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Progression-free survival as surrogate endpoint in advanced pancreatic cancer: meta-analysis of 30 randomized first-line trials

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Hepatobiliary & Pancreatic Diseases International 2015年第2期14卷 124-131页

作者： Fausto Petrelli Andrea Coinu Karen Borgonovo Mary Cabiddu sandro barni Medical Oncology Unit Oncology Department Azienda Ospedaliera Treviglio Piazzale Ospedale 124047 Treviglio (BG)

BACKGROUND：Progression-free survival（PFS）has not been extensively investigated as a surrogate for survival in the firstline treatments of pancreatic *** aim of this review was to evaluate PFS as a potential surrogate endpoint for overall survival（OS）in advanced pancreatic cancer in trials comparing poly-chemotherapy to gemcitabine *** SOURCES： A systematic literature search in PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials was conducted. The key words included randomized trial, first-line chemotherapy, pancreatic cancer, gemcitabine and poly-chemotherapy. Adjusted weighted linear regression was used to calculate Rs （Spearman＇s rank-order correlation coefficient） between PFS and post-progression survival （PPS） with OS （Rs） and between treatment effects on PFS and OS （RHR）. RESUEFS： A total of 30 trials including 8467 patients met the inclusion criteria. Correlation between the treatment effects on PFS and OS （RHR=0.78） and between the endpoint PFS and OS was high across all studies （Rs=0.75）. The slope of the re- gression line was 0.76±0.26, indicating that an agent produc- ing a 10% risk reduction for PFS will provide a 7.6%±2.6% risk reduction for OS. Correlation between PPS and OS was very strong （Rs=0.71） and accounted for more than 50% of the whole OS variability （R2=0.57）. CONCLUSION： Because of the robust correlation with OS and the potential influence of PPS caused by the second line therapies, it may be justified to consider PFS as a surrogate endpoint in trials evaluating new cytotoxic agents when gemcitabine is the control arm.

关键词： pancreatic cancer surrogate endpoints progression-free survival overall survival correlation randomized studies

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Which strategy after first-line therapy in advanced colorectal cancer?

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World Journal of Gastroenterology 2014年第27期20卷 8921-8927页

作者： Coinu Andrea Petrelli Fausto Borgonovo Karen Francesca Cabiddu Mary Ghilardi Mara Lonati Veronica barni sandro Medical Oncology Unit Oncology Department Azienda Ospedaliera di Treviglio Treviglio 24047 BG Italy

Second-line therapy for advanced colorectal cancer is an integral part of the treatment strategy that needs to be set from the beginning for each patient, bearing in mind the expected toxicities of chosen treatments, the patient's clinical condition, comorbidities, preferences, the aims of the treatment and the molecular status. Furthermore, the distinction between lines of therapy is no longer absolute. The perspective of "continuum of care" includes switching chemotherapy prior to disease progression, maintenance therapy, drug "holidays" if needed, surgical resection of metastases in selected patients, and seems to allow a tailored treatment, in which patients are more likely to benefit from exposure to all active agents, which is known to correlate with overall survival. The scenario of second-line treatment has changed dramatically over the years and could currently benefit from several options including chemotherapy with a single agent or in combination and the addition of molecular-targeted agents developed in the last decade, such as epidermal growth factor receptor antibodies(cetuximab, panitumumab) and vascular endothelial growth factor-targeting agents(bevacizumab, aflibercept), with the possibility of bevacizumab use even beyond first progression. The purpose of this review is to summarize the most important scientific data supporting the use of chemotherapy and the new biologic agents in the second-line setting in advanced colorectal cancer.

关键词： Advanced colorectal cancer Second-line Targeted agents Polychemotherapy Overall survival

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Single-neuron neurodegeneration as a degenerative model for Parkinson’s disease

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Neural Regeneration Research 2024年第3期19卷 529-535页

作者： sandro Huenchuguala Juan Segura-Aguilar Escuela de Tecnología Médica Facultad de SaludUniversidad Santo TomásLos CarrerasOsornoChile Molecular&Clinical Pharmacology Instituto de Ciencias Biomedicas(ICBM)Faculty of medicineUniversity of ChileIndependenciaSantiagoChile

