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Nutrient restriction-activated Fra-2 promotes tumor progression via IGF1R in miR-15a downmodulated pancreatic ductal adenocarcinoma

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1132-1146页

作者： Gian Luca Rampioni Vinciguerra Marina Capece Luca Reggiani Bonetti Giovanni Nigita Federica Calore Sydney Rentsch Paolo Magistri Roberto Ballarin Fabrizio Di Benedetto Rosario Distefano Roberto Cirombella Andrea Vecchione Barbara Belletti Gustavo Baldassarre Francesca Lovat carlo M.Croce Department of Cancer Biology and Genetics and Comprehensive Cancer Center The Ohio State UniversityColumbus 43210 OHUSA Department of Clinical and Molecular Medicine Faculty of Medicine and PsychologySant’Andrea HospitalUniversity of Rome“Sapienza”Rome 00189Italy Department of Diagnostic Clinic and Public Health MedicineUniversity of Modena and Reggio EmiliaModena 41100Italy Hepato-pancreato-biliary Surgery and Liver Transplantation Unit University of Modena and Reggio EmiliaModena 41100Italy Division of Molecular Oncology Centro di Riferimento Oncologico di Aviano(CRO)Istituto di Ricovero e Cura a Carattere Scientifico(IRCCS)National Cancer InstituteAviano 33081Italy

Pancreatic ductal adenocarcinoma(PDAC)is a lethal disease,characterized by an intense desmoplastic reaction that compresses blood vessels and limits nutrient *** aggressiveness largely relies on its extraordinary capability to thrive and progress in a challenging tumor *** of the onco-suppressor miR-15a has been extensively documented in ***,we identified the transcription factor Fos-related antigen-2(Fra-2)as a miR-15a target mediating the adaptive mechanism of PDAC to nutrient *** report that the IGF1 signaling pathway was enhanced in nutrient deprived PDAC cells and that Fra-2 and IGF1R were significantly overexpressed in miR-15a downmodulated PDAC ***,we discovered that miR-15a repressed IGF1R expression via Fra-2 *** miR-15a-low context,IGF1R hyperactivated mTOR,modulated the autophagic flux and sustained PDAC growth in nutrient *** a genetic mouse model,Mir15aKO PDAC showed Fra-2 and Igf1r upregulation and mTOR activation in response to diet ***,nutrient restriction improved the efficacy of IGF1R inhibition in a Fra-2 dependent ***,our results point to a crucial role of Fra-2 in the cellular stress response due to nutrient restriction typical of pancreatic cancer and support IGF1R as a promising and vulnerable target in miR-15a downmodulated PDAC.

关键词： IGF1R Fra miR

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你的奖励由谁买单:信用卡市场的再分配

新金融 2024年第1期 59-66页

作者： Sumit Agarwal Andrea Presbitero Andre F.Silva carlo Wix 新加坡国立大学国际货币基金组织经济政策研究中心美国联邦储备委员会

将信用卡奖励作为一个理想的实验进行研究,以量化零售金融市场中消费者之间的再分配。通过对有奖励和无奖励的信用卡进行比较,可以发现:无论收入如何,成熟的消费者都能从有奖励的信用卡中获利,而有的消费者则要付出代价。为了探究其背... 详细信息

将信用卡奖励作为一个理想的实验进行研究,以量化零售金融市场中消费者之间的再分配。通过对有奖励和无奖励的信用卡进行比较,可以发现:无论收入如何,成熟的消费者都能从有奖励的信用卡中获利,而有的消费者则要付出代价。为了探究其背后的机制,本文利用银行在信用卡层面主动提高账户限额的方法进行研究。结果表明:奖励卡会诱发更多的消费,使消费者有更高的未付余额;消费者在偿还信用卡时还会遵循次优平衡匹配启发模式,从而产生更高的成本;银行通过提供比无奖励的同类信用卡更低的利率来激励消费者使用奖励卡;从教育程度较低的地区到较高的地区,从较贫穷的地区到较富裕的地区,信用卡奖励以重新分配的方式扩大了现有的差距。本刊编译此篇美联储的工作论文,以期就信用卡相关问题为读者带来启发。

关键词：消费金融信用卡金融复杂性用卡奖励

Whole-eye transplantation: Current challenges and future perspectives

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World Journal of Transplantation 2024年第2期14卷 28-39页

