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Anatomic Eligibility for Endovascular Aneurysm Repair Preserved Over Two Years of Surveillance.

J Vasc Surg 2021 May 3. Epub 2021 May 3.

School of Medicine and Public Health, Division of Vascular Surgery, University of Wisconsin.

Objective: Endovascular aneurysm repair (EVAR) is a widely used option for patients with suitable vascular anatomy who have a large infrarenal abdominal aortic aneurysm (AAA). Patients with small AAAs are managed with careful surveillance and it is a common concern that their anatomy may change with AAA growth, and their option for EVAR may become limited. Device innovation has resulted in expanded ranges of anatomy that may be eligible for EVAR. Read More

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The PDB and protein homeostasis: from chaperones to degradation and disaggregase machines.

Authors:
Helen R Saibil

J Biol Chem 2021 May 3:100744. Epub 2021 May 3.

Institute of Structural and Molecular Biology, Birkbeck, University of London, Malet St, London, WC1E 7HX, UK. Electronic address:

This review contains a personal account of the role played by the PDB in the development of the field of molecular chaperones and protein homeostasis, from the viewpoint of someone who experienced the concurrent advances in the structural biology, electron microscopy and chaperone fields. The emphasis is on some key structures, including those of Hsp70, GroEL, Hsp90 and small heat shock proteins, that were determined as the molecular chaperone concept and systems for protein quality control were emerging. These structures were pivotal in demonstrating how seemingly non-specific chaperones could assist the specific folding pathways of a variety of substrates. Read More

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Structure and Mechanics of Dynein Motors.

Annu Rev Biophys 2021 May;50:549-574

Biophysics Graduate Group, University of California, Berkeley, California 94720, USA; email:

Dyneins make up a family of AAA+ motors that move toward the minus end of microtubules. Cytoplasmic dynein is responsible for transporting intracellular cargos in interphase cells and mediating spindle assembly and chromosome positioning during cell division. Other dynein isoforms transport cargos in cilia and power ciliary beating. Read More

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The entry reaction of the plant shikimate pathway is subjected to highly complex metabolite-mediated regulation.

Plant Cell 2021 May;33(3):671-696

Department of Botany, University of Wisconsin-Madison, 430 Lincoln Dr. Madison, WI 53706, USA.

The plant shikimate pathway directs bulk carbon flow toward biosynthesis of aromatic amino acids (AAAs, i.e. tyrosine, phenylalanine, and tryptophan) and numerous aromatic phytochemicals. Read More

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Compound heterozygous p. Arg949Trp and p. Gly970Ala mutations deteriorated the function of PEX1p: A study on PEX1 in a patient with Zellweger syndrome.

J Cell Biochem 2021 May 6. Epub 2021 May 6.

Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Postal Code 81746-73441, Iran.

The peroxisome is responsible for a variety of vital pathways in primary metabolism, including the very long-chain fatty-acid oxidation and plasmalogen lipid biosynthesis. Autosomal recessive disorder of the Zellweger spectrum (ZSD) is a major subset of peroxisome biogenesis disorders (PBDs) that can be caused by mutations in any of the 14 PEX genes. Zellweger syndrome (ZS) is the foremost common and severe phenotype within the heterogeneous ZSD. Read More

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Chemerin-9 Attenuates Experimental Abdominal Aortic Aneurysm Formation in ApoE Mice.

J Oncol 2021 17;2021:6629204. Epub 2021 Apr 17.

Department of Vascular Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Chronic inflammation plays an essential role in the pathogenesis of abdominal aortic aneurysm (AAA), a progressive segmental abdominal aortic dilation. Chemerin, a multifunctional adipocytokine, is mainly generated in the liver and adipose tissue. The combination of chemerin and chemokine-like receptor 1 (CMKLR1) has been demonstrated to promote the progression of atherosclerosis, arthritis diseases, and Crohn's disease. Read More

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Unconventional p97/VCP-Mediated ER to Endosomal Trafficking of a Retroviral Protein.

J Virol 2021 May 5. Epub 2021 May 5.

