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The combination of chidamide with the CHoEP regimen in previously untreated patients with peripheral T-cell lymphoma: a prospective, multicenter, single arm, phase 1b/2 study

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Cancer Biology & Medicine 2021年第3期18卷 841-848页

作者： Wei Zhang Liping Su Lihong Liu Yuhuan Gao Quanshun Wang Hang Su Yuhuan Song Huilai Zhang Jing Shen Hongmei Jing Shuye Wang Xinan Cen Hui Liu Aichun Liu Zengjun Li Jianmin Luo Jianxia He Jingwen Wang o.a.o’connor Daobin Zhou Department of Hematology Peking Union Medical College HospitalBeijing 100730China Department of Hematology Shanxi Provincial Cancer HospitalTaiyuan 030013China Department of Hematology Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011China Department of Hematology Chinese PLA General HospitalBeijing 100039China Department of Lymphoma the 307 Hospital of PLABeijing 100071China Department of Lymphoma Peking University Cancer Hospital and InstituteBeijing 100142China Department of Lymphoma Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China Department of Hematology Beijing Friendship HospitalBeijing 100050China Department of Hematology Peking University Third HospitalBeijing 100191China Department of Hematology the First Affiliated Hospital of Harbin Medical UniversityHarbin 150081China Department of Hematology Peking University First HospitalBeijing 100034China Department of Hematology Beijing HospitalBeijing 100730China Department of Lymphoma Harbin Medical University Cancer HospitalHarbin 150081China Lymphoma Diagnosis and Treatment Center Institute of Hematology and Blood Diseases HospitalTianjin 300052China Department of Hematology Second Hospital of Hebei Medical UniversityShijiazhuang 050000China Department of Hematology Shanxi Provincial People’s HospitalTaiyuan 030012China Department of Hematology Beijing Tongren HospitalBeijing 100730China Columbia University Medical Center New York 10032-3784NYUSA

objective:To assess the efficacy and safety of the novel histone deacetylase inhibitor,chidamide,in combination with cyclophosphamide,doxorubicin,vincristine,etoposide,and prednisone(Chi-CHoEP)for untreated peripheral T-cell lymphoma(PTCL).Methods:A prospective,multicenter,single arm,phase 1 b/2 study was conducted.A total of 128 patients with untreated PTCL(18–70 years of age)were enrolled between March 2016 and November 2019,and treated with up to 6 cycles with the Chi-CHoEP *** the phase 1 b study,3 dose levels of chidamide were evaluated and the primary endpoint was determination of the maximumtolerated dose and recommended phase 2 dose(RP2 D).The primary endpoint of the phase 2 study was 2-year progression-free survival(PFS).Results:Fifteen patients were enrolled in the phase 1 b study and the RP2 D for chidamide was determined to be 20 mg,twice a week.A total of 113 patients were treated at the RP2 D in the phase 2 study,and the overall response rate was 60.2%,with a complete response rate of 40.7%.At a median follow-up of 36 months,the median PFS was 10.7 months,with 1-,2-,and 3-year PFS rates of 49.9%,38.0%,and 32.8%,*** Chi-CHoEP regimen was well-tolerated,with grade 3/4 neutropenia occurring in approximately two-thirds of the *** unexpected adverse events(AEs)were reported and the observed AEs were ***:This large cohort phase 1 b/2 study showed that Chi-CHoEP was well-tolerated with modest efficacy in previously untreated PTCL patients.

关键词： Peripheral T-cell lymphoma chidamide histone deacetylase inhibitor epigenetic

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Public perspectives on AI diagnosis of mental illness

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General Psychiatry 2024年第3期37卷 348-351页

作者： Cliodhna o'connor University College Dublin DublinIreland

To the editor:Psychiatric theory,policy and practice are currently grappling with the risks and opportunities presented by artificial intelligence(AI)applications in mental *** data to generate diagnosis is an aspect of mental healthcare where AI is anticipated to have the greatest and soonest impact.1-4 While such technologies remain some distance from clinical application,preliminary evidence suggests AI-derived classifications may predict certain treatment outcomes and clinical trajectories,and could soon become available to supplement or replace traditional manual-based diagnostic assessment.

