tbuckley/cabot-search huggingface dataset:
Topographic Phenotypes of Alopecia Areata and Development of a Prognostic Prediction Model and Grading System
Authors: Solam Lee, Beom Jun Kim, Chung-Hyeok Lee, Won-Soo Lee
Journal: JAMA Dermatology (2019)

Diverse assessment tools and classification have been used for alopecia areata; however, their prognostic values are limited.To identify the topographic phenotypes of alopecia areata using cluster analysis and to establish a prediction model and grading system for stratifying prognoses.A retrospective cohort study of 321 patients with alopecia areata who visited a single tertiary referral center between October 2012 and February 2017 and underwent 4-view photographic assessment.Clinical photographs were reviewed to evaluate hair loss using the Severity of Alopecia Tool 2. Topographic phenotypes of alopecia areata were identified using hierarchical clustering with Ward's method. Differences in clinical characteristics and prognosis were compared across the clusters. The model was evaluated for its performance, accuracy, and interobserver reliability by comparison to conventional methods.Topographic phenotypes of alopecia areata and their major (60%-89%) and complete regrowth probabilities (90%-100%) within 12 months.A total of 321 patients were clustered into 5 subgroups. Grade 1 (n = 200; major regrowth, 93.4%; complete regrowth, 65.2%) indicated limited hair loss, whereas grades 2A (n = 66; major regrowth, 87.8%; complete regrowth, 64.2%) and 2B (n = 20; major regrowth, 73.3%; complete regrowth, 45.5%) exhibited greater hair loss than grade 1. The temporal area was predominantly involved in grade 2B, but not in grade 2A, despite being comparable in total extent of hair loss. Grade 3 (n = 20; major regrowth, 45.5%; complete regrowth, 25.5%) included diffuse or extensive alopecia areata, and grade 4 (n = 15; major regrowth, 28.2%; complete regrowth, 16.7%) corresponded to alopecia (sub)totalis. No significant differences in prognosis (hazard ratio [HR] for major regrowth, 0.79; 95% CI, 0.56-1.12) were found between grades 2A and 1, whereas grades 2B (HR, 0.41; 95% CI, 0.21-0.81), 3 (HR, 0.24; 95% CI, 0.12-0.50), and 4 (HR, 0.16; 95% CI, 0.06-0.39) had significantly poorer response. Among multiple models, the cluster solution had the greatest prognostic performance and accuracy. The tree model of the cluster solution was converted into the Topography-based Alopecia Areata Severity Tool (TOAST), which revealed an excellent interobserver reliability among 4 dermatologists (median quadratic-weighted κ, 0.89).Temporal area involvement should be independently measured for better prognostic stratification. The TOAST is an effective tool for describing the topographical characteristics and prognosis of hair loss and may enable clinicians to establish better treatment plans.
Abstract 19552: Acute Coronary Occlusion is Common in Patients Without STEMI Undergoing Early Coronary Angiography After Out-of-Hospital Cardiac Arrest
Authors: Ronstan Lobo, Majd Khasawneh, Gregory W Barsness, Jacob C Jentzer
Journal: Circulation (2017)

Introduction: Acute coronary occlusion (ACO) is an important cause of Out-of-Hospital Cardiac Arrest (OHCA). We evaluated the incidence and prognostic relevance of ACO in patients undergoing coronary angiography (CAG) within 24 hours after OHCA. Hypothesis: ACO is common and will predict inpatient mortality after resuscitation from OHCA. Methods: Historical cohort study of 279 patients receiving targeted temperature management at a single tertiary care hospital after resuscitation from OHCA from Dec 2005 to Sept 2016. ACO was defined as 100% occlusion of a culprit vessel at CAG without evidence of chronic occlusion. Early CAG patients (within 24 hours of admission) with and without ACO were compared using t-tests and chi-squared tests. Univariate analysis was followed by multivariate logistic regression to determine predictors of inpatient mortality. Results: CAG was performed in 203 (73%) patients, of whom 155 (76%) underwent early CAG. Mean age of patients undergoing early CAG was 63 years, 144 (93%) ha...
Sunk Cost Bias and Withdrawal Aversion
Authors: Martin H. Turpin, Ethan A. Meyers, Jonathan A. Fugelsang, Ori Friedman, Michał Białek
Journal: The American Journal of Bioethics (2019)

