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  • 21 Jan 2022 Journal Article iScience

    Lifetime-based analysis of binary fluorophores mixtures in the low photon count limit

    Abstract

    Single biomolecule sensing often requires the quantification of multiple fluorescent species. Here, we theoretically and experimentally use time-resolved fluorescence via Time Correlated Single Photon Counting (TCSPC) to accurately quantify fluorescent species with similar chromatic signatures. A modified maximum likelihood estimator is introduced to include two

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  • Jan 2022 Journal Article Biomaterials

    Integrating engineered macro vessels with self-assembled capillaries in 3D implantable tissue for promoting vascular integration in-vivo

    Abstract

    A functional multi-scale vascular network can promote 3D engineered tissue growth and improve transplantation outcome. In this work, by using a combination of living cells, biological hydrogel, and biodegradable synthetic polymer we fabricated a biocompatible, multi-scale vascular network (MSVT) within thick, implantable engineered tissues. Using a templating technique

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  • 14 Dec 2021 Journal Article ACS Biomaterials Science & Engineering

    Microcomputed Tomography-Based Analysis of Neovascularization within Bioengineered Vascularized Tissues

    Abstract

    In the field of tissue engineering, evaluating newly formed vascular networks is considered a fundamental step in deciphering the processes underlying tissue development. Several common modalities exist to study vessel network formation and function. However, a proper methodology that allows through three-dimensional visualization of neovessels in a reproducible manner

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  • 13 Dec 2021 Journal Article Function

    ATP synthase K+-and H+-fluxes drive ATP synthesis and enable mitochondrial K+-'uniporter'function: I. Characterization of ion fluxes

    Magdalena Juhaszova, Evgeny Kobrinsky, Dmitry B Zorov, H Bradley Nuss, Yael Yaniv, Kenneth W Fishbein, Rafael de Cabo, Lluis Montoliu, Sandra B Gabelli, Miguel A Aon, Sonia Cortassa, Steven J Sollott
    Abstract

    ATP synthase (F1Fo) synthesizes daily our body's weight in ATP, whose production-rate can be transiently increased several-fold to meet changes in energy utilization. Using purified mammalian F1Fo-reconstituted proteoliposomes and isolated mitochondria, we show F1Fo can utilize both ΔΨm-driven H+- and K+-transport to synthesize ATP under physiological pH = 7.2 and K+

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  • 7 Dec 2021 Journal Article Polymer Chemistry

    Porous polycaprolactone and polycarbonate poly(urethane urea)s via emulsion templating: structures, properties, cell growth

    Abstract

    PolyHIPEs, macroporous polymers templated within high internal phase emulsions (HIPEs), emulsions with over 74% internal phase, are almost always crosslinked to prevent collapse during drying. Here, elastomeric poly(urethane urea) (PUU) polyHIPEs with highly interconnected open-cell structures were synthesized in water-in-oil (w/o) HIPEs. The urethane reactions between

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  • 3 Dec 2021 Journal Article Biofabrication

    Human-engineered auricular reconstruction (hEAR) by 3D-printed molding with human-derived auricular and costal chondrocytes and adipose-derived mesenchymal …

    Abstract

    Microtia is a small, malformed external ear, which occurs at an incidence of 1–10 per 10 000 births. Autologous reconstruction using costal cartilage is the most widely accepted surgical microtia repair technique. Yet, the method involves donor-site pain and discomfort and relies on the artistic skill of the surgeon to create an aesthetic ear. This study employed novel

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  • 1 Dec 2021 Journal Article IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control

    Ultrasonic Thermal Monitoring of the Brain Using Golay Coded Excitations – Feasibility Study

    Daniel Dahis, Noy Farti, Tomer Romano, Natalie Artzi, Haim Azhari
    Abstract

    Thermal monitoring during Focused Ultrasound (FUS) transcranial procedures is mandatory and commonly performed by MRI. Transcranial ultrasonic thermal monitoring is an attractive alternative. Furthermore, using the therapeutic FUS transducer itself for this task is highly desirable. Nonetheless, such application is challenged by massive skull-induced signal attenuation

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  • 21 Nov 2021 Conference Paper 74th Annual Meeting of the APS Division of Fluid Dynamics

    Mathematical modelling and in vitro studies of high shear blood clot formation in a microfluidic system

    Edwina F Yeo, Yathreb Asaad, James M Oliver, Netanel Korin, Sarah L Waters
    Abstract

    Arterial blood clot formation (thrombosis) is the leading cause of both stroke and heart attack. Accurate prediction of clotting dynamics under high shear is a key part of developing safe and effective treatments. We use in vitro and mathematical modelling to examine high shear thrombosis in a microfluidic system. Thrombosis under pathologically high shear stresses

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  • 16 Nov 2021 Journal Article Bioengineering & Translational Medicine

    Ventilation-induced epithelial injury drives biological onset of lung trauma in vitro and is mitigated with prophylactic anti-inflammatory therapeutics

    Abstract

    Mortality rates among patients suffering from acute respiratory failure remain perplexingly high despite the maintenance of blood oxygen homeostasis during ventilatory support. The biotrauma hypothesis advocates that mechanical forces from invasive ventilation trigger immunological mediators that spread systemically. Yet, how these forces elicit an immune response

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  • 8 Nov 2021 Journal Article Circulation

    Detecting Peripheral Arterial Stenosis and Monitoring Atherosclerosis Severity

    Tomer Heitner, Amit Livneh, M Vargas, Jonathan Lorber, Ron Karmeli, Amir Landesberg
    Abstract

