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Clinico-pathological and transcriptomic analysis of radiation-induced lung injury in non-human primates.

Int J Radiat Oncol Biol Phys 2021 Apr 10. Epub 2021 Apr 10.

Department of Pathology, Section on Comparative Medicine, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157-1040, USA. Electronic address:

Purpose: Radiation-induced lung injury (RILI) is a progressive condition, with an early phase, radiation pneumonitis (RP), and a late phase, lung fibrosis (LF). RILI may occur after partial-body ionizing radiation exposures or by internal radioisotope exposure, with wide individual variability in timing and extent of lung injury. This study aims to provide new insights into the pathogenesis and progression of RILI in the non-human primate (NHP) rhesus macaque model. Read More

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Inflammasome Genetic Variants, Macrophage Function, and Clinical Outcomes in Cystic Fibrosis.

Am J Respir Cell Mol Biol 2021 Apr 13. Epub 2021 Apr 13.

University of Washington, 7284, Biostatistics, Seattle, Washington, United States.

Cystic fibrosis (CF) is characterized by chronic airway infection, inflammation, and tissue damage that lead to progressive respiratory failure. NLRP3 and NLRC4 are cytoplasmic pattern recognition receptors that activate the inflammasome, initiating a caspase-1 mediated response. We hypothesized that gain of function inflammasome responses are associated with worse outcomes in children with CF. Read More

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Potential role of cannabidiol in Parkinson's disease by targeting the WNT/β-catenin pathway, oxidative stress and inflammation.

Aging (Albany NY) 2021 Apr 13;13. Epub 2021 Apr 13.

Centre de Recherche Clinique, Grand Hôpital de l'Est Francilien (GHEF), Meaux 77100, France.

Parkinson's disease (PD) is a major neurodegenerative disease (ND), presenting a progressive degeneration of the nervous system characterized by a loss of dopamine in the substantia nigra pars compacta. Recent findings have shown that oxidative stress and inflammation play key roles in the development of PD. However, therapies remain uncertain and research for new treatment is of the utmost importance. Read More

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Repeat stereotactic radiosurgery for progressive vestibular schwannomas after previous radiosurgery: a systematic review and meta-analysis.

Neurosurg Rev 2021 Apr 13. Epub 2021 Apr 13.

Department of Clinical Neurosciences, Neurosurgery Service and Gamma Knife Center, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.

Vestibular schwannomas (VS) are slow-growing intracranial extraaxial benign tumors, developing from the vestibular part of the eight cranial nerves. Stereotactic radiosurgery (SRS) has now a long-term scientific track record as first intention treatment for small- to medium-sized VS. Though its success rate is very high, SRS for VS might fail to control tumor growth in some cases. Read More

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Rotational Position of the Aortic Root is Associated with Increased Aortic Dimensions in Marfan and Loeys-Dietz Syndrome.

Pediatr Cardiol 2021 Apr 13. Epub 2021 Apr 13.

The Heart Institute, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH, 45229, USA.

Progressive aortic dilation is common in Marfan syndrome (MFS) and Loeys-Dietz syndrome (LDS). Risk factors for progression are poorly understood. Normal variation in the aortic root (AoR) rotational position relative to the left ventricular base may impact this risk. Read More

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Thromboelastography is a Marker for Clinically Significant Progressive Hemorrhagic Injury in Severe Traumatic Brain Injury.

Neurocrit Care 2021 Apr 12. Epub 2021 Apr 12.

Department of Pharmacy, Mayo Clinic, Rochester, MN, USA.

Background: Coagulopathy in traumatic brain injury (TBI) is associated with increased risk of poor outcomes, but accurate prediction of clinically significant progressive hemorrhagic injury (PHI) in patients with severe TBI remains a challenge. Thromboelastography (TEG) is a real-time test of whole blood coagulation that provides dynamic information about global hemostasis. This study aimed to identify differences in TEG values between patients with severe TBI who did or did not experience clinically significant PHI. Read More

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The curious consistency of carbon biosignatures over billions of years of Earth-life coevolution.

ISME J 2021 Apr 12. Epub 2021 Apr 12.

Department of Molecular and Cellular Biology, University of Arizona, Tucson, AZ, USA.