关键词： diagnosis replace editor

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Blood biomarkers of Alzheimer’s disease:important considerations for use in clinical practice

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Neural Regeneration Research 2025年第1期20卷 205-206页

作者： Sarah Fullam Sean o’Dowd Antoinette o’connor Department of Neurology Tallaght University HospitalDublinIreland Academic Unit of Neurology Trinity College DublinIreland

Introduction:Fluid and positron emission tomography(PET)biomarkers that enable the detection of the hallmark proteins of Alzheimer’s disease(AD)(amyloid and tau)have revolutionized our approach to the diagnosis of *** evolution of AD diagnostic criteria to include biological characterization(Alzheimer’s Association Working Group,2023)provides an appropriate framework to reduce levels of clinico-pathologic mismatch and improve in-vivo diagnostic *** the therapeutic landscape for neurodegenerative disease evolves,it is increasingly incumbent on clinicians to provide timely,and pathologically precise diagnoses for ***,the expensive and invasive nature of these tests limits their scalability.

关键词： Blood Alzheimer diagnosis

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Steroidal scaffold decorations in Solanum alkaloid biosynthesis

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Molecular Plant 2024年第8期17卷 1236-1254页

作者： Rosalind Lucier Mohamed o.Kamileen Yoko Nakamura Sofiia Serediuk Ranjit Barbole Jens Wurlitzer Maritta Kunert Sarah Heinicke Sarah E.o'connor Prashant D.Sonawane Department of Natural Product Biosynthesis Max Planck Institute for Chemical Ecology07745 JenaGermany Research Group Biosynthesis and NMR Max Planck Institute for Chemical Ecology07745 JenaGermany Biochemical Sciences Division CSIR-National Chemical LaboratoryPune 411008MaharashtraIndia

Steroidal glycoalkaloids(SGAs)are specialized metabolites produced by hundreds of Solanum species,including important vegetable crops such as to.a.o,po.a.o,and *** it has been known that SGAs play important roles in defense in plants and“anti-nutritional"effects(e.g.,toxicity and bitterness)to humans,many of these molecules have documented anti-cancer,anti-microbial,antiinflammatory,anti-viral,and anti-pyretic *** these,α-so.a.onine andα-solamargine isolated from black nightshade(Solanum nigrum)are reported to have potent anti-tumor,anti-proliferative,and anti-inflammatory ***,α-so.a.onine andα-solamargine,along with the core steroidal aglycone so.a.odine,are the most widespread SGAs produced among the Solanum ***,it is still unknown how plants synthesize these bioactive steroidal *** comparative metabolomictranscriptome-guided approach,biosynthetic logic,combinatorial expression in Nicotiana benthamiana,and functional recombinant enzyme assays,here we report the discovery of 12 enzymes from *** that converts the starting cholesterol precursorto so.a.odine aglycone,and the downstreamα-so.a.onine,α-solamargine,and malonyl-solamargine SGA *** further identified six enzymes from cultivated eggplant that catalyze the production ofα-so.a.onine,α-solamargine,and malonyl-solamargine SGAs from so.a.odine aglycone via glycosylation and atypical malonylation *** work provides the gene tool box and platform for engineering the production of high-value,steroidal bioactive molecules inheterologoushosts usingsyntheticbiology.