    Background: The AHA guidelines recommend measuring the Ankle-Brachial Index (ABI) for assessing the severity of atherosclerosis. There is also an unmet need for early detection of peripheral artery stenosis to reduce morbidity and tissue loss. However, the sensitivity of ABI in detecting arterial stenosis is limited in the presence of arterial stiffening (arteriosclerosis)

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  • 8 Nov 2021 Journal Article Circulation

    Quantifying the Respiratory Effort From Right Heart Catheterization Can Assist in Evaluating Heart Failure Severity

    Noa Markovitch, Shmuel Rispler, Yair Feld, Amir Solomonica, Sergey Yalonetsky, Anees Musallamis, Ariel Roguin, Arthur Kerner, Amir Landesberg
    Abstract

    Introduction: Right heart catheterization (RHC) provides objective assessment of heart failure (HF) severity. However, it is strongly affected by respiratory fluctuations, therefore various methods were suggested to correct these fluctuations. In contrast, we hypothesized that measurement of the respiratory effort in addition to the standard indices provides additional

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  • 1 Nov 2021 Conference Paper 2021 IEEE International Conference on Microwaves, Antennas, Communications and Electronic Systems (COMCAS)

    Deep-Learning based Motion Correction for Myocardial T1 Mapping

    Abstract

    Myocardial T 1 mapping is a cardiac MRI technique, used to assess myocardial fibrosis. In this technique, a series of T 1 -weighted MRI images are acquired with different saturation or inversion times. These images are fitted to the T 1 model to estimate the model parameters and construct the desired T 1 maps. In the presence of motion, the

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  • 1 Nov 2021 Journal Article 2021 IEEE International Conference on Microwaves, Antennas, Communications and Electronic Systems (COMCAS)

    Point-of-care detection of myocardial injury, a pre-clinical study

    Abstract

    Evaluation of myocardial function is critical in severe inflammations as myocarditis, COVID-19 and sepsis, since it can lead to organ failure and death. Point-of-care detection of myocardial injury may improve the treatment of these critically ill patients. The study aimed to develop point of care technology for assessing the systolic and diastolic cardiac functions in

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  • 1 Nov 2021 Conference Paper 2021 IEEE International Conference on Microwaves, Antennas, Communications and Electronic Systems (COMCAS)

    Peripheral Artery Stenosis Detection by Wavelet Coherence Analysis

    Abstract

    Peripheral arterial disease (PAD) is a pandemic affecting over 200 million patients facing a high risk of cardiovascular morbidity and mortality. Primary PAD evaluation and screening are performed by calculating the ankle to upper-arm (brachial) systolic pressure ratio (ABI) despite its severe limitations. Novel modality and indices are presented for non-invasive

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  • 1 Nov 2021 Conference Paper 2021 IEEE International Conference on Microwaves, Antennas, Communications and Electronic Systems (COMCAS)

    Non Parametric Data Augmentations Improve Deep-Learning based Brain Tumor Segmentation

    Abstract

    Automatic brain tumor segmentation from Magnetic Resonance Imaging (MRI) data plays an important role in assessing tumor response to therapy and personalized treatment stratification. Manual segmentation is tedious and subjective. Deep-learning based algorithms for brain tumor segmentation have the potential to provide objective and fast tumor segmentation. However, the

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  • 1 Nov 2021 Journal Article JACC: Clinical Electrophysiology

    Self-Similar Synchronization of Calcium and Membrane Potential Transitions During Action Potential Cycles Predict Heart Rate Across Species

    Syevda Tagirova Sirenko, Kenta Tsutsui, Kirill V Tarasov, Dongmei Yang, Ashley N Wirth, Victor A Maltsev, Bruce D Ziman, Yael Yaniv, Edward G Lakatta
    Abstract

    Objectives The purpose of this study was to discover regulatory universal mechanisms of normal automaticity in sinoatrial nodal (SAN) pacemaker cells that are self-similar across species. Background Translation of knowledge of SAN automaticity gleaned from animal studies to human dysrhythmias (e.g., “sick sinus” syndrome [SSS]) requiring electronic pacemaker insertion

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  • 28 Oct 2021 Journal Article Physiome

    Mathematical model of excitation-contraction in a uterine smooth muscle cell

    Weiwei Ai, Limor Freifeld, David Nickerson
    Abstract

    The Bursztyn et al. (2007) paper proposes a mathematical model of excitation-contraction in a myometrial smooth muscle cell (SMC). The model incorporates processes of intracellular Ca2+ concentration control, myosin light chain (MLC) phosphorylation and stress production. We create a modularized CellML implementation of the model, which is able to simulate these processes

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  • 28 Oct 2021 Patent

    PREDICTING VENTRICULAR FIBRILLATION

    Abstract

    A method comprising: at a training stage, training a machine learning algorithm on a training set comprising: (i) Heart Rate Variability (HRV) parameters extracted from temporal beat activity samples, wherein at least some of said samples include a representation of a Ventricular Fibrillation (VF) event, (ii) labels associated with one of: a first period of time

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  • 26 Oct 2021 Journal Article Advanced Functional Materials

    Engineered Vascularized Flaps, Composed of Polymeric Soft Tissue and Live Bone, Repair Complex Tibial Defects

    Idan Redenski, Shaowei Guo, Majd Machour, Ariel A Szklanny, Shira Landau, Ben Kaplan, Roberta I Lock, Yankel Gabet, Dana Egozi, Gordana Vunjak-Novakovic, Shulamit Levenberg
    Abstract