The oldest and most wide-ranging signal of biological activity (biosignature) on our planet is the carbon isotope composition of organic materials preserved in rocks. These biosignatures preserve the long-term evolution of the microorganism-hosted metabolic machinery responsible for producing deviations in the isotopic compositions of inorganic and organic carbon. Despite billions of years of ecosystem turnover, evolutionary innovation, organismic complexification, and geological events, the organic carbon that is a residuum of the global marine biosphere in the rock record tells an essentially static story. Read More

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The association of enteric neuropathy with gut phenotypes in acute and progressive models of Parkinson's disease.

Sci Rep 2021 Apr 12;11(1):7934. Epub 2021 Apr 12.

Department of Medicine, Western Health, Melbourne University, Sunshine, VIC, 3021, Australia.

Parkinson's disease (PD) is associated with neuronal damage in the brain and gut. This work compares changes in the enteric nervous system (ENS) of commonly used mouse models of PD that exhibit central neuropathy and a gut phenotype. Enteric neuropathy was assessed in five mouse models: peripheral injection of MPTP; intracerebral injection of 6-OHDA; oral rotenone; and mice transgenic for A53T variant human α-synuclein with and without rotenone. Read More

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The power of three-dimensional printing technology in functional restoration of rare maxillomandibular deformity due to genetic disorder: a case report.

J Med Case Rep 2021 Apr 12;15(1):197. Epub 2021 Apr 12.

Oral and Maxillofacial Surgery, Oral Medicine Institute, Galilee Medical Center, Nahariya, Israel.

Background: Thalassemia is an inherited autosomal recessive blood disorder causing abnormal formation of hemoglobin, known as a syndrome of anemia with microcytic erythrocytes. It is the most common genetic disorder worldwide, with a high prevalence among individuals of Mediterranean descent. The state of homozygosity of the beta-globin mutated gene is known as beta-thalassemia major, and these patients require regular blood transfusions and iron chelation therapy for survival. Read More

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Sacral chordoma with incidental rectal adenocarcinoma: a case report.

J Med Case Rep 2021 Apr 12;15(1):195. Epub 2021 Apr 12.

King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.

Background: We report a unique case of synchronous sacrococcygeal chordoma in association with rectal invasive adenocarcinoma. Retrorectal tumors are a rare disease caused by a variety of pathologies. To our knowledge, no prior cases of such a coincidental finding of both cancers have been reported in the literature. Read More

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Functional interpretation of ATAD3A variants in neuro-mitochondrial phenotypes.

Genome Med 2021 Apr 12;13(1):55. Epub 2021 Apr 12.

Aging and Metabolism Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, 73104, USA.

Background: ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear-encoded mitochondrial membrane-anchored protein involved in diverse processes including mitochondrial dynamics, mitochondrial DNA organization, and cholesterol metabolism. Biallelic deletions (null), recessive missense variants (hypomorph), and heterozygous missense variants or duplications (antimorph) in ATAD3A lead to neurological syndromes in humans.

Methods: To expand the mutational spectrum of ATAD3A variants and to provide functional interpretation of missense alleles in trans to deletion alleles, we performed exome sequencing for identification of single nucleotide variants (SNVs) and copy number variants (CNVs) in ATAD3A in individuals with neurological and mitochondrial phenotypes. Read More

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Longitudinal assessment of IFN-I activity and immune profile in critically ill COVID-19 patients with acute respiratory distress syndrome.

Crit Care 2021 04 12;25(1):140. Epub 2021 Apr 12.

Immunology Laboratory, Hôpital E. Herriot - Hospices Civils de Lyon, 5 place d'Arsonval, 69437, Lyon Cedex 03, France.

Background: Since the onset of the pandemic, only few studies focused on longitudinal immune monitoring in critically ill COVID-19 patients with acute respiratory distress syndrome (ARDS) whereas their hospital stay may last for several weeks. Consequently, the question of whether immune parameters may drive or associate with delayed unfavorable outcome in these critically ill patients remains unsolved.

Methods: We present a dynamic description of immuno-inflammatory derangements in 64 critically ill COVID-19 patients including plasma IFNα2 levels and IFN-stimulated genes (ISG) score measurements. Read More

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Potential of medicinal plants as neuroprotective and therapeutic properties against amyloid-β-related toxicity, and glutamate-induced excitotoxicity in human neural cells.

Curr Neuropharmacol 2021 Apr 11. Epub 2021 Apr 11.

