SOX9 is regulated by AURKA in response to Helicobacter pylori infection via EIF4E-mediated cap-dependent translation.

Helicobacter pylori (H. pylori) infection is the main risk factor for gastric cancer. The SRY-Box Transcription Factor 9 (SOX9) serves as a marker of stomach stem cells. We detected strong associations between AURKA and SOX9 expression levels in gastric cancers. Utilizing in vitro and in vivo mouse models, we demonstrated that H. pylori infection induced elevated levels of both AURKA and SOX9 proteins. Notably, the SOX9 protein and transcription activity levels were dependent on AURKA expression. AURKA knockdown led to a reduction in the number and size of gastric gland organoids. Conditional knockout of AURKA in mice resulted in a decrease in SOX9 baseline level in AURKA-knockout gastric glands, accompanied by diminished SOX9 induction following H. pylori infection. We found an AURKA-dependent increase in EIF4E and cap-dependent translation with an AURKA-EIF4E-dependent increase in SOX9 polysomal RNA levels. Immunoprecipitation assays demonstrated binding of AURKA to EIF4E with a decrease in EIF4E ubiquitination. Immunohistochemistry analysis on tissue arrays revealed moderate to strong immunostaining of AURKA and SOX9 with a significant correlation in gastric cancer tissues. These findings elucidate the mechanistic role of AURKA in regulating SOX9 levels via cap-dependent translation in response to H. pylori infection in gastric tumorigenesis.

Coupling of a streamlined solid-liquid extraction protocol with LC-ESI-MS/MS for the regular oversight of illegal bromate additive use: An accurate and sensitive determination method in preliminary and bakery products.

A reliable solid-liquid extraction protocol coupled with liquid chromatography-electrospray ionization-tandem mass spectrometry in the negative-ion mode was developed and validated for illegal bromate determination in preliminary and bakery products. Crude and dried-treated samples were directly extracted with acetonitrile-water (4:1, v/v). Bromate was determined using a Phenomenex Synergi™ Polar reversed-phase column and MS/MS under multiple reaction monitoring. The chosen solvent efficiently extracted bromate with all applied extraction-assisting techniques (p > 0.05). Although this assay avoids cleanup procedures, matrix effect of <-11% was achieved. Rapid bromate separation in only 8 min was attained by a reversed-phase column. In both commodities, linearity range, R2, recovery%, repeatability, intermediate precision, LOD and LOQ results were 0.05-100 ng mL-1, >0.9999, 88.6-103%, 2.93-9.80% and 9.64-10.10%, 0.015 µg kg-1 and 0.05 µg kg-1, respectively. Out of 288 tested real samples, 13.9% of violations were observed. This high-sensitivity protocol offers effective oversight and consumer protection.

Association of serum IL-30 and soluble GP130 with the risk of psoriasis vulgaris.

Cytokines play a major role in the pathogenesis and progression of psoriasis. Interleukin (IL)-30 is a multifunctional cytokine. It binds to glycoprotein 130 (GP130) and inhibits the GP130 signaling pathways of psoriasis associated cytokines such as IL-6, IL-11, and IL-27. The study intended to assess associations of IL-30 and GP130 with the risk of psoriasis and Psoriasis Area Severity Index (PASI) score. Therefore, we measured the serum levels of IL-30 and GP130 in psoriasis patients and in a control group. An enzyme linked immunosorbent assay (ELISA) technique was used to measure IL-30 and GP130 levels in the serum of 43 patients and 43 normal controls. Statistical analysis of IL-30 and GP130 serum levels among patients and control groups and their correlation with PASI scores were performed. IL-30 serum levels showed a significant increase in patients with psoriasis compared with controls (p < 0.001) and a positive correlation with PASI scores. While serum levels of GP130 were not different in psoriatic patients and in the control group. Furthermore, the receiver operating characteristic (ROC) curve showed that IL-30 had diagnostic ability for prediction of psoriasis in comparison to controls, at cut of point of >14.34 showed a sensitivity of 97.7%, 100% specificity. In conclusion, IL-30 was elevated in psoriasis patients than controls, therefore, it can be considered a sensitive biomarker for diagnosis of psoriasis.