The positive effect of levodopa in the treatment of Parkinson’s disease,although it is limited in time and has severe side effects,has encouraged the scientific community to look for new drugs that can stop the neurodegenerative process or even regenerate the neuromelanin-containing dopaminergic nigrostriatal *** preclinical studies with coenzyme Q10,mitoquinone,isradipine,nilotinib,TCH346,neurturin,zonisamide,deferiprone,prasinezumab,and cinpanemab prompted clinical ***,these failed and after more than 50 years levodopa continues to be the key drug in the treatment of the disease,despite its severe side effects after 4–6 years of chronic *** lack of translated successful results obtained in preclinical investigations based on the use of neurotoxins that do not exist in the human body as new drugs for Parkinson’s disease treatment is a big *** our opinion,the cause of these failures lies in the experimental animal models involving neurotoxins that do not exist in the human body,such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine,that induce a very fast,massive and expansive neurodegenerative process,which contrasts with the extremely slow one of neuromelanin-containing dopaminergic *** exceedingly slow progress of the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s patients is due to(i)a degenerative model in which the neurotoxic effect of an endogenous neurotoxin affects a single neuron,(ii)a neurotoxic event that is not expansive and(iii)the fact that the neurotoxin that triggers the neurodegenerative process is produced inside the neuromelanin-containing dopaminergic *** endogenous neurotoxin that fits this degenerative model involving one single neuron at a time is aminochrome,since it(i)is generated within neuromelanin-containing dopaminergic neurons,(ii)does not cause an expansive neurotoxic effect and(iii)triggers all the mechanisms involved in t

关键词： 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine 6-hydroxydopamine aminochrome dopaminergic neurons DT-diaphorase exogenous neurotoxins glutathione transferase M2-2

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Mapping the clinical practice of traditional,complementary and integrative medicine in oncology in Western countries:A multinational cross-sectional survey

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Journal of Integrative Medicine 2024年第1期22卷 64-71页

作者： Matthias Huemer sandro Graca Sarah Bitsche Guenter Hofmann Mike Armour Martin Pichler Palliative Care Unit Division of OncologyDepartment of Internal MedicineMedical University of Graz8036 GrazAustria Northern College of Acupuncture York YO16LJUnited Kingdom School of Health and Society Faculty of EducationHealth and WellbeingUniversity of WolverhamptonWolverhampton WV11LYUnited Kingdom National Institute of Complementary Medicine Health Research Institute Western Sydney UniversityPenrith NSW 2751Australia Translational Health Research Institute Western Sydney UniversityPenrith NSW 2751Australia Medical Research Institute of New Zealand Wellington 6021New Zealand Translational Oncology University Hospital of Augsburg86156 AugsburgGermany

Background Many cancer patients seek adjunctive therapies to biomedical cancer treatments at some point of their disease *** acupuncture is increasingly recommended by leading oncological associations,limited evidence exists concerning the evidence-informed practice and adherence to current guidelines of traditional complementary and integrative medicine(TCIM)practitioners treating cancer *** An international online-survey assessed the demographical data,clinical practice,and sources of information used by TCIM practitioners in Austria,Germany,United States of America,Australia,and New *** In total,404 respondents completed the survey,of which 254(62.9%)treated cancer *** practitioners were acupuncturists and herbalists(57.1%),had(16.8±9.9)years of clinical experience and see a median of 2(1,4)cancer patients per *** cancer(61.8%)is the most common cancer type seen in TCIM *** TCIM treatments are frequently concurrent with the patient’s cancer specific treatment(39.9%),which is also reflected by the main goal of a TCIM treatment to alleviate side effects(52.4%).However,only 28.0%of the respondents are in contact with the treating *** to the respondents,pain is most effectively treated using acupuncture,while herbal medicine is best for cancer-related *** practitioners mostly use certified courses(33.1%)or online databases(28.3%)but often believe that experts are more reliable to inform their practice(37.0%)than research publications(32.7%).Conclusion Acupuncturists and herbalists commonly treat cancer *** practitioners use TCIM as an adjunct to biomedicine as supportive care and use it largely in accordance with current oncological guidelines.

关键词： Integrative medicine Acupuncture Oncology Evidence-informed practice International survey

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Testosterone replacement therapy and vascular thromboembolic events: a systematic review and meta-analysis

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Asian Journal of Andrology 2024年第2期26卷 144-154页

作者： Rossella Cannarella Carmelo Gusmano Claudia Leanza Vincenzo Garofalo Andrea Crafa Federica Barbagallo Rosita A Condorelli sandro La Vignera Aldo E Calogero Department of Clinical and Experimental Medicine University of CataniaCatania 95123Italy Glickman Urological&Kidney Institute Cleveland Clinic FoundationClevelandOH44195USA