关键词： steroidal glycoalkaloids Solanum biosynthetic pathway α-solamargine malonyl-solamargine specialized metabolites

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晚白垩世真兽类Zalamdalestes揭示哺乳动物独特的枢椎及其复杂的进化过程

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Science Bulletin 2024年第11期69卷 1767-1775页

作者： Patrick Arnold Katarzyna Janiszewska 李茜 Jingmai K.o'connor Lucja Fostowicz-Frelik Institute of Biochemistry and Biology University of PotsdamPotsdam D-14476Germany Environmental Paleobiology Department Institute of PaleobiologyPolish Academy of SciencesWarsaw 00-818Poland Key Labo.a.ory of Evolutionary Systematics of Vertebrates Institute of Vertebrate Paleontology and PaleoanthropologyChinese Academy of SciencesBeijing 100044China The Field Museum of Natural History Chicago IL 60605USA Department of organismal Biology and Anatomy The University of ChicagoChicago IL 60637USA Evolutionary Paleobiology Department Institute of PaleobiologyPolish Academy of SciencesWarsaw 00-818Poland

The typical mammalian neck consisting of seven cervical vertebrae(C1–C7)was established by the Late Permian in the cynodont forerunners of modern *** structure is precisely adapted to facilitate movements of the head during feeding,locomotion,predator evasion,and social ***,the clade including crown placentals,has a fossil record extending back more than 125 million years revealing significant morphological diversification in the *** very little is known concerning the early evolution of eutherian cervical morphology and its functional adaptations.A specimen of Zalambdalestes lechei from the Late Cretaceous of Mongolia boasts exceptional preservation of an almost complete series of cervical vertebrae(C2–C7)revealing a highly modified axis(C2).The significance of this cervical morphology is explored utilizing an integrated approach combining comparative anatomical examination across mammals,muscle reconstruction,geometric morphometrics and virtual range of motion *** compared the shape of the axis in Zalambdalestes to a dataset of 88 mammalian species(monotremes,marsupials,and placentals)using three-dimensional landmark *** results indicate that the unique axis morphology of Zalambdalestes has no close analog among living *** range of motion analysis of the neck strongly implies Zalambdalestes was capable of exerting very forceful head movements and had a high degree of ventral flexion for an animal its *** findings reveal unexpected complexity in the early evolution of the eutherian cervical morphology and suggest a feeding behavior similar to insectivores specialized in vermivory and defensive behaviors in Zalambdalestes akin to modern spiniferous mammals.

关键词： Atlas Axis Vertebral column Stem placental Morphology paleoecology

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Human-artificial intelligence interaction in gastrointestinal endoscopy

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World Journal of Gastrointestinal Endoscopy 2024年第3期16卷 126-135页

作者： John R Campion Donal B o'connor Conor Lahiff Department of Gastroenterology Mater Misericordiae University HospitalDublin D07 AX57Ireland School of Medicine University College DublinDublin D04 C7X2Ireland Department of Surgery Trinity College DublinDublin D02 R590Ireland

The number and variety of applications of artificial intelligence(AI)in gastr-ointestinal(GI)endoscopy is growing *** technologies based on machine learning(ML)and convolutional neural networks(CNNs)are at various stages of development and deployment to assist patients and endoscopists in preparing for endoscopic procedures,in detection,diagnosis and classification of pathology during endoscopy and in confirmation of key performance *** based on ML and CNNs require regulatory approval as medical *** between humans and the technologies we use are complex and are influenced by design,behavioural and psychological *** to the substantial differences between AI and prior technologies,important differences may be expected in how we interact with advice from AI ***-AI interaction(HAII)may be optimised by developing AI algorithms to minimise false positives and designing platform interfaces to maximise *** factors influencing HAII may include automation bias,alarm fatigue,algorithm aversion,learning effect and *** of these areas merits further study in the specific setting of AI applications in GI endoscopy and professional societies should engage to ensure that sufficient emphasis is placed on human-centred design in development of new AI technologies.

