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Comparative efficacy of sodium glucose cotransporter-2 inhibitors in the management of type 2 diabetes mellitus:A real-world experience

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World Journal of Diabetes 2024年第3期15卷 463-474页

作者： Lubna Islam Dhanya Jose mohammed Alkhalifah Dania Blaibel vishnu Chandrabalan Joseph m Pappachan Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Department of Community medicine Goa Medical CollegeGoa 403202India Department of Family medicine King Faisal Specialist HospitalRiyadh 11564Saudi Arabia Department of Data Science Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityAll Saints BuildingManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

BACKGrOUND Sodium glucose cotransporter-2 inhibitors(SGLT-2i)are a class of drugs with modest antidiabetic efficacy,weight loss effect,and cardiovascular benefits as proven by multiple randomised controlled trials(rCTs).However,real-world data on the comparative efficacy and safety of individual SGLT-2i medications is sparse.AIm To study the comparative efficacy and safety of SGLT-2i using real-world clinical data.mETHODS We evaluated the comparative efficacy data of 3 SGLT-2i drugs(dapagliflozin,canagliflozin,and empagliflozin)used for treating patients with type 2 diabetes mellitus.Data on the reduction of glycated hemoglobin(HbA1c),body weight,blood pressure(BP),urine albumin creatinine ratio(ACr),and adverse effects were recorded retrospectively.rESULTS Data from 467 patients with a median age of 64(14.8)years,294(62.96%)males and 375(80.5%)Caucasians were analysed.median diabetes duration was 16.0(9.0)years,and the duration of SGLT-2i use was 3.6(2.1)years.SGLT-2i molecules used were dapagliflozin 10 mg(n=227;48.6%),canagliflozin 300 mg(n=160;34.3%),and empagliflozin 25 mg(n=80;17.1).Baseline median(interquartile range)HbA1c in mmol/mol were:dapagliflozin-78.0(25.3),canagliflozin-80.0(25.5),and empagliflozin-75.0(23.5)respectively.The respective median HbA1c reduction at 12 months and the latest review(just prior to the study)were:66.5(22.8)&69.0(24.0),67.0(16.3)&66.0(28.0),and 67.0(22.5)&66.5(25.8)respectively(Pr all comparisons from baseline).Significant improvements in body weight(in kilograms)from baseline to study end were noticed with dapagliflozin-101(29.5)to 92.2(25.6),and canagliflozin 100(28.3)to 95.3(27.5)only.Significant reductions in median systolic and diastolic BP,from 144(21)mmHg to 139(23)mmHg;(P=0.015),and from 82(16)mmHg to 78(19)mmHg;(Prespectively were also observed.A significant reduction of microalbuminuria was observed with canagliflozin only[ACr 14.6(42.6)at baseline to 8.9(23.7)at the study end;P=0.043].Adverse effects of SGLT-2i were as follows:genital thrush and ur

关键词： Sodium glucose cotransporter-2 inhibitors Empagliflozin Canagliflozin Dapagliflozin Type 2 diabetes mellitus Cardiovascular disease Albumin creatinine ratio Diabesity

A new perspective on intervertebral disc calcification—from bench to bedside

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Bone research 2024年第1期12卷 50-61页

作者： Emanuel J.Novais rajkishen narayanan Jose A.Canseco Koen van de Wetering Christopher K.Kepler Alan S.Hilibrand Alexander r.Vaccaro makarand V.risbud Department of Orthopaedic Surgery Sidney Kimmel Medical CollegeThomas Jefferson UniversityPhiladelphiaPAUSA Unidade Local de Saúde do Litoral Alentejano Orthopedic DepartmentSantiago do CacémPortugal rothman Orthopedic Institute at Thomas Jefferson University PhiladelphiaPAUSA

Disc degeneration primarily contributes to chronic low back and neck pain.Consequently,there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis,ectopic calcification,herniation,or mixed phenotypes.Amongst these phenotypes,disc calcification is the least studied.Ectopic calcification,by definition,is the pathological mineralization of soft tissues,widely studied in the context of conditions that afflict vasculature,skin,and cartilage.Clinically,disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment.It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics:hypertrophic chondrocyte-like cell differentiation;TNAP,ENPP1,and ANK upregulation;cell death;altered Pi and PPi homeostasis;and local inflammation.recent studies in mouse models have provided a better understanding of the mechanisms underlying this phenotype.It is essential to recognize that the presentation and nature of mineralization differ between AF,NP,and EP compartments.moreover,the combination of anatomic location,genetics,and environmental stressors,such as aging or trauma,govern the predisposition to calcification.Lastly,the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis,along with disc cell death and differentiation status.While there is limited understanding of this phenotype,understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.

