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Analysis of hepatitis B virus preS1 variability and prevalence of the rs2296651 polymorphism in a Spanish population

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World Journal of Gastroenterology 2018年第6期24卷 680-692页

作者： Rosario Casillas David Tabernero Josep Gregori Irene Belmonte maria francesca cortese Carolina González Mar Riveiro-Barciela Rosa maria López Josep Quer Rafael Esteban maria Buti Francisco Rodríguez-Frías Liver Pathology Unit Departments of Biochemistry and MicrobiologyHospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Liver Unit Liver Disease Laboratory-Viral HepatitisVall d’Hebron Institut Recerca-Hospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBERehd) Instituto de Salud Carlos IIIMadrid 28029Spain Roche Diagnostics SL Sant Cugat del Vallès 08174Spain Liver Unit Department of Internal MedicineHospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain

AIM To determine the variability/conservation of the domain of hepatitis B virus(HBV) pre S1 region that interacts with sodium-taurocholate cotransporting polypeptide(hereafter, NTCP-interacting domain) and the prevalence of the rs2296651 polymorphism(S267 F, NTCP variant) in a Spanish population. METHODS Serum samples from 246 individuals were included and divided into 3 groups: patients with chronic HBV infection(CHB)(n = 41, 73% Caucasians), patients with resolved HBV infection(n = 100, 100% Caucasians) and an HBV-uninfected control group(n = 105, 100% Caucasians). Variability/conservation of the amino acid(aa) sequences of the NTCPinteracting domain,(aa 2-48 in viral genotype D) and a highly conserved pre S1 domain associated with virion morphogenesis(aa 92-103 in viral genotype D) were analyzed by next-generation sequencing and compared in 18 CHB patients with viremia > 4 log IU/mL. The rs2296651 polymorphism was determined in all individuals in all 3 groups using an in-house real-time PCR melting curve *** The HBV pre S1 NTCP-interacting domain showed a high degree of conservation among the examined viral genomes especially between aa 9 and 21(in the genotype D consensus sequence). As compared with the virion morphogenesis domain, the NTCPinteracting domain had a smaller proportion of HBV genotype-unrelated changes comprising > 1% of the quasispecies(25.5% vs 31.8%), but a larger proportion of genotype-associated viral polymorphisms(34% vs 27.3%), according to consensus sequences from Gen Bank patterns of HBV genotypes A to H. Variation/conservation in both domains depended on viral genotype, with genotype C being the most highly conserved and genotype E the most variable(limited finding, only 2 genotype E included). Of note, proline residues were highly conserved in both domains, and serine residues showed changes only to threonine or tyrosine in the virion morphogenesis domain. The rs2296651 polymorphism was not detected in any ***

关键词： Hepatitis B virus Hepatitis B virus preS1 region sodium-taurocholate co-transporting polypeptide NTCP-interacting domain virion morphogenesis domain SNP rs2296651 next-generation sequencing real-time PCR melting curves

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Targeted NGS analysis reveals a complex genetic background of idiopathic erythrocytosis in a large Venetian family

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Genes & Diseases 2024年第2期11卷 561-563页

作者： Bertozzi Irene Benetti Andrea Regazzo Daniela Polese francesca Biagetti Giacomo Ceolotto Giulio Randi maria Luigia First Medical Clinic University of Padua Department of Medicine – DIMEDVia Giustiniani 2Padova 35123Italy Transfusion Medicine Department Ospedale dell'Angelo - Venezia MestreVia Paccagnella 1Venice 30174Italy Emergency Medicine University of Padua Department of Medicine – DIMEDVia Giustiniani 2Padova 35123Italy

Absolute erythrocytosis,due to an increased production of red blood cells,becomes manifest with hemoglobin(Hb)levels above 165 or 160 g/L or with a hematocrit(HCT)above 51%and 48%in males and females,respectively.1 A minority of patients have polycythemia vera(PV);acquired secondary erythrocytosis frequently occurs due to appropriate or inappropriate erythropoietin(EPO)excess,while congenital secondary erythrocytosis may derive from genetic defects causing tissue *** erythrocytosis occurs in patients with genetic mutations of the oxygen-sensing pathway(VHL,PHD2,_HIF-1-alpha)or the erythropoietin receptor(EPOR)genes.2 Recently,HFE gene variants have been described in sporadic erythrocytoses.3 In a high proportion(about 70%)of patients with erythrocytosis,a specific etiology remains elusive despite extensive testing,and the diagnosis of idiopathic erythrocytosis(IE)is ruled out.

