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Mechanisms of resistance to anti-epidermal growth factor receptor inhibitors in metastatic colorectal cancer

World Journal of Gastroenterology 2016年第28期22卷 6345-6361页

作者： Vincenzo Sforza Erika Martinelli Fortunato Ciardiello Valentina Gambardella Stefania Napolitano Giulia Martini Carminia della Corte Claudia Cardone Marianna L Ferrara Alfonso Reginelli Giuseppina Liguori Giulio Belli teresa troiani Oncologia medica Dipartimento di Medicina Clinica e Sperimentale "F. Magrassi e A. Lanzara" Seconda Università degli Studi di Napoli Department of Medical Oncology Biomedical Research Institute INCLIVA University of Valencia Department of Internal and Experimental Medicine Magrassi-Lanzara Institute of Radiology Seconda Università di Napoli Department of Pathology Istituto Nazionale Tumori "Fond. Pascale" - IRCCS Department of General and Hepato-Pancreato-Biliary Surgery S. M. Loreto Nuovo Hospital

The prognosis of patients with metastatic colorectal cancer (mCRC) remain poor despite the impressive improvement of treatments observed over the last 20 years that led to an increase in median overall survival from 6 mo, with the only best supportive care, to approximately 30 mo with the introduction of active chemotherapy drugs and targeted agents. The monoclonal antibodies (moAbs) cetuximab and panitumumab, directed against the epidermal growth factor receptor (EGFR), undoubtedly represent a major step forward in the treatment of mCRC, given the relevant efficacy in terms of progression-free survival, overall survival, response rate, and quality of life observed in several phase III clinical trials among different lines of treatment. However, the anti-EGFR moAbs were shown only to be effective in a subset of patients. For instance, KRAS and NRAS mutations have been identified as biomarkers of resistance to these drugs, improving the selection of patients who might derive a benefit from these treatments. Nevertheless, several other alterations might affect the response to these drugs, and unfortunately, even the responders eventually become resistant by developing secondary (or acquired) resistance in approximately 13-18 mo. Several studies highlighted that the landscape of responsible alterations of both primary and acquired resistance to anti-EGFR drugs biochemically converge into MEK-ERK and PIK3CA-AKT pathways. In this review, we describe the currently known mechanisms of primary and acquired resistance to anti-EGFR moAbs together with the various strategies evaluated to prevent, overcame or revert them.

关键词： Metastatic colorectal cancer Epidermal growth factor receptor Resistance Mutation KRAS NRAS BRAF PIK3CA MET Monoclonal antibodies

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Present and future of metastatic colorectal cancer treatment: A review of new candidate targets

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World Journal of Gastroenterology 2017年第26期23卷 4675-4688页

作者： Giulia Martini teresa troiani Claudia Cardone Pietropaolo Vitiello Vincenzo Sforza Davide Ciardiello Stefania Napolitano Carminia Maria Della Corte Floriana Morgillo Antonio Raucci Antonio Cuomo Francesco Selvaggi Fortunato Ciardiello Erika Martinelli Department of Internal and Experimental Medicine“F.Magrassi e A.Lanzara” Institute of Medical OncologyUniversitàdegli studi della Campania Luigi Vanvitelli Department of Internal and Experimental Medicine Magrassi-LanzaraInstitute of RadiologyUniversitàdegli studi della Campania Luigi Vanvitelli Gastroenterology Unit Ospedale Umberto I Unit of Colorectal Surgery Department of MedicalSurgicalNeurologicalMetabolic and Ageing SciencesUniversità degli studi della Campania Luigi Vanvitelli

In the last two decades, great efforts have been made in the treatment of metastatic colorectal cancer(m CRC) due to the approval of new target agents for cytotoxic drugs. Unfortunately, a large percentage of patients present with metastasis at the time of diagnosis or relapse after a few months. The complex molecular heterogeneity of this disease is not completely understood; to date, there is a lack of predictive biomarkers that can be used to select subsets of patients who may respond to target drugs. Only the RAS-mutation status is used to predict resistance to anti-epidermal growth factor receptor agents in patients with m CRC. In this review, we describe approved targeted therapies for the management of metastatic m CRC and discuss new candidate targets on the horizon.

