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Classification of patients with metastatic colorectal cancer into consensus molecular subtypes into real-world: A pilot study

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World Journal of Clinical Oncology 2023年第10期14卷 409-419页

作者： Jaime González-Montero Mauricio Burotto Guillermo Valenzuela Debora Mateluna Florencia Buen-Abad Jessica Toro olga barajas Katherine Marcelain Bradford Hill Clinical Research Center Santiago 8420383Chile Basic and Clinical Oncology Department University of ChileSantiago 8380453Chile

BACKGROUND Colorectal cancer is a complex disease with high mortality rates.Over time,the treatment of metastatic colorectal cancer(mCRC)has gradually improved due to the development of modern chemotherapy and targeted therapy regimens.However,due to the inherent heterogeneity of this condition,identifying reliable predictive biomarkers for targeted therapies remains challenging.A recent promising classification system—the consensus molecular subtype(CMS)system—offers the potential to categorize mCRC patients based on their unique biological and molecular characteristics.Four distinct CMS categories have been defined:immune(CMS1),canonical(CMS2),metabolic(CMS3),and mesenchymal(CMS4).Nevertheless,there is currently no standardized protocol for accurately classifying patients into CMS categories.To address this challenge,reverse transcription polymerase chain reaction(RT-qPCR)and next-generation genomic sequencing(NGS)techniques may hold promise for precisely classifying mCRC patients into their CMSs.AIM To investigate if mCRC patients can be classified into CMS categories using a standardized molecular biology workflow.METHODS This observational study was conducted at the University of Chile Clinical Hospital and included patients with unresectable mCRC who were undergoing systemic treatment with chemotherapy and/or targeted therapy.Molecular biology techniques were employed to analyse primary tumour samples from these patients.RT-qPCR was utilized to assess the expression of genes associated with fibrosis(TGF-βandβ-catenin)and cell growth pathways(c-MYC).NGS using a 25-gene panel(TumorSec)was performed to identify specific genomic mutations.The patients were then classified into one of the four CMS categories according to the clinical consensus of a Tumour Board.Informed consent was obtained from all the patients prior to their participation in this study.All techniques were conducted at University of Chile.RESULTS Twenty-six patients were studied with the techniques and then evaluated by the Tumour Board to dete

关键词： Metastatic colorectal cancer Targeted therapy Consensus molecular subtypes Personalized medicine

K^(+) channel-mediated retarded maturation of interneurons and its role in neurodevelopmental disorders

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Neural Regeneration Research 2024年第7期19卷 1403-1404页

作者： Kaizhen Li Daria Savitska olga Garaschuk Laboratory of Systems Neuroscience Department of PhysiologyUniversity of BernBernSwitzerland Institute of Physiology Department of NeurophysiologyEberhard Karls University of TübingenTübingenGermany

De novo mutations in genes encoding K^(+)channels are implicated in many severe neurodevelopmental disorders.Specifically,mutations in KCNA2,encoding the Shaker-type voltage-gated K^(+)channel Kv1.2,and KCNJ2,encoding the inwardly rectifying K^(+)channel Kir2.1,associate with focal and generalized epilepsies,brain atrophy,autism,ataxia and hereditary spastic paraplegia(Syrbe et al.,2015;Masnada et al.,2017;Cheng et al.,2021).

关键词： disorders atrophy

Averaged Dynamics of Fluids near the Oscillating Interface in a Hele-Shaw Cell

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Fluid Dynamics & Materials Processing 2024年第4期20卷 847-857页

作者： Anastasia Bushueva olga Vlasova Denis Polezhaev Laboratory of Vibrational Hydromechanics Perm State Humanitarian Pedagogical UniversityPerm614990Russia

The steady flow in a Hele-Shaw cell filled with fluids with a high viscosity contrast in the presence of fluid oscillations is experimentally studied.The control of oscillatory dynamics of multiphase systems with interfaces is a challenging technological problem.We consider miscible(water and glycerol)and immiscible(water and high-viscosity silicone oil PMS-1000)fluids under subsonic oscillations perpendicular to the interface.Observations show that the interface shape depends on the amplitude and frequency of oscillations.The interface is undisturbed only in the absence of oscillations.Under small amplitudes,the interface between water and glycerol widens due to mixing.When the critical amplitude is reached,the interface becomes unstable to the fingering instability:Aqueous fingers penetrate the high-viscosity glycerol and induce intensive mixing of miscible fluids and associated decay of the instability.After the disappearance of the fingers,the interface takes a U-shape in the central part of the cell.A similar effect is observed for immiscible fluids:The oscillating interface tends to bend to the side of a high-viscosity fluid.Again,when the critical amplitude is reached,the fingering instability arises at the convex interface.This paper focuses on the causes of bending of the initially undisturbed interface between miscible or immiscible fluids.For this purpose,we measure the steady flow velocity near the interface and in the bulk of a high-viscosity fluid using Particle Image Velocimetry(PIV).