    Functional regeneration of complex large‐scaled defects requires both soft‐ and hard‐tissue grafts. Moreover, bone constructs within these grafts require an extensive vascular supply for survival and metabolism during the engraftment. Soft‐tissue pedicles are often used to vascularize bony constructs. However, extensive autologous tissue‐harvest required for the

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  • 25 Oct 2021 Journal Article International Journal of Molecular Sciences

    Heparin and Arginine Based Plasmin Nanoformulation for Ischemic Stroke Therapy

    Ramsha Aamir, Cameron Fyffe, Netanel Korin, Daniel A Lawrence, Enming J Su, Mathumai Kanapathipillai
    Abstract

    Ischemic stroke is the most common type of stroke and thrombolytic therapy is the only approved treatment. However, current thrombolytic therapy with tissue plasminogen activator (tPA) is often hampered by the increased risk of hemorrhage. Plasmin, a direct fibrinolytic, has a significantly superior hemostatic safety profile; however, if injected intravenously it

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  • 22 Oct 2021 Journal Article Frontiers in Bioengineering and Biotechnology

    Editorial: Innovative In Vitro Models for Pulmonary Physiology and Drug Delivery in Health and Disease

    Claus-Michael Lehr, Leslie Yeo, Josué Sznitman
    Abstract

    Respiratory diseases continue to exemplify a global leading cause of disability and mortality (Wisnivesky and De-Torres, 2019), with little signs of receding. In the midst of it, there is an ongoing and unmet need in treating such respiratory conditions. The situation has only been further exacerbated with the current COVID-19 pandemic and ensuing therapeutic challenges

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  • 19 Oct 2021 Journal Article Cancer Research

    T cells promote metastasis by regulating extracellular matrix remodeling following chemotherapy

    Jozafina Haj-Shomaly, Avital Vorontsova, Tamar Barenholz-Cohen, Oshrat Levi-Galibov, Mahesh Devarasetty, Michael Timaner, Ziv Raviv, Tim J Cooper, Shay Soker, Peleg Hasson, Daphne Weihs, Ruth Scherz-Shouval, Yuval Shaked
    Abstract

    Metastasis is the main cause of cancer-related mortality. Despite intense efforts to understand the mechanisms underlying the metastatic process, treatment of metastatic cancer is still challenging. Here we describe a chemotherapy-induced, host-mediated mechanism that promotes remodeling of the extracellular matrix (ECM), ultimately facilitating cancer cell seeding and

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  • 19 Oct 2021 Patent

    Flap for de-novo tissue regeneration

    Shulamit Levenberg, Dana Egozi, Jacob Koffler, Yulia Shandalov
    Abstract

    The present invention provides an implant which includes: (a) an autologous engineered tissue; and (b) a vasculature, wherein the engineered tissue is a porous scaffold embedded with endothelial cell, a fibroblast, a myoblast, a mesenchymal cell, an adipocyte, or any combination thereof, wherein the vasculature feeds the cells. Further, the invention provides a method

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  • 15 Oct 2021 Journal Article Science Advances

    GLUT4-overexpressing engineered muscle constructs as a therapeutic platform to normalize glycemia in diabetic mice

    Margarita Beckerman, Chava Harel, Inbal Michael, Amira Klip, Philip J Bilan, Emily J Gallagher, Derek Leroith, Lewis Eli Chaim, Eddy Karnieli, Shulamit Levenberg
    Abstract

    Skeletal muscle insulin resistance is a main defect in type 2 diabetes (T2D), which is associated with impaired function and content of glucose transporter type 4 (GLUT4). GLUT4 overexpression in skeletal muscle tissue can improve glucose homeostasis. Therefore, we created an engineered muscle construct (EMC) composed of GLUT4-overexpressing (OEG4) cells. The ability

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  • 6 Oct 2021 Journal Article iScience

    Leaders of the field: What does the future hold for single molecule technology?

    Chirlmin Joo, Amit Meller
    Abstract

    In recent years, single molecule technology has experienced a rapid growth, with exciting developments in fundamental research and real-world applications. Detecting and studying biological phenomena on the single molecule level requires a unique synergy between researchers working on instrumentation, physics, and the life sciences. In the iScience special issue ‘‘Single

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  • Oct 2021 Journal Article Advanced Materials

    3D Bioprinting of Engineered Tissue Flaps with Hierarchical Vessel Networks (VesselNet) for Direct Host-To-Implant Perfusion

    Abstract

    Engineering hierarchical vasculatures is critical for creating implantable functional thick tissues. Current approaches focus on fabricating mesoscale vessels for implantation or hierarchical microvascular in vitro models, but a combined approach is yet to be achieved to create engineered tissue flaps. Here, millimetric vessel-like scaffolds and 3D bioprinted vascularized

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  • 27 Sep 2021 Preprint medRxiv

    Descriptive characteristics of continuous oximetry measurement in moderate to severe COVID-19 patients

    Jonathan A Sobel, Jeremy Levy, Ronit Almog, Anat Reiner Benaim, Asaf Miller, Danny Eytan
    Abstract

    Background Non-invasive oxygen saturation (SpO2) measurement is a central vital sign that supports the management of COVID-19 patients. However, reports on SpO2 characteristics (patterns and dynamics) are scarce and none, to our knowledge, has analysed high resolution continuous SpO2 in COVID-19. Methods SpO2 signal sampled at 1Hz and clinical data were collected from

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  • 24 Sep 2021 Journal Article Journal of Biomechanics

    Mechanical interactions of invasive cancer cells through their substrate evolve from additive to synergistic

    Abstract

    Non-contacting, adjacent cancer cells can mechanically interact through their substrate to increase their invasive and migratory capacities that underly metastases-formation. Such mechanical interactions may induce additive or synergistic enhancement of invasiveness, potentially indicating different underlying force-mechanisms. To identify cell–cell-gel interactions

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  • 14 Sep 2021 Preprint Research Square

    Synthetic neuromorphic computing in living cells

    Abstract

    Biological regulatory networks in cells and neuronal networks employ complex circuit topologies with highly interconnected nodes to perform sophisticated information processing. Despite the complexity of neuronal networks, their information processing and computational capabilities can be recapitulated using simplified models comprising repeated connected nodes, e.g.