To evaluate the relationship between testosterone replacement therapy(TRT)and arterial and/or venous thrombosis in patients with pre-treatment total testosterone(TT)<12 nmol I^(-1),we performed a meta-analysis following the Population Intervention Comparison Outcome ***:men with TT<12 nmol I^(-1) or clear mention of hypogonadism in the inclusion criteria of patients;intervention:TRT;comparison:placebo or no therapy;outcomes:arterial thrombotic events(stroke,myocardial infarction[MI],upper limbs,and lower limbs),VTE(deep vein thrombosis[DVT],portal vein thrombosis,splenic thrombosis,and pulmonary embolism),and mortality.A total of 2423 abstracts were assessed for ***-four studies,including 14 randomized controlled trials(RCTs),were finally included,with a total of 4027 and 310288 hypotestosteronemic male patients,from RCTs and from observational studies,*** on RCT-derived data,TRT did not influence the risk of arterial thrombosis(odds ratio[OR]=1.27,95%confidence interval[CI]:0.47-3.43,P=0.64),stroke(OR=1.34,95%CI:0.09-18.97,P=0.83),MI(OR=0.51,95%CI:0.11-2.31,P=0.39),VTE(OR=1.42,95%CI:0.22-9.03,P=0.71),pulmonary embolism(OR=1.38,95%CI:0.27-7.04,P=0.70),and mortality(OR=0.70,95%CI:0.20-2.38,P=0.56).Meanwhile,when only observational studies are considered,a significant reduction in the risk of developing arterial thrombotic events,Ml,venous thromboembolism,and mortality was *** risk for DVT remains uncertain,due to the paucity of RCT-based *** in men with TT<12 nmol I^(-1) is safe from the risk of adverse cardiovascular *** studies specifically assessing the risk of DVT in men on TRT are needed.

关键词： hypogonadism testosterone testosterone replacement therapy thromboembolism thrombosis TRT

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High Amounts of Halogenated Natural Products in Sperm Whales(Physeter macrocephalus)from Two Italian Regions in the Mediterranean Sea

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Environment & Health 2024年第4期2卷 233-242页

作者： Sina Schweizer Kristin Halder Annika Schafer Jakob Hauns Letizia Marsili sandro Mazzariol Maria Cristina Fossi Juan Muñoz-Arnanz Begoña Jiménez Walter Vetter Institute of Food Chemistry Department of Food Chemistry(170b)University of Hohenheim70599 StuttgartGermany European Union Reference Laboratory(EURL)for Halogenated POPs in Feed and Food 79114 FreiburgGermany Department of Environmental Earth and Physical SciencesUniversity of Siena53100 SienaItaly Department of Public Health Comparative Pathology and Veterinary HygieneUniversity of Padova35020 LegnaroItaly Department of Instrumental Analysis and Environmental Chemistry Institute of Organic Chemistry(IQOG-CSIC)28006 MadridSpain

Halogenated natural products(HNPs)are considered to be emerging contaminants whose environmental distribution and fate are only incompletely ***,several persistent and bioaccumulative HNP groups,together with manmade polychlorinated biphenyls(PCBs)and polybrominated diphenyl ethers(PBDEs),were quantified in the blubber of nine sperm whales(Physeter macrocephalus)stranded on the coast of the Mediterranean Sea in *** naturally occurring polybrominated hexahydroxanthene derivatives(PBHDs;sum of TetraBHD and TriBHD)were the most prominent substance class with up to 77,000 ng/g *** mean PBHD content(35,800 ng/g blubber)even exceeded the one of PCBs(28,400 ng/g blubber),although the region is known to be highly contaminated with manmade *** on mean values,Q1∼PBDEs>MeO-BDEs∼2,2′-diMeO-BB 80 and several other HNPs followed with decreasing *** blubber samples contained an abundant compound whose molecular formula(C_(16)H_(19)Br_(3)O_(2))was verified using high-resolution mass *** only plausible matching isomer was(2S,4′S,9R,9′S)-2,7-dibromo-4′-bromomethyl-1,1-dimethyl-2,3,4,4′,9,9′-9,9′-hexahydro-1H-xanthen-9-ol(OH-TriBHD),a hydroxylated secondary metabolite previously detected together with TriBHD and TetraBHD in a sponge known to be a natural producer of *** estimated mean amount of the presumed OH-TriBHD was 3000 ng/g blubber,which is unexpectedly high for hydroxylated compounds in the lipids of marine mammals.