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.

Bioengineered Wheat Arabinoxylan - Fostering Next-Generation Prebiotics Targeting Health-Related Gut Microbes.

Dietary prebiotic fibers play an important role in modulating gut microbiota by enhancing the abundance of beneficial microorganisms and their bioactive metabolites. However, dietary fibers are a structurally heterogeneous class of polysaccharides, varying in molar mass, branching patterns, and monosaccharide composition, which could influence their utilization by various gut microorganisms. The present study aimed to investigate the effects of molar mass and chemical structure of wheat arabinoxylan fiber (AX) on the growth and metabolism of two key gut resident bacteria (Faecalibacterium prausnitzii and Lacticaseibacillus rhamnosus LGG), which are linked to human health. For this purpose, low, medium, and high molar masses of AX (LAX, MAX, and HAX, respectively) were modified with specific α-arabinofuranosidases to leave only singly substituted, only doubly substituted, or unsubstituted xylose units. Almost all the modified AX samples showed a better prebiotic score than unmodified AX for different molar masses. The modified LAX exhibited a better prebiotic effect than HAX and MAX. In addition, LAX, with doubly substituted xylose units, exhibited the highest prebiotic potential and SCFA production by both microorganisms. Furthermore, AX, either singly or doubly substituted, had a consistent impact on L. rhamnosus growth, whereas AX, with all arabinose residues removed, had a greater impact on F. prausnitzii. These findings support the potential of bioengineered AX as next-generation prebiotics targeting health-related gut microbes.

Benchmarking ChatGPT-4 on a radiation oncology in-training exam and Red Journal Gray Zone cases: potentials and challenges for ai-assisted medical education and decision making in radiation oncology.

Purpose: The potential of large language models in medicine for education and decision-making purposes has been demonstrated as they have achieved decent scores on medical exams such as the United States Medical Licensing Exam (USMLE) and the MedQA exam. This work aims to evaluate the performance of ChatGPT-4 in the specialized field of radiation oncology. Methods: The 38th American College of Radiology (ACR) radiation oncology in-training (TXIT) exam and the 2022 Red Journal Gray Zone cases are used to benchmark the performance of ChatGPT-4. The TXIT exam contains 300 questions covering various topics of radiation oncology. The 2022 Gray Zone collection contains 15 complex clinical cases. Results: For the TXIT exam, ChatGPT-3.5 and ChatGPT-4 have achieved the scores of 62.05% and 78.77%, respectively, highlighting the advantage of the latest ChatGPT-4 model. Based on the TXIT exam, ChatGPT-4's strong and weak areas in radiation oncology are identified to some extent. Specifically, ChatGPT-4 demonstrates better knowledge of statistics, CNS & eye, pediatrics, biology, and physics than knowledge of bone & soft tissue and gynecology, as per the ACR knowledge domain. Regarding clinical care paths, ChatGPT-4 performs better in diagnosis, prognosis, and toxicity than brachytherapy and dosimetry. It lacks proficiency in in-depth details of clinical trials. For the Gray Zone cases, ChatGPT-4 is able to suggest a personalized treatment approach to each case with high correctness and comprehensiveness. Importantly, it provides novel treatment aspects for many cases, which are not suggested by any human experts. Conclusion: Both evaluations demonstrate the potential of ChatGPT-4 in medical education for the general public and cancer patients, as well as the potential to aid clinical decision-making, while acknowledging its limitations in certain domains. Owing to the risk of hallucinations, it is essential to verify the content generated by models such as ChatGPT for accuracy.

Multivalent tyrosine kinase inhibition promotes T cell recruitment to immune-desert gastric cancers by restricting epithelial-mesenchymal transition via tumour-intrinsic IFN-γ signalling.