关键词： Artificial intelligence Machine learning Human factors Computer-aided detection Colonoscopy Adenoma detection rate

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Helicobacter pylori:High dose amoxicillin does not improve primary or secondary eradication rates in an Irish cohort

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World Journal of Clinical Cases 2024年第16期12卷 2773-2779页

作者： Conor Costigan Aoife M o'Sullivan Jim o'Connell Shreyashee Sengupta Thomas Butler Stephen Molloy Fintan John o'Hara Barbara Ryan Niall Breslin Sarah o'Donnell Anthony o'connor Sinead Smith Deirdre McNamara Trinity Academic Gastroenterology Group School of Medicine-Trinity College DublinDublin D2Ireland Department of Gastroenterology Tallaght University HospitalDublin D24 NR0AIreland

BACKGRoUND Helicobacter pylori(***)eradication rates have fallen globally,likely in large part due to increasing antibiotic resistance to traditional *** areas of high clarithromycin and metronidazole resistance such as ours,Maastricht VI guidelines suggest high dose amoxicillin dual therapy(HDADT)can be considered,subject to evidence for local *** this study we assess efficacy of HDADT therapy for *** eradication in an Irish *** To assess the efficacy of HDADT therapy for *** eradication in an Irish cohort as both first line,and subsequent therapy for patients diagnosed with *** All patients testing positive for *** in a tertiary centre were treated prospectively with HDADT(amoxicillin 1 g tid and esomeprazole 40 mg bid×14 d)over a period of 8 *** was confirmed with Urea Breath Test at least 4 wk after cessation of therapy.A delta-over-baseline>4%was considered *** demographics and treatment outcomes were recorded,analysed and controlled for basic demographics and prior *** *** one hundred and ninety-eight patients were identified with *** infection,10 patients were excluded due to penicillin allergy and 38 patients refused follow up *** all 139 were included in the analysis,55%(n=76)were female,mean age was 46.6 ***,93(67%)of patients were treatment-naïve and 46(33%)had received at least one previous course of *** groups were statistically ***-reported compliance with HDADT was 97%,mild side-effects occurred in 7%.There were no serious adverse drug *** the eradication rate for our cohort was 56%(78/139).Eradication rates were worse for those with previous treatment[43%(20/46)vs 62%(58/93),P=0.0458,odds ratio=2.15].Age and Gender had no effect on eradication *** overall eradication rates with HDADT were *** being a simple and possibly better tolerated regime,these results do not

关键词： Helicobacter pylori eradication Helicobacter pylori High dose amoxicillin High dose amoxicillin dual therapy Triple therapy

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Preface to the Special Issue on Modeling and Data Analysis Methods for the SMILE mission

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Earth and Planetary Physics 2024年第1期8卷 1-4页

作者： TianRan Sun Hyunju connor Andrey Samsonov National Space Science Center Chinese Academy of SciencesBeijing 100190China NASA Goddard Space Flight Center US Mullard Space Science Labo.a.ory University College LondonUK

The SMILE(Solar wind Magnetosphere Ionosphere Link Explorer)project(http://***/smile/,https://***/web/smile/mission)is a joint spacecraft mission of the European Space Agency(ESA)and the Chinese Academy of Sciences(CAS)with an expected launch in *** aims to study the global interactions of solar wind–magnetosphere–ionosphere innovatively by imaging the Earth’s magnetosheath and cusps in soft X-rays and the northern auroral region in ultraviolet(UV)while simultaneously measuring plasma and magnetic field parameters in the solar wind and magnetosheath along a highly-elliptical and highly-inclined *** special issue is composed of 22 articles,presenting recent progress in modeling and data analysis techniques developed for the SMILE *** this preface,we categorize the articles into the following seven topics and provide brief summaries:(1)instrument descriptions of the Soft X-ray Imager(SXI),(2)numerical modeling of the X-ray signals,(3)data processing of the X-ray images,(4)boundary tracing methods from the simulated images,(5)physical phenomena and a mission concept related to the scientific goals of SMILE-SXI,(6)studies of the aurora,and(7)ground-based support for SMILE.

