Engineering Nano/Microscale Chiral Self‑Assembly in 3D Printed Constructs

Helical hierarchy found in biomolecules like cellulose,chitin,and collagen underpins the remarkable mechanical strength and vibrant colors observed in living organisms.This study advances the integration of helical/chiral assembly and 3D printing technology,providing precise spatial control over chiral nano/microstructures of rod-shaped colloidal nanoparticles in intricate geometries.We designed reactive chiral inks based on cellulose nanocrystal(CNC)suspensions and acrylamide monomers,enabling the chiral assembly at nano/microscale,beyond the resolution seen in printed materials.We employed a range of complementary techniques including Orthogonal Superposition rheometry and in situ rheo-optic measurements under steady shear rate conditions.These techniques help us to understand the nature of the nonlinear flow behavior of the chiral inks,and directly probe the flow-induced microstructural dynamics and phase transitions at constant shear rates,as well as their post-flow relaxation.Furthermore,we analyzed the photo-curing process to identify key parameters affecting gelation kinetics and structural integrity of the printed object within the supporting bath.These insights into the interplay between the chiral inks self-assembly dynamics,3D printing flow kinematics and photopolymerization kinetics provide a roadmap to direct the out-of-equilibrium arrangement of CNC particles in the 3D printed filaments,ranging from uniform nematic to 3D concentric chiral structures with controlled pitch length,as well as random orientation of chiral domains.Our biomimetic approach can pave the way for the creation of materials with superior mechanical properties or programable photonic responses that arise from 3D nano/microstructure and can be translated into larger scale 3D printed designs.

Computer-Aided Diagnosis for Tuberculosis Classification with Water Strider Optimization Algorithm

Computer-aided diagnosis(CAD)models exploit artificial intelligence(AI)for chest X-ray(CXR)examination to identify the presence of tuberculosis(TB)and can improve the feasibility and performance of CXR for TB screening and triage.At the same time,CXR interpretation is a time-consuming and subjective process.Furthermore,high resemblance among the radiological patterns of TB and other lung diseases can result in misdiagnosis.Therefore,computer-aided diagnosis(CAD)models using machine learning(ML)and deep learning(DL)can be designed for screening TB accurately.With this motivation,this article develops a Water Strider Optimization with Deep Transfer Learning Enabled Tuberculosis Classification(WSODTL-TBC)model on Chest X-rays(CXR).The presented WSODTL-TBC model aims to detect and classify TB on CXR images.Primarily,the WSODTL-TBC model undergoes image filtering techniques to discard the noise content and U-Net-based image segmentation.Besides,a pre-trained residual network with a two-dimensional convolutional neural network(2D-CNN)model is applied to extract feature vectors.In addition,the WSO algorithm with long short-term memory(LSTM)model was employed for identifying and classifying TB,where the WSO algorithm is applied as a hyperparameter optimizer of the LSTM methodology,showing the novelty of the work.The performance validation of the presented WSODTL-TBC model is carried out on the benchmark dataset,and the outcomes were investigated in many aspects.The experimental development pointed out the betterment of the WSODTL-TBC model over existing algorithms.

Optimal Synergic Deep Learning for COVID-19 Classification Using Chest X-Ray Images

A chest radiology scan can significantly aid the early diagnosis and management of COVID-19 since the virus attacks the lungs.Chest X-ray(CXR)gained much interest after the COVID-19 outbreak thanks to its rapid imaging time,widespread availability,low cost,and portability.In radiological investigations,computer-aided diagnostic tools are implemented to reduce intra-and inter-observer variability.Using lately industrialized Artificial Intelligence(AI)algorithms and radiological techniques to diagnose and classify disease is advantageous.The current study develops an automatic identification and classification model for CXR pictures using Gaussian Fil-tering based Optimized Synergic Deep Learning using Remora Optimization Algorithm(GF-OSDL-ROA).This method is inclusive of preprocessing and classification based on optimization.The data is preprocessed using Gaussian filtering(GF)to remove any extraneous noise from the image’s edges.Then,the OSDL model is applied to classify the CXRs under different severity levels based on CXR data.The learning rate of OSDL is optimized with the help of ROA for COVID-19 diagnosis showing the novelty of the work.OSDL model,applied in this study,was validated using the COVID-19 dataset.The experiments were conducted upon the proposed OSDL model,which achieved a classification accuracy of 99.83%,while the current Convolutional Neural Network achieved less classification accuracy,i.e.,98.14%.