OBJECTIVE: Gastric cancer (GC) ranks fifth in incidence and fourth for mortality worldwide. The response to immune checkpoint blockade (ICB) therapy in GC is heterogeneous due to tumour-intrinsic and acquired immunotherapy resistance. We developed an immunophenotype-based subtyping of human GC based on immune cells infiltration to develop a novel treatment option. DESIGN: A algorithm was developed to reclassify GC into immune inflamed, excluded and desert subtypes. Bioinformatics, human and mouse GC cell lines, syngeneic murine gastric tumour model, and CTLA4 blockade were used to investigate the immunotherapeutic effects by restricting receptor tyrosine kinase (RTK) signalling in immune desert (ICB-resistant) type GC. RESULTS: Our algorithm restratified subtypes of human GC in public databases and showed that immune desert-type and excluded-type tumours are ICB-resistant compared with immune-inflamed GC. Moreover, epithelial-mesenchymal transition (EMT) signalling was highly enriched in immune desert-type GC, and syngeneic murine tumours exhibiting mesenchymal-like, compared with epithelial-like, properties are T cell-excluded and resistant to CTLA4 blockade. Our analysis further identified a panel of RTKs as potential druggable targets in the immune desert-type GC. Dovitinib, an inhibitor of multiple RTKs, strikingly repressed EMT programming in mesenchymal-like immune desert syngeneic GC models. Dovitinib activated the tumour-intrinsic SNAI1/2-IFN-γ signalling axis and impeded the EMT programme, converting immune desert-type tumours to immune inflamed-type tumours, sensitising these mesenchymal-like 'cold' tumours to CTLA4 blockade. CONCLUSION: Our findings identified potential druggable targets relevant to patient groups, especially for refractory immune desert-type/ 'cold' GC. Dovitinib, an RTK inhibitor, sensitised desert-type immune-cold GC to CTLA4 blockade by restricting EMT and recruiting T cells.

Risk factors and outcomes of occurrence of anastomotic leakage and reoperations for its management after colorectal surgery

Background: Anastomotic leakage (AL) is still the most annoying postsurgery complication after colorectal resection due to its serious complications up to death. Limited data were available regarding differences in AL incidence, management, and consequences for different types of colorectal resection. The aim of the present work was to evaluate differences in incidence of AL, incidence of postoperative complications, and length of hospital stay in a large number of patients who underwent elective colorectal resection for management of colorectal lesions. In addition to detect when and what type of reoperation for management of AL occur after colorectal resection. Patients: All 250 included patients underwent elective surgeries for colorectal resection with performance of primary anastomosis for management of colorectal neoplastic and non-neoplastic diseases in the period between May 2016 and July 31, 2021. We followed the patients for 90 days; we registered the follow-up findings. Results: the rates of AL occurrence were variable after the different procedures. The lowest rate of AL occurrence was found in patients who underwent right hemicolectomy, then in patients who underwent sigmoidectomy, left hemicolectomy, transversectomy and anterior resection (p= 0.004). A stoma was frequently performed during reoperation (79.5%) which was significantly different between different procedures: 65.5% in right hemicolectomy, 75.0% in transversectomy, 85.7% in left hemicolectomy, and 93.0% in sigmoid resection (p< 0.001). Conclusion Rates, types, time of occurrence and severity of AL vary according to the type of colectomy performed and selective construction of stoma during AL reoperation is currently safely applied with comparable mortality rates for patients who did and who did not have a stoma after reoperation. (AU)

Prognostic roles and survival benefits of endoscopic resection versus surgical resection in the management of malignant colon polyps

