tbuckley/cabot-search huggingface dataset:
Abstract P090: Health Informatics Approach to Investigation of Hyperlipidemia in Families
Authors: Lee A Pyles, Amy P Joseph, Matthew Armistead, Christa I Lilly, Jeff Cox, Michael Denney, William A Neal, Charles J Mullett
Journal: Circulation (2018)

Introduction: West Virginia exhibits pervasive cardiovascular disease (CVD) that may relate to a combination of ancestry and shared environment in families, including vulnerabilities related to diet, physical activity and tobacco use. Coronary Artery Risk Detection in Appalachian Communities (CARDIAC) is a school-based child risk factor screening program that has evaluated over 90,000 WV fifth graders in the past 20 years. Reverse Cascade screening for Familial Hypercholesterolemia (FH) has been difficult with the CARDIAC population. The WVU CTSI Integrated Data Repository (IDR) includes over 2 million records. Hypothesis: Linkage of child CARDIAC data to parent IDR data will allow new information discovery to inform management of CVD. Methods: We used direct demographic data linkage via Oracle with Soundex conversion of names, in the IDR, to find parents of the CARDIAC participants. Data was analyzed in the VMWare SSL environment. Results: 4759 children have a parent(s) identified. 959 mothers and 524 fathers have an LDL level from IDR. Race, BMI and gender was recorded from CARDIAC. 6.8 % of children, 40% of mothers and 44.8% of fathers have an abnormal LDL level &gt;130 mg/dl in IDR. Positive predictive value of the abnormal child lipid level (≥130 mg/dl) is 17% for some parent (56/325) to be abnormal. 4 parents had LDL &gt;190 mg/dl with child &gt; 160, indicating likely FH in the pair (2.7% of pairs or 1 in 371 pairs). Conclusion: Formation of a virtual cohort of CARDIAC children and parents allows Virtual Reverse Cascade Screening to find FH. This project highlights the importance of familial tendency to hyperlipidemia that can aid detection of early lipid abnormality and cardiovascular risk in children and their young parents to promote wellness and potentially avoid early coronary artery disease. We are constructing a virtual longitudinal cohort to study CVD in WV as a part of a Learning Health System in which data management is at the forefront of healthcare improvement.
Adaptive Introgression across Semipermeable Species Boundaries between Local Helicoverpa zea and Invasive Helicoverpa armigera Moths
Authors: Wendy A Valencia-Montoya, Samia Elfekih, Henry L North, Joana I Meier, Ian A Warren, Wee Tek Tay, Karl H J Gordon, Alexandre Specht, Silvana V Paula-Moraes, Rahul Rane, Tom K Walsh, Chris D Jiggins
Journal: Molecular Biology and Evolution (2020)

Abstract Hybridization between invasive and native species has raised global concern, given the dramatic increase in species range shifts and pest outbreaks due to anthropogenic dispersal. Nevertheless, secondary contact between sister lineages of local and invasive species provides a natural laboratory to understand the factors that determine introgression and the maintenance or loss of species barriers. Here, we characterize the early evolutionary outcomes following secondary contact between invasive Helicoverpa armigera and native H. zea in Brazil. We carried out whole-genome resequencing of Helicoverpa moths from Brazil in two temporal samples: during the outbreak of H. armigera in 2013 and 2017. There is evidence for a burst of hybridization and widespread introgression from local H. zea into invasive H. armigera coinciding with H. armigera expansion in 2013. However, in H. armigera, the admixture proportion and the length of introgressed blocks were significantly reduced between 2013 and 2017, suggesting selection against admixture. In contrast to the genome-wide pattern, there was striking evidence for adaptive introgression of a single region from the invasive H. armigera into local H. zea, including an insecticide resistance allele that increased in frequency over time. In summary, despite extensive gene flow after secondary contact, the species boundaries are largely maintained except for the single introgressed region containing the insecticide-resistant locus. We document the worst-case scenario for an invasive species, in which there are now two pest species instead of one, and the native species has acquired resistance to pyrethroid insecticides through introgression.
Safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes (PIONEER 10): an open-label, randomised, active-controlled, phase 3a trial
Authors: Daisuke Yabe, Jiro Nakamura, Hideaki Kaneto, Srikanth Deenadayalan, Andrea Navarria, Mette Gislum, Nobuya Inagaki, T Arisaka, T Asakura, N Azuma, S Fukuda, Y Fukushima, N Harada, S Inoue, H Ishida, H Ishii, S Ishikawa, H Jinnouchi, S Kaneko, K Kanno, M Kato, Y Kato, T Kawada, H Kim, A Kiyosue, O Matsuoka, O Miho, S Nakamoto, S Nakamura, S Nakanishi, H Nishimura, A Numata, T Ohama, T Okabe, F Okuguchi, T Osonoi, T Sasaki, H Seino, K Shin, T Shiraiwa, T Sugiura, S Wada, A Yamauchi
Journal: The Lancet Diabetes & Endocrinology (2020)
Cost-effectiveness of Telemedicine-directed Specialized vs Standard Care for Patients With Inflammatory Bowel Diseases in a Randomized Trial
Authors: Marin J. de Jong, Annelies Boonen, Andrea E. van der Meulen-de Jong, Mariëlle J. Romberg-Camps, Ad A. van Bodegraven, Nofel Mahmmod, Tineke Markus, Gerard Dijkstra, Bjorn Winkens, Astrid van Tubergen, Ad Masclee, Daisy M. Jonkers, Marie J. Pierik
Journal: Clinical Gastroenterology and Hepatology (2020)
Monitoring Clinical Course and Treatment Response in Chronic Inflammatory Demyelinating Polyneuropathy During Routine Care
Authors: Jeffrey A. Allen, Ingemar S. J. Merkies, Richard A. Lewis
Journal: JAMA Neurology (2020)