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  • 8 Sep 2021 Journal Article Frontiers in Physiology

    Ca2+ and Membrane Potential Transitions During Action Potentials Are Self-Similar to Each Other and to Variability of AP Firing Intervals Across the Broad Physiologic Range of AP Intervals During Autonomic Receptor Stimulation

    Dongmei Yang, Christopher H Morrell, Alexey E Lyashkov, Syevda Tagirova Sirenko, Ihor Zahanich, Yael Yaniv, Tatiana M Vinogradova, Bruce D Ziman, Victor A Maltsev, Edward G Lakatta
    Abstract

    Ca2+ and Vm transitions occurring throughout action potential (AP) cycles in sinoatrial nodal (SAN) cells are cues that (1) not only regulate activation states of molecules operating within criticality (Ca2+ domain) and limit-cycle (Vm domain) mechanisms of a coupled-clock system that underlies SAN cell automaticity, (2) but are also regulated by the activation states

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  • 6 Sep 2021 Preprint medRxiv

    Development of a machine-learning model to assess terminal ileum Endoscopic healing in pediatric Crohn's disease from Magnetic Resonance Enterography data

    Itai Guez, Gili Focht, Mary-Louise C Greer, Ruth Cytter-Kuint, Li-tal Pratt, Denise A Castro, Dan Turner, Anne M Griffiths, Moti Freiman
    Abstract

    Background and Aims Endoscopic healing (EH), is a major treatment goal for Crohn’s disease (CD). However, terminal ileum (TI) intubation failure is common, especially in children. We evaluated the added-value of machine-learning models in imputing a TI Simple Endoscopic Score for CD (SES-CD) from Magnetic Resonance Enterography (MRE) data of pediatric CD patients. Methods

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  • 1 Sep 2021 Preprint arXiv

    Fabrication of diffractive optical elements by programmable thermocapillary shaping of thin liquid films

    Abstract

    Diffractive optical elements (DOEs) enable precise manipulation of wavefronts and are widely used in a variety of optical systems. However, their fabrication relies on lithography or high precision machining processes that are long, expensive, and infrastructure-heavy. We here present a one-step rapid fabrication method that leverages the thermocapillary effect to shape

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  • 1 Sep 2021 Journal Article Current Opinion in Biotechnology

    Advances in vascularization and innervation of constructs for neural tissue engineering

    Abstract

    A growing number of technologies are being developed to promote vascularization and innervation in engineered tissues. Organ-on-a-chip, organoid and 3D printing technologies, as well as pre-vascularized and oriented scaffolds, have been employed for vascularization and innervation of engineered tissues both in vivo and in vitro. Both vascularization and innervation are

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  • 27 Aug 2021 Journal Article Science

    Airborne transmission of respiratory viruses

    Chia C Wang, Kimberly A Prather, Josué Sznitman, Jose L Jimenez, Seema S Lakdawala, Zeynep Tufekci, Linsey C Marr
    Abstract

    The COVID-19 pandemic has revealed critical knowledge gaps in our understanding of and a need to update the traditional view of transmission pathways for respiratory viruses. The long-standing definitions of droplet and airborne transmission do not account for the mechanisms by which virus-laden respiratory droplets and aerosols travel through the air and lead to

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  • 26 Aug 2021 Journal Article Frontiers in Molecular Biosciences

    The Dynamics of Lamin a During the Cell Cycle

    Abstract

    Lamin proteins play an essential role in maintaining the nuclear organization and integrity; and lamin A, in particular, plays a major role in the whole volume of the nuclear interior. Although the nucleus is highly organized, it is rather dynamic, it affects crucial nuclear processes and its organization must change as cells progress through the cell cycle. Although

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  • 24 Aug 2021 Journal Article Bioengineering & Translational Medicine

    Biophysical targeting of high-risk cerebral aneurysms

    Mark Epshtein, Moran Levi, Afif M Kraitem, Hikaia Zidan, Robert M King, Meinrad Gawaz, Matthew J Gounis, Netanel Korin
    Abstract

    Localized delivery of diagnostic/therapeutic agents to cerebral aneurysms, lesions in brain arteries, may offer a new treatment paradigm. Since aneurysm rupture leading to subarachnoid hemorrhage is a devastating medical emergency with high mortality, the ability to noninvasively diagnose high-risk aneurysms is of paramount importance. Moreover, treatment of unruptured

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  • 15 Aug 2021 Preprint arXiv

    NPBDREG: A Non-parametric Bayesian Deep-Learning Based Approach for Diffeomorphic Brain MRI Registration

    Abstract

    Quantification of uncertainty in deep-neural-networks (DNN) based image registration algorithms plays an important role in the safe deployment of real-world medical applications and research-oriented processing pipelines, and in improving generalization capabilities. Currently available approaches for uncertainty estimation, including the variational encoder-decoder