关键词： Hele-Shaw cell oscillations steady flow miscible fluids immiscible fluids interface

Detection and evaluation of different morphological forms of Mycoplasma hominis in human semen

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Asian Journal of Andrology 2024年第1期26卷 71-76页

作者： Elizaveta Bragina Tatyana Sorokina Avtandil Chogovadze Yulia Shevchenko Vyacheslav Chernykh olga Barkhatova Irina Rakovskaya Research Centre for Medical Genetics Moscow 115522Russia A.N.Belozersky Institute of Physico-Chemical Biology Lomonosov Moscow State University Moscow 119992Russia Reprolab Limited Liability Company Moscow 119333Russia N.I.Pirogov Russian National Research Medical University Moscow 117997Russia Federal Government Budgetary Institution"National Research Center for Epidemiology and Microbiology Named after Honorary Academician N.F.Gamaleya of the Ministry of Health of the Russian Federation" Moscow 123098Russia

Recently discovered microcolonial forms of Mycoplasma hominis(M.hominis)and their impact on human spermatogenesis are studied.The spermatozoa of 125 fertile men(sperm donors;from Reprobank[Reproductive Tissue Bank,Moscow,Russial)and of 93 patients with fertility problems(from the Federal State Budgetary Institution"Research Centre for Medical Genetics[RCMG]",Moscow,Russia)were used.Classical colonies of M.hominis and microcolonies were detected by molecular biological methods,culture of bacteria,and transmission electron microscopy.The unique structure of microcolonial cells,in which the cytoplasmic cylinder is surrounded by concentric electron-dense and electron-light layers with a periodicity of 12-14 nm,and the ability of microcolonial cells to attach to spermatozoa are shown.In patients with lower sperm quality,microcolonies of M.hominis were detected 2.5 times more frequently than classical colonies.The detection of microcolonies in the ejaculate and the frequent isolation of microcolonies from sperm samples of patients with fertility problems suggest that microcolonial cells may be one cause of infertility.

关键词： ejaculate fertility Mycoplasma hominis spermatogenesis transmission electron microscopy

Airway management of a patient with linear immunoglobulin A bullous dermatosis:A case report

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World Journal of Clinical Cases 2024年第13期12卷 2263-2268页

作者： olga C Nin Robert Hutnik Neil N Chheda David Hutchinson Department of Anesthesiology University of Florida College of MedicineGainesvilleFL 32610United States Department of Otolaryngology University of Florida College of MedicineGainesvilleFL 32610United States

BACKGROUND There is limited literature on managing the airway of patients with linear immunoglobulin A(IgA)bullous dermatosis,a rare mucocutaneous disorder that leads to the development of friable bullae.Careful clinical decision making is necessary when there is a risk of bleeding into the airway,and a multidisciplinary team approach may lead to decreased patient morbidity during these high-risk scenarios,especially when confronted with an unusual cause for bleeding.CASE SUMMARY A 45-year-old African American female presented to our ambulatory surgical center for right corneal transplantation due to corneal perforation after blunt trauma in the setting of cicatricial conjunctivitis and diffuse corneal neovascularization from linear IgA bullous dermatosis.The diagnosis of IgA dermatosis was recent,and the patient had been lost to follow-up.The severity of the disease and extent of airway involvement was unknown at the time of the surgery.Significant airway bleeding was noticed upon intubation and the otorhinolaryngology team had to be called to the operating room.The patient required transfer to the intensive care unit where a multidisciplinary team was involved in her case.The patient was extubated on postoperative day 4.CONCLUSION A multidisciplinary approach to treating this disease is the best course of action before a surgical procedure.In our case,key communication between the surgery,anesthesia,and dermatology teams led to the quick and safe treatment of our patient’s disease.Ambulatory surgery should not be considered for these cases unless they are in full remission and there is no mucous membrane involvement.