关键词： Halogenated natural product naturally occurring polyhalogenated compound persistent organic pollutant sperm whale Italy polar metabolite

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Liquid crystal immunosensors for the selective detection of Escherichia coli with a fast analysis tool

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Photonics Research 2024年第7期12卷 1564-1573页

作者： sandro C.OLIVEIRA MARIA S.SOARES BÁRBARA V.GONÇALVES ANDREIA C.M.RODRIGUES AMADEU M.V.M.SOARES RITA G.SOBRAL NUNO F.SANTOS JAN NEDOMA PEDRO L.ALMEIDA CARLOS MARQUES CICECO-Aveiro Institute of Materials Physics DepartmentUniversity of Aveiro3810-193 AveiroPortugal i3N Physics DepartmentUniversity of Aveiro3810-193 AveiroPortugal Associate Laboratory i4HB-Institute for Health and Bioeconomy School of Sciences and TechnologyNOVA University of Lisbon1099-085 LisbonPortugal CESAM-Centre for Environmental and Marine Studies and Department of Biology University of Aveiro3810-193 AveiroPortugal Department of Telecommunications VSB-Technical University of OstravaOstrava 70800Czech Republic i3N-CENIMAT School of Sciences and TechnologyNOVA University of Lisbon1099-085 LisbonPortugal UnIRE ISELPolytechnic Institute of Lisbon1549-020 LisbonPortugal Department of Physics VSB-Technical University of OstravaOstrava 70800Czech Republic

The consumption of contaminated food may cause serious illnesses,and traditional methods to detect Escherichia coli are still associated with long waiting times and high costs given the necessity to transport samples to specialized *** is a need to develop new technologies that allow cheap,fast,and direct monitoring at the site of ***,in this work,we developed optical immunosensors for the selective detection of ***,based on liquid crystal technology,whose molecules can align in different manners depending on the boundary conditions (such as substrates) as well as the environment that they *** glass substrate was functionalized with *** antibody using cysteamine as an intermediate,and a vertical alignment was imposed on the liquid crystal molecules by using DMOAP during *** presence of bacteria disrupts the alignment of the liquid crystal molecules,changing the intensity of light emerging between cross polarizers,measured using a polarized optical microscope and a *** was possible to detect *** in suspensions in the concentration range from 2.8 cells/mL to 2.8×10^(9) cells∕*** was also evaluated,and the sensors were used to analyze contaminated water samples.A prototype was developed to allow faster,in-situ,and easier analysis avoiding bulky instruments.

关键词： crystal alignment analysis

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集成乙二醇烷硫醇的CMUT共振生物传感器用于提升DNA无标记检测选择性（英文）

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Engineering 2024年第10期41卷 231-241页

作者： Zhikang Li Yihe Zhao Gian Luca Barbruni Jie Li Zixuan Li Jiawei Yuan Ping Yang Libo Zhao Zhuangde Jiang sandro Carrara State Key Laboratory for Manufacturing Systems Engineering the International Joint Laboratory for Micro/Nano Manufacturing and Measurement Technologies Xi'an Jiaotong University Xi'an Jiaotong University (Yantai) Research Institute for Intelligent Sensing Technology and System School of Instrument Science and Technology Xi'an Jiaotong University School of Mechanical Engineering Xi'an Jiaotong University Shandong Laboratory of Yantai Advanced Materials and Green Manufacturing Bio/CMOS Interfaces Laboratory Institute of Electrical and Microengineering School of Engineering école Polytechnique F éd érale de Lausanne College of Mechanical and Electrical Engineering Shaanxi University of Science and Technology

Gravimetric resonant-inspired biosensors have attracted increasing attention in industrial and point-ofcare applications,enabling label-free detection of biomarkers such as DNA and *** micromachined ultrasonic transducers（CMUTs） are promising tools for developing miniaturized highperformance biosensing complementary metal-oxide-silicon（CMOS） ***,their operability is limited by inefficient functionalizatio n,aggregation,crosstalk in the buffer,and the requirement for an external high-voltage（HV） power *** this study,we aimed to propose a CMUTs-based resonant biosensor integrated with a CMOS front-end interface coupled with ethylene-glycol alkanethiols to detect single-stranded DNA oligonucleotides with large *** topography of the functionalized surface was characterized by energy-dispersive X-ray *** selectivity for onchip hybridization was demonstrated by comparing complementary and non-complementary singlestranded DNA oligonucleotides using fluorescence imaging *** sensor array was further characterized using a five-element lumped equivalent *** 4 mm2application-specific integrated circuit chip was designed and developed through 0.18 μm HV bipolar-CMOS-double diffused metaloxide-silicon（DMOS） technology（BCD） to generate on-chip 20 V HV boosting and to track feedback frequency under a standard 1.8 V supply,with a total power consumption of 3.8 mW in a continuous *** measured results indicated a detection sensitivity of 7.943 × 10-3μmol·***-1 over a concentration range of 1 to 100 μmol·*** conclusion,the label-free biosensing of DNA under dry conditions was successfully demonstrated using a microfabricated CMUT array with a 2 MHz frequency on CMOS electronics with an internal HV ***,ethylene-glycol alkanethiols successfully deposited self-assembled monolayers on aluminum electrodes,which has never been attempted thus far on CMUTs,to enhance the selectivity o