Department of Health Sciences, Faculty of Medicine and Health Sciences, University of Mauritius, Réduit. Mauritius.

Alzheimer's disease (AD) and Parkinson disease (PD) are notorious neurodegenerative diseases amongst the general population. Being age-associated diseases, the prevalence of AD and PD is forecasted to rapidly escalate with the progressive aging population of the world. These diseases are complex and multifactorial. Read More

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Analysis of Clinical, Imaging, and Pathologic Features of 36 Patients with Primary Intraspinal Primitive Neuroectodermal Tumors: A Case Series and Literature Review.

J Neurol Surg A Cent Eur Neurosurg 2021 Apr 12. Epub 2021 Apr 12.

Department of Neurosurgery, General Hospital Of NingXia Medical University, Yinchuan, Republic of China.

Background And Study Aims:  Primary intraspinal primitive neuroectodermal tumors (PNETs) account for ∼0.4% of all intraspinal tumors, but information about these tumors in the medical literature is limited to single case reports. We report four cases of primary intraspinal PNETs and present a systematic literature review of the reported cases. Read More

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Classification of pedicle ossification after maxillofacial reconstruction with bony free flap: An observational study.

J Stomatol Oral Maxillofac Surg 2021 Apr 9. Epub 2021 Apr 9.

University of Lille, CHU Lille, INSERM, Service de Chirurgie Maxillo-Faciale et Stomatologie, U1008 - Controlled Drug Delivery Systems and Biomaterials, Lille, France.

Introduction: Maxillofacial reconstruction with bony free flap is a classical technique. However, pedicle ossification after such reconstruction is a misunderstood complication that is rarely reported in the literature. It is usually manifested as trismus, neck pain, and hard swelling, but it is predominantly asymptomatic and, thus, mainly incidentally discovered at a later stage. Read More

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Gabapentin attenuates somatic signs of precipitated THC withdrawal in mice.

Neuropharmacology 2021 Apr 9:108554. Epub 2021 Apr 9.

Department of Psychology, West Virginia University, Morgantown, WV, USA; School of Nursing, University of Connecticut, Storrs, CT, USA. Electronic address:

Cannabis is the most frequently used federally illicit substance in the United States. However, there are currently no FDA-approved pharmacotherapies to mitigate the withdrawal symptoms associated with cessation in heavy users. A promising, readily available non-cannabinoid therapy are the gabapentinoids. Read More

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Diabetes, insulin and new therapeutic strategies for Parkinson's disease: focus on glucagon-like peptide-1 receptor agonists.

Front Neuroendocrinol 2021 Apr 9:100914. Epub 2021 Apr 9.

Laboratory of Cellular and Molecular Neurobiology of Parkinson's disease, Research Center for Molecular Medicine and Chronic Diseases (CIMUS), IDIS, University of Santiago de Compostela, Santiago de Compostela, Spain; Networking Research Center on Neurodegenerative Diseases (CiberNed), Spain.

Parkinson's disease and diabetes mellitus are two chronic disorders associated with aging that are becoming increasingly prevalent worldwide. Parkinson is a multifactorial progressive condition with no available disease modifying treatments at the moment. Over the last few years there is growing interest in the relationship between diabetes (and impaired insulin signaling) and neurodegenerative diseases, as well as the possible benefit of antidiabetic treatments as neuroprotectors, even in non-diabetic patients. Read More

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Tremelimumab plus durvalumab retreatment and 4-year outcomes in patients with mesothelioma: a follow-up of the open label, non-randomised, phase 2 NIBIT-MESO-1 study.

Lancet Respir Med 2021 Apr 9. Epub 2021 Apr 9.

Center for Immuno-Oncology, Medical Oncology and Immunotherapy, Department of Oncology, University Hospital of Siena, Siena, Italy; EPigenetic Immune-Oncology Consortium Airc (EPICA), Rome, Italy; Department of Medicine, Surgery, and Neuroscience, University of Siena, Siena, Italy; Fondazione Italian Network for Tumour Biotherapy (NIBIT) Onlus, Siena, Italy. Electronic address:

Background: The NIBIT-MESO-1 study demonstrated the efficacy and safety of tremelimumab combined with durvalumab in patient with unresectable mesothelioma followed up for a median of 52 months [IQR 49-53]. Here, we report 4-year survival and outcomes after retreatment, and the role of tumour mutational burden (TMB) in identifying patients who might have a better outcome in response to combined therapy.