关键词： Novel biomarkers Monoclonal antibodies Resistance Mutation RAS Target therapy Metastatic colorectal cancer

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On the effect of pitch and yaw angles in oblique impacts of smallcaliber projectiles

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Defence Technology（防务技术） 2024年第1期31卷 73-94页

作者： teresa Fras French-German Research Institute of Saint-Louis(ISL) Saint-LouisFrance

A terminal ballistic analysis of the effects of 7.62 mm × 51 AP P80 rounds on inclined high-strength armor steel plates is the focus of the presented *** findings of an instrumented ballistic testing combined with 3D advanced numerical simulations performed using the IMPETUS Afea? software yielded the *** experimental verification proved that slight differences in the pitch-andyaw angles of a projectile upon an impact caused different damage types to the projectile’s *** residual velocities predicted numerically were close to the experimental values and the calculated core deviations were in satisfactory agreement with the experimental *** extended matrix of the core deviation angles with combinations of pitch-and-yaw upon impact angles was subsequently built on the basis of the numerical *** presented experimental and numerical investigation examined thoroughly the influence of the initial pitch and yaw angles on the after-perforation projectile’s performance.

关键词： Ballistic impact Small-caliber projectile Pitch and yaw impact angles Shadowgraphy IMPETUS Afea Numerical simulations

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Potential risk genes for primary Sjogren's syndrome from a meta-analysis by linear regression and random forest classification

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Genes & Diseases 2024年第3期11卷 128-131页

作者： Tomas Cerdo teresa Torres Moral Maimonides Biomedical Research Institute of Cordoba(IMIBIC) Reina Sofia University HospitalUniversity of CordobaCordoba 14004Spain Centre for Rheumatology Research Division of MedicineUniversity College LondonLondon W1T 4JFUK Faculty of Computer Sciences Multimedia and TelecommunicationUniversitat Oberta de CatalunyaBarcelona 08018Spain Dermatology Department Melanoma UnitAugust Pi i Sunyer Biomedical Research Institute(IDIBAPS)and Hospital ClinicBarcelona 08036Spain Center for Networked Biomedical Research on Rare Diseases(CIBERER) Carlos II Health InstituteMadrid 28029Spain

Primary Sjogren's syndrome(psS)is one of the most widespread autoimmune diseases with unknown origin,characterized by a lymphocytic infiltrate of the exocrine glands and the production of anti-SSA/Ro and anti-SSB/La antibodies that cause dysfunction and destruction mainly of salivary and lachrymal glands,leading to dry eyes and dry *** the absence of a standardized evidence-based screening tool to decide which patients with dry eye must be referred for study of this pathology.

关键词： Sjogren lymphocytic salivary

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A Comparison between Late Preterm and Term Infants with Respiratory Distress Syndrome, Early-Onset Sepsis, and Neonatal Jaundice in Ecuadorian Newborns

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Open Journal of Pediatrics 2024年第1期14卷 22-35页

作者： teresa Altamirano Molina Colegio Ciencias de la Salud Universidad San Francisco de Quito USFQ calle Diego de Robles s/n y Pampite Quito Ecuador Servicio de Neonatología Hospital General del Sur de Quito calle Moraspungo s/n y Pinllopata Quito Ecuador