作者： Anna Scarabosio Pier Luigi Surico Vlad Tereshenko Rohan Bir Singh carlo Salati Leopoldo Spadea Glenda Caputo Pier Camillo Parodi Caterina Gagliano Jonathan M Winograd Marco Zeppieri Department of Plastic Surgery University Hospital of UdineUdine 33100Italy Department of Plastic Surgery Massachusetts General HospitalHarvard Medical SchoolBostonMA 02114United States Schepens Eye Research Institute of Mass Eye and Ear Harvard Medical SchoolBostonMA 02114United States Department of Ophthalmology University Hospital of UdineUdine 33100Italy Eye Clinic Policlinico Umberto I"Sapienza"University of RomeRome 00142Italy Department of Medicine and Surgery University of Enna"Kore"Enna 94100Italy Eye Clinic Catania University San Marco Hospital Viale Carlo Azeglio Ciampi 95121 CataniaItaly

Whole-eye transplantation emerges as a frontier in ophthalmology,promising a transformative approach to irreversible *** advancements,formidable challenges *** of donor eye viability post-enucleation necessitates meticulous surgical techniques to optimize retinal integrity and ganglion cell *** the inhibitory milieu of the central nervous system for successful optic nerve regeneration remains elusive,prompting the exploration of neurotrophic support and immunomodulatory *** tolerance,paramount for graft acceptance,confronts the distinc-tive immunogenicity of ocular tissues,driving research into targeted immunosup-pression *** and legal considerations underscore the necessity for stringent standards and ethical *** collaboration and ongoing research endeavors are imperative to navigate these ***,stem cell therapies,and precision immunomodulation represent promising avenues in this ***,the aim of this review is to critically assess the current landscape of whole-eye transplantation,elucidating the challenges and advancements while delineating future directions for research and clinical *** concerted efforts,whole-eye transplantation stands to revolu-tionize ophthalmic care,offering hope for restored vision and enhanced quality of life for those afflicted with blindness.

关键词： Eye Transplantation Optic nerve Nerve regeneration Immunological tolerance

Herpes simplex keratitis:A brief clinical overview

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World Journal of Virology 2024年第1期13卷 5-32页

作者： Mutali Musa Ehimare Enaholo Gladness Aluyi-Osa George Nnamdi Atuanya Leopoldo Spadea carlo Salati Marco Zeppieri Department of Optometry University of BeninBenin 300283Nigeria Department of Ophthalmology Africa Eye Laser CentreKm 7Benin 300105Nigeria Department of Ophthalmology Centre for Sight AfricaNkpor 434101Nigeria Eye Clinic Policlinico Umberto I"Sapienza"University of RomeRome 00142Italy of Ophthalmology University Hospital of UdineUdine 33100Italy

The aim of our minireview is to provide a brief overview of the diagnosis,clinical aspects,treatment options,management,and current literature available regarding herpes simplex keratitis(HSK).This type of corneal viral infection is caused by the herpes simplex virus(HSV),which can affect several tissues,including the *** significant aspect of HSK is its potential to cause recurrent episodes of inflammation and damage to the *** the initial infection,the HSV can establish a latent infection in the trigeminal ganglion,a nerve cluster near the *** virus may remain dormant for extended *** reactivation of the virus can occur,leading to recurrent episodes of *** triggering reactivation include stress,illness,immunosuppression,or *** episodes can manifest in different clinical patterns,ranging from mild epithelial involvement to more severe stromal or endothelial *** severity and frequency of recurrences vary among *** cases of HSK,especially those involving the stroma and leading to scarring,can result in vision impairment or even blindness in extreme *** cornea's clarity is crucial for good vision,and scarring can compromise this,potentially leading to visual *** management of HSK involves not only treating acute episodes but also implementing long-term strategies to prevent recurrences and attempt repairs of corneal nerve endings via *** medications,such as oral Acyclovir or topical Ganciclovir,may be prescribed for *** immune response to the virus can contribute to corneal ***,caused by the body's attempt to control the infection,may inadvertently harm the corneal *** should be informed about triggers and advised on measures to minimize the risk of *** summary,the recurrent nature of HSK underscores the importance of both acute and long-term management strategies to preserve corneal health and maintai

关键词： Herpes simplex virus Herpes simplex keratitis Acyclovir Neurotization Reactivation

Minimally invasive surgical therapies(MISTs)for lower urinary tract symptoms(LUTS):promise or panacea?

