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Concurrent chemoradiation for high-risk prostate cancer

World Journal of Clinical Oncology 2015年第4期6卷 35-42页

作者： benjamin t cooper Nicholas J Sanfilippo Department of Radiation Oncology New York University School of Medicine

there are estimated to be 220800 cases of prostate cancer diagnosed in 2015, making up 26% of all cancer diagnoses. Fortunately, adenocarcinoma of the prostate is often a highly treatable malignancy. Even though the majority of prostate cancer patients present with localized disease, prostate cancer still accounts for over 27000 deaths a year. there is a subset of patients thatare likely to recur after locoregional treatment that is thought of as a "high-risk" population. this more aggressive subset includes patients with clinical stage greater than t2 b, Gleason score greater than 7, and prostate specific antigen greater than 20 ng/d L. the rate of biochemical relapse in this high risk group is 32%-70% within five years of definitive focal therapy. Given these discouraging outcomes, attempts have been made to improve cure rates by radiation dose escalation, addition of androgen depravation therapy, and addition of chemotherapy either sequentially or concurrently with radiation. One method that has been shown to improve clinical outcomes is the addition of chemotherapy to radiotherapy for definitive treatment. Concurrent chemoradiation with 5-fluorouracil, estramustine phosphate, vincristine, docetaxel, and paclitaxel has been studied in the phase I and/or II setting. these trials have identified the maximum tolerated dose of chemotherapy and radiation that can be safely delivered concurrently and established the safety and feasibility of this technique. this review will focus on the addition of concurrent chemotherapy to radiotherapy in the definitive management of high-risk prostate cancer.

关键词： Prostate cancer Chemoradiation Highrisk prostate cancer Concurrent chemotherapy Chemotherapy Intensity modulated radiation therapy

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the role of melatonin receptor 1B gene(MtNR1B)in the susceptibility to depression and type 2 diabetes comorbidity

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Genes & Diseases 2024年第3期11卷 113-115页

作者： Mutaz Amin benjamin Rafla Rongling Wu teodor t.Postolache Cclaudia Gragnoli INSERM US14-OrphanetParis 75014France Department of Biochemistry and Molecular Biology Faculty of MedicineAl-Neelain UniversityKhartoum 11121Sudan Division of Endocrinology Department of MedicineCreighton University School of MedicineOmahaNE 68124USA Department of Public Health Sciences Penn State College of MedicineHersheyPA 17033USA Department of Statistics Penn State College of MedicineHersheyPA 17033USA Mood and Anxiety Program Department of PsychiatryUniversity of Maryland School of MedicineBaltimoreMD 21201USA Rocky Mountain Mental llness Research Education and Clinical Center(MIRECC) Veterans Integrated Service Network(VISN)19Military and Veteran Microbiome:Consortium for Research and Education(MVM-CoRE)DenverCO 80246USA Mental Ilness Research Education and Clinical Center(MIRECC) Veterans Integrated Service Network(VISN)5VA Capitol Health Care NetworkBaltimoreMD 21090USA Molecular Biology Laboratory Bios Biotech Multi-Diagnostic Health CenterRome00197Italy

Melatonin is an endogenous monoamine hormone secreted by the pineal *** signaling has been shown to play a role in circadian rhythm regulation,lipid and glucose metabolism,and obesity,and it has anti-inflammatory and antioxidant *** melatonin receptor 1B gene(MtNR1B)is expressed in,among other tissues,the brain and pancreatic beta cells,and risk variants for t2D have been reported as impairing early insulin secretion and increasing fasting glucose levels.^(1) Variants in the MtNR1B gene also have been reported in patients with depression(MDD).

关键词： MtNR1B metabolism properties.