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  • 5 Aug 2021 Journal Article European Heart Journal - Digital Health

    Atrial fibrillation risk prediction from the 12-lead electrocardiogram using digital biomarkers and deep representation learning

    Shany Biton, Sheina Gendelman, Antônio H Ribeiro, Gabriela Miana, Carla Moreira, Antonio Luiz P Ribeiro, Joachim Behar
    Abstract
    Aims This study aims to assess whether information derived from the raw 12-lead electrocardiogram (ECG) combined with clinical information is predictive of atrial fibrillation (AF) development. Methods We use a subset of the Telehealth Network of Minas Gerais (TNMG) database consisting of patients that had repeated 12-lead ECG measurements between 2010-2017 that is… show more
  • 3 Aug 2021 Journal Article PNAS

    Investigating lymphangiogenesis in vitro and in vivo using engineered human lymphatic vessel networks

    Abstract

    The lymphatic system is involved in various biological processes, including fluid transport from the interstitium into the venous circulation, lipid absorption, and immune cell trafficking. Despite its critical role in homeostasis, lymphangiogenesis (lymphatic vessel formation) is less widely studied than its counterpart, angiogenesis (blood vessel formation). Although

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  • 1 Aug 2021 Journal Article American Journal of Hematology

    Imaging the dynamics and microstructure of fibrin clot polymerization in cardiac surgical patients using spectrally encoded confocal microscopy

    Diane M Tshikudi, Olivier Simandoux, Dongkyun Kang, Elizabeth M Van Cott, Michael N Andrawes, Dvir Yelin, Seemantini K Nadkarni
    Abstract

    During cardiac surgery with cardiopulmonary bypass (CPB), altered hemostatic balance may disrupt fibrin assembly, predisposing patients to perioperative hemorrhage. We investigated the utility of a novel device termed spectrally-encoded confocal microscopy (SECM) for assessing fibrin clot polymerization following heparin and protamine administration in CPB patients

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  • 29 Jul 2021 Journal Article Advanced Drug Delivery Reviews

    Advanced human-relevant in vitro pulmonary platforms for respiratory therapeutics

    Abstract

    Over the past years, advanced in vitro pulmonary platforms have witnessed exciting developments that are pushing beyond traditional preclinical cell culture methods. Here, we discuss ongoing efforts in bridging the gap between in vivo and in vitro interfaces and identify some of the bioengineering challenges that lie ahead in delivering new generations of human-relevant

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  • 26 Jul 2021 Preprint Social Science Research Network

    Single-Molecule, Non-Chromatic Discrimination in Binary Fluorophores Mixtures

    Abstract

    SummarySingle biomolecule sensing often involves quantification of multiple fluorescent species, coupled for example to different DNAs or proteins resides. While chromatic separation of the fluorescent species is well-established and broadly used it involves several limitations, particularly when the total photon budget is limited. Here we theoretically and experimentally

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  • 23 Jul 2021 Journal Article Cells

    Spinal Cord Repair: From Cells and Tissue Engineering to Extracellular Vesicles

    Abstract

    Spinal cord injury (SCI) is a debilitating condition, often leading to severe motor, sensory, or autonomic nervous dysfunction. As the holy grail of regenerative medicine, promoting spinal cord tissue regeneration and functional recovery are the fundamental goals. Yet, effective regeneration of injured spinal cord tissues and promotion of functional recovery remain

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  • 19 Jul 2021 Conference Paper OSA Imaging and Applied Optics Congress 2021

    Three-Dimensional Localization Microscopy by Deep Learning

    Abstract

    In this talk I will describe how joint optimization of the microscope’s point-spread-function alongside the image processing algorithm, both using neural nets, enables dense emitter fitting for super-resolution microscopy and other challenging volumetric microscopy applications.

  • 19 Jul 2021 Journal Article Optics Express

    Deep-ROCS: from speckle patterns to superior-resolved images by deep learning in rotating coherent scattering microscopy

    Alon Saguy, Felix Jünger, Aviv Peleg, Boris Ferdman, Elias Nehme, Alexander Rohrbach, Yoav Shechtman
    Abstract

    Rotating coherent scattering (ROCS) microscopy is a label-free imaging technique that overcomes the optical diffraction limit by adding up the scattered laser light from a sample obliquely illuminated from different angles. Although ROCS imaging achieves 150 nm spatial and 10 ms temporal resolution, simply summing different speckle patterns may cause loss of sample

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  • 16 Jul 2021 Preprint In Review

    P-selectin Targeting Stimulates Caveolin-1-Mediated Endothelial Transcytosis in Medulloblastoma

    Daniel Tylawsky, Hiro Kiguchi, Jake Vaynshteyn, Jeffrey Gerwin, Janki Shah, Taseen Islam, Matija Snuderl, Matthew B Greenblatt, Daniel Boué, Yosi Shamay, Praveen Raju, Daniel A Heller
    Abstract

    Medulloblastoma (MB) is the most common malignant pediatric brain tumor with ~30% mediated by Sonic hedgehog (SHH) signaling. While SHH effector Smoothened inhibition is promising, therapeutic index is reduced by high systemic doses required for sufficient intracranial drug concentrations. Treatment-related toxicities associated with radiation therapy result in lifelong

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  • 12 Jul 2021 Conference Paper IEEE International Workshop on Medical Measurement and Applications (MEMEA)

    Measurement of Enhanced Photothermal Effects of CuO-encapsulated Polymeric Nanospheres