关键词： diagnosis patients congenital

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Detection of hyper-conserved regions in hepatitis B virus X gene potentially useful for gene therapy

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World Journal of Gastroenterology 2018年第19期24卷 2095-2107页

作者： Carolina González David Tabernero maria francesca cortese Josep Gregori Rosario Casillas Mar Riveiro-Barciela Cristina Godoy Sara Sopena Ariadna Rando Marcal Yll Rosa Lopez-Martinez Josep Quer Rafael Esteban maria Buti Francisco Rodríguez-Frías Liver Pathology Unit Departments of Biochemistry and MicrobiologyHospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Liver Unit Liver Disease Laboratory-Viral HepatitisVall d’Hebron Institut Recerca-Hospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas(CIBERehd) Instituto de Salud Carlos IIIMadrid 28029Spain Roche Diagnostics SL Sant Cugat del Vallès 08174Spain Liver Unit Department of Internal MedicineHospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain

AIM To detect hyper-conserved regions in the hepatitis B virus(HBV) X gene(HBX) 5' region that could be candidates for gene *** The study included 27 chronic hepatitis B treatmentnaive patients in various clinical stages(from chronic infection to cirrhosis and hepatocellular carcinoma, both HBeA g-negative and HBeA g-positive), and infected with HBV genotypes A-F and H. In a serum sample from each patient with viremia > 3.5 log IU/m L, the HBX 5' end region [nucleotide(nt) 1255-1611] was PCRamplified and submitted to next-generation sequencing(NGS). We assessed genotype variants by phylogenetic analysis, and evaluated conservation of this region by calculating the information content of each nucleotide position in a multiple alignment of all unique sequences(haplotypes) obtained by NGS. Conservation at the HBx protein amino acid(aa) level was also *** NGS yielded 1333069 sequences from the 27 samples, with a median of 4578 sequences/sample(2487-9279, IQR 2817). In 14/27 patients(51.8%), phylogenetic analysis of viral nucleotide haplotypes showed a complex mixture of genotypic variants. Analysis of the information content in the haplotype multiple alignments detected 2 hyper-conserved nucleotide regions, one in the HBX upstream non-coding region(nt 1255-1286) and the other in the 5' end coding region(nt 1519-1603). This last region coded for a conserved amino acid region(aa 63-76) that partially overlaps a Kunitz-like *** Two hyper-conserved regions detected in the HBX 5' end may be of value for targeted gene therapy, regardless of the patients' clinical stage or HBV genotype.

关键词： Hepatitis B virus Hepatitis B X gene Hepatitis B X protein Gene therapy Next-generation sequencing HBV conserved regions Small interference RNA

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Characterization of hepatitis B virus X gene quasispecies complexity in mono-infection and hepatitis delta virus superinfection

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World Journal of Gastroenterology 2019年第13期25卷 1566-1579页

作者： Cristina Godoy David Tabernero Sara Sopena Josep Gregori maria francesca cortese Carolina González Rosario Casillas Mar?al Yll Ariadna Rando Rosa López-Martínez Josep Quer Gloria González-Aseguinolaza Rafael Esteban Mar Riveiro-Barciela maria Buti Francisco Rodríguez-Frías Liver Pathology Unit Departments of Biochemistry and Microbiology Hospital Universitari Vall d’Hebron Universitat Autònoma de Barcelona Liver Unit Liver Disease Laboratory-Viral Hepatitis Vall d’Hebron Institut Recerca-Hospital Universitari Vall d'Hebron Universitat Autònoma de Barcelona Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd) Instituto de Salud Carlos Ⅲ Roche Diagnostics SL Centro de Investigación Médica Aplicada (CIMA) Universidad de Navarra Liver Unit Department of Internal MedicineHospital Universitari Vall d’Hebron Universitat Autònoma de Barcelona (UAB)