关键词： degeneration metabolism intervertebral

Nonlinear dynamic modeling of planar moving Timoshenko beam considering non-rigid non-elastic axial effects

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Applied mathematics and mechanics(English Edition) 2024年第3期45卷 479-496页

作者： m.ABBASI GAVArI m.r.HOmAEINEZHAD Faculty of mechanical Engineering K.N.Toosi University of TechnologyTehran 19991-43344Iran

Due to the importance of vibration effects on the functional accuracy of mechanical systems,this research aims to develop a precise model of a nonlinearly vibrating single-link mobile flexible manipulator.The manipulator consists of an elastic arm,a rotary motor,and a rigid carrier,and undergoes general in-plane rigid body motion along with elastic transverse deformation.To accurately model the elastic behavior,Timoshenko’s beam theory is used to describe the flexible arm,which accounts for rotary inertia and shear deformation effects.By applying Newton’s second law,the nonlinear governing equations of motion for the manipulator are derived as a coupled system of ordinary differential equations(ODEs)and partial differential equations(PDEs).Then,the assumed mode method(Amm)is used to solve this nonlinear system of governing equations with appropriate shape functions.The assumed modes can be obtained after solving the characteristic equation of a Timoshenko beam with clamped boundary conditions at one end and an attached mass/inertia at the other.In addition,the effect of the transverse vibration of the inextensible arm on its axial behavior is investigated.Despite the axial rigidity,the effect makes the rigid body dynamics invalid for the axial behavior of the arm.Finally,numerical simulations are conducted to evaluate the performance of the developed model,and the results are compared with those obtained by the finite element approach.The comparison confirms the validity of the proposed dynamic model for the system.According to the mentioned features,this model can be reliable for investigating the system’s vibrational behavior and implementing vibration control algorithms.

关键词： planar moving Timoshenko beam non-rigid non-elastic axial effect as-sumed mode method(Amm) nonlinear motion analysis

Pile foundation in alternate layered liquefiable and non-liquefiable soil deposits subjected to earthquake loading

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Earthquake Engineering and Engineering Vibration 2024年第2期23卷 359-376页

作者： Praveen Huded m Suresh r Dash LEA Associates South East Asia Pvt.Ltd. New Delhi 110044India Indian Institute of Technology Bhubaneswar Khurda 752050India

Pile foundations are still the preferred foundation system for high-rise structures in earthquake-prone regions.Pile foundations have experienced failures in past earthquakes due to liquefaction.research on pile foundations in liquefiable soils has primarily focused on the pile foundation behavior in two or three-layered soil profiles.However,in natural occurrence,it may occur in alternative layers of liquefiable and non-liquefiable soil.However,the experimental and/or numerical studies on the layered effect on pile foundations have not been widely addressed in the literature.most of the design codes across the world do not explicitly mention the effect of sandwiched non-liquefiable soil layers on the pile response.In the present study,the behavior of an end-bearing pile in layered liquefiable and non-liquefiable soil deposit is studied numerically.This study found that the kinematic bending moment is higher and governs the design when the effect of the sandwiched non-liquefied layer is considered in the analysis as opposed to when its effect is ignored.Therefore,ignoring the effect of the sandwiched non-liquefied layer in a liquefiable soil deposit might be a nonconservative design approach.

关键词： pile foundation liquefaction alternately layered soil fixity effect layered effect

Kinematic analysis of flexible bipedal robotic systems

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Applied mathematics and mechanics(English Edition) 2024年第5期45卷 795-818页

作者： r.FAZEL A.m.SHAFEI S.r.NEKOO Department of mechanical Engineering Shahid Bahonar University of KermanKerman ***Iran Departamento de Ingenieria de Sistemas y Automatica Escuela Técnica Superior de IngenieriaUniversidad de SevillaSeville 41092Spain