This article refers to:Withholding and Withdrawing Life-Sustaining Treatment: Ethically Equivalent?Withdrawal Aversion and the Equivalence Test
Effectiveness and safety of sofosbuvir-based direct-acting antiviral combinations in HCV-2 and HCV-3 kidney transplant recipients
Authors: Roberta D’Ambrosio, Maria Vinci, Marianna Franchina, Lucia Parlati, Serena Zaltron, Luisa Pasulo, Mariarosaria Campise, Piergiorgio Messa, Stanislas Pol, Pietro Lampertico
Journal: Kidney International (2019)
A multicenter study of body mass index in cancer patients treated with anti-PD-1/PD-L1 immune checkpoint inhibitors: when overweight becomes favorable
Authors: Alessio Cortellini, Melissa Bersanelli, Sebastiano Buti, Katia Cannita, Daniele Santini, Fabiana Perrone, Raffaele Giusti, Marcello Tiseo, Maria Michiara, Pietro Di Marino, Nicola Tinari, Michele De Tursi, Federica Zoratto, Enzo Veltri, Riccardo Marconcini, Francesco Malorgio, Marco Russano, Cecilia Anesi, Tea Zeppola, Marco Filetti, Paolo Marchetti, Andrea Botticelli, Gian Carlo Antonini Cappellini, Federica De Galitiis, Maria Giuseppa Vitale, Francesca Rastelli, Federica Pergolesi, Rossana Berardi, Silvia Rinaldi, Marianna Tudini, Rosa Rita Silva, Annagrazia Pireddu, Francesco Atzori, Rita Chiari, Biagio Ricciuti, Andrea De Giglio, Daniela Iacono, Alain Gelibter, Mario Alberto Occhipinti, Alessandro Parisi, Giampiero Porzio, Maria Concetta Fargnoli, Paolo Antonio Ascierto, Corrado Ficorella, Clara Natoli
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Recent evidence suggested a potential correlation between overweight and the efficacy of immune checkpoint inhibitors (ICIs) in cancer patients. <h3>Patients and methods</h3> We conducted a retrospective study of advanced cancer patients consecutively treated with anti-PD-1/PD-L1 inhibitors, in order to compare clinical outcomes according to baseline BMI levels as primary analysis. Based on their BMI, patients were categorized into overweight/obese (≥ 25) and non-overweight (&lt; 25). A gender analysis was also performed, using the same binomial cut-off. Further subgroup analyses were performed categorizing patients into underweight, normal weight, overweight and obese. <h3>Results</h3> Between September 2013 and May 2018, 976 patients were evaluated. The median age was 68 years, male/female ratio was 663/313. Primary tumors were: NSCLC (65.1%), melanoma (18.7%), renal cell carcinoma (13.8%) and others (2.4%). ECOG-PS was ≥2 in 145 patients (14.9%). PD-1/PD-L1 inhibitors were administered as first-line treatment in 26.6% of cases. Median BMI was 24.9: 492 patients (50.6%) were non-overweight, 480 patients (50.4%) were overweight/obese. 25.2% of non-overweight patients experienced irAEs of any grade, while 55.6% of overweight/obese patients (<i>p</i> &lt; 0.0001). ORR was significantly higher in overweight/obese patients compared to non-overweight (p &lt; 0.0001). Median follow-up was 17.2 months. Median TTF, PFS and OS were significantly longer for overweight/obese patients in univariate (p &lt; 0.0001, for all the survival intervals) and multivariate models (<i>p</i> = 0.0009, p &lt; 0.0001 and p &lt; 0.0001 respectively). The significance was confirmed in both sex, except for PFS in male patients (<i>p</i> = 0.0668). <h3>Conclusions</h3> Overweight could be considered a tumorigenic immune-dysfunction that could be effectively reversed by ICIs. BMI could be a useful predictive tool in clinical practice and a stratification factor in prospective clinical trials with ICIs.
Overall Survival with Fulvestrant plus Anastrozole in Metastatic Breast Cancer
Authors: Rita S. Mehta, William E. Barlow, Kathy S. Albain, Ted A. Vandenberg, Shaker R. Dakhil, Nagendra R. Tirumali, Danika L. Lew, Daniel F. Hayes, Julie R. Gralow, Hannah M. Linden, Robert B. Livingston, Gabriel N. Hortobagyi
Journal: New England Journal of Medicine (2019)