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SARS-CoV-2 and innate immunity:the good,the bad,and the"goldilocks"

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Cellular & Molecular Immunology 2024年第2期21卷 171-183页

作者： benjamin L.Sievers Mark t.K.Cheng Kata Csiba Bo Meng Ravindra K.Gupta Department of Medicine University of CambridgeCambridgeUK Cambridge Institute of therapeutic Immunology&Infectious Disease(CItID) Department of MedicineUniversity of CambridgeCambridgeUk

An ancient conflict between hosts and pathogens has driven the innate and adaptive arms of *** about this interplay can not only help us identify biological mechanisms but also reveal pathogen vulnerabilities that can be leveraged *** humoral response to SARS-CoV-2 infection has been the focus of intense research,and the role of the innate immune system has received significantly less ***,we review current knowledge of the innate immune response to SARS-CoV-2 infection and the various means SARS-CoV-2 employs to evade innate defense *** also consider the role of innate immunity in SARS-CoV-2 vaccines and in the phenomenon of long COVID.

关键词： SARS-CoV-2 Innate immune response Interferon Cytokines Inflammation Antiviral targets

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Customized scaffolds for large bone defects using 3D‑printed modular blocks from 2D‑medical images

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Bio-Design and Manufacturing 2024年第1期7卷 74-87页

作者： Anil AAcar Evangelos Daskalakis Paulo Bartolo Andrew Weightman Glen cooper Gordon Blunn Bahattin Koc Faculty of Engineering and Natural Sciences Sabanci UniversityIstanbul 34956Türkiye D Bioprinting Laboratory Sabanci University Nanotechnology Research and Application CenterIstanbul 34956Türkiye School of Mechanical Aerospace and Civil EngineeringManchester Institute of BiotechnologyUniversity of ManchesterManchester M139PLUK Singapore Centre for 3D Printing School of Mechanical and Aerospace EngineeringNanyang Technological UniversitySingapore 639798Singapore School of Pharmacy and Biomedical Sciences University of PortsmouthPortsmouth PO12UPUK

Additive manufacturing(AM)has revolutionized the design and manufacturing of patient-specific,three-dimensional(3D),complex porous structures known as scaffolds for tissue engineering *** use of advanced image acquisition techniques,image processing,and computer-aided design methods has enabled the precise design and additive manufacturing of anatomically correct and patient-specific implants and ***,these sophisticated techniques can be timeconsuming,labor-intensive,and ***,the necessary imaging and manufacturing equipment may not be readily available when urgent treatment is needed for trauma *** this study,a novel design and AM methods are proposed for the development of modular and customizable scaffold blocks that can be adapted to fit the bone defect area of a *** modular scaffold blocks can be combined to quickly form any patient-specific scaffold directly from two-dimensional(2D)medical images when the surgeon lacks access to a 3D printer or cannot wait for lengthy 3D imaging,modeling,and 3D printing during *** proposed method begins with developing a bone surface-modeling algorithm that reconstructs a model of the patient’s bone from 2D medical image measurements without the need for expensive 3D medical imaging or *** algorithm can generate both patient-specific and average bone ***,a biomimetic continuous path planning method is developed for the additive manufacturing of scaffolds,allowing porous scaffold blocks with the desired biomechanical properties to be manufactured directly from 2D data or *** algorithms are implemented,and the designed scaffold blocks are 3D printed using an extrusion-based AM *** and instructions are also provided to assist surgeons in assembling scaffold blocks for the self-repair of patient-specific large bone defects.

关键词： Additive manufacturing Modular scaffolds Large bone defect Customized scaffold design Patient-specific scaffolds

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Development,validation,and transportability of several machine-learned,non-exercise-based VO_(2max)prediction models for older adults

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Journal of Sport and Health Science 2024年第5期13卷 611-620页