Hepatitis delta virus(HDV) seems to strongly suppress hepatitis B virus(HBV)replication, although little is known about the mechanism of this interaction. Both these viruses show a dynamic distribution of mutants, resulting in viral quasispecies. Next-generation sequencing is a viable approach for analyzing the composition of these mutant spectra. As the regulatory hepatitis B X protein(HBx) is essential for HBV replication, determination of HBV X gene(HBX)quasispecies complexity in HBV/HDV infection compared to HBV monoinfection may provide information on the interactions between these two *** To compare HBV quasispecies complexity in the HBX 5' region between chronic hepatitis delta(CHD) and chronic HBV mono-infected *** Twenty-four untreated patients were included: 7/24(29.2%) with HBeAgnegative chronic HBV infection(CI, previously termed inactive carriers), 8/24(33.3%) with HBeAg-negative chronic hepatitis B(CHB) and 9/24(37.5%) with CHD. A serum sample from each patient was first tested for HBV DNA *** HBX 5' region [nucleotides(nt) 1255-1611] was then PCR-amplified for subsequent next-generation sequencing(MiSeq, Illumina, United States). HBV quasispecies complexity in the region analyzed was evaluated using incidencebased indices(number of haplotypes and number of mutations), abundancebased indices(Hill numbers of order 1 and 2), and functional indices(mutation frequency and nucleotide diversity). We also evaluated the pattern of nucleotide changes to investigate which of them could be the cause of the quasispecies *** CHB patients showed higher median HBV-DNA levels [5.4 logIU/mL,interquartile range(IQR) 3.5-7.9] than CHD(3.4 logIU/mL, IQR 3-7.6)(P = n.s.)or CI(3.2 logIU/mL, IQR 2.3-3.5)(P < 0.01) patients. The incidence and abundance indices indicated that HBV quasispecies complexity was significantly greater in CI than CHB. A similar trend was observed in CHD patients, although only Hill numbers of order 2 showed

关键词： Hepatitis B virus Hepatitis delta virus Hepatitis B X gene Next-generation sequencing Viral quasispecies Hepatitis B virus-hepatitis delta virus interaction

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Conservation and variability of hepatitis B core at different chronic hepatitis stages

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World Journal of Gastroenterology 2020年第20期26卷 2584-2598页

作者： Marcal Yll maria francesca cortese Mercedes Guerrero-Murillo Gerard Orriols Josep Gregori Rosario Casillas Carolina González Sara Sopena Cristina Godoy Marta Vila David Tabernero Josep Quer Ariadna Rando Rosa Lopez-Martinez Rafael Esteban Mar Riveiro-Barciela maria Buti Francisco Rodríguez-Frías Liver Pathology Unit Departments of Biochemistry and MicrobiologyHospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Liver Unit Liver Disease Laboratory-Viral HepatitisVall d'Hebron Institut Recerca-Hospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Department of Microbiology Hospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas Instituto de Salud Carlos ⅢMadrid 28029Spain Liver Unit Department of Internal MedicineHospital Universitari Vall d'HebronUniversitat Autónoma de BarcelonaBarcelona 08035Spain