We previously reported prolonged progression-free survival and marginally prolonged overall survival among postmenopausal patients with hormone receptor–positive metastatic breast cancer who had been randomly assigned to receive the aromatase inhibitor anastrozole plus the selective estrogen-receptor down-regulator fulvestrant, as compared with anastrozole alone, as first-line therapy. We now report final survival outcomes.
Fluorous-phase iron oxide nanoparticles as enhancers of acoustic droplet vaporization of perfluorocarbons with supra-physiologic boiling point
Authors: Alexander M. Vezeridis, Caroline de Gracia Lux, Sarah A. Barnhill, Sejung Kim, Zhe Wu, Sungho Jin, Jacques Lux, Nathan C. Gianneschi, Robert F. Mattrey
Journal: Journal of Controlled Release (2019)
Restrictive Versus Liberal Red Blood Cell Transfusion for Cardiac Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Babikir Kheiri, Ahmed Abdalla, Mohamed Osman, Tarek Haykal, Sai Chintalapati, James Cranford, Sahar Ahmed, Mustafa Hassan, Ghassan Bachuwa, Deepak L. Bhatt
Journal: Blood (2018)
Safety and Feasibility of Repeated and Transient Blood–Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma
Authors: Ahmed Idbaih, Michael Canney, Lisa Belin, Carole Desseaux, Alexandre Vignot, Guillaume Bouchoux, Nicolas Asquier, Bruno Law-Ye, Delphine Leclercq, Anne Bissery, Yann De Rycke, Clementine Trosch, Laurent Capelle, Marc Sanson, Khe Hoang-Xuan, Caroline Dehais, Caroline Houillier, Florence Laigle-Donadey, Bertrand Mathon, Arthur André, Cyril Lafon, Jean-Yves Chapelon, Jean-Yves Delattre, Alexandre Carpentier
Journal: Clinical Cancer Research (2019)

The blood-brain barrier (BBB) limits the efficacy of drug therapies for glioblastoma (GBM). Preclinical data indicate that low-intensity pulsed ultrasound (LIPU) can transiently disrupt the BBB and increase intracerebral drug concentrations.A first-in-man, single-arm, single-center trial (NCT02253212) was initiated to investigate the transient disruption of the BBB in patients with recurrent GBM. Patients were implanted with a 1-MHz, 11.5-mm diameter cranial ultrasound device (SonoCloud-1, CarThera). The device was activated monthly to transiently disrupt the BBB before intravenous carboplatin chemotherapy.Between 2014 and 2016, 21 patients were registered for the study and implanted with the SonoCloud-1; 19 patients received at least one sonication. In 65 ultrasound sessions, BBB disruption was visible on T1w MRI for 52 sonications. Treatment-related adverse events observed were transient and manageable: a transient edema at H1 and at D15. No carboplatin-related neurotoxicity was observed. Patients with no or poor BBB disruption (n = 8) visible on MRI had a median progression-free survival (PFS) of 2.73 months, and a median overall survival (OS) of 8.64 months. Patients with clear BBB disruption (n = 11) had a median PFS of 4.11 months, and a median OS of 12.94 months.SonoCloud-1 treatments were well tolerated and may increase the effectiveness of systemic drug therapies, such as carboplatin, in the brain without inducing neurotoxicity.See related commentary by Sonabend and Stupp, p. 3750.
Abstract 19980: Comparison of Dabigatran and Rivaroxaban versus Warfarin in Patients With Persistent and Long-Standing Atrial Fibrillation Undergoing Electrical Cardioversion With High Risk of Stroke And Embolism
Authors: Oskars Kalejs, Kristine Jubele, Aldis Strelnieks, Iveta Sime, Irina Cgojeva-Sproge, Ginta Kamzola, Marina Berzina, Iveta Mintale, Maija Vikmane, Sandis Sakne, Aivars Lejnieks, Andrejs Erglis
Journal: Circulation (2016)

Introduction: The important factor for efficacy and safety for patients (pts) with atrial fibrillation (AF) undergoing electrical cardioversion (ECV) is appropriate use of oral anticoagulant (OAC). Hypothesis: Novel anticoagulants (NOAC) are a possible alternative OAC before and after ECV versus warfarin Methods: We have analysed the data before and after ECV in 2215 pts undergoing ECV. All pts had AF, 1718 persistent and 497 defined as long-standing, CHA2 DS2 VASc score was 3.6 ± 1.8, 1578 had one or two ECV previously. 1431 (64.6%) pts started the use of NOAC: dabigatran 490 pts 150 mg twice or 344 pts 110 mg twice or 597 rivaroxaban 20 mg daily before ECV for at least 21 day, 748 (35.4%) started warfarin therapy and 21 day start after INR was in range 2.0 - 3.0. 110 mg twice were prescribed for pts ≥ 75 year, HASBLEED ≥3 and chronic kidney disease. Transesophageal echocardiography (TEE) was encouraged before ECV in all pts with CHA2DS2VASc score ≥ 4, left atrial (LA) dilatation and AF duration ≥ 6 mont...
Repeat-Associated Non-ATG Translation: Molecular Mechanisms and Contribution to Neurological Disease
Authors: Lien Nguyen, John Douglas Cleary, Laura P.W. Ranum
Journal: Annual Review of Neuroscience (2019)

