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Elucidating the clinical and immunological value of m6A regulatormediated methylation modification patterns in adrenocortical carcinoma

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Oncology Research 2023年第5期31卷 819-831页

作者： WENHAO XU HAOmING lI YASIR HAmEED mOSTAFA A.ABDEl-mAKSOUD SAEEDAH mUSAED AlmUTAIRI ayman mUBARAK mOHAmmED AUFY WAEl AlTURAIKI ABDUlAZIZ J.AlSHAlANI ayman m.mAHmOUD CHEN lI Department of Urology Urological Surgery Research InstituteFirst Affiliated HospitalArmy Medical University(Third Military Medical University)ChongqingChina Department of Urology Affiliated Hospital of Guilin Medical UniversityGuilinChina Department of Applied Biological Sciences Tokyo University of ScienceTokyoJapan Department of Botany and microbiology College of ScienceKing Saud UniversityRiyadhSaudi Arabia Department of Pharmaceutical Sciences Division of Pharmacology and ToxicologyUniversity of ViennaViennaAustria Department of medical laboratory Sciences College of Applied Medical SciencesKing Saud UniversityRiyadhSaudi Arabia Department of life Sciences Faculty of Science and EngineeringManchester Metropolitan UniversityManchesterUK Department of Biology ChemistryPharmacyFree University of BerlinBerlinGermany

N6-methyladenosine methylation(m6A)is a common type of epigenetic alteration that prominently affects the prognosis of tumor ***,it is unknown how the m6A regulator affects the tumor microenvironment(TmE)cell infiltration in adrenocortical carcinoma(ACC)and how it affects the prognosis of ACC patients *** m6A alteration patterns of 112 ACC patients were evaluated,furthermore,the association with immune infiltration cell features was *** unsupervised clustering method was applied to typify the m6A alteration patterns of ACC *** principal component analysis(PCA)technique was taken to create the m6A score to assess the alteration pattern in specific *** found two independent patterns of m6A alteration in ACC *** TmE cell infiltration features were significantly in accordance with phenotypes of tumor immune-inflamed and immune desert in both *** m6Ascore also served as an independent predictive factor in ACC *** somatic copy number variation(CNV)and patients prognosis can be predicted by m6A alteration ***,the ACC patients with high m6A scores had better overall survival(OS)and higher efficiency in immune checkpoint blockade *** work demonstrated the significance of m6A alteration to the ACC patients *** individual m6A alteration patterns analysis might contribute to ACC patients prognosis prediction and immunotherapy choice.

关键词： m6A Tumor microenvironment Adrenocortical carcinoma Immunotherapy Prognosis

Pancreatits after endoscopic retrograde cholangio-pancreatography

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World Journal of Gastroenterology 2007年第19期13卷 2655-2668页

作者： ayman m Abdel Aziz Glen A lehman Division of Gastroenterology and Hepatology Indiana University Medical Center United States

Pancreatitis is the most common complication after endoscopic retrograde cholangio-pancreatography (ERCP); the reported incidence of this complication varies from less than 1% to 40%, but a rate of 4%-8% is reported in most prospective studies involving non-selected patients. Differences in criteria for defining pancreatitis, methods of data collection, and patient populations (i.e. number of high-risk patients included in the published series) are factors that are likely to affect the varying rates of post-ERCP pancreatitis. The severity of post-ERCP pancreatitis (PEP) can range from a minor inconvenience with one or two days of added hospitalization with full recovery to a devastating illness with pancreatic necrosis, multiorgan failure, permanent disability, and even death. Although, most episodes of PEP are mild (about 90%), a small percentage of patients (about 10%) develop moderate or severe pancreatitis. In the past, PEP was often viewed as an unpredictable and unavoidable complication, with no realistic strategy for its avoidance. New data have aided in stratifi cation of patients into PEP risk categories and new measures have been introduced to decrease the risk of PEP. As most ERCPs are performed on an outpatient basis, the majority of patients will not develop PEP and can be discharged. Alternatively, early detection of those patients who will go on to develop PEP can guide decisions regarding hospital admission and aggressive management. In the last decade, great efforts have been addressed toward prevention of this complication. Points of emphasis have included technical measures, pharmacological prophylaxis, and patient selection. This review provides a comprehensive, evidence-based assessment of published data on PEP and current suggestions for its avoidance.