Background: To examine the differences in prevalence of respiratory distress syndrome, early-onset sepsis and jaundice, between late preterm infants versus term infants in Ecuadorian newborns. Methods: Study design: Epidemiological, observational, and cross-sectional, with two cohorts of patients. Settings: IESS Quito Sur Hospital at Quito, Ecuador, from February to April of 2020. Participants: This study included 204 newborns, 102 preterm infants, 102 term infants. Results: There are significant differences between late preterm infants and term infants, with a p-value of 0.000 in the prevalence of early sepsis, 70.59% vs. 35.29%. In respiratory distress syndrome between late and term premature infants, significant differences were observed with a p-value of 0.000, the proportion being 55.58% vs. 24.51% respectively. The prevalence of jaundice is higher in term infants with a p value of 0.002, 72.55%, versus 51.96% in late preterm infants, and the mean value of bilirubins in mg/dL was higher in term infants 14.32 versus 12.33 in late preterm infants;this difference is statistically significant with a p value of 0.004. Admission to the NICU is more frequent in late preterm infants with a p-value of 0.000, being 42.16% for late preterm infants vs. 7.84% in term infants;the mean of the hospital days with p-value 0.005, was higher in late preterm infants 4.97 days vs. 3.55 days for term newborns. Conclusion: Due to the conditions of their immaturity, late preterm infants are 2.86 times more likely to present early sepsis than full-term newborns. It is shown that late preterm infants are 2.69 times more likely to have respiratory distress syndrome compared to term infants, therefore, late preterm infants have a longer hospital stay of 4.97 days versus 3.55 days in term infants. Jaundice and mean bilirubin levels are higher in term infants due to blood group incompatibility and insufficient breastfeeding.

关键词： Late Preterm Term Newborn Respiratory Distress Syndrome Early Onset Sepsis Jaundice

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Weight regain after intragastric balloon for pre-surgical weight loss

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 2040-2046页

作者： Danielle Abbitt Kevin Choy Alexandra Kovar teresa S Jones Krzysztof J Wikiel Edward L Jones Department of Surgery University of ColoradoAuroraCO 80045United States Department of Surgery Rocky Mountain Regional Veteran Affairs Medical CenterAuroraCO 80045United States

BACKGROUND Over one-third of Americans carry the diagnosis of obesity,many also with obesity-related *** can place patients at increased risk of operative and postoperative *** intragastric balloon has been shown to aid in minor weight loss,however its weight recidivism in patients requiring short interval weight loss has not been well *** To evaluate weight loss,ability to undergo successful elective surgery after intragastric balloon placement,and weight management after balloon *** This study is a retrospective review of patients in a single academic institution undergoing intragastric balloon placement from 2019-2023 to aid in weight loss prior to undergoing elective *** outcomes including weight loss,duration of balloon placement,successful elective surgery,weight regain postballoon and post-procedure complications were *** criteria included those with balloon in place at time of *** Thirty-three patients completed intragastric balloon therapy from 2019-2023 as a bridge to elective *** patients were required to participate in a 12-month weight management program to be eligible for balloon *** surgeries included incisional hernia repair,umbilical hernia repair,inguinal hernia repair,and knee and hip *** average age at placement was 53 years±11 years,majority(91%)were *** average duration of intragastric balloon therapy was 186 days±41 *** average weight loss was 14.0 kg±7.4 kg and with an average percent excess body weight loss of 30.0%(7.9%-73.6%).Over half of the patients(52.0%)achieved the goal of 30-50 lbs(14-22 kg)weight ***-one patients(64%)underwent their intended elective surgery,2 patients(6%)deferred surgery due to symptom relief with weight loss ***-one of the patients(64%)have documented weights in 3 months after balloon removal,in these patients the majority(76%)gained weight after balloon *** pat

关键词： Intragastric balloon Weight loss Obesity Bariatric Body mass index

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Integration of Environmental and Social Values in Cultural Spaces:Sustainable and Inclusive Wayfinding Materials for Museums

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Journal of Civil Engineering and Architecture 2024年第5期18卷 207-217页

作者： Cristiana Cellucci teresa Villani Department of Architecture and Arts IUAV University of VeniceVenice 219630123Italy Department of Planning Designand TechnologyFaculty of ArchitectureSapienza University of RomeRome 00185Italy