Microsatellite mutations involving the expansion of tri-, tetra-, penta-, or hexanucleotide repeats cause more than 40 different neurological disorders. Although, traditionally, the position of the repeat within or outside of an open reading frame has been used to focus research on disease mechanisms involving protein loss of function, protein gain of function, or RNA gain of function, the discoveries of bidirectional transcription and repeat-associated non-ATG (RAN) have blurred these distinctions. Here we review what is known about RAN proteins in disease, the mechanisms by which they are produced, and the novel therapeutic opportunities they provide.
PCL19-114: Development of Locally Deliverable Polymeric Microspheres With Environmentally Specific Release for the Improvement of Cancer Therapy
Authors: Karol Sokolowski, Jason S. Buhrman, Richard A. Gemeinhart
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Cancer therapy has made incredible leaps in extending patient lifespans. Unfortunately, most therapy is delivered via a systemic route and often suffers from dose-limiting systemic toxicities, resulting in cessation of therapy or decline in quality of life. Nanotechnology efforts to improve tolerability of systemic agents have suffered limited market viability due to problems such as rapid clearance, circulation instability, and low tumor site accumulation. While local delivery allows for overcoming the aforementioned hurdles, pre-set formulations and nonspecific release pose alternate issues. To approach these challenges, we aimed to investigate our previously developed solid nanoparticles for delivery of protein-based therapy capable of addressing a tumor-specific profile and with selective release within the tumor environment due to elevated thrombin levels. Methods: Poly(ethylene glycol) diacrylate microspheres [PEGDAmS] were prepared using previously described polymerization within a reverse phase emulsion. Compounding patient-specific therapy was evaluated using fluorophore labeled glutathione-S-transferase (GST) and GST-green fluorescent protein (GFP) fusion proteins. Protein loading was analyzed using fluorescence reading and concurrent gel densitometry. Loaded PEGDAmS were delivered into the frontal lobes of Sprague-Dawley rats through a syringe and analyzed using fluorescence microscopy after sacrifice at 48 hours. Results: The addition of 0.2% tween20 surfactant to polymerization reduced PEGDAmS diameter (38.3±30.7 μm to 8.6±6.5 μm) and allowed for minimally invasive delivery to the cranial cavity through a 26S gauge needle. Compounding a tumor-specific regimen is achievable as premixed protein solutions exhibited solution-representative loading on PEGDAmS. Additionally, preloaded vehicles did not demonstrate appreciable cross contamination over 7 days when incubated in close proximity, demonstrating the feasibility of concurrent delivery of various preloaded formulations. Loaded PEGDAmS exhibited environment specific delivery with extensive release of thrombin cleavable GST-GFP in plasma but greatly reduced in anticoagulated plasma. Conclusion: We have shown the ability to locally administer a delivery system with modular therapy-loading and responsiveness to the tumor microenvironment. Further investigation is warranted to explore local delivery of GST-tagged oncology-relevant biologic agents in the presence of a tumor in vivo.
Random isn't real: How the patchy distribution of ecological rewards may generate “incentive hope”
Authors: Laurel Symes, Thalia Wheatley
Journal: Behavioral and Brain Sciences (2019)

Abstract Anselme &amp; Güntürkün generate exciting new insights by integrating two disparate fields to explain why uncertain rewards produce strong motivational effects. Their conclusions are developed in a framework that assumes a random distribution of resources, uncommon in the natural environment. We argue that, by considering a realistically clumped spatiotemporal distribution of resources, their conclusions will be stronger and more complete.
Short telomeres are associated with inferior outcome, genomic complexity, and clonal evolution in chronic lymphocytic leukemia
Authors: Billy Michael Chelliah Jebaraj, Eugen Tausch, Dan A. Landau, Jasmin Bahlo, Sandra Robrecht, Amaro N. Taylor-Weiner, Johannes Bloehdorn, Annika Scheffold, Daniel Mertens, Sebastian Böttcher, Michael Kneba, Ulrich Jäger, Thorsten Zenz, Michael K. Wenger, Guenter Fingerle-Rowson, Clemens Wendtner, Anna-Maria Fink, Catherine J. Wu, Barbara Eichhorst, Kirsten Fischer, Michael Hallek, Hartmut Döhner, Stephan Stilgenbauer
Journal: Leukemia (2019)
Carbapenem-resistant Acinetobacter baumannii: in pursuit of an effective treatment
Authors: E.-T. Piperaki, L.S. Tzouvelekis, V. Miriagou, G.L. Daikos
Journal: Clinical Microbiology and Infection (2019)

