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effects of P301l-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

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Neural Regeneration Research 2025年第8期20卷 2348-2360页

作者： Mohamed Aghyad al Kabbani Christoph Köhler Hans Zempel Institute of Human Genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular Medicine Cologne(CMMC) University of CologneCologneGermany Center Anatomy Department ⅡMedical FacultyUniversity of CologneCologneGermany

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the *** is missorted and aggregated in an array of diseases known as *** are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing *** impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule *** therefore aimed to study the effects of a disease-causing mutation of TAU(P301l)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301l-TAU causes stability-changing modifications to *** investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301l-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301l-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301l mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301l-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301l-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic *** sum,P301l-TAU results in changes in micr

关键词： human induced pluripotent stem cell microtubules P301l pR5 mice TAU tauopathy tubulin code

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Diet fortification for mild and moderate picky eating in typically developed children:Opinion review of Middle east consensus

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World Journal of Clinical Pediatrics 2025年第1期14卷 139-148页

作者： Mohammed al-Beltagi elie Choueiry Najat alahmadi Zeinab Demerdash Wafaa Helmi Ayesh Khoula al-Said Fatima al-Haddad Sanaa Y Shaaban eslam Tawfik Department of Pediatric Faculty of MedicineTanta UniversityTanta 31511Egypt Department of Pediatric University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671ManamaBahrain Paediatric Intensive and Critical Care Unit Hospital Hôtel Dieu de FranceBeirut 166830BeyrouthLebanon Department of Pediatric Gastroenterology Hepatology and NutritionMadina Maternity and Children HospitalKing Salman Medical CityAlmadina Almonawarh 41412Almadina AlmonawarhSaudi Arabia Department of Gastroenterology Hepatology and NutritionAl Amiri HospitalKuwait City 999044Kuwait Department of Nutrition Altadawi Speciality HospitalDubai 1853DubayyUnited Arab Emirates Department of Paediatric Gastroenterology Royal HospitalMuscat 1331MuscatOman Department of Dietetic Salmaniya Medical ComplexGovernment HospitalsAl Salmaniya 12ManamaBahrain Department of Pediatrics Faculty of MedicineAin Shams UniversityCairo 11591Egypt Department of Paediatric Faculty of MedicineSuez UniversitySuez 41522Egypt Department of Paediatric Sheikh Khalifa Medical CityAbu Dhabi 00000Abu DhabiUnited Arab Emirates

BACKGROUND Picky eating is a commonly observed behavior among children globally,negatively impacting their physical and mental *** common characteristics distinguish peaky eaters,including food selectivity,food neophobia,and food avoidance,there is no clear definition to assess this *** to the unavailability of data regarding picky eating,it wasn’t easy to estimate its *** To develop a regional protocol to help healthcare professionals identify and manage mild and moderate picky eating *** A virtual roundtable discussion was held in April 2021 to gather the opinions of seven pediatricians and two pediatric dietitians from eight Middle eastern countries who had great experience in the management of picky *** discussion covered different topics,including clearly defining mild and moderate picky eating,identifying the role of diet fortification in these cases,and the possibility of developing a systematic approach to diet *** The panel identified picky eating as consuming an inadequate amount and variety of foods by rejecting familiar and unfamiliar *** of the time,moderate picky eating cases had micronutrient deficiencies with over-or undernutrition;the mild cases only showed inadequate food consumption and/or poor diet *** attention to the organic red flags like growth faltering and development delay and behavioral red flags,including food fixation and anticipatory gagging,will help healthcare professionals evaluate the picky eaters and the caregivers to care for their *** dietary supplementation and commercial food fortification play an important role in picky eating,they were no benefit in the Middle *** The panel agreed that food fortification through a food-first approach and oral nutritional supplements would be the best for Middle eastern *** recommendations would facilitate identifying and managing picky-eating children in the Middle east.