Identifying clinical change in many neurologic diseases, including chronic inflammatory demyelinating polyneuropathy (CIDP), can be challenging. At the same time, how change is defined heavily influences a patient's diagnostic and treatment pathway. It can be especially problematic when equivocal subjective observations are interpreted as clinically meaningful and then used to make diagnostic and treatment decisions. Change in clinical trials is strictly defined by a preselected metric, but there is a perception that formal outcomes collection during routine clinical care is neither feasible nor necessary. Given the importance placed on how change is interpreted, there is a need to select assessments that can be applied to routine care that are representative of the neurologic disease state.For an outcome measure to be useful during clinical trials, it must have good reliability, validity, be responsive to change, and have clinical meaning. To be useful during routine clinical care, the assessment must additionally be easy to collect without the need for extensive training or equipment and should provide an immediately available result that can be rapidly quantified and interpreted. Chronic inflammatory demyelinating polyneuropathy is clinically heterogeneous and so is best evaluated with a diverse group of assessment tools. Assessing strength impairment, disability, and quality of life is ideally suited for everyday practice when caring for patients with CIDP. While electrophysiologic studies, imaging, cerebrospinal fluid, and nodal/paranodal antibodies can provide diagnostic data, they are less practical and helpful longitudinal assessment tools.Sound clinimetric outcome measures in CIDP are widely available and have the potential to help clinicians objectify treatment response and disease progression. Such data are critically important when justifying the need for ongoing or periodic immunotherapy, documenting relapse or deterioration, or providing reassurance of disease improvement, stability, or remission.
Clare Gerada: Understanding burnout
Authors: Clare Gerada
Journal: BMJ (2020)

In my early 40s I felt exhausted: I was juggling general practice, motherhood, and carving a career in addiction. More than this, I’d lost my joy and zest for work. It had become routine—and, if I’m honest, caring for patients had become a burden. Until then I’d been an idealistic, enthusiastic, engaged GP and had truly loved my work, especially the patient facing aspects. But now, medicine had lost its spark.

Looking back, I had classic burnout. Burnout is formally defined as a state of physical, emotional, and mental exhaustion caused by long term involvement in demanding situations. For me it conjures up an image of “destroyed” individuals, shells of their former selves, …
Longitudinal Antibody Signatures Following FVIII Replacement Therapy in Previously Untreated Patients with Severe Hemophilia Α- New Insights from the Hemophilia Inhibitor PUP Study (HIPS)
Authors: Bagirath Gangadharan, Birgit Reipert, Fritz Scheiflinger, Joel Bowen, Elizabeth Donnachie, Karin Fijn van Draat, Ralph A. Gruppo, Jenny Klintman, Christoph Male, Catherine E. McGuinn, Shannon L. Meeks, Michael Recht, Margaret V. Ragni, Hassan M. Yaish, Amy D. Shapiro, Donald L Yee, Vlad Calin Radulescu, Elena Santagostino, Deborah Brown
Journal: Blood (2017)
Mitigating the Consequences of Subconcussive Head Injuries
Authors: Eric A. Nauman, Thomas M. Talavage, Paul S. Auerbach
Journal: Annual Review of Biomedical Engineering (2020)