In spite of its intrinsic complexities,the passive gait of bipedal robots on a sloping ramp is a subject of interest for numerous researchers.What distinguishes the present research from similar works is the consideration of flexibility in the constituent links of this type of robotic systems.This is not a far-fetched assumption because in the transient(impact)phase,due to the impulsive forces which are applied to the system,the likelihood of exciting the vibration modes increases considerably.moreover,the human leg bones that are involved in walking are supported by viscoelastic muscles and ligaments.Therefore,for achieving more exact results,it is essential to model the robot links with viscoelastic properties.To this end,the Gibbs-Appell formulation and Newton's kinematic impact law are used to derive the most general form of the system's dynamic equations in the swing and transient phases of motion.The most important issue in the passive walking motion of bipedal robots is the determination of the initial robot configuration with which the system could accomplish a periodic and stable gait solely under the effect of gravitational force.The extremely unstable nature of the system studied in this paper and the vibrations caused by the impulsive forces induced by the impact of robot feet with the inclined surface are some of the very serious challenges encountered for achieving the above-mentioned goal.To overcome such challenges,an innovative method that uses a combination of the linearized equations of motion in the swing phase and the algebraic motion equations in the transition phase is presented in this paper to obtain an eigenvalue problem.By solving this problem,the suitable initial conditions that are necessary for the passive gait of this bipedal robot on a sloping surface are determined.The effects of the characteristic parameters of elastic links including the modulus of elasticity and the Kelvin-Voigt coefficient on the walking stability of this type of robotic systems are also studied.The findings o

关键词： bipedal robot flexible link swing phase transient phase eigenvalue problem Kelvin-Voigt coefficient

Control system design for a pressure-tube-type supercritical water-cooled nuclear reactor via a higher order sliding mode method

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Nuclear Science and Techniques 2024年第1期35卷 145-154页

作者： m.Hajipour G.r.Ansarifar Department of Nuclear Engineering Faculty of PhysicsUniversity of IsfahanIsfahan 81746-73441Iran

Nuclear power plants exhibit non-linear and time-variable dynamics.Therefore,designing a control system that sets the reactor power and forces it to follow the desired load is complicated.A supercritical water reactor(SCWr)is a fourth-generation conceptual reactor.In an SCWr,the non-linear dynamics of the reactor require a controller capable of control-ling the nonlinearities.In this study,a pressure-tube-type SCWr was controlled during reactor power maneuvering with a higher order sliding mode,and the reactor outgoing steam temperature and pressure were controlled simultaneously.In an SCWr,the temperature,pressure,and power must be maintained at a setpoint(desired value)during power maneuvering.reactor point kinetics equations with three groups of delayed neutrons were used in the simulation.Higher-order and classic sliding mode controllers were separately manufactured to control the plant and were compared with the PI controllers speci-fied in previous studies.The controlled parameters were reactor power,steam temperature,and pressure.Notably,for these parameters,the PI controller had certain instabilities in the presence of disturbances.The classic sliding mode controller had a higher accuracy and stability;however its main drawback was the chattering phenomenon.HOSmC was highly accurate and stable and had a small computational cost.In reality,it followed the desired values without oscillations and chattering.

关键词： Supercritical water nuclear reactor Higher order sliding mode controller Steam temperature Steam pressure Point kinetics model

Parametric investigation on the novel and cost-effective nano fly ash impregnated geopolymer system for sustainable construction

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Frontiers of Structural and Civil Engineering 2024年第2期18卷 170-183页

作者： r.mOHANA S.m.Leela BHArATHI Department of Civil Engineering Mepco Schlenk Engineering CollegeSivakasi 626123India

The hazardous environmental effects of greenhouse gas emissions and climate change demand alternative sources for cementitious materials in the construction industry.The development of geopolymer structures provides a way of producing 100%cement-free construction.In this research work,a novel and simple way of deriving nano particles from waste fly ash particles is promoted.The effect of adding the synthesized nano fly ash particles as a filler medium in geopolymer mortars was investigated by considering strength and durability properties.Parameter optimization was done by using regression analysis on the geopolymer mortar and the impact of adding nano fly ash particles was studied by varying different percentages of addition ranging from 0 to 7.5%by weight of binder content.From the results,it was observed that 1%nano fly ash acted not only as a filler but also as nano-sized precursors of the polymerization process,resulting in denser geopolymer medium.This can explain the extraordinary gain in strength of 72.11 mPa as well as the denser core with negligible level of chloride ion penetration,making the material suitable for the development of structures susceptible to marine environment.