基于微流控技术的微液滴融合研究进展

随着芯片实验(Lab-on-a-chip)研究的不断发展,利用微流控技术(Microfluidics)对微通道中的液滴进行精准操控,引起了越来越多的研究者关注。本文介绍了微通道液滴基本理论及融合机理,通过改变微通道几何结构和表面特性等影响因素实现微液滴融合的被动融合方式,通过施加外电场、磁场、温度场、表面声波和激光聚焦等作用实现微液滴融合的主动融合方式,以及液滴融合过程中的流体动力学特性。最后对微流控芯片液滴融合技术研究的发展前景进行了展望,为微流控器件设计、微液滴控制技术的广泛利用提供有价值的参考。

基于直接反投影图像重建算法的放疗计划计算方法

立体定向放射治疗的剂量累积过程和二维CT图像重建中的直接反投影过程是类似的。本文提出一种用图像描述放射治疗计划的方法 ,并利用直接反投影图像的重建算法进行放射治疗计划设计。计算机仿真实验的结果证明了该方法的可行性。

咪喹莫特联合高强度聚焦超声治疗小鼠黑色素瘤实验研究

目的探讨咪喹莫特(imiquimod,IMQ)联合高强度聚焦超声(high intensity focused ultrasound,HIFU)治疗荷B16黑色素瘤小鼠的效果及其机制。方法采用黑色素瘤细胞B16皮下接种小鼠建模,设荷瘤对照组(A组)、IMQ组(B组)、HIFU组(C组)及IMQ联合HIFU组(D组)。观察各组小鼠肿瘤生长情况及小鼠生存时间;制备小鼠脾淋巴细胞,与B16细胞共培养,台盼蓝拒染法检测小鼠脾淋巴细胞对B16细胞的细胞毒性,酶联免疫吸附试验(ELISA)法检测培养上清液中γ干扰素(IFN-γ)和肿瘤坏死因子-α(TNF-α)的水平。结果 A组、B组、C组小鼠中位生存时间分别为29 d,65 d,29 d,均明显短于D组的113 d(P<0.01);A组、B组、C组脾淋巴细胞毒性分别为(23.00±1.73)%,(35.33±5.03)%,(37.50±2.21)%,均明显低于D组的(55.33±7.64)%(P<0.01);A组、B组、C组培养上清液中IFN-γ质量浓度分别为(427.57±42.55)pg/mL,(778.45±27.85)pg/mL,(756.26±81.33)pg/mL,明显低于D组的(965.56±46.29)pg/mL(P<0.01);A组、B组、C组培养上清液中TNF-α质量浓度分别为(278.45±21.72)pg/mL,(399.37±35.29)pg/mL,(365.86±36.95)pg/mL,均明显低于D组的(565.56±46.29)pg/mL(P<0.01)。结论 IMQ联合HIFU治疗能有效延长黑色素瘤小鼠生存期,提高其抗肿瘤免疫功能,其机制可能与Th2向Th1逆转增强有关。

一个数字化的孕妇物理人模型的开发及其在核医药学上的应用

具有物理性质的人体解剖模型的开发是当今世界的前沿课题。国内的虚拟数字人体开发正在进行阶段 ,并将涉及物理性质的人体解剖模型的开发。本文结合实例阐述应用于核医学上的一个孕妇物理人模型的具体开发步骤 ,包括图像的获取、配准、分割、三维显示、以及如何将分割后的结果导入蒙特卡罗模拟计算程序EGS4。本文还介绍了相应的注意事项及应用软件工具 。