关键词： Picky eating Diet fortification Children Protocol Roundtable discussion Middle east

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Current and future perspectives in the management and treatment of colorectal cancer

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World Journal of Clinical Oncology 2025年第2期16卷 9-17页

作者： Sigfredo e Romero-Zoghbi evita Krumina Fernando lópez-Campos Felipe Couñago Department of Radiation Oncology GenesisCare Talavera de la ReinaToledo 45600Spain Department of Radiation Oncology GenesisCare GuadalajaraGuadalajara 19004Spain Department of Radiation Oncology Hospital Universitario Ramón Y CajalMadrid 28034Spain Department of Radiation Oncology GenesisCare-Hospital Universitario Vithas Madrid La MilagrosaMadrid 28010Spain

In this editorial,we reviewed the article by Fadlallah et al that was recently published in the World Journal of Clinical *** article provided a comprehensive and in-depth view of the management and treatment of colorectal cancer(CRC),one of the leading causes of cancer-related morbidity and mortality *** article analyzed the therapeutic modalities and their sequencing,focusing on total neoadjuvant therapy for locally advanced rectal *** highlighted the role of immunotherapy in tumors with high microsatellite instability or deficient mismatch repair,addressing recent advances that have improved prognosis and therapeutic response in localized and metastatic *** in surgical techniques,advanced radiotherapy,and systemic agents targeting specific mutational profiles are also discussed,reflecting on how they revolutionized clinical *** tumor DNA has emerged as a promising tool for detecting minimal residual disease,prognosis,and therapeutic monitoring,solidifying its role in precision *** review emphasized the importance of technological and therapeutic advancements in improving clinical outcomes and personalizing CRC treatment.

关键词： Colorectal cancer Metastatic colorectal cancer Total neoadjuvant therapy Chemoradiotherapy Colon surgery Rectal surgery Chemotherapy Immunotherapy

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Unveiling the impact:COVID-19's influence on bacterial resistance in the Kingdom of Bahrain

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World Journal of Virology 2025年第1期14卷 83-98页

作者： Nermin K Saeed Safiya K almusawi Noor A albalooshi Mohammed al-Beltagi Medical Microbiology Section Department of PathologySalmaniya Medical ComplexGovernmental HospitalsManama 12Bahrain Medical Microbiology Section Department of PathologyRoyal College of Surgeons in Ireland-Medical University of BahrainBusaiteen 15503MuharraqBahrain Department of Paediatrics Faculty of MedicineTanta UniversityTanta 31511AlghrabiaEgypt Department of Pediatric University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671AlgharbiaBahrain

BACKGROUND Antibiotic resistance is a growing global health threat,and understanding local trends in bacterial isolates and their susceptibility patterns is crucial for effective infection control and antimicrobial *** coronavirus disease 2019(COVID-19)pandemic has introduced additional complexities,potentially influencing these *** To analyze trends in bacterial isolates and their antibiotic susceptibility patterns at Salmaniya Medical Complex from 2018 to 2023,with a specific focus on the impact of the COVID-19 pandemic on these *** A retrospective analysis of microbiological data was conducted,covering the period from 2018 to *** study included key bacterial pathogens such as escherichia coli(***),Klebsiella pneumoniae,Acinetobacter baumannii,Pseudomonas aeruginosa,and Staphylococcus aureus,among *** antibiotic susceptibility profiles of these isolates were assessed using standard laboratory *** contextualize the findings,the findings were compared with similar studies from other regions,including China,India,Romania,Saudi Arabia,the United Arab emirates,Malaysia,and United *** The study revealed fluctuating trends in the prevalence of bacterial isolates,with notable changes during the COVID-19 *** example,a significant increase in the prevalence of Staphylococcus aureus was observed during the pandemic years,while the prevalence of *** showed a more variable *** resistance rates varied among the different pathogens,with a concerning rise in resistance to commonly used antibiotics,particularly among Klebsiella pneumoniae and ***,the study identified an alarming increase in the prevalence of multidrug-resistant(MDR)strains,especially within Klebsiella pneumoniae and *** *** impact of the COVID-19 pandemic on these trends was evident,with shifts in the frequency,resistance patterns,and the emergence of MDR bacteria among several key ***

关键词： Multidrug-resistant organisms Antibiotic susceptibility COVID-19 pandemic Antimicrobial stewardship Bacterial isolates Salmaniya Medical Complex Bahrain