Background: Due to few sufficient data regarding the comparison between endoscopic and surgical resection of malignant colorectal polyps regarding outcomes and survival benefits, there are no clear guidelines of management strategies of malignant colorectal polyps. The aims of the present study were to compare endoscopic resection alone and surgical resection in patients with malignant polyps in the colon (T1N0M0) readings advantages, disadvantages, recurrence risks, survival benefits, and long-term prognosis to detect how management strategy affects outcome. Patients and methods: we included 350 patients. All included patients were divided into 2 groups; the first group included 100 patients who underwent only endoscopic polypectomy and the second group included 250 patients who underwent endoscopic polypectomy followed by definitive surgical resection after histopathological diagnosis. We followed all patients for about 5 years, ranging from 18 to 55 months. The primarily evaluated parameters are surgical consequences and patients' morbidity. The secondary evaluated parameters are recurrence risks, recurrence free survival, and overall survival rates. Results: The age of patients who underwent polypectomy is usually younger than the surgical group, males have more liability to polypectomy in comparison with females. Patients with tumors in the left colon have more liability to polypectomy in comparison with the right colon (p< 0.0001). Tumor factors associated with more liability to surgical resection are presence of lymphovascular invasion, high grade, and poor tumor differentiation (p< 0.0001). The management strategy was the most significant predictor of overall and recurrence free survival rates in patients with malignant colon polyps (p< 0.001). Conclusions: We found that survival benefits and lower incidence of recurrence are detected in the surgical resection group more than in the polypectomy group. (AU)

Development and Validation of a Modified QuEChERS protocol Coupled to Liquid Chromatography-Tandem Mass Spectrometry for the Rapid and Accurate Determination of Acrylamide in Cereal-Based Baby Foods.

BACKGROUND: With the widespread consumption by children of cereal-based baby food, acrylamide contamination is a prevalent risk that may have carcinogenic consequences. OBJECTIVE: This study aims to develop and validate a modified QuEChERS protocol (quick, easy, cheap, effective, rugged, and safe) without solvent exchange, followed by rapid separation and accurate determination of acrylamide in cereal-based baby foods using reversed-phase (RP)-LC-MS/MS. METHODS: Samples were extracted using a modified QuEChERS protocol of the AOAC version and cleaned up with basic alumina. Separation was performed on a Phenomenex® Kinetex C18 column (100 Å × 3.5 µm × 4.6 mm × 150 mm) using a gradient elution program with a mobile phase of 10 mM ammonium formate-methanol. Determinations were conducted using electrospray ionization (ESI)-MS/MS in positive-ion mode. RESULTS: Basic alumina yielded clean extracts, resulting in acceptable recovery percentages and a tolerable matrix effect (ME) <5%. This allowed extraction without a solvent exchange step. Efficient separation was achieved at a retention time (tR) of 3.39 ± 0.05 min employing an RP-C18 column with core-shell properties in a relatively short analysis run time of only 5 min. Trueness, precision, LOD, LOQ, linearity range, and R2 results were 92.5-104.6%, RSD ≤12.2%, 5 µg/kg, 20 µg/kg, 4.0-1000.0 µg/kg, and > 0.9999, respectively. The test method applicability was demonstrated by proficiency testing (PT) and 50 real samples of cereal-based baby foods. Most of the tested samples were in violation of acrylamide's established European Union benchmark (40 µg/kg). CONCLUSION: Acetate-buffered QuEChERS protocol in conjunction with optimized amounts of basic alumina was confirmed as an efficient extraction protocol for acrylamide from cereal-based baby foods resulting in optimal method performance. Successful selection of the RP-C18 column is key for selective separation for acrylamide in a relatively short analysis run time. HIGHLIGHTS: The modified AOAC QuEChERS protocol with a dispersive solid phase extraction (d-SPE) of basic alumina assisted in reducing the ME to tolerable levels while maintaining acceptable method performance. The use of an RP-C18 column with core-shell properties enabled a rapid and accurate acrylamide determination.

A randomized-controlled trial of SOF/VEL/VOX with or without ribavirin for retreatment of chronic hepatitis C.