Department of Molecular Biosciences, Center for Infectious Disease, and Institute for Cellular and Molecular Biology, The University of Texas at Austin, Austin, TX

Mouse mammary tumor virus (MMTV) encodes a Rem precursor protein that specifies both regulatory and accessory functions. Rem is cleaved at the ER membrane into a functional N-terminal signal peptide (SP) and the C-terminus (Rem-CT). Rem-CT lacks a membrane-spanning domain and a known ER retention signal, yet was not detectably secreted into cell supernatants. Read More

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Aortic neck IFU violations during EVAR for ruptured infrarenal aortic aneurysms are associated with increased in-hospital mortality.

Ann Vasc Surg 2021 May 2. Epub 2021 May 2.

Division of Vascular Surgery and Endovascular Therapy, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.

Objective: Vascular surgeons treating patients with ruptured abdominal aortic aneurysm (rAAA) must make rapid treatment decisions and sometimes lack immediate access to endovascular devices meeting the anatomic specifications of the patient at hand. We hypothesized that endovascular treatment of rAAA (rEVAR) outside manufacturer instructions-for-use (IFU) guidelines would have similar in-hospital mortality compared to patients treated on-IFU or with an infrarenal clamp during open repair (rOAR).

Methods: Vascular Quality Initiative (VQI) datasets for endovascular and open aortic repair were queried for patients presenting with ruptured infrarenal AAA between 2013-2018. Read More

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Plasma amino acid profiles in dogs with closed extrahepatic portosystemic shunts are only partially improved 3 months after successful gradual attenuation.

J Vet Intern Med 2021 May 5. Epub 2021 May 5.

Small Animal Department, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.

Background: Dogs with portosystemic shunts have an altered blood amino acid profile, with an abnormal branched-chained amino acid (BCAA)-to-aromatic amino acid (AAA) ratio being the most common abnormality. Different liver diseases have distinctive amino acid profiles.

Objectives: Determine the changes in plasma amino acid profiles in dogs with extrahepatic portosystemic shunts (EHPSS) from diagnosis to complete closure. Read More

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Exergaming as a Functional Test Battery in Patients Who Received Arthroscopic Ankle Arthrodesis: Cross-sectional Pilot Study.

JMIR Rehabil Assist Technol 2021 May 5;8(2):e21924. Epub 2021 May 5.

Zuyderland Medical Centre, Sittard, Netherlands.

Background: Recently, movement-based videogames (exergames) have gained popularity in improving the rehabilitation process after surgery. During exergaming, participants are physically challenged as the game component stimulates adherence to the training program. There is no literature on the effect of exergame training interventions in patients who received arthroscopic ankle arthrodesis. Read More

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Development and implementation of a community-based research network.

J Clin Transl Sci 2020 May 18;4(6):508-514. Epub 2020 May 18.

Program in Occupational Therapy, Washington University in St. Louis, St. Louis, MO, USA.

Introduction: People aging with long-term physical disabilities (PAwLTPD), meaning individuals with onset of disability from birth through midlife, often require long-term support services (LTSS) to remain independence. The LTSS system is fragmented into aging and disability organizations with little communication between them. In addition, there are currently no evidence-based LTSS-type programs listed on the Administration for Community Living website that have been demonstrated to be effective for PAwLTPD. Read More

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Vitamin K Dependent Matrix Gla Protein Relating to Abdominal Aortic Aneurysm and Overall Mortality: A Combined Case Control and Cohort Study.

Eur J Vasc Endovasc Surg 2021 May 1. Epub 2021 May 1.

Department of Cardiac, Thoracic and Vascular Surgery, Odense University Hospital, Odense, Denmark; Vascular Research Unit, Regional Hospital Central Denmark, Viborg, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.

Objective: Inactivation of matrix Gla protein (MGP), using vitamin K antagonists or vitamin K deficiency results in increased vascular calcification, which has been associated with increased risk of symptomatic or ruptured abdominal aortic aneurysm (AAA). Insufficient activation of MGP leads to increased levels of undercarboxylated forms of MGP, measured as a dephosphorylated, undercarboxylated MGP (dp-ucMGP) in plasma. This study aimed to investigate whether the level of inactivated MGP influenced the risk of having an AAA, the risk of AAA progression, and overall mortality. Read More

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Ruptured abdominal aortic aneurysm repair using open proximal anastomosis under deep hypothermic circulatory arrest.

