots the light on the types of synthetic polymers-based carbon materials and presented state-of-art examples on their application in the area of biomedicine.

Rare Single Nucleotide and Copy Number Variants and the Etiology of Congenital Obstructive Uropathy: Implications for Genetic Diagnosis.

SIGNIFICANCE STATEMENT: Congenital obstructive uropathy (COU) is a prevalent human developmental defect with highly heterogeneous clinical presentations and outcomes. Genetics may refine diagnosis, prognosis, and treatment, but the genomic architecture of COU is largely unknown. Comprehensive genomic screening study of 733 cases with three distinct COU subphenotypes revealed disease etiology in 10.0% of them. We detected no significant differences in the overall diagnostic yield among COU subphenotypes, with characteristic variable expressivity of several mutant genes. Our findings therefore may legitimize a genetic first diagnostic approach for COU, especially when burdening clinical and imaging characterization is not complete or available. BACKGROUND: Congenital obstructive uropathy (COU) is a common cause of developmental defects of the urinary tract, with heterogeneous clinical presentation and outcome. Genetic analysis has the potential to elucidate the underlying diagnosis and help risk stratification. METHODS: We performed a comprehensive genomic screen of 733 independent COU cases, which consisted of individuals with ureteropelvic junction obstruction ( n =321), ureterovesical junction obstruction/congenital megaureter ( n =178), and COU not otherwise specified (COU-NOS; n =234). RESULTS: We identified pathogenic single nucleotide variants (SNVs) in 53 (7.2%) cases and genomic disorders (GDs) in 23 (3.1%) cases. We detected no significant differences in the overall diagnostic yield between COU sub-phenotypes, and pathogenic SNVs in several genes were associated to any of the three categories. Hence, although COU may appear phenotypically heterogeneous, COU phenotypes are likely to share common molecular bases. On the other hand, mutations in TNXB were more often identified in COU-NOS cases, demonstrating the diagnostic challenge in discriminating COU from hydronephrosis secondary to vesicoureteral reflux, particularly when diagnostic imaging is incomplete. Pathogenic SNVs in only six genes were found in more than one individual, supporting high genetic heterogeneity. Finally, convergence between data on SNVs and GDs suggest MYH11 as a dosage-sensitive gene possibly correlating with severity of COU. CONCLUSIONS: We established a genomic diagnosis in 10.0% of COU individuals. The findings underscore the urgent need to identify novel genetic susceptibility factors to COU to better define the natural history of the remaining 90% of cases without a molecular diagnosis.

Development of machine learning models for detection of vision threatening Behçet's disease (BD) using Egyptian College of Rheumatology (ECR)-BD cohort.

BACKGROUND: Eye lesions, occur in nearly half of patients with Behçet's Disease (BD), can lead to irreversible damage and vision loss; however, limited studies are available on identifying risk factors for the development of vision-threatening BD (VTBD). Using an Egyptian college of rheumatology (ECR)-BD, a national cohort of BD patients, we examined the performance of machine-learning (ML) models in predicting VTBD compared to logistic regression (LR) analysis. We identified the risk factors for the development of VTBD. METHODS: Patients with complete ocular data were included. VTBD was determined by the presence of any retinal disease, optic nerve involvement, or occurrence of blindness. Various ML-models were developed and examined for VTBD prediction. The Shapley additive explanation value was used for the interpretability of the predictors. RESULTS: A total of 1094 BD patients [71.5% were men, mean ± SD age 36.1 ± 10 years] were included. 549 (50.2%) individuals had VTBD. Extreme Gradient Boosting was the best-performing ML model (AUROC 0.85, 95% CI 0.81, 0.90) compared with logistic regression (AUROC 0.64, 95%CI 0.58, 0.71). Higher disease activity, thrombocytosis, ever smoking, and daily steroid dose were the top factors associated with VTBD. CONCLUSIONS: Using information obtained in the clinical settings, the Extreme Gradient Boosting identified patients at higher risk of VTBD better than the conventional statistical method. Further longitudinal studies to evaluate the clinical utility of the proposed prediction model are needed.

Rheumatoid arthritis study of the Egyptian College of Rheumatology (ECR): nationwide presentation and worldwide stance.

To depict the spectrum of rheumatoid arthritis (RA) in Egypt in relation to other universal studies to provide broad-based characteristics to this particular population. This work included 10,364 adult RA patients from 26 specialized Egyptian rheumatology centers representing 22 major cities all over the country. The demographic and clinical features as well as therapeutic data were assessed. The mean age of the patients was 44.8 ± 11.7 years, disease duration 6.4 ± 6 years, and age at onset 38.4 ± 11.6 years; 209 (2%) were juvenile-onset. They were 8750 females and 1614 males (F:M 5.4:1). 8% were diabetic and 11.5% hypertensive. Their disease activity score (DAS28) was 4.4 ± 1.4 and health assessment questionnaire (HAQ) 0.95 ± 0.64. The rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) were positive in 73.7% and 66.7% respectively. Methotrexate was the most used treatment (78%) followed by hydroxychloroquine (73.7%) and steroids (71.3%). Biologic therapy was received by 11.6% with a significantly higher frequency by males vs females (15.7% vs 10.9%, p = 0.001). The least age at onset, F:M, RF and anti-CCP positivity were present in Upper Egypt (p < 0.0001), while the highest DAS28 was reported in Canal cities and Sinai (p < 0.0001). The HAQ was significantly increased in Upper Egypt with the least disability in Canal cities and Sinai (p = 0.001). Biologic therapy intake was higher in Lower Egypt followed by the Capital (p < 0.0001). The spectrum of RA phenotype in Egypt is variable across the country with an increasing shift in the F:M ratio. The age at onset was lower than in other countries.

Antiviral Activity of Pyrimidine Containing Compounds: Patent Review.

Viruses are still the most prevalent infectious pathogens on a worldwide scale, with many of them causing life-threatening illnesses in humans. Influenza viruses, because of their significant morbidity and mortality, continue to pose a major threat to human health. According to WHO statistics, seasonal influenza virus epidemics are predicted to cause over 2 million severe illness cases with high death rates yearly. The whole world has been suffering from the COVID-19 epidemic for two years and is still suffering so far, and the deaths from this virus have exceeded three million cases. Because the great majority of viral infections do not have a specific medication or vaccination, discovering novel medicines remains a vital task. This review covers reports in the patent literature from 1980 to the end of 2021 on the antiviral activities of pyrimidine moieties. The patent database, SciFinder, was used to locate patent applications. A large variety of pyrimidine molecules have been produced and tested for antiviral activity over the last decade. These molecules were reported to inhibit a wide range of viruses, including influenza virus, respiratory syncytial virus, rhinovirus, dengue virus, herpes virus, hepatitis B and C, and human immunodeficiency virus. The cytotoxicity of the developed pyrimidine derivatives was tested in almost all reported studies and the selectivity index was calculated to show the selectivity and safety of such molecules. From the remarkable activity of pyrimidine compounds as antivirals for several dangerous viruses, we expect that these derivatives will be used as potent drugs in the very near future.