Mechanisms of rectangular groove-induced multiple-microdroplet coalescences

The mechanism of microdroplet coalescence is a fundamental issue for droplet-based microfluidics. We developed an asymmetric expansion (a rectangular groove) along one side of a microchannel to achieve multiple-microdroplet trapping, collision, and coalescence. Compared with reported symmetric expansions, this asymmetric groove could easily trap microdroplets and control two or three microdroplet coalescences precisely without a requirement for temporal and spatial synchronization. To reveal the mechanisms of multiple-droplet coalescences in a groove, we observed five different coalescence patterns under different flow conditions. Moreover, we characterized the flow behavior quantitatively by simulating the velocity vector fields in both the microdroplets and continuous phase, finding good agreement with experiments. Finally, a map of coalescence forms with different capillary numbers () and flow ratios () was obtained. The results could provide a useful guidance for the design and application of droplet-based microfluidic devices.

The dependences of osteocyte network on bone compartment, age, and disease

Osteocytes, the most abundant bone cells, form an interconnected network in the lacunar-canalicular pore system （LCS） buried within the mineralized matrix, which allows osteocytes to obtain nutrients from the blood supply, sense external mechanical signals, and communicate among themselves and with other cells on bone surfaces. In this study, we examined key features of the LCS network including the topological parameter and the detailed structure of individual connections and their variations in cortical and cancellous compa~ tments, at different ages, and in two disease conditions with altered mechanosensing （perlecan deficiency and diabetes）. LCS network showed both topological stability, in terms of conservation of connectivity among osteocyte lacunae （similar to the ＂nodes＂ in a computer network）, and considerable variability the pericellular annular fluid gap surrounding lacunae and canaliculi （similar to the ＂bandwidth＂ of individual links in a computer network）. Age, in the range of our study （15-32 weeks）, affected only the pericellular fluid annulus in cortical bone but not in cancellous bone. Diabetes impacted the spacing of the lacunae, while the perlecan deficiency had a profound influence on the pericellular fluid annulus. The LCS network features play important roles in osteocyte signaling and regulation of bone growth and adaptation.

mRNA vaccines: Past, present, future

mRNA vaccines have emerged as promising alternative platforms to conventional vaccines.Their ease of production,low cost,safety profile and high potency render them ideal candidates for prevention and treatment of infectious diseases,especially in the midst of pandemics.The challenges that face in vitro transcribed RNA were partially amended by addition of tethered adjuvants or co-delivery of naked mRNA with an adjuvanttethered RNA.However,it wasn’t until recently that the progress made in nanotechnology helped enhance mRNA stability and delivery by entrapment in novel delivery systems of which,lipid nanoparticles.The continuous advancement in the fields of nanotechnology and tissue engineering provided novel carriers for mRNA vaccines such as polymeric nanoparticles and scaffolds.Various studies have shown the advantages of adopting mRNA vaccines for viral diseases and cancer in animal and human studies.Self-amplifying mRNA is considered today the next generation of mRNA vaccines and current studies reveal promising outcomes.This review provides a comprehensive overview of mRNA vaccines used in past and present studies,and discusses future directions and challenges in advancing this vaccine platform to widespread clinical use.

Automatic detection of respiratory rate from electrocardiogram,respiration induced plethysmography and 3D acceleration signals

Respiratory monitoring is increasingly used in clinical and healthcare practices to diagnose chronic cardio-pulmonary functional diseases during various routine activities.Wearable medical devices have realized the possibilities of ubiquitous respiratory monitoring,however,relatively little attention is paid to accuracy and reliability.In previous study,a wearable respiration biofeedback system was designed.In this work,three kinds of signals were mixed to extract respiratory rate,i.e.,respiration inductive plethysmography(RIP),3D-acceleration and ECG.In-situ experiments with twelve subjects indicate that the method significantly improves the accuracy and reliability over a dynamic range of respiration rate.It is possible to derive respiration rate from three signals within mean absolute percentage error 4.37%of a reference gold standard.Similarly studies derive respiratory rate from single-lead ECG within mean absolute percentage error 17%of a reference gold standard.