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Advances and challenges in diagnosing and managing adult autoimmune enteropathy

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World Journal of Gastroenterology 2025年第2期31卷 128-131页

作者： Grigorios Christodoulidis Sara e Agko Marina N Kouliou Konstantinos e Koumarelas Dimitris Zacharoulis Department of General Surgery University Hospital of LarissaLarissa 41110Greece Department of Intensive Care Unit Asklepios Paulinen Clinic WiesbadenWiesbaden 65197Germany Department of emergency Medicine General Hospital of LarissaLarissa 41221Greece Department of Surgery University Hospital of LarissaLarissa 41334Greece

Autoimmune enteropathy(AIe)is a rare immune mediated disorder primarily affecting children,characterized by chronic diarrhea,malabsorption,vomiting,weight loss and villous *** has also been observed in adults presenting diagnostic and treatment challenges due to its overlap with other gastrointestinal disorders such as celiac *** diagnostic criteria for AIe include small bowel villous atrophy,lack of response to dietary restrictions,presence of anti-enterocyte antibodies,and predisposition to autoimmunity without severe *** criteria emphasize characteristic histological findings and exclusion of other causes of villous *** is associated with various autoimmune disorders and can present with overlapping features with Celiac disease,including villous atrophy but without significant intraepithelial *** primarily involves immunosuppression using corticosteroids,calcineurin inhibitors,and anti-tumor necrosis factor therapy,alongside nutri-tional *** the challenges,understanding AIe’s diverse manifest-ations and improving diagnostic criteria are essential for effective management and improved patient *** research is needed to elucidate the pathogenesis,disease progression and long-term outcomes of AIe.

关键词： Autoimmune enteropathy Diagnosis Prognosis Adult autoimmune enter-opathy and challenges Autoimmune enteropathy and treatment Autoimmune enteropathy and diagnostic criteria Pathophysiology of autoimmune enteropathy

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Diabetes-inducing effects of bronchial asthma

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World Journal of Diabetes 2025年第1期16卷 121-139页

作者： Mohammed al-Beltagi Adel Salah Bediwy Nermin Kamal Saeed Hosameldin A Bediwy Reem elbeltagi Department of Pediatric Faculty of MedicineTanta UniversityTanta 31511AlghrabiaEgypt Department of Pediatric University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671ManamaBahrain Department of Pulmonology Faculty of MedicineTanta UniversityTanta 31527AlghrabiaEgypt Department of Pulmonology University Medical CenterKing Abdulla Medical CityArabian Gulf UniversityManama 26671ManamaBahrain Medical Microbiology Section Department of PathologySalmaniya Medical ComplexMinistry of HealthKingdom of BahrainManama 26671ManamaBahrain Medical Microbiology Section Department of PathologyIrish Royal College of SurgeonBusaiteen 15503MuharraqBahrain Faculty of Medicine Tanta UniversityTanta 31527AlgharbiaEgypt Department of Medicine The Royal College of Surgeons in Ireland-BahrainBusiateen 15503MuharraqBahrain

BACKGROUND The relationship between diabetes mellitus(DM)and asthma is complex and can impact disease *** To explore the bidirectional influences between the two conditions on clinical outcomes and disease *** We systematically reviewed the literature on the relationship between DM and asthma,focusing on their impacts,mechanisms,and therapeutic *** studies were assessed,which investigated the effect of glycemic control on asthma outcomes,lung function,and *** study highlighted the role of specific diabetes medications in managing *** The results showed that poor glycemic control in diabetes can exacerbate asthma,increase hospitalizations,and reduce lung ***,severe asthma,especially in obese individuals,can complicate diabetes management and make glycemic control more *** diabetes-associated mechanisms,such as inflammation,microangiopathy,and oxidative stress,can exacerbate asthma and decrease lung *** diabetes medications exhibit anti-inflammatory effects that show promise in mitigating asthma *** The complex interrelationship between diabetes and asthma suggests bidirectional influences that affect disease course and *** and microvascular complications associated with diabetes may worsen asthma outcomes,while asthma severity,especially in obese individuals,complicates diabetes ***,the current research has limitations,and more diverse longitudinal studies are required to establish causal relationships and identify effective treatment strategies for individuals with both conditions.