关键词： Endoscopic retrograde cholangiopancreatography Post-ERCP pancreatitis

Neurogenesis dynamics in the olfactory bulb:deciphering circuitry organization, function, and adaptive plasticity

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Neural Regeneration Research 2025年第6期20卷 1565-1581页

作者： moawiah m.Naffaa Department of Psychology and Neuroscience Duke UniversityDurhamNCUSA Department of Cell Biology Duke University School of MedicineDurhamNCUSA

Adult neurogenesis persists after birth in the subventricular zone, with new neurons migrating to the granule cell layer and glomerular layers of the olfactory bulb, where they integrate into existing circuitry as inhibitory interneurons. The generation of these new neurons in the olfactory bulb supports both structural and functional plasticity, aiding in circuit remodeling triggered by memory and learning processes. However, the presence of these neurons, coupled with the cellular diversity within the olfactory bulb, presents an ongoing challenge in understanding its network organization and function. moreover,the continuous integration of new neurons in the olfactory bulb plays a pivotal role in regulating olfactory information processing. This adaptive process responds to changes in epithelial composition and contributes to the formation of olfactory memories by modulating cellular connectivity within the olfactory bulb and interacting intricately with higher-order brain regions. The role of adult neurogenesis in olfactory bulb functions remains a topic of debate. Nevertheless, the functionality of the olfactory bulb is intricately linked to the organization of granule cells around mitral and tufted cells. This organizational pattern significantly impacts output, network behavior, and synaptic plasticity, which are crucial for olfactory perception and memory. Additionally, this organization is further shaped by axon terminals originating from cortical and subcortical regions. Despite the crucial role of olfactory bulb in brain functions and behaviors related to olfaction, these complex and highly interconnected processes have not been comprehensively studied as a whole. Therefore, this manuscript aims to discuss our current understanding and explore how neural plasticity and olfactory neurogenesis contribute to enhancing the adaptability of the olfactory system. These mechanisms are thought to support olfactory learning and memory, potentially through increased

关键词： network adaptability neurogenesis neuronal communication olfactory bulb olfactory learning olfactory memory synaptic plasticity

SBl-JP-0004:A promising dual inhibitor of JAK2 and PI3KCD against gastric cancer

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Oncology Research 2025年第1期33卷 235-243页

作者： HASSAN m.OTIFI Department of Pathology College of MedicineKing Khalid UniversityAbha62521Saudi Arabia

Background:Gastric cancer(GC)remains a global health burden and is often characterized by heterogeneous molecular profiles and resistance to conventional *** phosphoinositide 3-kinase and PI3K and Janus kinase(JAK)signal transducer and activator of transcription(JAK-STAT)pathways play pivotal roles in GC progression,making them attractive targets for therapeutic ***:This study applied a computational and molecular dynamics simulation approach to identify and characterize SBl-JP-0004 as a potential dual inhibitor of JAK2 and PI3KCD *** and SNU-5 GC cells were used for in vitro ***:SBl-JP-0004 exhibited a robust binding affinity for JAK2 and PI3KCD kinases,as evidenced by molecular docking scores and molecular dynamics *** interactions and Gibbs binding free energy estimates confirmed stable and favorable interactions with target ***-JP-0004 displayed an half-maximal inhibitory concentration(IC_(50))value of 118.9 nm against JAK2 kinase and 200.9 nm against PI3KCD ***-JP-0004 exhibited potent inhibition of cell proliferation in KATOIII and SNU-5 cells,with half-maximal growth inhibitory concentration(GI50)values of 250.8 and 516.3 nm,respectively.A significant elevation in the early phase apoptosis(28.53%in KATOIII cells and 26.85%in SNU-5 cells)and late phase apoptosis(17.37%in KATOIII cells and 10.05%in SNU-5 cells)were observed with SBl-JP-0004 treatment compared to 2.1%and 2.83%in their respective ***:The results highlight SBl-JP-0004 as a promising dual inhibitor targeting JAK2 and PI3KCD kinases for treating GC and warrant further preclinical and clinical investigations to validate its utility in clinical settings.

关键词： Gastric cancer(GC) Dual inhibition JAK2 PI3KCD SBl-JP-0004 molecular docking molecular dynamics simulation

mitochondria–cGAS–STING axis is a potential therapeutic target for senescence-dependent inflammaging-associated neurodegeneration

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Neural Regeneration Research 2025年第3期20卷 805-807页

作者： Josém.Izquierdo Centro de Biología molecular Severo Ochoa(CBm) Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid(CSIC-UAM)MadridSpain

The word “senescence” comes from the latin senescens, meaning “to begin to age”, and is characterized by a long-lasting but reversible block in proliferation, resulting from stress-induced cell cycle arrest of pre... 详细信息

关键词： latin potential lasting

Getting physical with medical education:Exercise based virtual anatomy review classes for medical students

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World Journal of methodology 2025年第1期15卷 20-25页

作者： Nadeesha R Samarasinghe Taniya S Nagpal michele l Barbeau Charys m martin Division of General Surgery Faculty of MedicineUniversity of British ColumbiaVancouver V6T 1Z3BCCanada Faculty of Kinesiology Sport and RecreationUniversity of AlbertaEdmonton T6G 2R3ABCanada Anatomy and Cell Biology University of Western OntarioLondon N6A 3K7ONCanada Department of Anatomy and Cell Biology Schulich School of Medicine and DentistryThe University of Western OntarioLondon N6A 3K7ONCanada