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Asian Journal of Andrology 2024年第2期26卷 135-143页

作者： Gian Maria Busetto Andrea Checchia Marco Recchia Edoardo Tocci Ugo G Falagario Gennaro Annunziata Pasquale Annese Nicola d'Altilia Vito Mancini Matteo Ferro Felice Crocetto Octavian Sabin Tataru Luca Di Gianfrancesco Angelo Porreca Francesco Del Giudice Ettore De Berardinis carlo Bettocchi Luigi Cormio Giuseppe Carrieri University of Foggia Foggia 71122Italy Department of Urology and Renal Transplantation Policlinico of FoggiaFoggia 71122Italy Urology Unit "G.Tatarlla"HospitalCerignola 71042Italy Urology Unit European Institute of Oncology(IE0)IRCcSMilan 20141Italy University of Naples Federico Il Naples 80126Italy G.E.Palade University of Medicine PharmacyScienceand Technology of Targu MuresTargu Mures 540142Romania Department of Oncological Urology Veneto Institute of Oncology(IOv)IRccSPadua 35128Italy Department of Maternal-Infant and Urological Sciences Sapienza Rome UniversityRoma 00161Italy Urology Unit "L.Bonomo"HospitalAndria 76123Italy

The increasing importance of treatment of lower urinary tract symptoms(LUTS),while avoiding side effects and maintaining sexual function,has allowed for the development of minimally invasive surgical therapies(MiSTs).Recently,the European Association of Urology guidelines reported a paradigm shift from the management of benign prostatic hyperplasia(BPH)to the management of nonneurogenic male *** aim of the present review was to evaluate the efficacy and safety of the most commonly used MisTs:ablative techniques such as aquablation,prostatic artery embolization,water vapor energy,and transperineal prostate laser ablation,and nonablative techniques such as prostatic urethral lift and temporarily implanted nitinol device(iTIND).MiSTs are becoming a new promise,even if clinical trials with longer follow-up are still *** of them are still under investigation and,to date,only a few options have been given as a recommendation for *** cannot be considered as standard of care and are not suitable for all *** and disadvantages should be underlined,without forgetting our objective:treatment of LUTS and re-treatment avoidance.

关键词： aquablation iTIND prostatic artery embolization prostatic urethral lift transperineal prostate laser ablation water vapor energy

Antioxidant treatment for oligoasthenoteratozoospermia and varicocele:a DBPC trial to evaluate the impact of age and body mass index

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Asian Journal of Andrology 2024年第3期26卷 239-244页

作者： Gian Maria Busetto Bernarde F Rodrigues Ashraf Virmani Andrea Checchia Antonella Ninivaggi Anna Ricapito Giovanni Barbieri Piero Fischetti Ugo G Falagario Pasquale Annese Nicola d’Altilia Vito Mancini Matteo Ferro Felice Crocetto Angelo Porreca carlo Bettocchi Luigi Cormio Ashok Agarwal Giuseppe Carrieri University of Foggia Foggia 71122Italy Department of Urology and Renal Transplantation Policlinico of FoggiaFoggia 71122Italy Department of Urology Human Reproduction SectionFederal University of Sao PauloSao Paulo 05403-000Brazil Alfasigma Healthscience Utrecht 3528 BGThe Netherlands Urology Unit “G.Tatarella”HospitalCerignola 71042Italy Urology Unit European Institute of Oncology(IEO)IRCCSMilan 20142Italy University of Naples Federico II Naples80126Italy Department of Oncological Urology Veneto Institute of Oncology(IOV)IRCCSPadua 35039Italy Urology Unit “L.Bonomo”HospitalAndria 70031Italy Global Andrology Forum Moreland HillsOH 44022USA

Oxidative stress is one of the main mechanisms responsible for male *** conditions such as varicocele,obesity,advanced age,and lifestyle can lead to an increase in reactive oxygen species,causing an oxidative imbalance in the *** are sensitive to reactive oxygen species and require energy to carry out their main function of fertilizingthe *** reactive oxygen species can affect sperm metabolism,leading to immobility,impaired acrosome reaction,and celldeath,thereby impairing reproductive *** double-blind randomized study evaluated the effect of supplementation withL-carnitine,acetyl-L-carnitine,vitamins,and other nutrients on semen quality in 104 infertile patients with or without varicocele,while also investigating the impact of factors such as obesity and advanced age on *** concentration significantlyincreased in the supplemented group compared to the placebo group(P=0.0186).Total sperm count also significantly increasedin the supplemented group(P=0.0117),as did sperm motility(P=0.0120).The treatment had a positive effect on patients upto 35 years of age in terms of sperm concentration(P=0.0352),while a body mass index(BMI)above 25 kg m^(−2) had a negativeeffect on sperm concentration(P=0.0110).Results were not showing a net benefit in stratifying patients in accordance withtheir BMI since sperm quality increase was not affected by this *** conclusion,antioxidant supplementation may bebeneficial for infertile patients and has a more positive effect on younger patients with a normal weight.