In the context of use of large museum centers,numerous national and international methodological experiments show that the wayfinding project must consider the needs of both habitual users(user-centered design)and local communities(design for communities)and the importance of environmental protection(eco-design)as a priority interest of the ***“double target”,“user-centered”and“environment-centered”can be applied during the selection process of materials to be used in the *** respect to these possibilities,this contribution intends to present the results of research focused on material characterization of the reception and distribution spaces of large museum *** characterization is based on use of sensory materials and aims to evaluate their impact on the usability and sustainability of wayfinding *** paper directed towards a proposal for organization of integrated information on new generation so-called smart materials;within the design of a wayfinding system,these can balance the aesthetic-perceptual and performance and environmental impact,in order to allow designers to make informed decisions oriented towards inclusion and *** study was addressed by conducting two phases of systematic literature and library review of *** investigations conducted led to achievement of a first research result which consists in the identification of a“standard sheet”for the mapping and cataloging of the materials used for ***“standard sheet”allows organizing the information on smart,sensorial,and eco-friendly materials,balancing the aesthetic-perceptive component with the performance on the environmental impact along the entire life cycle in a circular *** tool could guide designers towards an environmental communication project oriented towards sustainability and is effective for usability and wayfinding.

关键词： Wayfinding eco-friendly materials sensory materials user-centered design eco-design innovative museum

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Lack of evidence for germline WWP1 pathogenic variants in gastrointestinal polyposis and other phenotypes suggestive of PTEN-hamartoma-tumor syndrome

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Genes & Diseases 2024年第2期11卷 524-527页

作者： Noemi Gonzalez-Abuin Tirso Pons teresa Fuster Isabel Quintana Mariona Terradas Gemma Aiza Joan Brunet Gabriel Capellá Heather Hampel Laura Valle Hereditary Cancer Program Catalan Institute of OncologyOncobell ProgramIDIBELLHospitalet de LlobregatBarcelona 08908Spain Department of Immunology and Oncology National Center for BiotechnologySpanish National Research Council (CNB-CSIC)Madrid 28049Spain Centro de Investigación Biomédica en Red de Cáncer (CIBERONC) Madrid 28029Spain Catalan Institute of Oncology IDIBGiGirona 17007Spain Division of Clinical Cancer Genomics Department of Medical Oncology & Therapeutic ResearchCity of Hope National Cancer CenterDuarteCA 91010USA

Germline activating variants in WWP1,which encodes an E3 ubiquitin ligase that antagonizes PTEN tumor suppressive function,have been proposed as an alternative mechanism of PTEN inactivation in PTEN-hamartoma-tumor syndrome(PHTS)-like patients with wildtype PTEN.1 More specifically,heterozygous,potentially activating wwP1 variants were first identified by Lee et al in patients affected with gastrointestinal oligopolyposis,including adenomatous,hyperplastic/serrated,and hamartomatous polyps,and occasionally with colorectal cancer(Table 1).Subsequently,based on the PHTS phenotypic features,wWP1 mutational screening was performed in patients with thyroid nodules,2 or normocephalic autism spectrum disorder(ASD),3 where germline WWP1 variants were also identified(Table S1).

关键词： WWP1 gastrointestinal polyposis

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Potential of Bamboo Species Guadua trinii and Guadua angustifolia for Nanocellulose Production

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Journal of Renewable Materials 2024年第9期12卷 1541-1555页

作者： Agatha E. R. Prado Gárate Fernando E. Felissia María Cristina Area teresa Suirezs María Evangelina Vallejos Círculo de Investigación del Bambú Universidad Nacional Agraria La Molina(UNALM)Lima15026Perú Instituto de Materiales de Misiones(IMAM) Universidad Nacional de Misiones(UNaM)Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET)Facultad de Ciencias ExactasQuímicas y Naturales(FCEQYN)Programa de Celulosa y Papel(PROCyP)Posadas3300Argentina Instituto de Materiales de Misiones(IMAM) Universidad Nacional de Misiones(UNaM)Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET)Facultad de Ciencias Forestales(FCF)Eldorado3380Argentina