    Sanzhar Korganbayev, Somayeh Asadi, Inbal Maor, Emiliano Schena, Haim Azhari, Iris S Weitz, Paola Saccomandi
    Abstract

    Copper oxide nanoparticles (CuO-NPs) have the potential of serving as an anticancer theranostic agent with photothermal capabilities. In order to control their toxicity and release, the CuO NPs were encapsulated within polymeric nanospheres composed of poly(lactic-co-glycolic acid) (PLGA) core and polydopamine (PDA)/polyethylene glycol (PEG) shell. After the characterization

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  • 5 Jul 2021 Journal Article ACS Nano

    Fast and Deterministic Fabrication of Sub-5 Nanometer Solid-State Pores by Feedback-Controlled Laser Processing

    Abstract

    Nanopores are single-molecule sensors capable of detecting and quantifying a broad range of unlabeled biomolecules including DNA and proteins. Nanopores’ generic sensing principle has permitted the development of a vast range of biomolecular applications in genomics and proteomics, including single-molecule DNA sequencing and protein fingerprinting. Owing to their

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  • 2 Jul 2021 Journal Article Nano Letters

    Multiplexed PSF Engineering for Three-Dimensional Multicolor Particle Tracking

    Abstract

    Three-dimensional spatiotemporal tracking of microscopic particles in multiple colors is a challenging optical imaging task. Existing approaches require a trade-off between photon efficiency, field of view, mechanical complexity, spectral specificity, and speed. Here, we introduce multiplexed point-spread-function engineering that achieves photon-efficient, 3D multicolor

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  • 1 Jul 2021 Journal Article IEEE Transactions on Pattern Analysis and Machine Intelligence

    Learning Optimal Wavefront Shaping for Multi-Channel Imaging

    Abstract

    Fast acquisition of depth information is crucial for accurate 3D tracking of moving objects. Snapshot depth sensing can be achieved by wavefront coding, in which the point-spread function (PSF) is engineered to vary distinctively with scene depth by altering the detection optics. In low-light applications, such as 3D localization microscopy, the prevailing approach is

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  • 1 Jul 2021 Journal Article Advanced Functional Materials

    Injectability of Biosynthetic Hydrogels: Consideration for Minimally Invasive Surgical Procedures and 3D Bioprinting

    Abstract

    Injectable hydrogels are often preferred when designing carriers for cell therapy or developing new bio-ink formulations. Biosynthetic hydrogels, which are a class of materials made with a hybrid design strategy, can be advantageous for endowing injectability while maintaining biological activity of the material. The chemical modification required to make these gels

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  • 30 Jun 2021 Journal Article Frontiers in Physiology

    Opening the Schrödinger Box: Short- and Long-Range Mammalian Heart Rate Variability

    Abstract

    Background: The interactions between the autonomic nervous system (ANS), intrinsic systems (e.g., endocrine), and internal pacemaker mechanisms govern short (milliseconds–seconds)- and long (seconds–minutes)-range heart rate variability (HRV). However, there is a debate regarding the identity of the mechanism underlying HRV on each time scale. We aim to design a general

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  • 22 Jun 2021 Preprint bioRxiv

    Computational neural network provides naturalistic solution for recovery of finger dexterity after stroke

    Abstract

    Finger dexterity is a fundamental movement skill of humans and the ability to individuate fingers imparts high motor flexibility. Disruption of dexterity due to brain injury imposes a detriment to quality of life, and thus understanding the neurological mechanisms responsible for recovery is imperative for neurorehabilitation. Two neuronal pathways have been proposed

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  • 21 Jun 2021 Conference Paper 2021 Conference on Lasers and Electro-Optics Europe (CLEO/Europe)

    Photon-efficient three-dimensional simultaneous multicolor particle tracking by multiplexed PSF engineering

    Abstract

    Real-time microscopic tracking of multicolor fluorescent probes in 3D is of key importance for understanding a variety of biological processes. Point-Spread-Function (PSF) engineering is an effective tool for such tasks – by modulating the PSF of the optical system, emitters can be tracked with nm-scale resolution in 3D by means of computational analysis [1] . Existing

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  • 21 Jun 2021 Conference Paper 2021 Conference on Lasers and Electro-Optics Europe (CLEO/Europe)

    Liquid immersion enables 3D printable diffractive optical elements

    Abstract

    Diffractive optical elements, used to shape the wavefront of incident light, are ubiquitous in optics thanks to the high flexibility in design and compactness that they offer [1]. However, the nanoscale-precision requirements typically necessitates a complicated fabrication process, e.g. nanolithography. Here we present the liquid immersed DOE. By immersing the DOE in

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  • 15 Jun 2021 Journal Article PNAS

    Meeting the unmet needs of clinicians from AI systems showcased for cardiology with deep-learning–based ECG analysis

    Abstract

    Despite their great promise, artificial intelligence (AI) systems have yet to become ubiquitous in the daily practice of medicine largely due to several crucial unmet needs of healthcare practitioners. These include lack of explanations in clinically meaningful terms, handling the presence of unknown medical conditions, and transparency regarding the system’s limitations

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  • 12 Jun 2021 Journal Article Biomechanics and Modeling in Mechanobiology

    Rapid, quantitative prediction of tumor invasiveness in non-melanoma skin cancers using mechanobiology-based assay

    Sally Kortam, Yulia Merkher, Aviv Kramer, Issa Metanes, Dean Ad-El, Judit Krausz, Yaron Har-Shai, Daphne Weihs
    Abstract