关键词： aging antioxidants body mass index oligoasthenoteratozoospermia varicocele

The outcomes and safety of patients undergoing endoscopic retrograde cholangiopancreatography combining a single-use cholangioscope and a single-use duodenoscope:A multicenter retrospective international study

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 71-76页

作者： Alessandro Fugazza Matteo Colombo Michel Kahaleh V.Raman Muthusamy Bick Benjamin Wim Laleman Carmelo Barbera carlo Fabbri Jose Nieto Abed Al-Lehibi Mohan Ramchandani Amy Tyberg Haroon Shahid Avik Sarkar Dean Ehrlich Stuart Shermand Cecilia Binda Marco Spadaccini Andrea Iannone Kareem Khalaf Nageshwar Reddy Andrea Anderloni Alessandro Repici Division of Gastroenterology and Digestive Endoscopy Humanitas Research Hospital-IRCCSVia Manzoni 5620089RozzanoMilanoItaly Gastroenterology Rutgers Robert Wood JohnsonNew BrunswickNew JerseyUSA Vatche and Tamar Manoukian Division of Digestive Diseases University of CaliforniaLos Angeles School of Medicine at UCLALos AngelesCaliforniaUSA Division of Digestive and Liver Disorders Indiana University School of MedicineIndianapolisINUSA Department of Gastroenterology and Hepatology University Hospitals LeuvenKU Leuven3000 LeuvenBelgium U.O.C.di Gastroenterologia ed Endoscopia Digestiva Ospedale Giuseppe MazziniASL TeramoItaly Gastroenterology and Digestive Endoscopy Unit Forlì-Cesena HospitalsAUSL RomagnaForlì-CesenaItaly Borland Groover Clinic JacksonvilleFloridaUSA Department of Gastroenterology and Hepatology King Fahad Medical CityRiyadhSaudi Arabia Asian Institute of Gastroenterology HyderabadIndia Section of Gastroenterology Department of Emergency and Organ TransplantationUniversity of BariBari 70124Italy Department of Biomedical Sciences Humanitas UniversityVia Rita Levi Montalcini 420090Pieve EmanueleMilanItaly

Background: Duodenoscope-related multidrug-resistant organism(MDRO) infections raise concerns. Disposable duodenoscopes have been recently introduced in the market and approved by regulatory agencies with the aim to reduce the risk of endoscopic retrograde cholangiopancreatography(ERCP) associated infections. The aim of this study was to evaluate the outcome of procedures performed with single-use duodenoscopes in patients with clinical indications to single-operator cholangiopancreatoscopy. Methods: This is a multicenter international, retrospective study combining all patients who underwent complex biliopancreatic interventions using the combination of a single-use duodenoscope and a single-use cholangioscope. The primary outcome was technical success defined as ERCP completion for the intended clinical indication. Secondary outcomes were procedural duration, rate of cross-over to reusable duodenoscope, operator-reported satisfaction score(1 to 10) on performance rating of the single-use duodenoscope, and adverse event(AE) rate. Results: A total of 66 patients(26, 39.4% female) were included in the study. ERCP was categorized according to ASGE ERCP grading system as 47(71.2%) grade 3 and 19(28.8%) grade 4. The technical success rate was 98.5%(65/66). Procedural duration was 64(interquartile range 15-189) min, cross-over rate to reusable duodenoscope was 1/66(1.5%). The satisfaction score of the single-use duodenoscope classified by the operators was 8.6 ± 1.3 points. Four patients(6.1%) experienced AEs not directly related to the single-use duodenoscope, namely 2 post-ERCP pancreatitis(PEP), 1 cholangitis and 1 ***: Single-use duodenoscope is effective, reliable and safe even in technically challenging procedures with a non-inferiority to reusable duodenoscope, making these devices a viable alternative to standard reusable equipment.

