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Revisiting mechanisms of resistance to immunotherapies in metastatic clear-cell renal-cell carcinoma

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Cancer Drug Resistance 2023年第2期6卷 314-326页

作者： Monica Sheila Chatwal Jad Chahoud philippe e.spiess Department of Genitourinary Oncology H.Lee Moffitt Cancer Center and Research InstituteTampaFL 33612USA

Renal-cell carcinoma(RCC)remains a leading cause of cancer-related mortality *** newer therapeutic combinations of immune checkpoint inhibitors and targeted therapies have greatly improved outcomes,resistance to these therapies is becoming a challenge for long-term *** of resistance have been explored in a variety of solid tumors,including *** upon our review of the current literature on the mechanisms of resistance to immunotherapies for the management of metastatic clear-cell renal cell carcinomas(mccRCC),the ensuing conclusions have been made:The management of mccRCC has progressed substantially with the advent of checkpoint inhibitors and targeted oral therapies,alone and/or in ***,innate or developed resistance to these therapies remains an ongoing challenge,particularly to immune checkpoint inhibitors(ICIs).Several of the known mechanisms of resistance have been well defined,but recent progression in cellular therapies helps to expand the armamentarium of potential combination options that may overcome these modes of resistance and improve long-term disease control and survival for an otherwise dismal *** the ensuing review and update of the literature on the mechanisms of resistance to immunotherapies in mccRCC,we have revisited the known resistance mechanisms of immunotherapies in metastatic clear-cell RCC and explored ongoing and future strategies to overcome them.

关键词： Metastatic clear-cell renal-cell carcinoma immune therapy checkpoint inhibitor resistance chimeric antigen receptor T-cell therapy

Updates in the use of radiotherapy in the management of primary and locally-advanced penile cancer

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Asian Journal of Urology 2022年第4期9卷 389-406页

作者： Akshar Patel Arash O.Naghavi Peter A.Johnstone philippe e.spiess G.Daniel Grass University of South Florida Morsani College of Medicine TampaFLUSA Department of Radiation Oncology H.Lee Moffitt Cancer Center and Research InstituteTampaFLUSA Department of Genitourinary Oncology H.Lee Moffitt Cancer Center and Research InstituteTampaFLUSA

Objective:Penile cancer is a rare malignancy in most developed countries,but may represent a significant oncologic challenge in certain African,Asian,and South American *** treatment approaches have been described in penile cancer,including *** review aimed to provide a synopsis of radiotherapy use in penile cancer management and the associated *** addition,we aimed to discuss palliative radiation for metastases to the penis and provide a brief overview of how tumor biology may assist with treatment ***:Peer-reviewed manuscripts related to the treatment of penile cancer with radio-therapy were evaluated by a PubMed search(1960-2021)in order to assess its role in the definitive and adjuvant *** manuscripts were also evaluated for descriptions of radiation-related ***:Though surgical resection of the primary is an excellent option for tumor control,select patients may be treated with organ-sparing radiotherapy by either external beam radiation or *** from randomized controlled trials comparing radiotherapy and surgery are lacking,and thus management is frequently determined by institutional practice patterns and available ***,this lack of clinical trial data leads to divergence in opinion regarding lymph node *** is further complicated in that many cited studies evaluating lymph node radiotherapy used non-modern radiotherapy delivery *** toxicity from either surgery or radiotherapy remains a challenging problem and further risk assessment is needed to guide intensification with multi-modal *** differences in tumor biology,based on human papillomavirus infection,may help aid future prognostic and predictive models in patient risk stratification or treatment ***:Penile cancer is a rare disease with limited clinical trial data driving the majority of treatment *** a result,the goal of management

关键词： Brachytherapy Chemoradiation Radiation Radiotherapy Penile cancer Squamous cell carcinoma of the penis Penile-sparing Penile metastase Human papillomavirus

Genitourinary melanoma:An overview for the clinician

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Asian Journal of Urology 2022年第4期9卷 407-422页

作者： Danielle K.DePalo Kelly M.elleson Michael J.Carr philippe e.spiess Jonathan S.Zager Department of Cutaneous Oncology Moffitt Cancer CenterTampaFLUSA Department of Surgery University of LouisvilleLouisvilleKYUSA Department of Genitourinary Oncology Moffitt Cancer CenterTampaFLUSA