BACKGROUND & AIMS: The combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) is recommended for the retreatment of patients with HCV infection in whom previous direct-acting antiviral (DAA) treatment failed. However, whether ribavirin further increases the therapeutic efficacy of SOF/VEL/VOX retreatment remains unclear. We aimed to test this hypothesis in a randomized-controlled trial. METHODS: We randomly assigned 315 patients with DAA treatment failure from five Egyptian sites into two groups. Group A (n = 158) received SOF/VEL/VOX for 12 weeks, and group B (n = 157) received SOF/VEL/VOX + weight-based ribavirin for 12 weeks. Therapeutic efficacy was defined as SVR12 (sustained virologic response 12 weeks after treatment end). Safety and tolerability were evaluated by monitoring treatment-related adverse events (AEs) and laboratory abnormalities. RESULTS: Males comprised 53.9% of group A and 57.1% of group B (p = 0.58); mean ages were 51.8 and 47.3 years in group A and B, respectively. Seventeen patients in each group were lost to follow-up. SVR12 rates were 87.3% (138/158) by intention-to-treat analysis and 97.8% (138/141) by per-protocol analysis in group A; and 87.9% (138/157) and 98.5% (138/140), respectively, in group B (p = n.s. for intention-to-treat and per-protocol analyses). Both regimens were well-tolerated, with no deaths and only one serious AE (anemia) in group B, which required ribavirin discontinuation. Fifty-five patients in group A vs. 77 in group B experienced any AE (p = 0.002). CONCLUSION: This randomized-controlled trial showed equal, high efficacy of both regimens for the retreatment of previous DAA failures, although ribavirin was associated with more AEs. Therefore SOF/VEL/VOX monotherapy should be the preferred retreatment strategy. CLINCIALTRIALS. GOV NUMBER: NCT04695769. IMPACT AND IMPLICATIONS: HCV treatment guidelines recommend retreatment of direct-acting antiviral (DAA) treatment failures with the combination of sofosbuvir, velpatasvir and voxilaprevir (SOF/VEL/VOX) for 12 weeks. However, whether ribavirin exerts an additional/synergistic effect remains unclear. The present study confirmed that SOF/VEL/VOX without ribavirin is the best regimen for retreatment of DAA treatment failures, and thus will help guide clinicians caring for patients who are not cured with a first course of DAA therapy.

LncRNA-GAS5 and ß-Catenin as Independent Predictors of Asymptomatic Organ Damage in Nondiabetic Hypertensive Patients.

Hypertension is a serious medical condition that can increase the risk of developing heart, brain, kidney, and other diseases. Many asymptomatic hypertension patients experience asymptomatic organ damage (AOD). The purpose of this study was to determine the roles of LncRNA-GAS5 and ß-catenin in predicting AOD in hypertensive nondiabetic patients. This study included 256 subjects, 128 hypertension patients (75 of whom had AOD, and 53 of whom did not) and 128 healthy controls. qRT-PCR was used to assess LncRNA-GAS5, and ELISA was used to assess ß-catenin. The LncRNA-GAS5 expression level was decreased in hypertensive patients compared to controls (p-value < 0.001). On the other hand, ß-catenin levels showed higher levels in the patients in comparison with controls (p-value < 0.001). A 0.38-fold change in LncRNA-GAS5 expression predicted AOD with 86.6% sensitivity and 88.7% specificity. ß-Catenin > 80.5 pg/mL predicted AOD with a sensitivity of 82.6% and specificity of 69.8%. LncRNA-GAS5 expression was a better diagnostic predictor of AOD than ß-catenin. According to multivariate logistic regression analysis, decreased LncRNA-GAS5 expression independently increased the risk of AOD (adjusted odds ratio = 0.03 (95% CI: 0.01-0.1) (p < 0.001). Furthermore, elevated ß-catenin levels may be an independent risk factor for AOD (adjusted odds ratio = 14.3 (95% confidence interval, 3.3-61.9) (p < 0.001). Collectively, in hypertensive patients, LncRNA GAS5 and ß-catenin can distinguish patients with AOD from those who do not have AOD. LncRNA GAS5 and ß-catenin can be used as independent predictors of AOD in hypertensive patients.

Efficacy of Cryotherapy Combined With Intralesional Purified Protein Derivative (PPD) Versus Intralesional PPD Monotherapy in the Treatment of Multiple Common Warts.