Multiple cells of origin in cholangiocarcinoma underlie biological,epidemiological and clinical heterogeneity

Recent histological and molecular characterization of cholangiocarcinoma(CCA) highlights the heterogeneity of this cancer that may emerge at different sites of the biliary tree and with different macroscopic or morphological features.Furthermore,different stem cell niches have been recently described in the liver and biliarytree,suggesting this as the basis of the heterogeneity of intrahepatic(IH)-and extrahepatic(EH)-CCAs,which are two largely different tumors from both biological and epidemiological points of view.The complexity of the organization of the liver stem cell compartments could underlie the CCA clinical-pathological heterogeneity and the criticisms in classifying primitive liver tumors.These recent advances highlight a possible new classification of CCAs based on cells of origin and this responds to the need of generating homogenous diagnostic,prognostic and,hopefully,therapeutic categories of IH-and EH-CCAs.

Combined functional and anatomical diagnostic endpoints for assessing arteriovenous fistula dysfunction

Failure of arteriovenous fistulas(AVF) to mature and thrombosis in matured fistulas have been the major causes of morbidity and mortality in hemodialysis patients. Stenosis, which occurs due to adverse remodeling in AVFs, is one of the major underlying factors under both scenarios. Early diagnosis of a stenosis in an AVF can provide an opportunity to intervene in a timelymanner for either assisting the maturation process or avoiding the thrombosis. The goal of surveillance strategies was to supplement the clinical evaluation(i.e., physical examination) of the AVF for better and earlier diagnosis of a developing stenosis. Surveillance strategies were mainly based on measurement of functional hemodynamic endpoints, including blood flow(Q a) to the vascular access and venous access pressure(VAP). As the changes in arterial pressure(MAP) affects the level of VAP, the ratio of VAP to MAP(VAPR = VAP/MAP) was used for diagnosis. A Q a < 400-500 m L/min or a VAPR > 0.55 is considered sign of significant stenosis, which requires immediate intervention. However, due to the complex nature of AVFs, the surveillance strategies have failed to consistently detect stenosis under different scenarios. VAPR has been primarily developed to detect outflow stenosis in arteriovenous grafts, and it hasn't been successful in accurate diagnosis of outflow lesions in AVFs. Similarly, AVFs can maintain relatively high blood flow despite the presence of a significant outflow stenosis and thus, Q a has been found to be a better predictor of only inflow lesions. Similar shortcomings have been reported in the detection of functional severity of coronary stenosis using diagnostic endpoints that were based on either flow or pressure. This limitation has been associated with the fact that both pressure and flow change in the presence of a stenosis and thus, hemodynamic diagnostic endpoints that employ only one of these parameters are inherently prone to inaccuracies. Recent attempts have resulted in development of new diagnostic endpoints that can combine the effects of pressure and flow. These new hemodynamic diagnostic endpoints have shown to be better predictors of functional severity of lesions as compared to either flow or pressure based counterparts. In this review article, we discussed the advantages and limitations of current functional and anatomical diagnostic endpoints in AVFs.

Insight into the effects of electrochemical factors on host-guest interaction induced signature events in a biological nanopore

The signature events caused by host-guest interactions in the nanopore system can be used as a novel and characteristic signal in quantitative detection and analysis of various molecules.However,the effect of several electrochemical factors on the host-guest interactions in nanopore still remains unknown.Here,we systematically studied host-guest interactions,especially oscillation of DNA-azide adamantane@cucurbit[6]inα-Hemolysin nanopore under varying pH,concentration of electrolytes and counterions(Li+,Na+,K+).Our results indicate correlations between the change of pH and the duration of the oscillation signal.In addition,the asymmetric electrolyte concentration and the charge of the counterions affects the frequency of signature events in oscillation signals,and even the integrity of the protein nanopore.This study provides insight into the design of a future biosensing platform based on signature oscillation signals of the host-guest interaction within a nanopore.