Methods: NIBIT-MESO-1 was an open-label, non-randomised, phase 2 trial of patients with unresectable pleural or peritoneal mesothelioma who received intravenous tremelimumab (1 mg/kg bodyweight) and durvalumab (20 mg/kg bodyweight) every 4 weeks for four doses, followed by maintenance intravenous durvalumab at the same dose and schedule for nine doses. Read More

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[Thrombotic thrombocytopenic purpura, in a HIV-infected patient. Case report].

Rev Chilena Infectol 2021 Feb;38(1):108-113

Fundación Cardio-infantil, Bogotá, Colombia.

Hematological manifestations for human immunodeficiency virus (HIV) infection are frequent and diverse due to its ability to affect almost all cell lines. Among these, thrombotic thrombocytopenic purpura (TTP) is one of the thrombotic microangiopathies syndromes, characterized by the presence of thrombocytopenia and microangiopathic hemolytic anemia with impaired renal function. Nowadays, the relationship between these two entities is rare given the current highly active antiretroviral therapy (HAART). Read More

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February 2021

Elevated Ambulatory Blood Pressure Measurements are Associated with a Progressive Form of Fabry Disease.

High Blood Press Cardiovasc Prev 2021 Apr 12. Epub 2021 Apr 12.

Department of Medicine and Surgery, University of Milano-Bicocca, Via G.B. Pergolesi, 33, 20900, Monza, Italy.

 INTRODUCTION: Published data on hypertension incidence and management in Anderson-Fabry disease are scant and the contribution of elevated blood pressure to organ damage is not well recognized.

Aim: Therefore, we have assessed blood pressure values and their possible correlations with clinical findings in a well described cohort of Fabry patients.

Methods: Between January 2015 and May 2019, all adult Fabry patients (n = 24 females, n = 8 males) referred to our institute were prospectively enrolled. Read More

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Nrf2 as a potential target for Parkinson's disease therapy.

J Mol Med (Berl) 2021 Apr 12. Epub 2021 Apr 12.

The Institute of Medicine, Qiqihar Medical University, 333 BuKui Street, JianHua District, Qiqihar, 161006, China.

Parkinson's disease (PD) is a complex neurodegenerative disorder featuring both motor and nonmotor symptoms associated with a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Conventionally, PD treatment options have focused on dopamine replacement and provide only symptomatic relief. However, disease-modifying therapies are still unavailable. Read More

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Uncovering the prevalence and neural substrates of anhedonia in frontotemporal dementia.

Brain 2021 Apr 12. Epub 2021 Apr 12.

The University of Sydney, Brain and Mind Centre, Sydney, New South Wales, Australia.

Much of human behaviour is motivated by the drive to experience pleasure. The capacity to envisage pleasurable outcomes and to engage in goal-directed behaviour to secure these outcomes depends upon the integrity of frontostriatal circuits in the brain. Anhedonia refers to the diminished ability to experience, and to pursue, pleasurable outcomes, and represents a prominent motivational disturbance in neuropsychiatric disorders. Read More

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Optimizing the treatment sequence from second-line to third-line therapy in patients with metastatic colorectal cancer.

Clin Adv Hematol Oncol 2020 Jan;18 Suppl 2(1):1-24

Division of Oncology, Medical University of Vienna, Vienna, Austria.

In clinical trials of metastatic colorectal cancer, progressive disease after second-line therapy is often defined according to Response Evaluation Criteria in Solid Tumors criteria. In the clinic, however, disease progression can be identified through a composite of factors, including new lesions, carcinoembryonic antigen level, and symptoms such as pain and fatigue. It is optimal to switch to third-line treatment before the patient's performance status deteriorates. Read More

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January 2020

Physeal Fractures of Distal Tibia: A Systematic Review and Meta-analysis.

J Pediatr Orthop 2021 Apr 12. Epub 2021 Apr 12.

Department of Pediatric Surgery, Kuopio University Hospital, Kuopio Department of Pediatric Surgery and Orthopaedics, PEDEGO Research Unit, Oulu University Hospital, University of Oulu, Oulu Department of Orthopedics and Traumatology, HEPO Research Unit, Helsinki University Central Hospital, Helsinki, Finland.