Non-traditional lignocellulosic materials are a significant resource for producing high-value products, including nanocellulose. This work studied the nanocellulose obtention from chemical pulps of the two fast-growing bamboo species, Guadua trinii , and Guadua angustifolia . Chemical pulps were produced by soda-anthraquinone (S) pulping from both autohydrolysis-pretreated (H) and unpretreated bamboo chips. Autohydrolysis-pretreated (SHP) and unpretreated soda-anthraquinone (AQ) (SP) pulps were characterized by yield, Kappa number, alpha, beta, and gamma cellulose, degree of polymerization, water retention value, and crystallinity. The nanocellulose was produced by a sequential chemical oxidation treatment (2,2,6,6-tetramethylpiperidine-1-oxyl, TEMPO reagent) and mechanical nanofibrillation. Nanocellulose was characterized by carboxylic group content and viscosity. The results revealed that autohydrolysis pretreatment resulted in a higher hemicelluloses extraction in G. angustifolia . In contrast, the pulping yield of unpretreated samples was higher for G. trinii , and the soda-AQ pulps from this species exhibited better delignification than the autohydrolysis-pretreated pulps. The crystallinity index values of the obtained pulps were high (>80%), and the alpha-cellulose contents were similar. The viscosities of the aqueous nanocellulose suspensions were higher for the nanocellulose solutions obtained from the unpretreated soda-AQ pulps. Besides, nanocellulose from G. trinii unpretreated soda-AQ pulps had a higher rate of carboxylic groups. The results of this work are significant in assessing the potential of both bamboo species as a source of high-value products within the biorefinery framework because the viscosities of the aqueous nanocellulose suspensions depend on the size and shape of nanofibrils. It has significant importance for industrial unit operations and potential applications.

关键词： Natural fiber Guadua angustifolia Guadua trinii soda-anthraquinone pulp nanocellulose

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Isochronous singing in 3 crested gibbon species(Nomascus spp.)

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Current Zoology 2024年第3期70卷 291-297页

作者： Chiara De Gregorioa teresa Raimondi Valeria Bevilacqua Chiara Pertosa Daria Valente Filippo Carugati Francesca Bandoli Livio Favaro Brice Lefaux Andrea Ravignani Marco Gamba Department of Life Sciences and Systems Biology University of Turinvia Accademia Albertina 13Torino 10125Italy Department of Biology University of PaduaVia VIII Febbraio2Padova 35122Italy Giardino Zoologico di Pistoia Via Pieve a Celle160/APistoia 5110Italy Botanical and Zoological Garden of Mulhouse 11 Av.de la 1ère Division BlindéeMulhouse 68100France Comparative Bioacoustics Group Max Planck Institute for PsycholinguisticsWundtlaan 1Nijmegen 6525 XDThe Netherlands Center for Music in the Brain Department of Clinical MedicineAarhus UniversityBuilding 1710Universitetsbyen 38000AarhusDenmark Department of Human Neuroscience Sapienza University of RomeViale Regina Elena 334Rome 00185Italy

The search for common characteristics between the musical abilities of humans and other animal species is still taking its frst *** of the most promising aspects from a comparative point of view is the analysis of rhythmic components,which are crucial features of human communicative performance but also well-identifable patterns in the vocal displays of other ***,the study of rhythm is becoming essential to understand the mechanisms of singing behavior and the evolution of human *** fndings provided evidence that particular rhythmic structures occur in human music and some singing animal species,such as birds and rock hyraxes,but only 2 species of nonhuman primates have been investigated so far(Indri indri and Hylobates lar).Therefore,our study aims to consistently broaden the list of species studied regarding the presence of rhythmic *** investigated the temporal organization in the singing of 3 species of crested gibbons(Nomascus gabriellae,Nomascus leucogenys,and Nomascus siki)and found that the most prominent rhythmic category was ***,we found slight variation in songs’tempo among species,with *** and *** singing with a temporal pattern involving a gradually increasing tempo(a musical accelerando),and *** with a more regular ***,we show how the prominence of a peak at the isochrony establishes itself as a shared characteristic in the small apes considered so far.

关键词： accelerando isochrony music rhythm singing primates song tempo

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