BACKGROUND Since it is currently not possible to eradicate hepatitis B virus(HBV)infection with existing treatments,research continues to uncover new therapeutic *** core protein,encoded by the HBV core gene(HBC),intervenes in both structural and functional processes,and is a key protein in the HBV life *** this reason,both the protein and the gene could be valuable targets for new therapeutic and diagnostic ***,alterations in the protein sequence could serve as potential markers of disease *** To detect,by next-generation sequencing,HBC hyper-conserved regions that could potentially be prognostic factors and targets for new *** Thirty-eight of 45 patients with chronic HBV initially selected were included and grouped according to liver disease stage[chronic hepatitis B infection without liver damage(CHB,n=16),liver cirrhosis(LC,n=5),and hepatocellular carcinoma(HCC,n=17)].HBV DNA was extracted from patients’plasma.A region between nucleotide(nt)1863 and 2483,which includes HBC,was amplified and analyzed by next-generation sequencing(Illumina Mi Seq platform).Sequences were genotyped by distance-based discriminant *** and intergroup nt and amino acid(aa)conservation was determined by sliding window *** presence of nt insertion and deletions and/or aa substitutions in the different groups was determined by aligning the sequences with genotype-specific consensus *** Three nt(nt 1900-1929,2249-2284,2364-2398)and 2 aa(aa 117-120,159-167)hyper-conserved regions were shared by all the clinical *** groups showed a similar pattern of conservation,except for five nt regions(nt 1946-1992,2060-2095,2145-2175,2230-2250,2270-2293)and one aa region(aa 140-160),where CHB and LC,respectively,were less conserved(P<0.05).Some group-specific conserved regions were also observed at both nt(2306-2334 in CHB and 1935-1976 and 2402-2435 in LC)and aa(between aa 98-103 in CHB and 28-30 and 5

关键词： Hepatitis B virus Hepatitis B core gene Next-generation sequencing Genetic conservation Amino acid substitution Gene therapy Small interfering RNA

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Cross-sectional evaluation of circulating hepatitis B virus RNA and DNA: Different quasispecies?

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World Journal of Gastroenterology 2021年第41期27卷 7144-7158页

作者： Selene Garcia-Garcia maria francesca cortese David Tabernero Josep Gregori Marta Vila Beatriz Pacín Josep Quer Rosario Casillas Laura Castillo-Ribelles Roser Ferrer-Costa Ariadna Rando-Segura Jesús Trejo-Zahínos Tomas Pumarola Ernesto Casis Rafael Esteban Mar Riveiro-Barciela maria Buti Francisco Rodríguez-Frías Clinical Biochemistry Research Group Department of BiochemistryVall d'Hebron Institut Recerca-Hospital Universitari Vall d'HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas Instituto de Salud Carlos IIIMadrid 28029Spain Liver Unit Liver Disease Laboratory-Viral HepatitisVall d'Hebron Institut Recerca-Hospital Universitari Vall d'HebronVall d’Hebron Barcelona Hospital CampusBarcelona 08035Spain Liver Pathology Unit Departments of Biochemistry and MicrobiologyHospital Universitari Vall d’HebronUniversitat Autònoma de BarcelonaBarcelona 08035Spain Department of Microbiology Hospital Universitari Vall d'HebronVall d'Hebron Barcelona Hospital CampusBarcelona 08035Spain Liver Unit Department of Internal MedicineHospital Universitari Vall d'HebronUniversitat Autónoma de BarcelonaBarcelona 08035Spain

BACKGROUND Different forms of pregenomic and other hepatitis B virus(HBV)RNA have been detected in patients’*** circulating HBV-RNAs may be useful for monitoring covalently closed circular DNA activity,and predicting hepatitis B eantigen seroconversion or viral rebound after nucleos(t)ide analog *** on serum HBV-RNA quasispecies,however,is *** is therefore important to develop methodologies to thoroughly analyze this quasispecies,ensuring the elimination of any residual *** circulating HBV-RNA quasispecies may facilitate achieving functional cure of HBV *** To establish a next-generation sequencing(NGS)methodology for analyzing serum HBV-RNA and comparing it with DNA *** Thirteen untreated chronic hepatitis B patients,showing different HBV-genotypes and degrees of severity of liver disease were enrolled in the study and a serum sample with HBV-DNA>5 Log10 IU/mL and HBV-RNA>4 Log10 copies/mL was taken from each ***-RNA was treated with DNAse I to remove any residual DNA,and the region between nucleotides(nt)1255-1611 was amplified using a 3-nested polymerase chain reaction protocol,and analyzed with ***/conservation and complexity was compared between HBV-DNA and RNA *** No HBV-DNA contamination was detected in cDNA samples from HBV-RNA *** quasispecies complexity showed heterogeneous behavior among *** Rare Haplotype Load at 1%was greater in DNA than in RNA quasispecies,with no statistically significant differences(P=0.1641).Regarding conservation,information content was equal in RNA and DNA quasispecies in most nt positions[218/357(61.06%)].In 102 of the remaining 139(73.38%),HBV-RNA showed slightly higher *** window analysis identified 4 hyper-conserved sequence fragments in each quasispecies,3 of them coincided between the 2 quasispecies:nts 1258-1286,1545-1573 and *** 2 hyper-variable sequence fragments also coincid