Subconcussive head injury represents a pathophysiology that spans the expertise of both clinical neurology and biomechanical engineering. From both viewpoints, the terms injury and damage, presented without qualifiers, are synonymously taken to mean a tissue alteration that may be recoverable. For clinicians, concussion is evolving from a purely clinical diagnosis to one that requires objective measurement, to be achieved by biomedical engineers. Subconcussive injury is defined as subclinical pathophysiology in which underlying cellular- or tissue-level damage (here, to the brain) is not severe enough to present readily observable symptoms. Our concern is not whether an individual has a (clinically diagnosed) concussion, but rather, how much accumulative damage an individual can tolerate before they will experience long-term deficit(s) in neurological health. This concern leads us to look for the history of damage-inducing events, while evaluating multiple approaches for avoiding injury through reduction or prevention of the associated mechanically induced damage.
Telomere length in patients with unclassifiable interstitial lung disease: a cohort study
Authors: Brett Ley, Shuo Liu, Brett M. Elicker, Travis S. Henry, Eric Vittinghoff, Jeffrey A. Golden, Kirk D. Jones, Paul J. Wolters
Journal: European Respiratory Journal (2020)

Up to 15% of patients with chronic interstitial lung disease (cILD) will remain clinically unclassifiable ( i.e. unclassifiable ILD, uILD) despite thorough clinical evaluation and multidisciplinary team discussion (MDT) [1, 2]. This diagnostic uncertainty translates into uncertainty in expected prognosis and initial treatment approach ( e.g. immunosuppression versus anti-fibrotic medications) for patients with uILD, and it often precludes enrolment into clinical trials. Peripheral blood telomere length (TL) is a genomic biomarker that has been associated with prognosis and harm from immunosuppression in IPF [3, 4]. TL has recently been associated with idiopathic pulmonary fibrosis (IPF)-like morphologic features ( i.e. features of usual interstitial pneumonia, UIP) and reduced survival in other forms of cILD [5–7]. Whether TL demonstrates similar associations in patients with uILD is unknown, but if so, its clinical measurement could reduce diagnostic and therapeutic uncertainty by determining which patients with uILD will have an IPF-like course. The aim of this study was to determine whether TL is associated with clinical features and outcomes in a cohort of patients with uILD. Peripheral blood telomere length predicts survival in patients with unclassifiable interstitial lung disease <https://bit.ly/3e3j0sL>
Victoria Adetola Adewole
Authors: Tehmina Bharucha, Lucy-Anne Frank
Journal: BMJ (2020)

Brilliant, lively, and unassuming, Victoria Adetola Adewole (“Vicky”) began her medical career as a student at Imperial College London, having received a student opportunities scholarship. She graduated with a distinction and received the Royal Society of Medicine pathology section prize during her intercalated BSc in infection and immunity. Her early clinical exposure instigated her desire to pursue a career in surgery. Therefore, after having worked as a foundation year doctor at University College London Hospital and Watford General Hospital, she ventured out of her beloved city to complete core surgical training in Brighton …
A Randomized Clinical Trial in Patients With a Pedophilic Disorder
Authors: Peer Briken
Journal: JAMA Psychiatry (2020)

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The Clinical Drug Ebselen Attenuates Inflammation and Promotes Microbiome Recovery in Mice after Antibiotic Treatment for CDI
Authors: Megan Garland, Andrew J. Hryckowian, Martina Tholen, Kristina Oresic Bender, William W. Van Treuren, Sebastian Loscher, Justin L. Sonnenburg, Matthew Bogyo
Journal: Cell Reports Medicine (2020)