    Non-melanoma skin cancers, including basal and squamous cell carcinomas (BCC and SCC), are the most common malignancies worldwide. BCC/SCC cancers are generally highly localized and can be surgically excised; however, invasive tumors may be fatal. Current diagnosis of skin cancer and prognosis of potential invasiveness are based mainly on clinical-pathological factors

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  • 10 Jun 2021 Journal Article The Journal of Physical Chemistry B

    Automated Analysis of Fluorescence Kinetics in Single-Molecule Localization Microscopy Data Reveals Protein Stoichiometry

    Alon Saguy, Tim N Baldering, Lucien E Weiss, Elias Nehme, Christos Karathanasis, Marina S Dietz, Mike Heilemann, Yoav Shechtman
    Abstract

    Understanding the function of protein complexes requires information on their molecular organization, specifically, their oligomerization level. Optical super-resolution microscopy can localize single protein complexes in cells with high precision, however, the quantification of their oligomerization level, remains a challenge. Here, we present a Quantitative Algorithm

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  • 9 Jun 2021 Journal Article Journal of Biomechanics

    Towards homogenization of liquid plug distribution in reconstructed 3D upper airways of the preterm infant

    Abstract

    Liquid plug therapies are commonly instilled in premature babies suffering from infant respiratory distress syndrome (IRDS) by a procedure called surfactant replacement therapy (SRT) in which a surfactant-laden bolus is instilled endotracheally in the neonatal lungs, dramatically reducing mortality and morbidity in neonatal populations. Since data are frequently limited

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  • 9 Jun 2021 Journal Article Vascularization for Tissue Engineering and Regenerative Medicine

    Co-culture systems for vasculogenesis

    Abstract

    Vascularization is a fundamental aspect of tissue engineering and is one of the main challenges in the field when trying to construct thick tissues. Co-culture systems have demonstrated promising potential in construction of vascularized tissues, and in enhancing graft viability and persistence in vivo. In this chapter, we discuss pivotal studies integrating co-cultures

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  • 7 Jun 2021 Journal Article Nature Methods

    The emerging landscape of single-molecule protein sequencing technologies

    Javier Antonio Alfaro, Peggy Bohländer, Mingjie Dai, Mike Filius, Cecil J Howard, Xander F van Kooten, Shilo Ohayon, Adam Pomorski, Sonja Schmid, Aleksei Aksimentiev, Eric V Anslyn, Georges Bedran, Chan Cao, Mauro Chinappi, Etienne Coyaud, Cees Dekker, Gunnar Dittmar, Nicholas Drachman, Rienk Eelkema, David Goodlett, Sébastien Hentz, Umesh Kalathiya, Neil L Kelleher, Ryan T Kelly, Zvi Kelman, Sung Hyun Kim, Bernhard Kuster, David Rodriguez-Larrea, Stuart Lindsay, Giovanni Maglia, Edward M Marcotte, John P Marino, Christophe Masselon, Michael Mayer, Patroklos Samaras, Kumar Sarthak, Lusia Sepiashvili, Derek Stein, Meni Wanunu, Mathias Wilhelm, Peng Yin, Amit Meller, Chirlmin Joof
    Abstract

    Single-cell profiling methods have had a profound impact on the understanding of cellular heterogeneity. While genomes and transcriptomes can be explored at the single-cell level, single-cell profiling of proteomes is not yet established. Here we describe new single-molecule protein sequencing and identification technologies alongside innovations in mass spectrometry

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  • 5 Jun 2021 Journal Article International Journal of Molecular Sciences

    Photo-Polymerization Damage Protection by Hydrogen Sulfide Donors for 3D-Cell Culture Systems Optimization

    Silvia Buonvino, Matteo Ciocci, Dror Seliktar, Sonia Melino
    Abstract

    Photo-polymerized hydrogels are ideally suited for stem-cell based tissue regeneration and three dimensional (3D) bioprinting because they can be highly biocompatible, injectable, easy to use, and their mechanical and physical properties can be controlled. However, photo-polymerization involves the use of potentially toxic photo-initiators, exposure to ultraviolet light

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  • Jun 2021 Journal Article Journal of Aerosol Medicine and Pulmonary Drug Delivery

    Surfactant foam therapy for severe COVID-19 patients with acute respiratory distress syndrome (ARDS)

    Abstract

    The SARS-CoV-2 virus enters primarily through the respiratory tract and penetrates epithelial cells. In severe cases, the disease deteriorates to a form of acute respiratory distress syndrome (ARDS) and is accountable for most deaths. To date, there is no effective pharmacological treatment in ARDS in adults with mortality rates around 40%. One of the hallmarks of ARDS

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  • 30 May 2021 Journal Article International Journal of Molecular Sciences

    Tumor Extracellular Matrix Stiffness Promptly Modulates the Phenotype and Gene Expression of Infiltrating T Lymphocytes

    Maila Chirivì, Fabio Maiullari, Marika Milan, Dario Presutti, Chiara Cordiglieri, Mariacristina Crosti, Maria Lucia Sarnicola, A Soluri, Marina Volpi, Wojciech Swieszkowski, Daniele Prati, Marta Rizzi, Marco Costantini, Dror Seliktar, Chiara Parisi, Claudia Bearzi, Roberto Rizzi
    Abstract

    The immune system is a fine modulator of the tumor biology supporting or inhibiting its progression, growth, invasion and conveys the pharmacological treatment effect. Tumors, on their side, have developed escaping mechanisms from the immune system action ranging from the direct secretion of biochemical signals to an indirect reaction, in which the cellular actors of

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  • 27 May 2021 Preprint bioRxiv