Factors affecting use of ballistics gelatin in laboratory studies of bacterial contamination in projectile wounds

Background: Ballistics gelatin is a common tissue surrogate used in bacterial contamination models for projectile wounds. Although these studies have demonstrated that bacteria are transferred from the surface of the gelatin to the wound track by a projectile, quantifiable results have been inconsistent and not repeatable in successive tests.Methods: In this study, five areas of a typical contamination model in which bacterial recovery or survival are affected were identified for optimization. The first was a contaminated "skin" surrogate, where the novel use of vacuum filtration of a bacterial culture and buffer onto filter paper was employed. The other possibly problematic areas of the bacterial distribution model included the determination of bacterial survival when the contamination model is dried, survival in solid and molten gelatin, and the effect of high-intensity lights used for recording high-speed video.Results: Vacuum filtration of bacteria and buffer resulted in a consistent bacterial distribution and recovery. The use of phosphate buffer M9(pH 7) aided in neutralizing the ballistics gelatin and improving bacterial survival in solid gelatin. Additionally, the use of high-intensity lights to record high-speed video and the use of a 42℃ water bath to melt the gelatin were found to be bactericidal for gram-positive and gram-negative bacteria.Conclusion: Multiple areas of a typical contamination model in which bacterial survival may be impeded were identified, and methods were proposed to improve survival in each area. These methods may be used to optimize the results of bacterial contamination models for medical applications, such as understanding the progression of infection in penetrating wounds and to identify possible sources of contamination for forensic purposes.

Simultaneous follow-up of mouse colon lesions by colonoscopy and endoluminal ultrasound biomicroscopy

AIM:To evaluate the potential use of colonoscopy and endoluminal ultrasonic biomicroscopy(eUBM)to track the progression of mouse colonic lesions.METHODS:Ten mice were treated with a single azoxy-methane intraperitoneal injection(week 1)followed by seven days of a dextran sulfate sodium treatment in their drinking water(week 2)to induce inflammationassociated colon tumors.eUBM was performed simultaneously with colonoscopy at weeks 13,17-20 and21.A 3.6-F diameter 40 MHz mini-probe catheter was used for eUBM imaging.The ultrasound mini-probe catheter was inserted into the accessory channel of a pediatric flexible bronchofiberscope,allowing simultaneous acquisition of colonoscopic and eUBM images.During image acquisition,the mice were anesthetized with isoflurane and kept in a supine position over a stainless steel heated surgical waterbed at 37℃.Both eUBM and colonoscopic images were captured and stored when a lesion was detected by colonoscopy or when the eUBM image revealed a modified colon wall anatomy.During the procedure,the colon was irrigated with water that was injected through a flush port on the mini-probe catheter and that acted as the ultrasound coupling medium between the transducer and the colon wall.Once the acquisition of the last eUBM/colonoscopy section for each animal was completed,the colons were fixed,paraffin-embedded,and stained with hematoxylin and eosin.Colon images acquired at the first time-point for each mouse were compared with subsequent eUBM/colonoscopic images of the same sites obtained in the following acquisitions to evaluate lesion progression.RESULTS:All 10 mice had eUBM and colonoscopic images acquired at week 13(the first time-point).Two animals died immediately after the first imaging acquisition and,consequently,only 8 mice were subjected to the second eUBM/colonoscopy imaging acquisition(at the second time-point).Due to the advanced stage of colonic tumorigenesis,5 animals died after the second time-point image acquisition,and thus,only three were subjected to the third eUBM/colonoscopy imaging acquisition(the third time-point).eUBM was able to detect the four layers in healthy segments of colon:the mucosa(the first hyperechoic layer moving away from the mini-probe axis),followed by the muscularis mucosae(hypoechoic),the submucosa(the second hyperechoic layer)and the muscularis externa(the second hypoechoic layer).Hypoechoic regions between the mucosa and the muscularis externa layers represented lymphoid infiltrates,as confirmed by the corresponding histological images.Pedunculated tumors were represented by hyperechoic masses in the mucosa layer.Among the lesions that decreased in size between the first and third time-points,one of the lesions changed from a mucosal hyperplasia with ulceration at the top to a mucosal hyperplasia with lymphoid infiltrate and,finally,to small signs of mucosal hyperplasia and lymphoid infiltrate.In this case,while lesion regression and modification were observable in the eUBM images,colonoscopy was only able to detect the lesion at the first and second time-points,without the capacity to demonstrate the presence of lymphoid infiltrate.Regarding the lesions that increased in size,one of them started as a small elevation in the mucosa layer and progressed to a pedunculated tumor.In this case,while eUBM imaging revealed the lesion at the first time-point,colonoscopy was only able to detect it at the second time-point.All colonic lesions(tumors,lymphoid infiltrate and mucosal thickening)were identified by eUBM,while colonoscopy identified just76%of them.Colonoscopy identified all of the colonic tumors but failed to diagnose lymphoid infiltrates and increased mucosal thickness and failed to differentiate lymphoid infiltrates from small adenomas.During the observation period,most of the lesions(approximately67%)increased in size,approximately 14%remained unchanged,and 19%regressed.CONCLUSION:Combining eUBM with colonoscopy improves the diagnosis and the follow-up of mouse colonic lesions,adding transmural assessment of the bowel wall.