关键词： Single-operator cholangioscopy Single-use duodenoscope Endoscopic retrograde cholangiopancreatography Indeterminate biliary stricture Difficult biliary stones

Fat management in upper blepharoplasty:Addition or subtraction blepharoplasties,how and when

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World Journal of Clinical Cases 2024年第16期12卷 2796-2802页

作者： Giovanni Miotti Jacopo Di Filippo Martina Grando carlo Salati Pier Camillo Parodi Leopoldo Spadea Caterina Gagliano Mutali Musa Marco Zeppieri Department of Plastic Surgery University Hospital of UdineUdine 33100Italy Department of Internal Medicine Azienda Sanitaria Friuli OccidentaleSan Vito al Tagliamento 33078Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy Eye Clinic Policlinico Umberto I"Sapienza"University of RomeRome 00142Italy Department of Medicine and Surgery University of Enna"Kore"Enna 94100Italy Eye Clinic Catania University San Marco HospitalCatania 95121Italy Department of Optometry University of BeninBenin 3000283Nigeria Department of Ophthalmology Centre for Sight AfricaNkporOnitsha 434112Niger

BACKGROUND As one of the most common aesthetic surgical procedures carried out today,blepharoplasty should be in the repertoire of every plastic *** term blepharoplasty encompasses a wide range of techniques and options that must be tailored to the specific defect and patient one has to treat.A sound knowledge of the upper and lower eyelids’anatomy is essential for proper surgical *** have shifted towards more conservative methods(especially of the fat compartment)and sometimes in combination with augmentation techniques,helping to reach a rejuvenated *** To present an overview of the surgical techniques considered for upper lid blepharoplasty and fat pad management,in addition to information on how a surgeon may approach the best treatment for his patient based on current publications in *** We searched the literature published between 2013,to 2023 using Medline and Reference Citation *** database was searched using the keywords“upper blepharoplasty”AND“fat”.Papers without full text/abstracts and reviews were *** search strategy followed the *** American Society of Plastic Surgeons guidelines for Therapeutic Studies checklist was used to assess all *** authors individually reviewed each article and rated them for importance and relevance to the topic.A consensus was sought and the most relevant *** After the application of the selection criteria used in our review,13 publications were found to address upper lid blepharoplasty *** of these studies were reviews and three were retrospective *** publications were comparative studies and a further two were clinical *** The tendency of modern surgery is to be conservative,by removing adipose tissue only if strictly necessary and restoring the volume of the upper eyelid in a concept of beauty that espouses a"full"*** is no gold standard technique to achieve younger and enhanced eyelids

关键词： Blepharoplasty Fat pads Eye lid surgery Cosmetic aesthetic surgery Rejuvenation Plastic surgery

Uveal melanoma:Recent advances in immunotherapy

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World Journal of Clinical Oncology 2024年第1期15卷 23-31页

作者： Francesco Saverio Sorrentino Francesco De Rosa Patrick Di Terlizzi Giacomo Toneatto Andrea Gabai Lucia Finocchio carlo Salati Leopoldo Spadea Marco Zeppieri Department of Surgical Sciences Unit of OphthalmologyOspedale MaggioreBologna 40100Italy Department of Oncology IRCCS Istituto Romagnolo per lo Studio dei Tumori“Dino Amadori”Meldola 47014Italy Department of Ophthalmology University Hospital of UdineUdine 33100Italy Eye Clinic Policlinico Umberto I“Sapienza”University of RomeRome 00142Italy

Uveal melanoma(UM)is the most common primary intraocular cancer in *** incidence in Europe and the United States is 6-7 per million population per *** most primary UMs can be successfully treated and locally controlled by irradiation therapy or local tumor resection,up to 50%of UM patients develop metastases that usually involve the liver and are fatal within 1 *** date,chemotherapy and targeted treatments only obtain minimal responses in patients with metastatic UM,which is still characterized by poor *** standard therapeutic approaches for its prevention or treatment have been *** application of immunotherapy agents,such as immune checkpoint inhibitors that are effective in cutaneous melanoma,has shown limited effects in the treatment of ocular *** is due to UM’s distinct genetics,natural history,and complex interaction with the immune *** cutaneous melanomas characterized mainly by BRAF or NRAS mutations,UMs are usually triggered by a mutation in GNAQ or *** a result,more effective immunotherapeutic approaches,such as cancer vaccines,adoptive cell transfer,and other new molecules are currently being *** this review,we examine novel immunotherapeutic strategies in clinical and preclinical studies and highlight the latest insight in immunotherapy and the development of tailored treatment of UM.

关键词： Uveal melanoma Immunotherapy Ocular oncology Tumor Metastatic disease Genetic mutations