    Separation of multiple motor memories through implicit and explicit processes

    Abstract

    Acquisition of multiple motor skills without interference is a remarkable ability in sport and daily life. During adaptation to opposing perturbations, a common paradigm to study this ability, each perturbation can be successfully learned when a dynamical contextual cue, such as a follow-through movement, is associated with the direction of the perturbation. It is still

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  • 25 May 2021 Journal Article Nature Communications

    Synthetic neural-like computing in microbial consortia for pattern recognition

    Abstract

    Complex biological systems in nature comprise cells that act collectively to solve sophisticated tasks. Synthetic biological systems, in contrast, are designed for specific tasks, following computational principles including logic gates and analog design. Yet such approaches cannot be easily adapted for multiple tasks in biological contexts. Alternatively, artificial

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  • 25 May 2021 Journal Article Scientific Reports

    Alginate hydrogel beads embedded with drug-bearing polycaprolactone microspheres for sustained release of paclobutrazol

    Alexandra Mun, Haneen Simaan Yameen, Giora Edelbaum, Dror Seliktar
    Abstract

    In recent years there has been a growing demand for the development of agrochemical controlled release (CR) technologies. In the present study, we aimed to create a novel agricultural CR device using two polymeric systems that have been predominantly employed in biomedical applications: beads of alginate hydrogel embedded with drug-bearing Polycaprolactone (PCL)

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  • 24 May 2021 Journal Article Nature Communications

    3D printable diffractive optical elements by liquid immersion Associated Content

    Abstract

    Diffractive optical elements (DOEs) are used to shape the wavefront of incident light. This can be used to generate practically any pattern of interest, albeit with varying efficiency. A fundamental challenge associated with DOEs comes from the nanoscale-precision requirements for their fabrication. Here we demonstrate a method to controllably scale up the relevant

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  • 21 May 2021 Preprint bioRxiv

    Bioluminescent Synthetic Cells Communicate with Natural Cells and Self-Activate Light-Responsive Proteins

    Abstract

    Development of regulated cellular processes and signaling methods in synthetic cells is essential for their integration with living materials. Light is an attractive tool to achieve this, but the limited penetration depth into tissue of visible light restricts its usability for in-vivo applications. Here, we describe the synthesis and application of blue-light-generating

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  • 21 May 2021 Journal Article ACS Synthetic Biology

    A Whole-Cell Bacterial Biosensor for Blood Markers Detection in Urine

    Abstract

    The early detection of blood in urine (hematuria) can play a crucial role in the treatment of serious diseases (e.g., infections, kidney disease, schistosomiasis, and cancer). Therefore, the development of low-cost portable biosensors for blood detection in urine has become necessary. Here, we designed an ultrasensitive whole-cell bacterial biosensor interfaced with an

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  • 21 May 2021 Journal Article Nucleic Acids Research

    Topologies of synthetic gene circuit for optimal fold change activation

    Abstract

    Computations widely exist in biological systems for functional regulations. Recently, incoherent feedforward loop and integral feedback controller have been implemented into Escherichia coli to achieve a robust adaptation. Here, we demonstrate that an indirect coherent feedforward loop and mutual inhibition designs can experimentally improve the fold change of promoters

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  • 14 May 2021 Journal Article frontiers in Medicine

    Comparing COVID-19 and Influenza Presentation and Trajectory

    Anat Reiner Benaim, Jonathan A Sobel, Ronit Almog, Snir Lugassy, Tsviel Ben Shabbat, Alistair E W Johnson, Danny Eytan, Joachim Behar
    Abstract

    Background: COVID-19 is a newly recognized illness with a predominantly respiratory presentation. It is important to characterize the differences in disease presentation and trajectory between COVID-19 patients and other patients with common respiratory illnesses. These differences can enhance knowledge of pathogenesis and help in guiding treatment. Methods: Data from

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  • 14 May 2021 Journal Article Physiological Measurement

    From sleep medicine to medicine during sleep - a clinical perspective

    Nitai Bar, Jonathan A Sobel, Thomas Penzel, Yosi Shamay, Joachim Behar
    Abstract

    Objective. In this perspective paper, we aim to highlight the potential of sleep as an auspicious time for diagnosis, management and therapy of non-sleep-specific pathologies. Approach. Sleep has a profound influence on the physiology of body systems and biological processes. Molecular studies have shown circadian-regulated shifts in protein expression patterns across

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  • 5 May 2021 Journal Article IEEE Transactions on NanoBioscience

    Formation of Large Intracellular Actin Networks Following Plasmonic Cell Fusion

    Abstract

    Following fusion between two or more individual cells, the resulting cellular entity must undergo extensive restructuring of its plasma membrane and cytoskeleton in order to maintain its mechanical and physiological function. In artificial cell fusion that is executed by external triggering, such restructuring could be problematic due to the absence of preconditioning

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  • 5 May 2021 Journal Article Arteriosclerosis, Thrombosis, and Vascular Biology

    Circulating Wnt Ligands Activate the Wnt Signaling Pathway in Mature Erythrocytes

    Ronen Siman-Tov, Natalie Zelikson, Michal Caspi, Yakir Levi, Chava Perry, Fayhaa Khair, Hagit Stauber, Josué Sznitman, Rina Rosin-Arbesfeld
    Abstract

    Objective: The deformation ability of erythrocytes is critical for their function and affects their mobility in the circulation. To circulate and travel through narrow vessels, erythrocytes must continuously alter their shape by modifying their cytoskeleton, which controls their elasticity and stability. Erythrocytes lack nuclei and other major organelles, and thus most

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