Genitourinary (GU) melanoma is a rare presentation of melanoma accounting for approximately 0.5% of all *** melanomas include primary melanomas of the vulva,vagina,uterine cervix,ovary,penis,scrotum,urethra,bladder,ureter,and *** melanomas are often diagnosed in advanced stages and stigma is thought to contribute to delays in *** the likely diagnosing provider,it is imperative that dermatologists,urologists,and gynecologists are aware of these uncommon sites of *** there have been major advances in the treatment of melanomas as a whole in the last 10 years,their applications to GU melanomas have often been *** melanomas have not been included in many of the major phase II clinical trials which brought contemporary advanced treatments to market and the prognoses for GU melanomas remain *** to the rarity of GU melanomas,much of the literature provides gener alized recommendations across multiple different organs affected by GU melanomas or omits certain topics,making it difficult to appreciate the funda-mentals of the individual *** review aimed to provide background information on the pathogenesis and epidemiology of the different sites of GU melanomas and categorize data specific to the presentation,staging,treatment,and prognosis of each type of GU melanoma to guide the *** was also meant to encourage a multidisciplinary approach to the management of these patients as it spans the expertise of surgical oncologists,medical oncologists,radiation oncologist,dermatologists,urologists,and gynecologists.

关键词： Genitalia Female Male Melanoma Rare diseases Staging Treatment Urinary tract

Genitourinary manifestations of Lynch syndrome in the urological practice

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Asian Journal of Urology 2022年第4期9卷 443-450页

作者： Chiara Lonati Claudio Simeone Nazareno Suardi philippe espiess Andrea Necchi Marco Moschini Urology Unit ASST Spedali Civili di BresciaDepartment of Medical and Surgical SpecialtiesRadiological Science and Public HealthUniversity of BresciaBresciaItaly Department of Urology Luzerner KantonsspitalLucerneSwitzerland Department of Genitourinary Oncology H.Lee Moffitt Cancer Center and Research InstituteTamplaFLUSA University Vita-Salute San Raffaele MilanItaly Department of Medical Oncology IRCCS San Raffaele Hospital and Scientific InstituteMilanItaly Division of experimental Oncology/Unit of Urology Urological Research InstituteIRCCS Ospedale San RaffaeleMilanItaly

Objective:Lynch syndrome(LS)is an autosomal dominant hereditary disorder resulting from germline mutation in at least one of the four mismatch repair genes or in ePCAM *** a clinical perspective,LS patients exhibit an increased predisposition to multiple primary malignancies and early age of onset compared to general *** aimed to provide a comprehensive overview of all the genitourinary manifestations of LS,focusing on incidence,diagnosis,clinical features,therapeutic strategies,and screening ***:Previous literature was assessed through Medline,Scopus,and Google Scholar data-bases.A narrative review of the most relevant articles from January 1996 to June 2021 on urological manifestations of LS was ***:In the LS tumor spectrum,upper tract urothelial carcinoma(UTUC)represents the third most frequent malignancy,and the first most common cancer in the urological field,with an approximately 14-fold increased risk of developing UTUC compared to general *** diagnosis among patients experiencing UTUC as first malignancy is a step-by-step process,including(i)clinical criteria,(ii)molecular testing,and(iii)genetic testing to confirm the hereditary *** current european Association of Urology(eAU)guidelines recommend to perform molecular testing among UTUC patients under 65 years old,or UTUC patients with personal history of LS-related tumor,or UTUC patients with one first-degree relative under the age of 50 years with LS-related tumor,or UTUC patients with two first-degree relatives with LS-related tumor regardless of age of *** diagnosed LS patients should be referred to a multidisci-plinary management,including gastroenterologists and ***,considering the increased risk of metachronous recurrence,treatments other than radical nephroureterectomy may be a valuable therapeutic *** urological malignancies other than UTUC should be included in the LS tumor spectrum is still cont

关键词： Hereditary disease Hereditary nonpolyposis colorectal cancer Lynch syndrome Mismatch repair Upper tract urothelial carcinoma

Three-dimensional mapping and comparative analysis of the distal human corpus cavernosum and the inflatable penile prosthesis

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Asian Journal of Andrology 2013年第4期15卷 567-570,I0012页