Twist deformation and buckling behavior of veins

Introduction Twisted arteries and veins disrupt normal blood flow and elevate the risk for clinical complications such as thrombosis,heart attack,stroke,and organ dysfunction.Veins should remain mechanically stable for normal function.However,compared to arteries,veins are more vulnerable to collapse because they are thin-walled and under lower lumen pressure.Twisted veins have been shown to occur with head turning or after inadvertent twist during various vascular surgeries.In vivo and cadaver studies have demonstrated that turning the head to one side can result in torsion and compression of the internal jugular vein and can compromise cranial drain-

A lab-on-a-CD system for point-of-care testing of whole blood samples

Point-of-care(POC)testing offers rapid results of diagnostics near the site of patient care,which can significantly improve health care and management of infectious diseases.POC testing now plays a crucial role in healthcare delivery of both developed and developing countries,particularly in developing countries where medical resources are limited.Challenges remain for the biomedical engineering community to develop truly portable,automatic,low-cost and easyto-use POC tools.Blood tests are the most commonly-used diagnostic methods nowadays because blood analyses provide definitive information of medical conditions of patients.Traditional blood tests,including sample collection,preparation and detection,are conducted using large-scale blood an-

Reversal current observed in micro-and submicro-channel flow under non-continuous DC electric field

In practical applications of biochips and bio-sensors, electrokinetic mechanisms are commonly employed to manipulate and analyze the characteristics of single bio-molecules. To accurately and flexibly control the movement of single molecule within micro-/submicro-fluidic channels, the characteristics of current signals at the initial stage of the flow are systematically studied based on a three-electrode system. The current response of micro-/submicro-fluidic channels filled with different electrolyte solutions in non-continuous external electric field are investigated. It is found, there always exists a current reversal phenomenon, which is an inherent property of the current signals in micro/submicro-fluidics Each solution has an individual critical voltage under which the steady current value is equal to zero The interaction between the steady current and external applied voltage follows an exponential function. All these results can be attributed to the overpotentials of the electric double layer on the electrodes. These results are helpful for the design and fabrication of functional micro/nano-scale fluidic sensors and biochips.

MRI-Based Patient-Specific Left Ventricular Model to Determine the Effects of Trabeculae Carneae on the Diastolic and Systolic Functions

