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Prognostic model of survival outcomes in non-small cell lung cancer patients initiated on afatinib: pooled analysis of clinical trial data

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Cancer Biology & Medicine 2019年第2期16卷 341-349页

作者： Ashley M. Hopkins Adel Shahnam Sasha Zhang Chris S. Karapetis andrew rowland Michael J. Sorich Flinders Centre for Innovation in Cancer Department of Clinical Pharmacology College of Medicine and Public Health Flinders University Adelaide 5042 Australia The Canberra Hospital Garran 2605 Australia

Objective: Several predictors of survival have been identified in EGFR-positive non-small cell lung cancer(NSCLC) patients treated with first generation EGFR inhibitors. Prognostic models of survival outcomes with afatinib have not been evaluated.Methods: A prognostic tool for overall survival(OS)/progression free survival(PFS) based on pre-treatment clinicopathological factors was developed for EGFR-positive advanced NSCLC patients treated with first-line afatinib using penalised regression of individual-participant data from LUX-Lung 3 and 6(n = 468). Favourable, intermediate and poor risk groups were identified and externally validated using LUX-Lung 1(n = 390) and LUX-Lung 2(n = 129) trials that initiated afatinib following previous chemotherapy or EGFR inhibitor treatment.Results: Discriminative performance was good in the development and validation cohorts. For patients treated with first-line afatinib, the median OS for the favourable, intermediate and poor risk groups were > 47.7, 29.3 and 16.4 months, respectively, and the median PFS were 17.3, 13.2 and 8.3 months, respectively. The improvement in median OS with afatinib use compared to chemotherapy was > 12.4 months for the favourable risk group, whereas no OS benefit was apparent for the poor risk group. The improvement in median PFS with afatinib use compared to chemotherapy was 10.2 months for the favourable risk group and 3.2 months for the poor risk group.Conclusions: A prognostic tool was developed and validated to identify favourable, intermediate and poor risk groups for OS/PFS in EGFR-positive advanced NSCLC patients treated with afatinib. The prognostic groups can inform the likely absolute OS/PFS benefit expected from afatinib compared to chemotherapy in first-line treatment.

关键词： Afatinib non-small cell lung cancer prognostic model

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On the apparent line-of-sight alignment of the peak X-ray intensity of the magnetosheath and the tangent to the magnetopause,as viewed by SMILE-SXI

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Earth and Planetary Physics 2024年第1期8卷 155-172页

作者： andrew Read Department of Physics&Astronomy University of LeicesterLeicesterLE17RHUK

The Soft X-ray Imager(SXI)on board the Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)spacecraft will be able to view the Earth’s magnetosheath in soft X-rays.Simulated images of the X-ray emission visible from the position of SMILE are created for a range of solar wind densities by using 3 years of the SMILE mission orbit,together with models of the expected X-ray emissivity from the Earth’s magnetosheath.Results from global magnetohydrodynamic simulations and a simple model for exospheric neutral densities are used to compare the locations of the lines of sight along which integrated soft X-ray intensities peak with the lines of sight lying tangent to surfaces(defined here to be the magnetopause)along which local soft X-ray intensities peak or exhibit their strongest gradients,or both,for strongly southward interplanetary magnetic field conditions when no depletion or low-latitude boundary layers are expected.Where,in the parameter space of the various times and seasons,orbital phases,solar wind conditions,and magnetopause models,the alignment of the X-ray emission peak with the magnetopause tangent is good,or is not,is presented.The main results are as follows.The spacecraft needs to be positioned well outside the magnetopause;low-altitude times near perigee are not good.In addition,there are seasonal aspects:dayside-apogee orbits are generally very good because the spacecraft travels out sunward at high altitude,but nightside-apogee orbits,behind the Earth,are bad because the spacecraft only rarely leaves the magnetopause.Dusk-apogee and dawnapogee orbits are intermediate.Dayside-apogee orbits worsen slightly over the first three mission years,whereas nightside-apogee orbits improve slightly.Additionally,many more times of good agreement with the peak-to-tangent hypothesis occur when the solar wind is in a high-density state,as opposed to a low-density state.In a high-density state,the magnetopause is compressed,and the spacecraft is more often a good distance outside the magnetopause.