作者： benjamin t.Schumacher Michael J.LaMonte Andrea Z.LaCroix Eleanor M.Simonsick Steven P.Hooker Humberto Parada Jr. John Bellettiere Arun Kumar Herbert Wertheim School of Public Health and Human Longevity Science University of California San DiegoLa JollaCA 92093USA Department of Epidemiology and Environmental Health School of Public Health and Health ProfessionsUniversity at BuffaloState University of New YorkBuffaloNY 14214USA translational Gerontology Branch Intramural Research ProgramNational Institute on AgingNational Institutes of HealthBaltimoreMD 21225USA College of Health and Human Services San Diego State UniversitySan DiegoCA 92182USA Division of Epidemiology and Biostatistics School of Public HealthSan Diego State UniversitySan DiegoCA 92182USA University of California San Diego Moores Cancer Center La JollaCA 92093USA Computer Science and Engineering and Halicioglu Data Science Institute University of California San DiegoLa JollaCA 92093USA

Background:there exist few maximal oxygen uptake(VO_(2max))non-exercise-based prediction equations,fewer using machine learning(ML),and none specifically for older *** direct measurement of VO_(2max)is infeasible in large epidemiologic cohort studies,we sought to develop,validate,compare,and assess the transportability of several ML VO_(2max)prediction ***:the Baltimore Longitudinal Study of Aging(BLSA)participants with valid VO2_(max)tests were included(n=1080).Least absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine(SVM)algorithms were trained to predict VO_(2max)*** developed these algorithms for:(a)the overall BLSA,(b)by sex,(c)using all BLSA variables,and(d)variables common in aging ***,we quantified the associations between measured and predicted VO_(2max)and ***:the age was 69.0±10.4 years(mean±SD)and the measured VO_(2max)was 21.6±5.9 mL/kg/*** absolute shrinkage and selection operator,linear-and tree-boosted extreme gradient boosting,random forest,and support vector machine yielded root mean squared errors of 3.4 mL/kg/min,3.6 mL/kg/min,3.4 mL/kg/min,3.6 mL/kg/min,and 3.5 mL/kg/min,*** quartiles of measured VO_(2max)showed an inverse gradient in mortality *** VO_(2max)variables yielded similar effect estimates but were not robust to ***:Measured VO_(2max)is a strong predictor of *** ML can improve the accuracy of prediction as compared to simpler approaches but estimates of association with mortality remain sensitive to *** studies should seek to reproduce these results so that VO_(2max),an important vital sign,can be more broadly studied as a modifiable target for promoting functional resiliency and healthy aging.

关键词： Cardiorespiratory fitness Prediction algorithms Epidemiology Mortality

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CO_(2)capture costs of chemical looping combustion of biomass:A comparison of natural and synthetic oxygen carrier

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Journal of Energy Chemistry 2024年第5期92卷 296-310页

作者： benjamin Fleiß Juraj Priscak Martin Hammerschmid Josef Fuchs Stefan Müller Hermann Hofbauer Institute of Chemical Environmental and Bioscience EngineeringTU WienVienna1060 ViennaAustria BESt–Bioenergy and Sustainable technologies GmbH Graz8010 StyriaAustria

Chemical looping combustion has the potential to be an efficient and low-cost technology capable of contributing to the reduction of the atmospheric concentration of CO_(2) in order to reach the 1.5/2°C goal and mitigate climate *** this process,a metal oxide is used as oxygen carrier in a dual fluidized bed to generate clean CO_(2) via combustion of *** commonly,natural ores or synthetic materials are used as oxygen carrier whereas both must meet special requirements for the conversion of solid *** oxygen carriers are characterized by higher reactivity at the expense of higher costs versus the lower-cost natural *** determine the viability of both possibilities,a techno-economic comparison of a synthetic material based on manganese,iron,and copper to the natural ore ilmenite was *** synthetic oxygen carrier was characterized and tested in a pilot plant,where high combustion efficiencies up to 98.4%and carbon capture rates up to 98.5%were *** techno-economic assessment resulted in CO_(2) capture costs of 75 and 40€/tCO_(2) for the synthetic and natural ore route respectively,whereas a sensitivity analysis showed the high impact of production costs and attrition rates of the synthetic *** synthetic oxygen carrier could break even with the natural ore in case of lower production costs and attrition rates,which could be reached by adapting the production process and recycling *** comparison to state-of-the-art technologies,it is demonstrated that both routes are viable and the capture cost of CO_(2) could be reduced by implementing the chemical looping combustion technology.