Introduction Trabeculae carneae are irregular structures that cover the endocardial surfaces of both ventricles of human heart and account for a significant portion of the ventricular mass.However,the role of trabeculae carneae in left ventricular(LV)function is not well understood.Previous reports suggested that trabeculae help squeeze blood from the apical region during systole[1].Our recent study suggests that trabeculae carneae hypertrophy and fibrosis contribute to increased LV stiffness in patients with diastolic heart failure,and severing free-running trabeculae carneae may improve diastolic compliance of the LV[2].Objective To understand the role of trabeculae carneae in the left ventricular diastolic and systolic functions using anatomically detailed patient-specific finite element models of the human LV.Methods(1)Image acquisition An explanted human heart was collected from a 63 year old female donor with a history of stroke and congestive heart failure within 24 hours postmortem from South Texas Blood and Tissue Center(San Antonio,TX).The heart was de-identified in accordance with Institutional Review Board(IRB)requirements and informed consent for research was obtained from the donor’s family.Three-dimensional MRI scanning was conducted on a 3T(128 MHz)MRI system(TIM Trio,Siemens Medical Solutions),comprised of a superconducting magnet with a 60 cm diameter accessible bore,when the heart was submerged in a saline filled plastic container.(2)Finite element analysis Three distinct LV models were derived from the MR images.The first model was the intact trabeculated model(TM)which contained all trabeculae carneae and papillary muscles.This high-resolution anatomically detailed 3D model of the LV was segmented from 2D MR images in DICOM format using Mimics(Materialise NV,Leuven,Belgium).The second model was the papillary model(PM),in which the papillary muscles remain intact but most of the trabeculae carneae were excluded in the smoothing process.The third model was the smooth model(SM)in which the trabeculae carneae and papillary muscles were excluded during image segmentation.Finite element(FE)models of the TM,PM and SM were created by meshing 3D reconstructions of the acquired MR images using tetrahedral elements(ICEM,Ansys Inc.,Canonsburg,PA).The mesh size was selected after a pilot study on mesh sensitivity.The passive cardiac muscle was characterized as a hyperelastic,incompressible,transversely isotropic material with a Fung exponential strain energy function.The material constants were determined by matching the end-diastolic pressure-volume relationship with the empirical Klotz relation[3].A rule-based myocardial fiber algorithm was adopted to generate the myofiber directions [4].The active contraction(i.e.,systolic contraction)was modeled by the time varying'Elastance'active contraction model.The contractile parameter Tmax was determined and calibrated so that the FE predicted ejection fraction(EF)of TM matched the EF of a normal human heart at the specified end-systolic pressure[3].The analysis of the TM,PM,and SM models were implemented using the open-source finite element package FEBio(www.febio.org).In all models,the rigid body motion was suppressed by constraining the base from moving in all directions.The end-diastolic and end-systolic pressure-volume relationships(EDPVR and ESPVR)were obtained and characterized by an exponential function and the slope,respectively.Results Our simulation results showed that independent of the material model,the EDPVR curve shifts to the right in PM and SM compared to TM.However,the ESPVR curve may shift to the right or left in PM compared to TM,while shifting tothe right in SM for all material models.EDPVR was steeper in TM compared to PM and SM;however,ESPVR was found to be steeper in PM than in TM and SM.The predicted parameters of EDPVR and ESPVR showed lower average exponential term in PM and SM compared to TM,indicating a significant improvement in the compliance and global diastolic function of less trabeculated LV models(P<0.01).Similarly,the higher average elastance EEs and lower volume intersect in PM compared to TM,suggests that mild cutting of trabeculae carneae slightly improves the global systolic function of the LV(P=0.89).However,cutting all trabeculae carneae and papillary muscles in SM had a significant adverse effect on the global systolic function(P<0.01).Discussion and conclusions Most patient-specific LV studies in the literature have used smoothed ventricular geometries.We used high resolution MRI to capture the endocardial details of the LV.Though reproducing very fine trabeculae carneae was restricted by the MRI resolution,our results demonstrated the importance of considering endocardial structures,i.e.papillary muscles and trabeculae carneae,in the assessment of LV global function in patient-specific computational LV models.The present work is consistent with the observation that diastolic performance improved after severing trabeculae carneae due to a reduction in LV stiffness[2].Furthermore,our results also suggest that severing trabeculae carneae(without affecting papillary muscle)may improve LV systolic function.Our model results are consistent with experimental measurements using ex vivo rabbit heart perfusion [5].This improvement would be greater in hypertrophic hearts because trabeculae carneae are also hypertrophic and more fibrotic.Left ventricular hypertrophy is often associated with heart failure with preserved ejection fraction(HFpEF).There is no effective treatment for HFpEF,which is characterized by impaired diastolic relaxation due to increased LV stiffness.Our results indicate that trabecular cutting could be an effective treatment for HFpEF.