Clostridium difficile infection (CDI) is an enteric bacterial disease that is increasing in prevalence worldwide. C. difficile capitalizes on gut inflammation and microbiome dysbiosis to establish infection, with symptoms ranging from watery diarrhea to toxic megacolon. We reported that the safe-in-human clinical drug ebselen (ClinicalTrials.gov: NCT03013400, NCT01452607, NCT00762671, and NCT02603081) has biochemical, cell-based, and in vivo efficacy against the toxins of C. difficile. Here, we show that ebselen treatment reduces recurrence rates and decreases colitis in a hamster model of relapsing CDI. Furthermore, ebselen treatment does not alter microbiome diversity and promotes recovery back to that of healthy controls after antibiotic-induced dysbiosis in healthy and C. difficile-infected mice. This increased microbiome recovery upon ebselen treatment correlates with a decrease in host-derived inflammatory markers, suggesting that the anti-inflammatory properties of ebselen, combined with its anti-toxin function, help to mitigate the major clinical challenges of CDI, including recurrence, microbial dysbiosis, and colitis.
Sex as a Biological Variable in Atherosclerosis
Authors: Joshua J. Man, Joshua A. Beckman, Iris Z. Jaffe
Journal: Circulation Research (2020)

Atherosclerosis is a chronic inflammatory vascular disease and the predominant cause of heart attack and ischemic stroke. Despite the well-known sexual dimorphism in the incidence and complications of atherosclerosis, there are relatively limited data in the clinical and preclinical literature to rigorously address mechanisms underlying sex as a biological variable in atherosclerosis. In multiple histological and imaging studies, overall plaque burden and markers of inflammation appear to be greater in men than women and are predictive of cardiovascular events. However, while younger women are relatively protected from cardiovascular disease, by the seventh decade, the incidence of myocardial infarction in women ultimately surpasses that of men, suggesting an interaction between sex and age. Most preclinical studies in animal atherosclerosis models do not examine both sexes, and even in those that do, well-powered direct statistical comparisons for sex as an independent variable remain rare. This article reviews the available data. Overall, male animals appear to have more inflamed yet smaller plaques compared to female animals. Plaque inflammation is often used as a surrogate end point for plaque vulnerability in animals. The available data support the notion that rather than plaque size, plaque inflammation may be more relevant in assessing sex-specific mechanisms since the findings correlate with the sex difference in ischemic events and mortality and thus may be more reflective of the human condition. Overall, the number of preclinical studies directly comparing plaque inflammation between the sexes is extremely limited relative to the vast literature exploring atherosclerosis mechanisms. Failure to include both sexes and to address age in mechanistic atherosclerosis studies are missed opportunities to uncover underlying sex-specific mechanisms. Understanding the mechanisms driving sex as a biological variable in atherosclerotic disease is critical to future precision medicine strategies to mitigate what is still the leading cause of death of men and women worldwide.
Abstract 189: Intraosseous Transfusion With Hemoglobin Vesicles for Severe Hemorrhagic Shock Rabbits
Authors: Kohsuke Hagisawa, Manabu Kinoshita
Journal: Circulation (2018)