Background: Fractures involving the distal tibia growth plate are common in children. Injury or treatment that damages the growth plate may result in progressive angular deformity or leg length discrepancy. There is no consensus on treatment and follow-up of these injuries. Read More

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Difficulty in articulation following left progressive blurred vision.

Eur J Ophthalmol 2021 Apr 10:11206721211008037. Epub 2021 Apr 10.

College of Medicine, Chang Gung University, Taoyuan.

Purpose: To report a case of Paracentral acute middle maculopathy (PAMM) caused by severe internal carotid artery (ICA) stenosis and discuss the correlation between PAMM and ICA stenosis.

Case Description: A 67-year-old male patient presented with left acute blurred vision for 1 week. The best-corrected visual acuity of the left eye was 0. Read More

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AAV-mediated overexpression of IL-10 affects the immunomodulatory properties of equine bone marrow-derived mesenchymal stem cells.

Hum Gene Ther 2021 Apr 11. Epub 2021 Apr 11.

University of Pennsylvania, 6572, Clinical Studies, New Bolton Center, 382 West Street Road, Kennett Square, Pennsylvania, United States, 19348;

Joint injury can cause posttraumatic inflammation, which if severe enough can lead to posttraumatic osteoarthritis (PTOA), a progressive and debilitating condition. Posttraumatic inflammation is characterized by an influx of T lymphocytes and upregulation of inflammatory cytokines and degradative enzymes by activated chondrocytes and synoviocytes. Intra-articular bone marrow-derived mesenchymal stem cell (BM-MSC) injection for the treatment of OA has been of interest due to the immunomodulatory properties of these cells. Read More

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A Bayesian Disease Progression Model for Clinical Trajectories.

Graphs Biomed Image Anal Integr Med Imaging Nonimaging Modalities (2018) 2018 Sep 16;11044:57-65. Epub 2018 Sep 16.

Schools of ECE and BME, Cornell University, Ithaca, USA.

In this work, we consider the problem of predicting the course of a progressive disease, such as cancer or Alzheimer's. Progressive diseases often start with mild symptoms that might precede a diagnosis, and each patient follows their own trajectory. Patient trajectories exhibit wild variability, which can be associated with many factors such as geno-type, age, or sex. Read More

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September 2018

Targeting metastatic breast cancer: problems and potential.

F1000 Fac Rev 2015 4;4. Epub 2015 Jun 4.

Metastasis Susceptibility Section, Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Breast cancer is one of the leading causes of cancer-related mortality of women in the United States. Since the majority of cancer deaths are due to metastases rather than the primary tumor, a better understanding of the biological mechanisms that lead to metastatic disease is critical to reduce breast cancer associated mortality. Current adjuvant therapies use the same broadly cytotoxic and targeted strategies against metastases as are used against the primary tumor. Read More

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Posterior Spinal Correction and Fusion Surgery in Patients with Spinal Muscular Atrophy-Associated Scoliosis for Whom Treatment with Nusinersen Was Planned.

Spine Surg Relat Res 2021 31;5(2):109-113. Epub 2020 Aug 31.

Department of Orthopaedic Surgery, School of Medicine, Kitasato University, Sagamihara, Kanagawa, Japan.

Introduction: Spinal muscular atrophy (SMA) is defined as a neuromuscular disorder induced by progressive weakness of the skeletal muscle and is usually accompanied by progressive spinal deformity including scoliosis. The newly developed Nusinersen, which is the first approved drug worldwide for SMA, requires accurate intrathecal injection, which is sometimes difficult in patients with severe spinal deformity.

Technical Note: For an accurate intrathecal approach in patients who have spinal fusion surgery to treat neuromuscular scoliosis, we have combined an L3 laminectomy with spinal correction and fusion surgery. Read More

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Aberrantly Expressed Galectin-9 Is Involved in the Immunopathogenesis of Anti-MDA5-Positive Dermatomyositis-Associated Interstitial Lung Disease.

Front Cell Dev Biol 2021 25;9:628128. Epub 2021 Mar 25.

Department of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship Hospital, Beijing, China.

Background: Dermatomyositis (DM) associated rapidly progressive interstitial lung disease (RP-ILD) has high mortality rate and poor prognosis. Galectin-9 (Gal-9) plays multiple functions in immune regulation. We investigated Gal-9 expression in DM patients and its association with DM-ILD. Read More

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