关键词： X-rays magnetosphere magnetosheath magnetopause Solar wind Magnetosphere Ionosphere Link Explorer(SMILE) Earth solar wind charge exchange

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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 2025.Magnetosheath conditions,namely,plasma density,velocity,and temperature,are key parameters for predicting and analyzing soft X-ray images from the LEXI and SMILE missions.We 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 models.Using 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 models.First,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 conditions.We 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 velocity.Second,we compiled a suite of magnetosheath models incorporating previous magnetosheath models(gas-dynamic,analytic),and did two case studies to test the performance.The MHD-based model was comparable to or better than the previous models while providing self-consistency among the magnetosheath parameters.Third,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 Github repository.

关键词： magnetosheath python modeling

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Development of novel 5-FU modified siRNA against BCL-2 with enhanced efficacy and vehicle-free cellular uptake

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Genes & Diseases 2024年第1期11卷 23-25页

作者： andrew Fesler Ga-Ram Hwang Jingfang Ju Department of Pathology Renaissance School of MedicineStony Brook UniversityStony BrookNY 11794USA The Northport Veteran's Administration Medical Center NorthportNY 11768USA Curamir Therapeutics Inc. WoburnMA 01801USA

One of the major obstacles for nucleic acid-based medicine is cellular uptake due to the concern of efficiencyand potential toxicity of the vehicle.In this work,we developed a novel approach to eliminate the need for a vehicle to allow for the cellular uptake of siRNA-based therapy with a unique modification strategy that also further enhances therapeutic efficacy.This discovery may be of great importance for the development of siRNA-based therapeutics as cellular uptake remains a critical challenge.In this study,we have tested the potential of this modification strategy for siRNA using a siRNA that targets B-cell lymphoma-2(BCL-2).

关键词： eliminate uptake modified

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Rational Schur Superalgebras

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Algebra Colloquium 2024年第2期31卷 209-220页

作者： andrew Riesen Shun-Jen Cheng Department of Mathematical and Statistical Sciences University of Alberta 1132489 Ave NWEdmontonAlbertaCanada 不详

We develop and study the generalization of rational Schur algebras to the super setting.Similar to the classical case,this provides a new method for studying rational supermodules of the general linear supergroup GL(m|n).Furthermore,we establish a Schur-Weyl duality result for rational Schur superalgebras and conclude that under certain conditions these objects will be semisimple.

关键词： Schur algebra supermathematics general linear supergroup

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A Stochastic Model to Assess the Epidemiological Impact of Vaccine Booster Doses on COVID-19 and Viral Hepatitis B Co-Dynamics with Real Data

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Computer Modeling in Engineering & Sciences 2024年第3期138卷 2973-3012页

作者： andrew Omame Mujahid Abbas Dumitru Baleanu Department of Mathematics Federal University of TechnologyOwerri460114Nigeria Abdus Salam School of Mathematical Sciences Government College UniversityLahore54000Pakistan Department of Mathematics Government College UniversityLahore54000Pakistan Department of Computer Science and Mathematics Labanese American UniversityBeirutLebanon Institute of Space Sciences Magurele-BucharestRomania Department of Medical Research China Medical University HospitalChina Medical UniversityTaichung40402Taiwan

A patient co-infected with COVID-19 and viral hepatitis B can be atmore risk of severe complications than the one infected with a single infection.This study develops a comprehensive stochastic model to assess the epidemiological impact of vaccine booster doses on the co-dynamics of viral hepatitis B and COVID-19.The model is fitted to real COVID-19 data from Pakistan.The proposed model incorporates logistic growth and saturated incidence functions.Rigorous analyses using the tools of stochastic calculus,are performed to study appropriate conditions for the existence of unique global solutions,stationary distribution in the sense of ergodicity and disease extinction.The stochastic threshold estimated from the data fitting is given by:R_(0)^(S)=3.0651.Numerical assessments are implemented to illustrate the impact of double-dose vaccination and saturated incidence functions on the dynamics of both diseases.The effects of stochastic white noise intensities are also highlighted.