关键词： Capacitive micromachined ultrasonic transducers (CMUTs) DNA detection Self-assembled monolayer (SAM) Ethylene-glycol alkanethiols Application-specific integrated circuit (ASIC)

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Challenges and advancing strategies of endoscopic submucosal dissection for early gastric cancer:The puzzle of eCura C1

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World Journal of Gastrointestinal Endoscopy 2024年第8期16卷 439-444页

作者： Giulio Calabrese Guido Manfredi Marcello F Maida Francesco V Mandarino Endrit Shahini Francesco Pugliese Paolo Cecinato Liboria Laterza Emanuele Sinagra sandro Sferrazza Department of Gastroenterology and Endoscopy ARNAS Civico–Di Cristina–BenfratelliPalermo 90127SiciliaItaly Department of Gastroenterology and Digestive Endoscopy Ospedale MaggioreCrema 26013Italy Department of Medicine and Surgery University of Enna"Kore"Enna 94100SiciliaItaly Department of Gastroenterology and Digestive Endoscopy IRCCS Ospedale San RaffaeleMilan 20132LombardyItaly Department of Gastroenterology National Institute of Gastroenterology-IRCCS“Saverio de Bellis”Castellana GrotteBari 70013Italy Department of Digestive and Interventional Endoscopy Niguarda HospitalASST NiguardaMilan 20162LombardyItaly Department of Medical and Surgical Sciences IRCCS Azienda Ospedaliero-Universitaria di BolognaPoliclinico Sant’OrsolaBologna 40138Emilia-RomagnaItaly Department of Gastroenterology and Endoscopy Fondazione Instituto San Raffaele GiglioCefalù90015PalermoItaly

In this editorial,we explore the challenges of managing noncurative resections in early gastric cancer after endoscopic submucosal dissection(ESD),starting from the consideration recently made by Zhu et ***,we evaluate the management of eCura C1 lesions,where decisions regarding further interventions are pivotal yet *** among endoscopists,surgeons,and pathologists is underscored to refine risk assessment and personalize therapeutic *** advancements in ESD techniques and interdisciplinary collaboration offer opportunities for outcome optimization in managing eCura C1 ***,despite needing further clinical validation,molecular biomarkers have emerged as promising tools for enhancing *** manuscript highlights the ongoing research attempts to define treatment paradigms effectively and evaluates the potential of emerging options,ultimately aiming to improve patient care and outcomes in this complex clinical scenario.

关键词： Early gastric cancer Endoscopic submucosal dissection eCura Non-curative resection Multidisciplinary approach

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Tomography of a simply magnetized toroidal plasma

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Plasma Science and Technology 2018年第2期20卷 87-96页

作者： Ruggero barni Stefano CALDIROLA Luca FATTORINI Claudia RICCARDI Dipartimento di Fisica G.Occhialini Università degli Studi di Milano-Bicocca piazza della Scienza 3 1-20126 Milano Italy Max Planck Institut fur Plasmaphysik Boltzmann Strasse 2 D-85748 Garching Germany

Optical emission spectroscopy is a passive diagnostic technique,which does not perturb the plasma *** particular,in a hydrogen plasma,Balmer-alpha（Hα） emission can be easily measured in the visible range along a line of sight from outside the plasma *** emission lines in the visible spectral range from hydrogen atoms and molecules can be exploited too,in order to gather complementary pieces of information on the plasma *** allows us to capture bi-dimensional *** propose to adopt an emission spectroscopy tomography for studying the transverse profiles of magnetized plasmas when Abel inversion is not *** experimental campaign was carried out at the Thorello device,a simple magnetized *** characteristics of the profile extraction method,which we implemented for this purpose are discussed,together with a few results concerning the plasma profiles in a simply magnetized torus configuration.

关键词： optical emission spectroscopy magnetized plasma simply magnetized torus plasma diagnostics

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