关键词： Hepatitis B virus RNA Hepatitis B X gene Quasispecies Next-generation sequencing Quasispecies conservation Quasispecies complexity

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Adherence to Pharmacotherapy in Post-Menopausal Women with Hypertension or Metabolic Syndrome: Real World Experience

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International Journal of Clinical Medicine 2024年第3期15卷 145-154页

作者： maria Maiello francesca Amati Vincenzo Ezio Santobuono Andrea Igoren Guaricci Cinzia Forleo Marco Matteo Ciccone Pasquale Palmiero Department of Cardiology ASL BR SSN3 Brindisi Italy Cardiovascular Diseases Section Interdisciplinary Department of Medicine (DIM) University of Bari “Aldo Moro” Bari Italy

Background: Adherence to medications is dependent upon a variety of factors, including individual characteristics of the patient, interactions with health care providers, and medication complexity. Even though several studies were conducted to test intervention strategies, results are uncertain. Aim: The aim of the study is to assess if a tailored combined intervention strategy improves medication adherence in a large population of post-menopausal women affected by hypertension or metabolic syndrome. Methods: We enrolled 6833 patients aged 50 to 69 years, 85.7% with hypertension, and 14.3% with metabolic syndrome. A network between patients, general practitioners, and cardiologists was established. Interventions included education, adequate information to patients, a simplified scheme of treatment, and periodic adherence assessment. These were either delivered as healthcare provider supports or using modern technology. Medication adherence was estimated by the proportion of days covered for all classes of drugs after the index date. Results: Non-adherent hypertensive women were 297 (5%), and those with metabolic syndrome were 73 (7.4%) (p Conclusions: The rate of non-adherence in both settings of postmenopausal women was 7.7%, much lower than that described in the literature. This rate was increased in patients with metabolic syndrome;probably it is related to the complexity of the therapeutic scheme or to a poor consciousness of the disease. Therefore, implementing a tailored combined intervention can improve significantly patients’ adherence to medical therapy.

关键词： Adherence Cardiovascular Prevention Postmenopausal Women Hypertensive Metabolic Syndrome

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Extravasated contrast volumetric assessment on computed tomography angiography in gastrointestinal bleeding:A useful predictor of positive angiographic findings

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World Journal of Radiology 2024年第5期16卷 115-127页

作者： Laura maria Cacioppa Chiara Floridi Alessandra Bruno NicolòRossini Tommaso Valeri Alessandra Borgheresi Riccardo Inchingolo Francesco cortese Giacomo Novelli Alessandro Felicioli Mario Torresi Pietro Boscarato Letizia Ottaviani Andrea Giovagnoni Division of Interventional Radiology Department of Radiological SciencesUniversity Politecnica Delle MarcheAncona 60126Italy Department of Clinical Special and Dental SciencesUniversity Politecnica Delle MarcheAncona 60126Italy Division of Radiology Department of Radiological SciencesUniversity Hospital"Azienda Ospedaliero Universitaria Delle Marche"Ancona 60126Italy Interventional Radiology Unit "F Miulli"Regional General HospitalAcquaviva delle Fonti 70021Italy Department of Radiology IRCCS INRCAAncona 60126Italy