INTRODUCTION: Intralesional antigen immunotherapy represents a promising therapeutic approach for the treatment of different types of warts, particularly if multiple and/or recalcitrant. AIM: to investigate the efficacy and safety of combined cryotherapy with intralesional purified protein derivative (PPD) immunotherapy in the treatment of multiple common warts. METHODS: Fifty patients were randomly divided into two groups (25 patients each): Group A: receiving intralesional PPD immunotherapy for the largest wart, while group B: receiving cryotherapy for all warts plus intralesional PPD for the largest wart. Treatments were performed every 2 weeks for a maximum of four sessions. Photographs were taken at baseline and at each visit and clinical response was evaluated by the reduction in number and size of warts. Adverse effects were recorded. RESULTS: There was a significant reduction in size and number of warts in both groups (P < .001), with no significant difference between the two groups. Complete clearance of the lesions was observed in 48% of patients in group A and 44% in group B (P = .39). Higher rates of near complete/complete response were achieved after fewer sessions (2, 3 sessions) in group B (P = .002). Blistering was common after cryotherapy. Higher rate of hypopigmentation was noticed after combined treatment than after PPD monotherapy (56%, 8% respectively; P < .001), which resolved gradually. CONCLUSION: Both intralesional PPD alone and combined cryotherapy with PPD are safe and effective in clearing of common warts. Cryotherapy may be a successful adjunct to intralesional PPD immunotherapy that helps in reducing the number of treatment sessions.The study protocol was registered at ClinicalTrials.gov with ID: NCT04288817.

Comparative Real Life Egyptian Experience of the Combination of Sofosbuvir Plus Daclatasvir or Simeprevir for 12 Weeks in Naïve Cirrhotic Patients Infected with HCV Genotype 4.

BACKGROUND: Chronic infection with HCV is progressive worldwide health problem and the core reason for liver cirrhosis, portal hypertension, or hepatocellular carcinoma. HCV-G4 represents the most common threat to transplantation of the liver in Egypt. New interferon-free regimens have been started consuming direct-acting antiviral oral tablets for HCV cure. OBJECTIVES: In the current study, comparing the safety and efficacy of DAAs combination regimens including sofosbuvir with daclatasvir or sofosbuvir with simeprevir plus ribavirin for naïve cirrhotic Egyptian patients infected with HCV-G4 was our main goal. METHODS: We recruited 150 naïve cirrhotic HCV patients from the Tropical patients' clinic at Fayoum General Hospital. They were classified randomly into two groups, group one (n=75 patients) were administrated Sofosbuvir plus simeprevir (400 mg and 150 mg once daily respectively ) for twelve weeks, and group two (n=75 patients) were administrated Sofosbuvir plus Daclatasvir (400 mg and 60 mg once daily respectively) with ribavirin (1-1.2 gm daily weight-based) for twelve weeks. Clinical follow-up, laboratory investigations, and viral PCR were measured to detect treatment efficacy, safety, and any adverse events. RESULTS: Sustained virological response rates (SVR12) were 92%and 90.7% in the first and second groups, respectively. The major unfavorable events were fatigue, arthralgia, and weight loss without statistically meaningful differences between study groups. However, anemia and headache were significantly widespread in the second group (P=0.0161 and 0.0495, respectively). We observed four patients with photosensitivity in group I and not observed in the second group. CONCLUSION: The current study revealed that DAAs are safe and effective in the cure of naïve cirrhotic patients chronically infected by HCV-G4 with better results in those treated with sofosbuvir plus simeprevir regimen.