The benefits of regular physical activity are well ***,few studies have examined the effectiveness of integrating physical activity(PA)into curricula within a post-secondary *** investigate the incorporation of PA into medical curriculum,we developed a series of optional exercise-based review sessions designed to reinforce musculoskeletal(mSK)anatomy course *** synchronous sessions were co-taught by a group fitness instructor and an anatomy *** fitness instructor would lead students through both strength and yoga style exercises,while the anatomy instructor asked questions about relevant anatomical structures related to course material previously *** the sessions,participants were asked to evaluate the classes on their self-reported exam preparedness in improving mSK anatomy knowledge,PA levels,and mental *** participants completed surveys;a majority agreed that the classes increased understanding of mSK concepts(90.0%)and activity levels(97.7%).many(70.0%)felt that the classes helped reduce *** majority of respondents(90.0%)agreed that the classes contributed to increased feelings of social ***,medical students saw benefit in PA based interventions to supplement mSK course *** with increasing activity levels and promoting health behaviours,integrating PA into medical curriculum may improve comprehension of learning material,alleviate stress and foster social connectivity among medical students.

关键词： medical education musculoskeletal Anatomy Exercise Online learning

Brain-penetrating neurotrophic factor mimetics: HER-096 as a disease-modifying therapy for Parkinson’s disease

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Neural Regeneration Research 2025年第4期20卷 1094-1095页

作者： Natalia Kulesskaya Kira m.Holmström Henri J.Huttunen Herantis Pharma Plc EspooFinland

Neurotrophic factors as a therapeutic approach in neurodegenerative diseases:A major unmet need in the field of central nervous system diseases is disease-modifying *** for decades there have been various symptomatic treatments available to alleviate the symptoms of the disease,disease-modification,*** that stop,significantly delay,or reverse the progression of the disease,has been turned out to a difficult goal to achieve.

关键词： diseases treatment therapeutic

Numerical Analysis of laterally loaded long Piles in Cohesionless Soil

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Computers, materials & Continua 2022年第5期71卷 2175-2190页

作者： ayman Abd-Elhamed mohamed Fathy Khaled m.Abdelgaber Physics and Engineering mathematics Department Faculty of Engineering-MattariaHelwan UniversityCairo11718Egypt Faculty of Engineering King Salman International UniversitySouth SinaiRas SedrEgypt Basic and Applied Science Department College of Engineering and TechnologyArab Academy for ScienceTechnology and Maritime TransportCairo11799Egypt

The capability of piles to withstand horizontal loads is a major design *** current research work aims to investigate numerically the responses of laterally loaded piles at working load employing the concept of a beam-on-Winkler-foundation *** governing differential equation for a laterally loaded pile on elastic subgrade is *** on legendreGalerkin method and Runge-Kutta formulas of order four and five,the flexural equation of long piles embedded in homogeneous sandy soils with modulus of subgrade reaction linearly variable with depth is solved for both free-and fixed-headed ***,as one of the world’s leading computational software,was employed for the implementation of *** proposed numerical techniques provide the responses for the entire pile length under the applied lateral *** utilized numerical approaches are validated against experimental and analytical results of previously published works showing a more accurate estimation of the response of laterally loaded ***,the proposed approaches can maintain both mathematical simplicity and comparable accuracy with the experimental results.

关键词： Numerical solution laterally loaded pile cohesionless soil legendre-Galerkin Runge-Kutta

Robust malicious Executable Detection Using Host-Based machine learning Classifier

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Computers, materials & Continua 2024年第4期79卷 1419-1439页

作者： Khaled Soliman mohamed Sobh ayman m.Bahaa-Eldin Department of Computer and Systems Engineering Ain Shams UniversityCairo11517Egypt Department of Computer Engineering Technology ElSewedy University of TechnologyCairo44629Egypt

The continuous development of cyberattacks is threatening digital transformation endeavors worldwide and leadsto wide losses for various organizations. These dangers have proven that signature-based approaches are insufficientto prevent emerging and polymorphic attacks. Therefore, this paper is proposing a Robust malicious ExecutableDetection (RmED) using Host-based machine learning Classifier to discover malicious Portable Executable (PE)files in hosts using Windows operating systems through collecting PE headers and applying machine learningmechanisms to detect unknown infected files. The authors have collected a novel reliable dataset containing 116,031benign files and 179,071 malware samples from diverse sources to ensure the efficiency of RmED *** most effective PE headers that can highly differentiate between benign and malware files were selected totrain the model on 15 PE features to speed up the classification process and achieve real-time detection formalicious executables. The evaluation results showed that RmED succeeded in shrinking the classification timeto 91 milliseconds for each file while reaching an accuracy of 98.42% with a false positive rate equal to 1.58. Inconclusion, this paper contributes to the field of cybersecurity by presenting a comprehensive framework thatleverages Artificial Intelligence (AI) methods to proactively detect and prevent cyber-attacks.

关键词： Portable executable malware intrusion detection cybersecurity zero-day threats Host IntrusionDetection System(HIDS) machine learning Anomaly-based Intrusion Detection System(AIDS) deep learning