关键词： Chemical looping combustion BECCS techno-economic assessment CO_(2)capture costs Oxygen carrier development Synthetic materials Ilmenite

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Application of novel constrained friction processing method to produce fine grained biomedical Mg-Zn-Ca alloy

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Journal of Magnesium and Alloys 2024年第2期12卷 516-529页

作者： ting Chen Banglong Fu Junjun Shen Uceu F.H.R.Suhuddin Björn Wiese Yuanding Huang Min Wang Jorge F.dos Santos Jean Pierre Bergmann benjamin Klusemann Solid State Materials Processing Institute of Material MechanicsHelmholtz-Zentrum HereonMax-Planck-Str.1Geesthacht 21502Germany Functional Magnesium Materials Institute of Metallic BiomaterialsHelmholtz-Zentrum HereonMax-Planck-Str.1Geesthacht 21502Germany Shanghai Key Laboratory of Materials Laser Processing and Modification Shanghai Jiao Tong UniversityDongchuan Road 800Shanghai 200240China Applied Materials and Manufacturing Energy and Environment DivisionPacific Northwest National LaboratoryPO Box 999RichlandWA 99352USA Production technology Group Technisiche Universität IlmenauGustav-Kirchhoff-Platz 2Ilmenau 98693Germany Institute for Production technology and Systems Leuphana University of LüneburgUniversitätsallee 1Lüneburg 21335Germany

In order to obtain Mg alloys with fine microstructures and high mechanical performances,a novel friction-based processing method,name as“constrained friction processing(CFP)”,was *** CFP,defect-free Mg-Zn-Ca rods with greatly refined grains and high mechanical properties were *** to the previous as-cast microstructure,the grain size was reduced from more than 1 mm to around 4μm within 3 s by a single process *** compressive yield strength was increased by 350%while the ultimate compressive strength by 53%.According to the established material flow behaviors by“tracer material”,the plastic material was transported by shear *** the base material to the rod,the material experienced three stages,*** by the tool,upward flow with additional tilt,followed by upward *** microstructural evolution was revealed by“stop-action”*** microstructural development at regions adjacent to the rod is mainly controlled by twinning,dynamic recrystallization(DRX)as well as particle stimulated nucleation,while that within the rod is related to DRX combined with grain growth.

关键词： Constrained friction processing Magnesium alloys Microstructure Mechanical properties Grain refinement Plastic deformation

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Compartmentalization of the inflammatory response during bacterial sepsis and severe COVID-19

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Journal of Intensive Medicine 2024年第3期4卷 326-340页

作者： Jean-Marc Cavaillon benjamin G.Chousterman tomasz Skirecki Institut Pasteur ParisFrance Department of Anesthesia and Critical Care Lariboisière University HospitalDMU ParabolAPHP NordParisFrance Inserm U942 University of ParisParisFrance Department of translational Immunology and Experimental Intensive Care Centre of Postgraduate Medical EducationWarsawPoland

Acute infections cause local and systemic disorders which can lead in the most severe forms to multi-organ failure and eventually to death. the host response to infection encompasses a large spectrum of reactions with a concomitant activation of the so-called inflammatory response aimed at fighting the infectious agent and removing damaged tissues or cells, and the anti-inflammatory response aimed at controlling inflammation and initiating the healing process. Fine-tuning at the local and systemic levels is key to preventing local and remote injury due to immune system activation. thus, during bacterial sepsis and Coronavirus disease 2019 (COVID-19), concomitant systemic and compartmentalized pro-inflammatory and compensatory anti-inflammatory responses are occurring. Immune cells (e.g., macrophages, neutrophils, natural killer cells, and t-lymphocytes), as well as endothelial cells, differ from one compartment to another and contribute to specific organ responses to sterile and microbial insult. Furthermore, tissue-specific microbiota influences the local and systemic response. A better understanding of the tissue-specific immune status, the organ immunity crosstalk, and the role of specific mediators during sepsis and COVID-19 can foster the development of more accurate biomarkers for better diagnosis and prognosis and help to define appropriate host-targeted treatments and vaccines in the context of precision medicine.