关键词： Airway management Bleeding risk Linear immunoglobulin A bullous dermatosis Multidisciplinary approach Outpatient procedure Case report

Hypoxia in the pulmonary vein increases pulmonary vascular resistance independently of oxygen in the pulmonary artery

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Animal Models and Experimental Medicine 2024年第2期7卷 156-165页

作者： Sigridur olga Magnusdottir Carsten Simonsen Dan Stieper Karbing Bodil Steen Rasmussen Benedict Kjaergaard Biomedical Research Laboratory Aalborg University HospitalAalborgDenmark Department of Clinical Medicine Aalborg UniversityAalborgDenmark Department of Cardiothoracic Surgery Aalborg University HospitalAalborgDenmark Department of Health Science and Technology Aalborg UniversityAalborgDenmark Department of Anesthesia and Intensive Care Aalborg University HospitalAalborgDenmark

Introduction:Hypoxic pulmonary vasoconstriction(HPV)can be a challenging clinical problem.It is not fully elucidated where in the circulation the regulation of resistance takes place.It is often referred to as if it is in the arteries,but we hypothesized that it is in the venous side of the pulmonary circulation.Methods:In an open thorax model,pigs were treated with a veno-venous extra corporeal membrane oxygenator to either oxygenate or deoxygenate blood passing through the pulmonary vessels.At the same time the lungs were ventilated with extreme variations of inspired air from 5%to 100%oxygen,making it possible to make combinations of high and low oxygen content through the pulmonary circulation.A flow probe was inserted around the main pulmonary artery and catheters in the pulmonary artery and in the left atrium were used for pressure monitoring and blood tests.Under different combinations of oxygenation,pulmonary vascular resistance(PVR)was calculated.Results:With unchanged level of oxygen in the pulmonary artery and reduced inspired oxygen fraction lowering oxygen tension from 29 to 6.7 kPa in the pulmonary vein,PVR was doubled.With more extreme hypoxia PVR suddenly decreased.Combinations with low oxygenation in the pulmonary artery did not systematic influence PVR if there was enough oxygen in the inspired air and in the pulmonary veins.Discussion:The impact of hypoxia occurs from the alveolar level and forward with the blood flow.The experiments indicated that the regulation of PVR is mediated from the venous side.

关键词： animal models cardiopulmonary support Hypoxic pulmonary vasoconstriction pulmonary circulation

Large-scale genome-wide SNP analysis reveals the rugged(and ragged)landscape of global ancestry,phylogeny,and demographic history in chicken breeds

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第4期25卷 324-340页

作者： Natalia V.DEMENTIEVA Yuri S.SHCHERBAKOV olga I.STANISHEVSKAYA Anatoly B.VAKHRAMEEV Tatiana A.LARKINA Artem P.DYSIN olga A.NIKOLAEVA Anna E.RYABOVA Anastasiia I.AZOVTSEVA olga V.MITROFANOVA Grigoriy K.PEGLIVANYAN Natalia R.REINBACH Darren K.GRIFFIN Michael N.ROMANOV Russian Research Institute of Farm Animal Genetics and Breeding-Branch of the L.K.Ernst Federal Research Centre for Animal Husbandry.Pushkin St.Petersburg196601Russia School of Biosciences University of KentCanterburyCT27NJUK L.K.Ernst Federal Research Center for Animal Husbandry DubrovitsyPodolskMoscow Oblast142132Russia

The worldwide chicken gene pool encompasses a remarkable,but shrinking,number of divergently selected breeds of diverse origin.This study was a large-scale genome-wide analysis of the landscape of the complex molecular architecture,genetic variability,and detailed structure among 49 populations.These populations represent a significant sample of the world's chicken breeds from Europe(Russia,Czech Republic,France,Spain,UK,etc.),Asia(China),North America(USA),and Oceania(Australia).Based on the results of breed genotyping using the Illumina 60K single nucleotide polymorphism(SNP)chip,a bioinformatic analysis was carried out.This included the calculation of heterozygosity/homozygosity statistics,inbreeding coefficients,and effective population size.It also included assessment of linkage disequilibrium and construction of phylogenetic trees.Using multidimensional scaling,principal component analysis,and ADMIXTURE-assisted global ancestry analysis,we explored the genetic structure of populations and subpopulations in each breed.An overall 49-population phylogeny analysis was also performed,and a refined evolutionary model of chicken breed formation was proposed,which included egg,meat,dual-purpose types,and ambiguous breeds.Such a large-scale survey of genetic resources in poultry farming using modern genomic methods is of great interest both from the viewpoint of a general understanding of the genetics of the domestic chicken and for the further development of genomic technologies and approaches in poultry breeding.In general,whole genome SNP genotyping of promising chicken breeds from the worldwide gene pool will promote the further development of modern genomic science as applied to poultry.