BACKGROUND Gastrointestinal bleeding(GIB)is a severe and potentially life-threatening condition,especially in cases of delayed *** tomography angiography(CTA)plays a pivotal role in the early identification of upper and lower GIB and in the prompt treatment of the *** To determine whether a volumetric estimation of the extravasated contrast at CTA in GIB may be a predictor of subsequent positive angiographic *** In this retrospective single-centre study,35 patients(22 men;median age 69 years;range 16-92 years)admitted to our institution for active GIB detected at CTA and further submitted to catheter angiography between January 2018 and February 2022 were ***-three(65.7%)patients underwent endoscopy before *** volumetry was evaluated in both arterial and venous phases via a semi-automated dedicated *** rate was obtained from volume change between the two phases and standardised for unit *** were divided into two groups,according to the angiographic signs and their concordance with *** Upper bleeding accounted for 42.9%and lower GIB for 57.1%.Mean haemoglobin value at the admission was 7.7 g/dL.A concordance between positive CTA and direct angiographic bleeding signs was found in 19(54.3%)*** no significant differences in terms of bleeding volume in the arterial phase(0.55 mL vs 0.33 mL,P=0.35),a statistically significant volume increase in the venous phase was identified in the group of patients with positive angiography(2.06 mL vs 0.9 mL,P=0.02).In the latter patient group,a significant increase in bleeding rate was also detected(2.18 mL/min vs 0.19 mL/min,P=0.02).CONCLUSION In GIB of any origin,extravasated contrast volumetric analysis at CTA could be a predictor of positive angiography and may help in avoiding further unnecessary procedures.

关键词： Gastrointestinal haemorrhage Computed tomography angiography Volumetric analysis Computer-assisted image interpretation Therapeutic embolization Transcatheter arterial embolization

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This pain drives me crazy:Psychiatric symptoms in women with interstitial cystitis/bladder pain syndrome

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World Journal of Psychiatry 2024年第6期14卷 954-984页

作者： marianna Mazza Stella Margoni Giuseppe Mandracchia Guglielmo Donofrio Alessia Fischetti Georgios D Kotzalidis Giuseppe Marano Alessio Simonetti Delfina Janiri Lorenzo Moccia Ilaria Marcelli Greta Sfratta Domenico De Berardis Ottavia Ferrara Evelina Bernardi Antonio Restaino Francesco maria Lisci Antonio maria D'Onofrio Caterina Brisi Flavia Grisoni Claudia Calderoni Michele Ciliberto Andrea Brugnami Sara Rossi maria Chiara Spera Valeria De Masi Ester maria Marzo francesca Abate Gianluca Boggio maria Benedetta Anesini Cecilia Falsini Anna Quintano Alberto Torresi Miriam Militenda Giovanni Bartolucci Marco Biscosi Sara Ruggiero Luca Lo Giudice Giulia Mastroeni Elisabetta Benini Luca Di Benedetto Romina Caso Francesco Pesaresi Francesco Traccis Luca Onori Luca Chisari Leonardo Monacelli mariateresa Acanfora Eleonora Gaetani Monia Marturano Sara Barbonetti Elettra Specogna francesca Bardi Emanuela De Chiara Gianmarco Stella Andrea Zanzarri Flavio Tavoletta Arianna Crupi Giulia Battisti Laura Monti Giovanni Camardese Daniela Chieffo Antonio Gasbarrini Giovanni Scambia Gabriele Sani Department of Neurosciences Fondazione Policlinico Universitario A Gemelli IRCCSUniversita Cattolica del Sacro CuoreRome 00168Italy Department of Psychiatry UniversitàCattolica del Sacro CuoreRome 00168Italy Department of Neurosciences Section of PsychiatryFondazione Policlinico Universitario Agostino Gemelli IRCCSUniversitàCattolica del Sacro CuoreRome 00168Italy Mental Health NHSASL 4 TeramoTeramo 64100Italy Medical and Surgical Sciences UniversitàCattolica del Sacro CuoreRome 00168Italy Division of Gynecologic Oncology UniversitàCattolica del Sacro CuoreRome 00168Italy UOS Psicologia Clinica Governo ClinicoFondazione Policlinico Universitario Agostino Gemelli IRCCSRome 00168Italy CEMAD Digestive Disease Center Fondazione Policlinico Universitario A.Gemelli-IRCCSRome 00168Italy Department of Woman and Child Health Catholic UniversityRome 00168Italy UOC Psichiatria Clinica e d’Urgenza Dipartimento di Scienze Dell’InvecchiamentoNeurologicheOrtopediche e Della Testa-colloFondazione Policlinico Universitario Agostino Gemelli IRCCSRome 00168Italy