关键词： Diabetes mellitus Bronchial asthma Glycemic control lung function Asthma exacerbation Disease interaction Microangiopathy

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Machine learning in solid organ transplantation:Charting the evolving landscape

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World Journal of Transplantation 2025年第1期15卷 165-177页

作者： Badi Rawashdeh Haneen al-abdallat emre Arpali Beje Thomas Ty B Dunn Matthew Cooper Division of Transplant Surgery Medical College of WisconsinMilwaukeeWI 53202United States Department of Medicine Jordan University HospitalAmman 11263Jordan Department of Nephrology Medical College of WisconsinMilwaukeeWI 53226United States

BACKGROUND Machine learning(Ml),a major branch of artificial intelligence,has not only demonstrated the potential to significantly improve numerous sectors of healthcare but has also made significant contributions to the field of solid organ *** provides revolutionary opportunities in areas such as donorrecipient matching,post-transplant monitoring,and patient care by automatically analyzing large amounts of data,identifying patterns,and forecasting *** To conduct a comprehensive bibliometric analysis of publications on the use of Ml in transplantation to understand current research trends and their *** On July 18,a thorough search strategy was used with the Web of Science *** and transplantation-related keywords were *** the aid of the VOS viewer application,the identified articles were subjected to bibliometric variable analysis in order to determine publication counts,citation counts,contributing countries,and institutions,among other *** Of the 529 articles that were first identified,427 were deemed relevant for bibliometric analysis.A surge in publications was observed over the last four years,especially after 2018,signifying growing interest in this *** 209 publications,the United States emerged as the top ***,the"Journal of Heart and lung Transplantation"and the"American Journal of Transplantation"emerged as the leading journals,publishing the highest number of relevant *** keyword searches revealed that patient survival,mortality,outcomes,allocation,and risk assessment were significant themes of *** The growing body of pertinent publications highlights Ml's growing presence in the field of solid organ *** bibliometric analysis highlights the growing importance of Ml in transplant research and highlights its exciting potential to change medical practices and enhance patient *** collaboration between signific

关键词： Machine learning Artificial Intelligence Solid organ transplantation Bibliometric analysis

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Beginning from the end:the presynaptic terminal as a pathomechanism hub in frontotemporal dementia and amyotrophic lateral sclerosis

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Neural Regeneration Research 2025年第11期20卷 3217-3218页

作者： laura Huggon emma l.Clayton UK Dementia Research Institute at King’s College london LondonUK Department of Basic and Clinical Neuroscience Institute of Psychiatry Psychology&NeuroscienceKing’s College LondonLondonUK

Frontotemporal dementia and amyotrophic lateral sclerosis:Frontotemporal dementia(F T D)and amyo t rophic lateral sclerosis(alS)are neurodegenerative diseases with significant overlapping *** these neurodegenerative diseases affect different neuronal populations(with FTD affecting neurons of the frontal and temporal lobes,and alS affecting upper and lower motor neurons),these two diseases are complexly *** and alS exist on a disease spectrum,with shared genetic causes,clinical presentations,and pathologies.

关键词： diseases amyotrophic sclerosis

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Novel heating-and deformation-induced phase transitions and mechanical properties for multicomponent Zr_(50)M_(50),Zr_(50)(M,Ag)_(50)and Zr_(50)(M,Pd)_(50)(M=Fe,Co,Ni,Cu)amorphous alloys

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Journal of Materials Science & Technology 2022年第9期104卷 109-118页

作者： J.Ding A.Inoue F.l.Kong S.l.Zhu Y.l.Pu e.Shalaan A.A.al-Ghamdi A.l.Greer School of Materials Science and engineering Tianjin UniversityTianjin 300072China International Institute of Green Materials Josai International UniversityTogane 283-8555Japan Institute of Massive Amorphous alloy Science China University of Mining TechnologyXuzhou 221116China Department of Physics King Abdulaziz UniversityJeddah 22254Saudi Arabia MISiS National University of Science and TechnologyMoscow 119049Russia School of Materials Science and engineering Lanzhou Jiaotong UniversityLanzhou 730070China Department of Materials Science and Metallurgy University of CambridgeCambridge CB30FSUK