Ann Vasc Surg 2021 May 1. Epub 2021 May 1.

Department of Cardiovascular Surgery, Iwate Medical University, 2-1-1 Idaidori, Yahaba-cho, Shiwa, Iwate 028-3695, Japan. Electronic address:

Proximal aortic clamping under normothermia is generally adequate for operative repair of abdominal aortic rupture; however, the hypothermic circulatory arrest technique is not as common. Proximal exposure and clamping are sometimes difficult due to the risk of bleeding, rerupture, and ischemia. We present a successful case of a ruptured abdominal aortic aneurysm (AAA) that was repaired using cardiopulmonary bypass with hypothermic circulatory arrest. Read More

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Lenvatinib in Patients With Advanced Grade 1/2 Pancreatic and Gastrointestinal Neuroendocrine Tumors: Results of the Phase II TALENT Trial (GETNE1509).

J Clin Oncol 2021 May 4:JCO2003368. Epub 2021 May 4.

Clinical Oncology Unit, AOU Careggi, Firenze, Italy and Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.

Purpose: Approved systemic therapies for advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have shown limited capacity to reduce tumor burden and no antitumor activity after progression to targeted agents (TAs). We investigated the efficacy and safety of lenvatinib in patients with previously treated advanced GEP-NETs.

Patients And Methods: This was a multicenter, single-arm, open-label, phase II trial with two parallel cohorts (ClinicalTrials. Read More

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Mol Pharmacol 2021 May 3. Epub 2021 May 3.

Biosciences Institute, Newcastle University, United Kingdom

DNA topoisomerase II (TOP2) poisons induce protein-DNA crosslinks termed TOP2-DNA covalent complexes, in which TOP2 remains covalently bound to each end of an enzyme-induced double strand DNA break (DSB) via a 5'-phosphotyrosyl bond. Repair of the enzyme-induced DSB first requires the removal of the TOP2 protein adduct which, among other mechanisms, can be accomplished through the proteasomal degradation of TOP2. VCP/p97 is a AAA ATPase which utilises energy from ATP hydrolysis to unfold protein substrates, which can facilitate proteasomal degradation by extracting target proteins from certain cellular structures (such as chromatin) and/or by aiding their translocation into the proteolytic core of the proteasome. Read More

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Aortic endograft sizing and endoleak, reintervention and mortality following endovascular aneurysm repair.

J Vasc Surg 2021 Apr 30. Epub 2021 Apr 30.

Division of Vascular and Endovascular Surgery, Department of Surgery, Saint Louis University. Electronic address:

Objectives: Endograft sizing for endovascular abdominal aortic repair (EVAR) is not consistent despite published instructions for use (IFU). We sought to identify factors associated with over/undersizing, determine sex influence on sizing, and examine sizing effects on endoleak, reintervention, and mortality by analyzing data obtained from the W.L. Read More

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Three-dimensional ultrasound improves identification of patients with abdominal aortic aneurysms reaching the threshold for repair.

J Vasc Surg 2021 Apr 30. Epub 2021 Apr 30.

Department of Vascular Surgery, Rigshospitalet, University of Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark; Copenhagen Academy of Medical Education and Simulation, Capital Region of Denmark, Copenhagen, Denmark.

Objectives: Conventional two-dimensional ultrasound (2D-US) is the recommended and preferred modality for diagnosis and surveillance of abdominal aortic aneurysms (AAAs). Aneurysm diameter based on three-dimensional ultrasound (3D-US) has shown promising results in a research setup, improving agreement and reproducibility. Studies evaluating 3D-US in a clinical context are lacking and may hinder optimal utilization of this new modality. Read More

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The Fate of Endoleaks After EVAR and the Impact of Oral Anticoagulation on Their Persistence.