Background: We developed a Hemoglobin vesicle (HbV) and which is an artificial substitute for Red blood cells (RBCs). Objective: To evaluate the efficacy of intraosseous HbV transfusion for alternative treatment instead of massive RBCs transfusion in rabbits with hemorrhagic shock. Methods: Hypohemoglobinemia (Hb 5.0 ± 0.7 g/dl) was induced in rabbits by blood withdrawal (70% of total blood volume) and half compensative infusion of normal saline (35% of total blood volume), which resulted severe hemorrhagic shock (mean arterial pressure 21 ± 2 mmHg). Immediately, shortage of the blood volume (35% of total blood volume) was intraosseously infused of lactate ringer (n=8), 5% human serum albumin (n=10) or HbV with 5% human serum albumin (3:2=vol: vol) (n=8). During the experiment hemodynamics and blood cell counts were measured with time. Results: Mean arterial pressure immediately recovered (44 ± 11 mmHg), improving hypohemoglobinemia (7.1 ± 0.6 g/dl) by administration with HbV, although rabbits receiving 5% Albumin and lactate ringer never improved hemodynamics and hypohemoglobinemia. (33 ± 7 mmHg / 3.4 ± 0.4 g/dl, 26 ± 4 mmHg / 4.5 ± 0.4 g/dl, p &lt; 0.05 vs HbV group, respectively) As a result, 75% of rabbits receiving HbV survived after 24hours, while half of rabbits with 5% Albumin were dead within 18hours and all rabbits with lactate ringer were dead within 6hours. Conclusions: Intraosseous infusion of HbV effectively restore the Hb and maintain the hemodynamics for acute hemorrhagic shock in the difficult situation to get blood access.
Proton-Beam Therapy: At the Heart of Cardiac Dose-Sparing in Mediastinal Radiotherapy for Thymic Carcinoma
Authors: Andrew R. Barsky, Michele M. Kim, Graeme R. Williams, Brian E. Lally, William S. Ingram, Keith A. Cengel, Steven J. Feigenberg
Journal: Journal of Thoracic Oncology (2020)
COVID-19–related Genes in Sputum Cells in Asthma. Relationship to Demographic Features and Corticosteroids
Authors: Michael C. Peters, Satria Sajuthi, Peter Deford, Stephanie Christenson, Cydney L. Rios, Michael T. Montgomery, Prescott G. Woodruff, David T. Mauger, Serpil C. Erzurum, Mats W. Johansson, Loren C. Denlinger, Nizar N. Jarjour, Mario Castro, Annette T. Hastie, Wendy Moore, Victor E. Ortega, Eugene R. Bleecker, Sally E. Wenzel, Elliot Israel, Bruce D. Levy, Max A. Seibold, John V. Fahy
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). ACE2 (angiotensin-converting enzyme 2), and TMPRSS2 (transmembrane protease serine 2) mediate viral infection of host cells. We reasoned that differences in ACE2 or TMPRSS2 gene expression in sputum cells among patients with asthma may identify subgroups at risk for COVID-19 morbidity.
A Modified Algorithm Adjusting Both High and Minor Allele Frequency Mutation to Redefine Blood-Based Tumor Mutational Burden (bTMB) for Optimal Prediction of Clinical Benefits From Immune Checkpoint Inhibitor Therapy
Authors: Zhichao Liu, Zhanhong Xie, Xiuyu Cai, Jianxing He, Wenhua Liang
Journal: Journal of Thoracic Oncology (2020)
Theranostic Targeting of CUB Domain Containing Protein 1 (CDCP1) in Pancreatic Cancer
Authors: Anna Moroz, Yung-Hua Wang, Jeremy M. Sharib, Junnian Wei, Ning Zhao, Yangjie Huang, Zhuo Chen, Alexander J. Martinko, Jie Zhuo, Shion A. Lim, Lydia H. Zhang, Youngho Seo, Sean Carlin, Kevin K. Leung, Eric A. Collisson, Kimberly S. Kirkwood, James A. Wells, Michael J. Evans
Journal: Clinical Cancer Research (2020)

The recent emergence of radioligand therapies for cancer treatment has increased enthusiasm for developing new theranostic strategies coupling both imaging and cytotoxicity in the same entity. In this study, we evaluated whether CUB domain containing protein 1 (CDCP1), a single-pass transmembrane protein highly overexpressed in diverse human cancers, might be a target for cancer theranostics.The ectodomain of CDCP1 was targeted using radiolabeled forms of 4A06, a potent and specific recombinant human antibody that we developed. Imaging and antitumor assessment studies were performed in animal models of pancreatic cancer, including two patient-derived xenograft models we developed for this study. For antitumor assessment studies, the endpoints were death due to tumor volume >3,000 mm3 or ≥20% loss in body weight. Specific tracer binding or antitumor effects were assessed with an unpaired, two-tailed Student t test and survival advantages were assessed with a log rank (Mantel-Cox) test. Differences at the 95% confidence level were interpreted to be significant.89Zr-4A06 detected a broad dynamic range of full length or cleaved CDCP1 expression on seven human pancreatic cancer tumors (n = 4/tumor). Treating mice with single or fractionated doses of 177Lu-4A06 significantly reduced pancreatic cancer tumor volume compared with mice receiving vehicle or unlabeled 4A06 (n = 8; P < 0.01). A single dose of 225Ac-4A06 also inhibited tumor growth, although the effect was less profound compared with 177Lu-4A06 (n = 8; P < 0.01). A significant survival advantage was imparted by 225Ac-4A06 (HR = 2.56; P < 0.05).These data establish that CDCP1 can be exploited for theranostics, a finding with widespread implications given its breadth of overexpression in cancer.