关键词： Chicken genome diversity Single nucleotide polymorphism(SNP)analysis Gene pool Global ancestry Phylogeny Demographic history

Fine-needle aspiration technique under endoscopic ultrasound guidance:A technical approach for RNA profiling of pancreatic neoplasms

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2663-2672页

作者： Sabina Sherafedinovna Seyfedinova olga Aleksandrovna Freylikhman Polina Sergeevna Sokolnikova Konstantin Aleksandrovich Samochernykh Anna Aleksandrovna Kostareva olga Viktorovna Kalinina Evgeniy Gennadievich Solonitsyn Research Laboratory of Digestive Cancer Almazov Medical Research CentreSaint-Petersburg 197341Russia Research Laboratory of Molecular and Cellular Modeling and Gene Therapy Almazov Medical Research CentreSaint-Petersburg 197341Russia Head of Russian Neurosurgical Institute Named after Prof.A.L.Polenova Russian Neurosurgical Institute Named after Prof.A.L.PolenovaSaint-Petersburg 191014Russia Head of Institute of Molecular Biology and Genetics Almazov National Medical Research CentreSaint-Petersburg 197341Russia Research Laboratory of Autoimmune and Autoinflammatory Diseases Almazov National Medical Research CentreSaint-Petersburg 197341Russia

BACKGROUND Early diagnosis of pancreatic ductal adenocarcinoma(PDAC)has been a longstanding challenge.The prognosis of patients with PDAC depends on the stage at diagnosis.It is necessary to identify biomarkers for the detection and differentiation of pancreatic tumors and optimize PDAC sample preparation procedures for DNA and RNA analysis.Most molecular studies are done using paraffin-embedded blocks;however,the integrity of DNA and RNA is often compromised in this format.Moreover,RNA isolated from human pancreatic tissue samples is generally of low quality,in part,because of the high concentration of endogenous pancreatic RNAse activity present.AIM To assess the potential of endoscopic ultrasound-guided fine-needle aspiration(EUS-FNA)to obtain specimens from pancreatic neoplasms for subsequent RNA molecular profiling,including next-generation sequencing(NGS).METHODS Thirty-four EUS-FNA samples were included in this study:PDAC(n=15),chronic pancreatitis(n=5),pancreatic cysts(n=14),mucinous cysts(mucinous cystic neoplasia/intraductal papillary mucinous neoplasia)n=7,serous cystic neoplasms n=5,and pseudocysts n=2.Cyst material consisted of cyst fluid and cyst wall samples obtained by through-the-needle biopsy(TTNB).Samples were stored at -80℃ until analysis.RNA purity(A260/230,A260/280 ratios),concentration,and integrity(RIN)were assessed.Real-time polymerase chain reaction was conducted on all samples,and small RNA libraries were prepared from solid mass samples.RESULTS RNA was successfully extracted from 29/34(85%)EUS-FNA samples:100% pancreatic adenocarcinoma samples,100% chronic pancreatitis samples,70% pancreatic fluid cyst samples,and 50%TTNB samples.The relative expression of GAPDH and HPRT were obtained for all successfully extracted RNA samples(n=29)including lowquality RNA specimens.Low concentration and nonoptimal RIN values(no less than 3)of RNA extracted from EUS-FNA samples did not prevent NGS library preparation.The suitability of cyst fluid samples for RNA profiling varied.The quality of RNA extr

关键词： Endoscopic ultrasound-guided,fine-needle aspiration Pancreatic cancer Pancreatic cysts RNA extraction Through-the-needle biopsy Next-generation sequencing

Environmental Impact Assessment of Onshore Wind Farms in the Region of Central Greece Using a Modified RIAM Method

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Journal of Environmental & Earth Sciences 2024年第1期6卷 71-82页

作者： olga Korozi Dimitra G.Vagiona Department of Spatial Planning and Development Aristotle University of ThessalonikiThessaloniki 54124Greece

Wind energy is one of the most basic forms of renewable energy,which shows an increasing rate of development worldwide and also at the European level.However,this rapid deployment of wind farms makes the need for an impact assessment of this type of projects on the natural and man-made environment imperative.The present paper aims to identify and assess the environmental impacts of wind farm projects in the Region of Central Greece.A modified Rapid Impact Assessment Matrix(RIAM)method is used for this purpose.The methodology includes the identification of the existing onshore wind farm projects in the study area,the appropriate modifications of the RIAM method to respond to the characteristics of the projects and the study area,the qualitative assessment of their potential impacts during construction and operational phases and the computation of the Environmental Performance Grade(EPG)of projects based on the pro-posed modified RIAM method.The results reveal that although there are some slight negative impacts on the natural environment of the study area,the examined wind farms contribute positively both to the atmosphere and to the socio-economic environment of the study.This study extends the potential for using RIAM as a tool in environmental impact assessment studies of renewable energy projects.

关键词： Environmental impact assessment Environmental components Region of central Greece Rapid impact assessment matrix(RIAM) Environmental performance grade(EPG)