关键词： SMILE X-ray imaging magnetosphere auroral ionosphere

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Mshpy23:a user-friendly,parameterized model of magnetosheath conditions

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Earth and Planetary Physics 2024年第1期8卷 89-104页

作者： Jaewoong Jung Hyunju connor Andrew Dimmock Steve Sembay Andrew Read Jan Soucek NASA Goddard Space Flight Center GreenbeltMDUSA Department of Astronomy University of MarylandCollege ParkMDUSA Swedish Institude of Space Physics UppsalaSweden University of Leicester LeicesterUK Institute of Atmospheric Physics Academy of Sciences of the Czech Republic

Lunar Environment heliospheric X-ray Imager(LEXI)and Solar wind−Magnetosphere−Ionosphere Link Explorer(SMILE)will observe magnetosheath and its boundary motion in soft X-rays for understanding magnetopause reconnection modes under various solar wind conditions after their respective launches in 2024 and *** conditions,namely,plasma density,velocity,and temperature,are key parameters for predicting and analyzing soft X-ray images from the LEXI and SMILE *** developed a userfriendly model of magnetosheath that parameterizes number density,velocity,temperature,and magnetic field by utilizing the global Magnetohydrodynamics(MHD)model as well as the pre-existing gas-dynamic and analytic *** this parameterized magnetosheath model,scientists can easily reconstruct expected soft X-ray images and utilize them for analysis of observed images of LEXI and SMILE without simulating the complicated global magnetosphere ***,we created an MHD-based magnetosheath model by running a total of 14 openGGCM global MHD simulations under 7 solar wind densities(1,5,10,15,20,25,and 30 cm)and 2 interplanetary magnetic field Bz components(±4 nT),and then parameterizing the results in new magnetosheath *** compared the magnetosheath model result with THEMIS statistical data and it showed good agreement with a weighted Pearson correlation coefficient greater than 0.77,especially for plasma density and plasma ***,we compiled a suite of magnetosheath models incorporating previous magnetosheath models(gas-dynamic,analytic),and did two case studies to test the *** MHD-based model was comparable to or better than the previous models while providing self-consistency among the magnetosheath ***,we constructed a tool to calculate a soft X-ray image from any given vantage point,which can support the planning and data analysis of the aforementioned LEXI and SMILE missions.A release of the code has been uploaded to a Git

关键词： magnetosheath python modeling

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Liver transplantation as an alternative for the treatment of intrahepatic cholangiocarcinoma: Past, present, and future directions

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Hepatobiliary & Pancreatic Diseases International 2024年第2期23卷 129-138页

作者： Sudha Kodali Ashton A connor Souhail Thabet Elizabeth W Brombosz R Mark Ghobrial Sherrie and Alan Conover Center for Liver Disease and Transplantation Houston Methodist HospitalHoustonTX 77030USA JC Walter Jr Transplant Center Houston Methodist HospitalHoustonTX 77030USA Department of Medicine Weill Cornell Medical CollegeNew YorkNYUSA Department of Surgery Houston Methodist HospitalHoustonTX 77030USA Department of Surgery Weill Cornell Medical CollegeNew YorkNYUSA School of Medicine New Giza UniversityGizaEgypt

Intrahepatic cholangiocarcinoma(iCCA)is a rare biliary tract cancer with high mortality *** resection of the iCCA lesion is the first choice of treatment,with good prognosis after margin-negative ***,only 12%-40% of patients are eligible for resection at presentation due to cirrhosis,portal hypertension,or large tumor *** transplantation(LT)offers margin-negative iCCA extirpation for patients with unresectable ***,iCCA was a contraindication for LT until size-based selection criteria were introduced to identify patients with satisfied post-LT *** studies have shown that tumor biology-based selection can yield high post-LT survival in patients with locally advanced *** selection criterion is the tumor response to neoadjuvant *** with response to neoadjuvant therapy have better outcomes after LT compared with those without tumor response to neoadjuvant *** index that helps predict the treatment outcome is the *** survival outcomes have also opened the door for living donor LT for *** undergoing LT for iCCA now have statistically similar survival rates as patients undergoing *** combination of surgery and locoregional and systemic therapies improves the prognosis of iCCA patients.

关键词： Liver transplantation Cholangiocarcinoma Hepatectomy Transplant oncology Liver neoplasm

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