Multicomponent alloys of Zr_(50)M_(50),Zr_(50)(M,Ag)_(50)and Zr_(50)(M,Pd)_(50)(M=Fe,Co,Ni,Cu)can be melt-spun to obtain amorphous *** maximum thickness for fully amorphous ribbons varies with composition in the range 34-53μ*** contrast,fully amorphous ribbons are not obtainable for binary Zr_(50)Ni_(50)or ternary Zr_(50)(Ni,Cu)_(50)***-induced crystallization occurs through:two stages of amorphous[am]→[~(am')+B2]→[B2+B33]for Zr_(50)M_(50);and[am]→[am'+B2]→[B2+AgZr]for Zr_(50)(M,Ag)_(50);and a single stage of[am]→[B2]for Zr_(50)(M,Pd)_(50),while no B2 phase is formed for the binary and ternary Zr_(50)Q_(50)(Q=Ni or/and Cu)***-spun amorphous ribbons have good bending ***,Zr_(50)M_(50)ribbons in tension show 0.22-0.28%plastic elongation and work-hardening(the yield stress is~820 MPa,the fracture stress is~1200 MPa).When cold-rolled at room temperature to 30%reduction in thickness,Zr_(50)M_(50)ribbons show 10%increase in hardness,while retaining good bending ***-rolling induces precipitation of spheroidal B2 and irregular B33 particles,while deformation in tension induces B2,B33 and also plate-like monoclinic *** B2 and B33 particles form by polymorphic transformation,and include a high density of internal *** novel deformationinduced precipitation has not been recognized for any Zr_(50)Q_(50)binary or ternary *** new multicomponent systems are encouraging for future progress as structural amorphous alloys.

关键词： Multicomponent Microstructure Mechanical properties Phase transition Amorphous alloy

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Immunohistochemical expression of matrix metalloproteinase-9 and 13 in oral squamous cell carcinoma and their role in predicting lymph node metastasis

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World Journal of Methodology 2025年第2期15卷 108-116页

作者： Bhari Sharanesha Manjunatha Keshav T Handge Vandana Sandeep Shah Yasser eid al-Thobaiti Deepak Gowda Sadashivappa Pateel Department of Basic Oral Medicine and allied Dental Sciences Taif UniversityAt`Taif 26571MakkahSaudi Arabia Department of Oral and Maxillofacial Pathology Dr.Vasantrao Pawar Medical CollegeHospital and Research CentreNashik 423101MaharashtraIndia Department of Oral Pathology and Microbiology KM Shah Dental College and HospitalSumandeep VidyapeethVadodara 391760GujaratIndia Department of Oral and Maxillofacial Surgery and Diagnostic Sciences Faculty of DentistryTaif UniversityAl-Haweiah 26571 MakkahSaudi Arabia Department of Oral Pathology and Microbiology Faculty of DentistryMAHSA UniversitySelangor 42610Malaysia

BACKGROUND One of the main characteristics of oral squamous cell carcinoma(OSCC)is that it metastasizes to cervical lymph nodes frequently with a high degree of local invasiveness.A primary feature of malignant tumors is their penetration of neighboring tissues,such as lymphatic and blood arteries,due to the tumor cells'capacity to break down the extracellular matrix(eCM).Matrix metalloproteinases(MMPs)constitute a family of proteolytic enzymes that facilitate tissue remo-deling and the degradation of the ***-9 and MMP-13 belong to the group of extracellular matrix degrading enzymes and their expression has been studied in OSCC because of their specific ***-13,a collagenase family member,is thought to play an essential role in the MMP activation cascade by breaking down the fibrillar collagens,whereas MMP-9 is thought to accelerate the growth of *** MMP-13 expression has been associated with tumor behavior and patient prognosis in a number of malignant *** authors wish to thank Jadhav KB for his valuable opinion during the preparation of the manuscript.

关键词： Matrix metalloproteinases Oral squamous cell carcinoma Tumor staging Immunohistochemistry Invasion lymph node metastasis TNM stage

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