BACKGROUND Interstitial cystitis/bladder pain syndrome(IC/BPS)is an at least 6-mo noninfectious bladder inflammation of unknown origin characterized by chronic suprapubic,abdominal,and/or pelvic *** the term cystitis suggests an inflammatory or infectious origin,no definite cause has been *** occurs in both sexes,but women are twice as much *** To systematically review evidence of psychiatric/psychological changes in persons with IC/*** Hypothesizing that particular psychological characteristics could underpin IC/BPS,we investigated in three databases the presence of psychiatric symptoms and/or disorders and/or psychological characteristics in patients with IC/BPS using the following strategy:("interstitial cystitis"OR"bladder pain syndrome")AND("mood disorder"OR depressive OR antidepressant OR depression OR depressed OR hyperthymic OR mania OR manic OR rapid cyclasterisk OR dysthymiasterisk OR dysphoriasterisk).RESULTS On September 27,2023,the PubMed search produced 223 articles,CINAHL 62,and the combined PsycLIT/PsycARTICLES/PsycINFO/Psychology and Behavioral Sciences Collection search *** on *** produced 14 studies,of which none had available *** were peer-reviewed articles reporting psychiatric/psychological symptoms in patients with IC/BPS,i.e.63 articles spanning from 2000 to October *** studies identified depression and anxiety problems in the IC/BPS population,along with sleep problems and the tendency to *** Psychotherapies targeting catastrophizing and life stress emotional awareness and expression reduced perceived pain in women with IC/*** concepts should be considered when implementing treatments aimed at reducing IC/BPS-related pain.

关键词： Interstitial cystitis/bladder pain syndrome Psychiatric symptoms Psychological symptoms Catastrophizing Anxiety Depression

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Aberrant Notch signaling in gliomas: a potential landscape of actionable converging targets for combination approach in therapies resistance

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Cancer Drug Resistance 2022年第4期5卷 939-953页

作者： maria D’Amico francesca De Amicis Department of Pharmacy Health and Nutritional SciencesUniversity of CalabriaVia P.BucciRende 87036Italy Health Center University of CalabriaVia P.BucciRende 87036Italy.

The current therapeutic protocols and prognosis of gliomas still depend on clinicopathologic and radiographiccharacteristics. For high-grade gliomas, the standard of care is resection followed by radiotherapy plustemozolomide chemotherapy. However, treatment resistance develops due to different mechanisms, among whichis the dynamic interplay between the tumor and its microenvironment. Different signaling pathways cause theproliferation of so-called glioma stem cells, a minor cancer cell population with stem cell-like characteristics andaggressive phenotype. In the last decades, numerous studies have indicated that Notch is a crucial pathway thatmaintains the characteristics of resistant glioma stem cells. Data obtained from preclinical models indicate thatdownregulation of the Notch pathway could induce multifaceted drug sensitivity, acting on the expression of drugtransporterproteins, inducing epithelial–mesenchymal transition, and shaping the tumor microenvironment. Thisreview provides a brief overview of the published data supporting the roles of Notch in drug resistance anddemonstrates how potential novel strategies targeting Notch could become an efficacious action to improve thetherapy of high-grade glioma to overcome drug resistance.

关键词： Tumor microenvironment notch inhibitors stem cells brain tumors drug resistance

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