J Vasc Surg 2021 Apr 30. Epub 2021 Apr 30.

Division of Vascular Surgery, Penn State Heart and Vascular Institute, Penn State College of Medicine, Hershey, PA.

Introduction: The impact of anticoagulation on late endoleaks after endovascular aneurysm repair (EVAR) is unclear despite multiple investigators studying the relationship. The purpose of this study was to determine if long-term anticoagulation impacted the development of late endoleaks and if specific anticoagulants were more likely to exacerbate the development of endoleaks.

Methods: Using the Society for Vascular Surgery Vascular Quality Initiative (VQI) database, patients undergoing EVAR between 2003 and 2019 for abdominal aortic aneurysms (AAA) were evaluated. Read More

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The relation between physical fitness, frailty and all-cause mortality after elective endovascular abdominal aortic aneurysm repair.

J Vasc Surg 2021 Apr 30. Epub 2021 Apr 30.

Department of Vascular Surgery, Rijnstate, Arnhem; Multi-Modality Medical Imaging group, TechMed Centre, University of Twente, Enschede, The Netherlands. Electronic address:

Background: Accurate determination of probable surgical outcomes is fundamental in decision-making regarding appropriate abdominal aortic aneurysm (AAA) treatment. These outcomes depend, among other factors, on patient-related factors such as physical fitness. The primary aim of this study was to evaluate the correlation between physical fitness, measured by the metabolic equivalent of task (MET) score and the 5-factor modified frailty index (MFI-5), and all-cause mortality. Read More

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Erratum to: AAA Research Methodology I: Overcoming Linguistic and Cultural Barriers in Aging Research Among Asians: Presenter Discussion.

Innov Aging 2021 22;5(2):igab007. Epub 2021 Apr 22.

Georgia Institute of Technology, Atlanta, Georgia, United States.

[This corrects the article DOI: 10.1093/geroni/igaa057.3519. Read More

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High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms and Improved Prognostic Stratification With the New World Health Organization 2019 Classification: A Validation Study From a Single-Institution Retrospective Analysis.

Pancreas 2021 Apr;50(4):516-523

From the Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital.

Objectives: There is a pressing need to develop clinical management pathways for grade 3 (G3) gastroenteropancreatic neuroendocrine neoplasms (GEP NEN).

Methods: We performed a retrospective study on patients with metastatic G3 GEP NEN. The relationship between baseline characteristics and progression-free survival and overall survival was analyzed using the Kaplan-Meier method. Read More

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Pilot Study of Endovascular Delivery of Mesenchymal Stromal Cells in the Aortic Wall in a Pig Model.

Cell Transplant 2021 Jan-Dec;30:9636897211010652

Stem Cell Center, 14644Texas Heart Institute, Houston, Texas, USA.

Abdominal aortic aneurysms (AAAs) have a high mortality. In small-animal models, multipotent mesenchymal stromal cells (MSCs) have shown benefits in attenuating aneurysm formation. However, an optimal cell delivery strategy is lacking. Read More

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CT-less Direct Correction of Attenuation and Scatter in the Image Space Using Deep Learning for Whole-Body FDG PET: Potential Benefits and Pitfalls.

Radiol Artif Intell 2021 Mar 2;3(2):e200137. Epub 2020 Dec 2.

Department of Radiology and Biomedical Imaging (J.Y., J.H.S., S.C.B., G.TG., Y.S.) and Physics Research Laboratory (J.Y., G.T.G., Y.S.), University of California, San Francisco, 185 Berry St, Suite 350, San Francisco, CA 94143-0946.

Purpose: To demonstrate the feasibility of CT-less attenuation and scatter correction (ASC) in the image space using deep learning for whole-body PET, with a focus on the potential benefits and pitfalls.

Materials And Methods: In this retrospective study, 110 whole-body fluorodeoxyglucose (FDG) PET/CT studies acquired in 107 patients (mean age ± standard deviation, 58 years ± 18; age range, 11-92 years; 72 females) from February 2016 through January 2018 were randomly collected. A total of 37. Read More

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Transposition of the Inferior Vena Cava (IVC) in a Patient with an Infrarenal Abdominal Aortic Aneurysm (AAA).