关键词： Viral hepatitis B COVID-19 stochastic model extinction ergodicity real data

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Some Mean Convergence Theorems for the Maximum of Normed Double Sums of Banach Space Valued Random Elements

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Acta Mathematica Sinica,English Series 2024年第7期40卷 1727-1740页

作者： andrew ROSALSKY Le Van THANH Nguyen Thi Department of Statistics University of FloridaGainesvilleFL 32611-8545USA Department of Mathematics Vinh UniversityVinhNghe AnViet Nam THUY High School for Gifted Students Vinh UniversityVinhNghe AnViet Nam

In this correspondence,we establish mean convergence theorems for the maximum of normed double sums of Banach space valued random elements.Most of the results pertain to random elements which are M-dependent.We expand and improve a number of particular cases in the literature on mean convergence of random elements in Banach spaces.One of the main contributions of the paper is to simplify and improve a recent result of Li,Presnell,and Rosalsky[Journal of Mathematical Inequalities,16,117–126(2022)].A new maximal inequality for double sums of M-dependent random elements is proved which may be of independent interest.The sharpness of the results is illustrated by four examples.

关键词： Double sum mean convergence Rademacher type p Banach space Banach space valued random element M-dependent random elements

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Eribulin in breast cancer:Current insights and therapeutic perspectives

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World Journal of Experimental Medicine 2024年第2期14卷 62-74页

作者： Oliver Oey Wynne Wijaya andrew Redfern Faculty of Medicine University of Western AustraliaNedlands 6009Australia Department of Medical Oncology Sir Charles Gairdner HospitalNedlands 6009WAAustralia Department of Oncology University of OxfordOxford OX37DQUnited Kingdom Department of Internal Medicine Universitas Gadjah MadaSleman 55281Indonesia Department of Medical Oncology Fiona Stanley HospitalMurdoch 6150WAAustralia

Eribulin is a non-taxane synthetic analogue approved in many countries as thirdline treatment for the treatment of patients with metastatic breast cancer.In addition to its mitotic property,eribulin has non-mitotic properties including but not limited to,its ability to induce phenotypic reversal of epithelial to mesenchymal transition,vascular remodelling,reduction in immunosuppressive tumour microenvironment.Since approval,there has been a surge in studies investigating the application of eribulin as an earlier-line treatment and also in combination with other agents such as immunotherapy and targeted therapy across all breast cancer sub-types,including hormone receptor positive,HER2 positive and triple negative breast cancer,many demonstrating promising activity.This review will focus on the application of eribulin in the treatment of metastatic breast cancer across all subtypes including its role as an earlier-line agent,its toxicity profile,and potential future directions.

关键词： Eribulin Breast cancer Metastatic breast cancer Chemotherapy Efficacy Safety

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Palladium-catalyzed S_(N)2 glycosylation of phenols

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Science China Chemistry 2024年第4期67卷 1037-1038页

作者： Yu Zhu P.andrew Evans Department of Chemistry Queen’s University90 Bader LaneKingstonK7L 3N6Canada Xiangya School of Pharmaceutical Sciences Central South UniversityChangsha 410013China

Glycosides are essential structural motifs present in an array of important medicines,materials,and natural products[1].Nevertheless,the chemo-and stereoselective construction of the glycosidic linkage is a long-standing challenge because relatively minor variations in the glycosyl donor or acceptor’s structure can impact stereoselectivity,thus influencing the product's functional properties.

关键词： properties Palladium catalyzed

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Using clinical cases to guide healthcare

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World Journal of Clinical Cases 2024年第9期12卷 1555-1559页

作者： Michael Colwill Samantha Baillie Richard Pollok andrew Poullis Department of Gastroenterology St George's University Hospital NHS Foundation TrustLondon SW170QTUnited Kingdom

Evidence-based practice(EBP)has been the gold standard in healthcare for nearly three centuries and aims to assist physicians in providing the safest and most effective healthcare for their patients.The well-established hierarchy of evidence lists systematic reviews and meta-analyses at the top however these methodologies are not always appropriate or possible and in these instances case-control studies,case series and case reports are utilised to support EBP.Case-control studies allow simultaneous study of multiple risk factors and can be performed rapidly and relatively cheaply.A recent example was during the Coronavirus pandemic where case-control studies were used to assess the efficacy of personal protective equipment for healthcare workers.Case series and case reports also play a role in EBP and are particularly useful to study rare diseases such as inflammatory bowel disease in transgender and gender non-conforming individuals.They are also vital in generating and disseminating early signals and encouraging further research.Whilst these methodologies have weaknesses,particularly with regards to bias and loss of patient confidentiality for rare pathologies,they have an important part to play in EBP and when appropriately utilised can significantly impact upon clinical practice.

关键词： Evidence based medicine Hierarchy of evidence Case reports Case series

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