Clinical significance of LncRNA-MIAT as a non-invasive diagnostic marker of nonHodgkin's lymphoma associated with occult hepatitis C virus infection

Aims: the current research aimed to investigate LncRNA-MIAT in patients with nonHodgkin lymphoma (NHL) and to assess its correlation with clinicopathological features and treatment protocols of NHLs among Egyptian patients with Occult hepatitis C virus (HCV) infection (OCI). Patients & Methods: This study was conducted on 20 patients with NHL and 30 healthy subjects as the control group. All subjects were screened for HCV-RNA in both plasma and PBMCs. RT-PCR determined lncRNA-MIAT. Results: lncRNA-MIAT relative expression level was upregulated in NHL groups (2.73±0.86) compared to controls (1.06±0.07), P ˂0.001*. Among NHL, patients with OCI (3.2±0.63) had significantly higher levels of lncRNA-MIAT compared to HCV (2.6±1.08) and non-HCV (2.4±0.4), P ˂0.001*. Additionally, the relative expression levels of lncRNA-MIAT were significantly positively correlated with laboratory and clinicopathological features of NHL. Interestingly, concerning the treatment of DLBCLNHL, there were significantly higher levels of lncRNA-MIAT in no treatment subgroup (n=10, 3.31±0.95) compared to successfully treated subgroups [CHOP (n=7, 1.58±0.34) and R-CHOP (n=3, 11.16±0.21), P ˂0.001* Conclusions: lncRNA-MIAT level was upregulated in NHL patients, particularly patients with OCI. Thus, circulatory lncRNA-MIAT may serve as a promising non-invasive diagnostic marker for NHL associated with OCI

Hepatologists' awareness and knowledge toward NAFLD and the familiarity with renaming from NAFLD to MAFLD.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is an emerging epidemic; it is a negative diagnosis that depends mainly on the presence of hepatic steatosis with or without inflammation after exclusion of other chronic liver diseases and excess alcohol intake. However, the new definition of MAFLD is a shift towards a diagnosis of inclusion based on the presence of metabolic dysfunction, regardless of alcohol consumption or other concomitant liver diseases. Given the growing relevance of the disease, data on hepatologists' views and understanding of NAFLD are limited, we aimed to determine hepatologists' awareness and expertise of NAFLD screening, diagnosis, and therapeutic options as well as the influence of changing the NAFLD name to MAFLD on awareness of the fatty liver disease (FLD). OBJECTIVE: Most of the hepatologists agreed that NAFLD can cause serious hepatic illness and may be linked to metabolic risk factors, necessitating a multidisciplinary approach to treatment. Hepatologists have a poor understanding of NAFLD care. The shift in terminology from NAFLD to MAFLD will be more known to hepatologists, and it may offer a better awareness of FLD. METHODS: A multicenter online questionnaire of 655 hepatologists was carried out, giving a sample of 207 respondents. A survey composed of 36 questions was used to assess the level of hepatologists' awareness and practices in the screening, diagnosis, and management of NAFLD/MAFLD, as well as their familiarity with the nomenclature change from NAFLD to MAFLD. RESULTS: A total of 207 hepatologists were included, of which 107 (51.4%) were males, with a mean age was 36.4 years. 50.2% (n=104) of the hepatologists were oriented with NAFLD. Only 41 (19.8%) realized that NAFLD may frequently result in severe hepatic disease. NAFLD is rarely screened by the majority of the participating hepatologists (118, 57%), and (135, 65.2%) of them use liver biopsy for diagnosis of NAFLD. In (104, 50.2%) of hepatologists, changing the nomenclature of NAFLD was relatively familiar. Furthermore, 71.9% of hepatologists thought that the new nomenclature offers a better awareness of FLD. CONCLUSION: A small percentage of hepatologists agreed that NAFLD can cause serious hepatic illness and may be linked to metabolic risk factors, and around half of them realize that NAFLD necessitates a multidisciplinary approach to treatment. Hepatologists have a poor understanding of NAFLD care. The shift in terminology from NAFLD to MAFLD will be more known to hepatologists, and it may offer better awareness of FLD.

Editorial: The Metabolic (Dysfunction)-Associated Fatty Liver Disease (MAFLD) and Non-Alcoholic Fatty Liver Disease (NAFLD) Debate: Why the American Association for the Study of Liver Diseases (AASLD) and European Association for the Study of the Liver (EASL) Consensus Process is Not Representative.