Eur J Vasc Endovasc Surg 2021 Apr 28. Epub 2021 Apr 28.

Vascular Surgery Unit, Department of Surgery, Mater Dei Hospital, Malta.

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Investigating the impact of driving automation systems on distracted driving behaviors.

Accid Anal Prev 2021 Apr 28;156:106152. Epub 2021 Apr 28.

AAA Foundation for Traffic Safety, 607 14thStreet NW, Suite 201, Washington D.C., 20005 USA.

Driving automation systems (e.g., SAE Level 2) ultimately aim to enhance the comfort and safety of drivers. Read More

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Significant Aortic Neck Dilation Occurs Following Repair of Juxtarenal Aneurysms with Fenestrated Endovascular Aneurysm Repair.

J Vasc Surg 2021 Apr 27. Epub 2021 Apr 27.

Division of Vascular Surgery, Department of Surgery. University of Washington, Seattle WA.

Objectives: Aortic neck dilation is a reported mode of failure and can be associated with aneurysm sac expansion following standard endovascular repair of aortic aneurysms. Fenestrated repairs of the juxtarenal segment increase the seal zone length and are often utilized to treat this disease progression. However, the frequency and risk factors for neck dilation following fenestrated repairs is unknown. Read More

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TROPHY-U-01: A Phase II Open-Label Study of Sacituzumab Govitecan in Patients With Metastatic Urothelial Carcinoma Progressing After Platinum-Based Chemotherapy and Checkpoint Inhibitors.

J Clin Oncol 2021 Apr 30:JCO2003489. Epub 2021 Apr 30.

Fred Hutchinson Cancer Research Center, University of Washington, Seattle Cancer Care Alliance, Seattle, WA.

Purpose: Patients with metastatic urothelial carcinoma (mUC) who progress on platinum-based combination chemotherapy (PLT) and checkpoint inhibitors (CPIs) have limited options that offer objective response rates (ORRs) of approximately 10% with a median overall survival (OS) of 7-8 months. Sacituzumab govitecan (SG) is a TROP-2-directed antibody-drug conjugate with an SN-38 payload that has shown preliminary activity in mUC.

Methods: TROPHY-U-01 (ClinicalTrials. Read More

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Molecular insights into substrate recognition and discrimination by the N-terminal domain of Lon AAA+ protease.

Elife 2021 Apr 30;10. Epub 2021 Apr 30.

Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.

The Lon AAA+ protease (LonA) is a ubiquitous ATP-dependent proteolytic machine, which selectively degrades damaged proteins or native proteins carrying exposed motifs (degrons). Here we characterize the structural basis for substrate recognition and discrimination by the N-terminal domain (NTD) of LonA. The results reveal that the six NTDs are attached to the hexameric LonA chamber by flexible linkers such that the formers tumble independently of the latter. Read More

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Cellular and Molecular Imaging with SPECT and PET in Brain Tumors.

Radiol Clin North Am 2021 May;59(3):363-375

The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, 601 North Caroline Street, JHOC 3150, Baltimore, MD 21287, USA. Electronic address:

This review highlights the 2 major molecular imaging modalities that are used in clinics, namely single-photon emission computed tomography (SPECT) and positron emission tomography (PET), and their added value in management of patients with brain tumors. There are a variety of SPECT and PET radiotracers that can allow imaging of different molecular processes. Those radiotracers target specific molecular features of tumors, resulting in improved specificity of these agents. Read More

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Imaging Predictive Factors of Abdominal Aortic Aneurysm Growth.

J Clin Med 2021 Apr 28;10(9). Epub 2021 Apr 28.

Vascular Surgery Department, Larissa University Hospital, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41110 Larissa, Greece.

Background: Variable imaging methods may add important information about abdominal aortic aneurysm (AAA) progression. The aim of this study is to assess available literature data regarding the predictive imaging factors of AAA growth.

Methods: This systematic review was conducted using the PRISMA guidelines. Read More

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