作者： Tariq S Hakky Daniel Ferguson philippe e spiess Paul Bradley Tom FLue Rafael e Carrion Department of Urology University of South Florida Tampa General Circle Tampa FL 33602 USA 23D3Solutions Burnaby BCV5J 5M8 Canada and Department of Urology University of Southern California San Francisco 400 Parnassus Ave San Francisco CA 94143 USA

The intricate anatomy of the corpus cavernosum in both the flaccid and tumescent state has not been fully elucidated. We report our experience using a three-dimensional （3D） scanner to reconstruct cadaveric casts and compare them with 3D images of two prototypes of penile prosthesis. Two different models of the Titan Coloplast inflatable penile prosthesis were analyzed using a 3D scanner. The first was the standard model and the second was a newer model with a rounder silicone tip. Two cadaveric phalluses were harvested using Smooth-Cast 300Q polyurethane molding. The molds were excised and scanned along side the penile prosthesis. 3D scans were completed and analyzed using Leios Mesh software, and GOM Inspect software. The 3D scans demonstrated the mean human corporal radii 2 mm from the distal tip to be 36.51 mm （36.01-37.0 mm）, which is an obtuse angle. The standard Titan penile prosthesis spherical radius at the same level was 202.52 mm, while the new silicone tip prosthesis had a radius of 139.33 mm. 3D mapping further demonstrated the trajectory of the cavernosa appeared curvilinear and the distal ends appeared blunt. The use of cadaveric cavernosal molds in combination with the 3D scanner allowed us to accurately image the corpus cavernosum for the first time. Our findings suggest that anatomically accurate corporal tips appear to be relatively blunt and that the new Titan silicone tip penile prosthesis more closely resembles the human corporal tip.

关键词： corpus cavernosum penile prosthesis three-dimensional analysis

Augmented reality assisted surgery： a urologic training tool

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Asian Journal of Andrology 2016年第5期18卷 732-734页

作者： Ryan M Dickey Neel Srikishen Larry I Lipshultz philippe e spiess Rafael e Carrion Tariq S Hakky Scott Department of Urology Baylor College of Medicine Houston 77030 USA University of South Florida Department of Urology Tampa 33606 USA.

Augmented reality is widely used in aeronautics and is a developing concept within surgery. In this pilot study, we developed an application for use on Google Glass optical head-mounted display to train urology residents in how to place an inflatable penile prosthesis. We use the phrase Augmented Reality Assisted Surgery to describe this novel application of augmented reality in the setting of surgery. The application demonstrates the steps of the surgical procedure of inflatable penile prosthesis placement. It also contains software that allows for detection of interest points using a camera feed from the optical head-mounted display to enable faculty to interact with residents during placement of the penile prosthesis. Urology trainees and faculty who volunteered to take part in the study were given time to experience the technology in the operative or perioperative setting and asked to complete a feedback survey. From 30 total participants using a lO-point scale, educational usefulness was rated 8.6, ease of navigation was rated 7.6, likelihood to use was rated 7.4, and distraction in operating room was rated 4.9. When stratified between trainees and faculty, trainees found the technology more educationally useful, and less distracting. Overall, 81% of the participants want this technology in their residency program, and 93% see this technology in the operating room in the future. Further development of this technology is warranted before full release, and further studies are necessary to better characterize the effectiveness of Augmented Reality Assisted Surgery in urologic surgical training.

关键词： andrology augmented reality assisted surgery Google glass inflatable penile prosthesis optical head mounted display surgical education

Cavity-agnostic acoustofluidic manipulations enabled by guided flexural waves on a membrane acoustic waveguide actuator

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Microsystems & Nanoengineering 2024年第2期10卷 153-171页

作者： philippe Vachon Srinivas Merugu Jaibir Sharma Amit Lal eldwin J.Ng Yul Koh Joshua e.-Y.Lee Chengkuo Lee Department of electrical and Computer engineering National University of SingaporeSingaporeSingapore Institute of Microelectronics Agency for ScienceTechnology and Research(A*STAR)SingaporeSingapore SonicMeMS Laboratory School of Electrical and Computer EngineeringCornell UniversityIthacaNYUSA School of electrical and Data engineering University of Technology SydneyUltimoNSWAustralia