A debate has recently arisen in hepatology on the redefinition of fatty liver disease associated with metabolic dysfunction. The definition of metabolic (dysfunction)-associated fatty liver disease (MAFLD) has been widely endorsed by multiple stakeholders and societies. More importantly, although robust evidence supports the utility of the definition of MAFLD in clinical practice and research, and for increasing awareness of liver disease, controversy still abounds. Recently, the American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) have undertaken similar consensus approaches for MAFLD. However, there are serious concerns with these regional consensus approaches. The views of hepatologists from the Middle East, North Africa, and sub-Saharan Africa are not represented. Also, the selection of experts raises concerns regarding the validity of the outcomes of the expert consensus process. We conclude that unless the process has global involvement, there will be no incentive for global adherence to these regional recommendations. This Editorial aims to highlight these concerns and to call for those involved in leading the AASLD and EASL consensus process to be more inclusive, which may facilitate the adoption of more unified recommendations that have global clinical importance.

The Impact of Direct-Acting Antiviral Agents on Cytomegalovirus Reactivation in Chronic Hepatitis C Infection.

OBJECTIVE: The co-infection of HCV/CMV may accelerate the progression of liver diseases and worsen responsiveness to IFN treatment. The Direct-acting antiviral agents (DAAs), currently approved therapy for HCV, may cause a transient change in immune status, favoring the reactivation of other viruses. The current study aims to evaluate the impact of DAAs treatment on the reactivation of latent CMV in HCV patients. METHODS: The serological IgG, IgM Abs against CMV were detected by ELISA on192 HCV patients. The seronegative CMV IgM patients received (sofosbuvir/daclatasvir) regimen, then the CMV reactivation was examined by measuring the CMV IgM by ELISA and CMV DNA by real-time PCR. RESULTS: The serological data revealed that all patients were positive for CMV IgG (100%) while (64%) patients were positive for CMV IgM. The seronegative CMV IgM (36%) received the DAAs protocol. The sustained virological response was monitored by measuring the HCV RNA viremia in the patient sera. The serological data revealed that 28.6% of patients had a reactivation of CMV, while 18.5% of patients had detectable CMV DNA viremia. Moreover, there was a significant improvement in liver function as well as a decrease in FIB-4 and APRI scores at EOT. SVR was reached 97.4% among the total studied patients (N= 192). CONCLUSION: CMV co-infection has no impact on the response rate to DAAs. However, the CMV reactivation might have occurred after the complete eradication of HCV by DAAs.

Unfolded Protein Response Is Activated by Aurora Kinase A in Esophageal Adenocarcinoma.

Unfolded protein response (UPR) protects malignant cells from endoplasmic reticulum stress-induced apoptosis. We report that Aurora kinase A (AURKA) promotes cancer cell survival by activating UPR in esophageal adenocarcinoma (EAC). A strong positive correlation between AURKA and binding immunoglobulin protein (BIP) mRNA expression levels was found in EACs. The in vitro assays indicated that AURKA promoted IRE1α protein phosphorylation, activating prosurvival UPR in FLO-1 and OE33 cells. The use of acidic bile salts to mimic reflux conditions in patients induced high AURKA and IRE1α levels. This induction was abrogated by AURKA knockdown in EAC cells. AURKA and p-IRE1α protein colocalization was observed in neoplastic gastroesophageal lesions of the L2-IL1b mouse model of Barrett's esophageal neoplasia. The combined treatment using AURKA inhibitor and tunicamycin synergistically induced cancer cell death. The use of alisertib for AURKA inhibition in the EAC xenograft model led to a decrease in IRE1α phosphorylation with a significant reduction in tumor growth. These results indicate that AURKA activates UPR, promoting cancer cell survival during ER stress in EAC. Targeting AURKA can significantly reverse prosurvival UPR signaling mechanisms and decrease cancer cell survival, providing a promising approach for the treatment of EAC patients.