关键词： geopolymer nano fly ash chloride ion penetration durability polymerization fillers

Semaglutide for the management of diabesity:The real-world experience

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World Journal of methodology 2024年第3期14卷 68-77页

作者： mohammed Alkhalifah Hafsa Afsar Anindya Shams Dania Blaibel vishnu Chandrabalan Joseph m Pappachan Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Department of Family medicine King Faisal Specialist HospitalRiyadh 11211Saudi Arabia Department of Data Science Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine&HealthThe University of ManchesterManchester M139PLUnited Kingdom

BACKGrOUND Diabesity(diabetes as a consequence of obesity)has emerged as a huge healthcare challenge across the globe due to the obesity pandemic.Judicious use of antidiabetic medications including semaglutide is important for optimal management of diabesity as proven by multiple randomized controlled trials.However,more real-world data is needed to further improve the clinical practice.AIm To study the real-world benefits and side effects of using semaglutide to manage patients with diabesity.mETHODS We evaluated the efficacy and safety of semaglutide use in managing patients with diabesity in a large academic hospital in the United States.Several parameters were analyzed including demographic information,the data on improvement of glycated hemoglobin(HbA1c),body weight reduction and insulin dose adjustments at 6 and 12 months,as well as at the latest follow up period.The data was obtained from the electronic patient records between January 2019 to may 2023.rESULTS 106 patients(56 males)with type 2 diabetes mellitus(T2Dm),mean age 60.8±11.2 years,mean durations of T2Dm 12.4±7.2 years and mean semaglutide treatment for 2.6±1.1 years were included.Semaglutide treatment was associated with significant improvement in diabesity outcomes such as mean weight reductions from baseline 110.4±24.6 kg to 99.9±24.9 kg at 12 months and 96.8±22.9 kg at latest follow up and HbA1c improvement from baseline of 82±21 mmol/mol to 67±20 at 12 months and 71±23 mmol/mol at the latest follow up.An insulin dose reduction from mean baseline of 95±74 units to 76.5±56.2 units was also observed at the latest follow up.Side effects were mild and mainly gastrointestinal like bloating and nausea improving with prolonged use of semaglutide.CONCLUSION Semaglutide treatment is associated with significant improvement in diabesity outcomes such as reduction in body weight,HbA1c and insulin doses without major adverse effects.reviews of largescale real-world data are expected to inform better clinical practice decision making to improve the care of

关键词： Type 2 diabetes mellitus Diabesity Glucagon-like peptide 1 receptor agonists Semaglutide Insulin dose reduction Weight loss

Design of a large-scale model for wind tunnel test of a multiadaptive flap concept

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Chinese Journal of Aeronautics 2024年第2期37卷 58-80页

作者： mürüvvet Sinem SICIm DEmIrCI rosario PECOrA metin Orhan KAYA Aeronautical Engineering Department Istanbul Technical UniversityIstanbulTurkey Industrial Engineering Department University of Naples Federico IINapoliItaly

The design and application of morphing systems are ongoing issues compelling the aviation industry.The Clean Sky-program represents the most significant aeronautical research ever launched in Europe on advanced technologies for greening next-generation aircraft.The primary purpose of the program is to develop new concepts aimed at decreasing the effects of aviation on the environment,increasing reliability,and promoting eco-friendly mobility.These ambitions are pursued through research on enabling technologies fostering noise and gas emissions reduction,mainly by improving aircraft aerodynamic performances.Within the Clean Sky framework,a multimodal morphing flap device was designed based on tight industrial requirements and tailored for large civil aircraft applications.The flap is deployed in one unique setting,and its cross section is morphed differently in take-off and landing to get the necessary extra lift for the specific flight phase.moreover,during the cruise,the tip of the flap is deflected for load control and induced drag reduction.Before manufacturing the first flap prototype,a high-speed(ma=0.3),large-scale test campaign(geometric scale factor 1:3)was deemed necessary to validate the performance improvements brought by this novel system at the aircraft level.On the other hand,the geometrical scaling of the flap prototype was considered impracticable due to the unscalability of the embedded mechanisms and actuators for shape transition.Therefore,a new architecture was conceived for the flap model to comply with the scaled dimensions requirements,withstand the relevant loads expected during the wind tunnel tests and emulate the shape transition capabilities of the true-scale flap.Simplified strategies were developed to effectively morph the model during wind tunnel tests while ensuring the robustness of each morphed configuration and maintaining adequate stiffness levels to prevent undesirable deviations from the intended aerodynamic shapes.Additionally,a simplified design was conceived for the flap-w

关键词： morphing structures Smart aircraft morphing flap Adaptive systems Finger-like ribs Wind tunnel tests Large-scale morphing archi-tectures Variable camber airfoil