This article presents an in-depth exploration of the acoustofluidic capabilities of guided flexural waves(GFWs)generated by a membrane acoustic waveguide actuator(MAWA).By harnessing the potential of GFWs,cavity-agnostic advanced particle manipulation functions are achieved,unlocking new avenues for microfluidic systems and lab-on-a-chip *** localized acoustofluidic effects of GFWs arising from the evanescent nature of the acoustic fields they induce inside a liquid medium are numerically investigated to highlight their unique and promising *** traditional acoustofluidic technologies,the GFWs propagating on the MAWA’s membrane waveguide allow for cavity-agnostic particle manipulation,irrespective of the resonant properties of the fluidic ***,the acoustofluidic functions enabled by the device depend on the flexural mode populating the active region of the membrane *** demonstrations using two types of particles include in-sessile-droplet particle transport,mixing,and spatial separation based on particle diameter,along with streaming-induced counter-flow virtual channel generation in microfluidic PDMS *** experiments emphasize the versatility and potential applications of the MAWA as a microfluidic platform targeted at lab-on-a-chip development and showcase the MAWA’s compatibility with existing microfluidic systems.

关键词： waveguide fluid cavity

Why people should run after positive affective experiences instead of health benefits

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Journal of Sport and Health Science 2024年第4期13卷 445-450页

作者： Silvio Maltagliati philippe Sarrazin Layan Fessler Mael Lebreton Boris Cheval University of Grenoble Alpes SENSGrenoble 38000France Paris School of economics Paris 75014France Swiss Center for Affective Sciences University of GenevaGeneva 1202Switzerland Laboratory for Behavioral Neurology and Imaging of Cognition Department of Fundamental NeurosciencesUniversity of GenevaGeneva 1202Switzerland Laboratory for the Study of emotion elicitation and expression(e3Lab) Department of PsychologyUniversity of GenevaGeneva 1202Switzerland

Over time,physical activity(PA)has shifted from being a necessity to being an *** a result,levels of PA have sharply decreased.1 Today,we are facing a worldwide pandemic of physical inactivity,with one death every 6 s attributed to insufficient PA.2 To counteract this trend,a tremendous effort is being made to promote regular PA across the lifespan,mainly through the dissemination of knowledge about the health benefits of accumulating sufficient PA.

关键词： sharply benefits attributed

Acetic acid additive in NaNO_(3)aqueous electrolyte for long-lifespan Mg-air batteries

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Journal of Magnesium and Alloys 2024年第2期12卷 825-839页

作者： Yaqing Zhou Fan Sun Gunahua Lin Sandrine Zanna Antoine Seyeux philippe Marcus Jolanta´Swiatowska Chimie ParisTech-CNRS PSL UniversityInstitut de Recherche de Chimie Paris11 rue Pierre et Marie CurieParis 75005France

Mg-air batteries have attracted tremendous attention as a potential next-generation power source for portable electronics and e-transportation due to their remarkable high theoretical volumetric energy density,environmental sustainability,and ***,the fast hydrogen evolution reaction(HeR)in NaCl-based aqueous electrolytes impairs the performance of Mg-air batteries and leads to poor specific capacity,low energy density,and low ***,the conventionally used NaCl solute was proposed to be replaced by NaNO_(3)and acetic acid additive as a corrosion inhibitor,therefore an electrolyte engineering for long-life time Mg-air batteries is *** resulting Mg-air batteries based on this optimized electrolyte demonstrate an improved discharge voltage reaching~1.8 V for initial 5 h at a current density of 0.5 mA/cm^(2) and significantly prolonged cells'operational lifetime to over 360 h,in contrast to only~17 h observed in NaCl electrolyte.X-ray photoelectron spectroscopy and time-of-flight secondary ion mass spectrometry were employed to analyse the composition of surface film and scanning electron microscopy combined with transmission electron microscopy to clarify the morphology changes of the surface layer as a function of acetic acid *** thorough studies of chemical composition and morphology of corrosion products have allowed us to elucidate the working mechanism of Mg anode in this optimized electrolyte for Mg-air batteries.

关键词： Acetic acid additive in NaNO_(3)electrolyte electrolyte engineering Corrosion surface film Surface characterization Hydrogen evolution