关键词： Acute respiratory distress syndrome Bone marrow Cytokines Lungs Mucosa Vaccines

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Androgens and prostate disease

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Asian Journal of Andrology 2014年第2期16卷 248-255,I0009页

作者： Lori A cooper Stephanie t Page Departments of Medicine Division of Endocrinology and Metabolism University of Washington Seattle University of Washington and Harborview Medical Center Seattle Washington USA.

A growing body of literature has established the anabolic benefits of testosterone （t） therapy in hypogonadal men. However, there remains a paucity of data regarding the risks of exogenous androgen use in older men and the potential for adverse effects on the prostate gland. Whether t therapy in older, hypogonadal men might worsen lower urinary tract symptoms or exacerbate, unmask, or even incite prostate cancer development has tempered enthusiasm for t therapy, while known prostatic disease has served as a relative contraindication to t therapy. Androgens are necessary for the development and maintenance of the prostate gland. However, epidemiologic studies do not consistently find a positive relationship between endogenous serum androgen concentrations and the risk of prostate disease. Recent data demonstrate that 5α-reductase inhibitors decrease the risk of low-grade prostate cancer, suggesting that modifying androgen metabolism may have beneficial effects on prostate health, yet similar reductions in high-grade disease have not been observed, thereby questioning the true clinical benefits of these agents for chemoprevention. Knowing how to best investigate the relationship between androgens and the development of prostate disease given the lack of large, randomized trials is difficult. Accumulating data challenges the assumption that alterations in serum androgens have parallel effects within the prostate hormonal environment or change androgen-regulated processes within the gland. Long-term intervention studies are needed to truly ascertain the effects of androgen manipulation on prostate tissue and disease risk. However, available data do not support the notion that restoring serum androgens to normal physiologic ranges drives prostate disease.

关键词： androgens male hypogonadism prostate testosterone

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Cost effectiveness of nonpharmacological prevention programs for diabetes:A systematic review of trial-based studies

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Chronic Diseases and translational Medicine 2024年第1期10卷 12-21页

作者： Yongyi Xiong Zhaohua Huo Samuel Y.S.Wong benjamin H.K.Yip Jockey Club School of Public Health and Primary Care Prince of Wales HospitalThe Chinese University of Hong KongShatinHong KongChina

trial-based economic value of prevention programs for diabetes is *** aimed to review the cost-effectiveness of nonpharmacological interventions to prevent type-2 diabetes mellitus(t2DM)for high-risk *** electronic databases were searched up to March *** assessing both the cost and health outcomes of nonpharmacological interventions for people at high-risk of t2DM were *** quality of the study was assessed by the Consolidated Health Economic Evaluation Reporting Standards 2022 *** primary outcome for synthesis was incremental cost-effectiveness ratios(ICER)for quality-adjusted life years(QALYs),and costs were standardized in 2022 US *** synthesis was performed,considering different types and delivery methods of *** studies included five based on the US diabetes prevention program(DPP),six on non-DPP-based lifestyle interventions,four on health education,and one on screening plus lifestyle *** with usual care,lifestyle interventions showed higher potential of cost-effectiveness than educational *** lifestyle interventions,DPP-based programs were less cost-effective(median of ICERs:$27,077/QALY)than non-DPP-based programs(median of ICERs:$1395/QALY)from healthcare perspectives,but with larger decreases in diabetes ***,the cost-effectiveness of interventions was more possibly realized through the combination of different delivery *** interventions to prevent t2DM in high-risk populations are both cost-effective and feasible in various ***,economic evidence from low-and middle-income countries is still lacking,and interventions delivered by trained laypersons and combined with peer support sessions or mobile technologies could be potentially a cost-effective solution in such settings with limited resources.

关键词： economic evaluation nonpharmacological interventions pre-diabetes prevention

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