BackgroundCarbapenem-resistant Acinetobacter baumannii (CRAB) has gained global notoriety as a critically important nosocomial pathogen. It mostly affects debilitated patients, causing pneumonia and bloodstream infections with high mortality rates. Difficulties in treating CRAB infections stem from a formidable resistance profile that leaves available only a few antibiotics of uncertain efficacy such as colistin and tigecycline. Despite the relentless attempts to improve therapeutic approaches (as depicted in colistin-oriented randomized clinical trials and the numerous observational studies), progress is still limited.AimsWe aim (a) to assist physicians to adapt therapeutic approaches in CRAB infections by considering all potentially available antimicrobials, and (b) to present directions for future investigations that emerge through treatment efforts in endemic settings.SourcesArticles and reviews from PubMed and Scopus databases; studies from ClinicalTrials.gov; presentations from ECCMID congresses and IDWeek meetings.ContentThe review provides a succinct overview of the important pharmacokinetic/pharmocodynamic parameters of relevant antimicrobial agents, a critical appraisal of randomized control trials and observational studies, suggestions for increasing the strength of observational studies and directions facilitating the choice of therapeutic regimens by severity of infection and status of the host.ImplicationsThe lack of an optimal therapeutic regimen for CRAB thus far, as shown in this review, suggests the need to thoroughly investigate alternative approaches through carefully designed trials that should include all relevant drugs. Some of these alternative directions are indicated in the present review.
Results from capnography studies in adults may not apply to neonates
Authors: Robert Tinnion, Helen Mactier, Colin Morley, Charles Roehr, Allan Jackson, Stephen Wardle
Journal: BMJ (2019)

In response to the editorial by Cook and Harrop-Griffiths on capnography,1 we reiterate the British Association of Perinatal Medicine’s position statement on waveform capnography in newborn infants2 published in response to the article by Foy et al in Anaesthesia .3

Detection of exhaled carbon dioxide is a useful adjunct to confirm correct placement of an endotracheal tube, but we …
Updated Efficacy and Safety Data and Impact of the EML4-ALK Fusion Variant on the Efficacy of Alectinib in Untreated ALK-Positive Advanced Non–Small Cell Lung Cancer in the Global Phase III ALEX Study
Authors: D. Ross Camidge, Rafal Dziadziuszko, Solange Peters, Tony Mok, Johannes Noe, Malgorzata Nowicka, Shirish M. Gadgeel, Parneet Cheema, Nick Pavlakis, Filippo de Marinis, Byoung Chul Cho, Li Zhang, Denis Moro-Sibilot, Ting Liu, Walter Bordogna, Bogdana Balas, Barbara Müller, Alice T. Shaw
Journal: Journal of Thoracic Oncology (2019)
Complete Inactivation of Sebum-Producing Genes Parallels the Loss of Sebaceous Glands in Cetacea
Authors: Mónica Lopes-Marques, André M Machado, Luís Q Alves, Miguel M Fonseca, Susana Barbosa, Mikkel-Holger S Sinding, Marianne Helene Rasmussen, Maria Refsgaard Iversen, Mads Frost Bertelsen, Paula F Campos, Rute da Fonseca, Raquel Ruivo, L Filipe C Castro
Journal: Molecular Biology and Evolution (2019)

Genomes are dynamic biological units, with processes of gene duplication and loss triggering evolutionary novelty. The mammalian skin provides a remarkable case study on the occurrence of adaptive morphological innovations. Skin sebaceous glands (SGs), for instance, emerged in the ancestor of mammals serving pivotal roles, such as lubrication, waterproofing, immunity, and thermoregulation, through the secretion of sebum, a complex mixture of various neutral lipids such as triacylglycerol, free fatty acids, wax esters, cholesterol, and squalene. Remarkably, SGs are absent in a few mammalian lineages, including the iconic Cetacea. We investigated the evolution of the key molecular components responsible for skin sebum production: Dgat2l6, Awat1, Awat2, Elovl3, Mogat3, and Fabp9. We show that all analyzed genes have been rendered nonfunctional in Cetacea species (toothed and baleen whales). Transcriptomic analysis, including a novel skin transcriptome from blue whale, supports gene inactivation. The conserved mutational pattern found in most analyzed genes, indicates that pseudogenization events took place prior to the diversification of modern Cetacea lineages. Genome and skin transcriptome analysis of the common hippopotamus highlighted the convergent loss of a subset of sebum-producing genes, notably Awat1 and Mogat3. Partial loss profiles were also detected in non-Cetacea aquatic mammals, such as the Florida manatee, and in terrestrial mammals displaying specialized skin phenotypes such as the African elephant, white rhinoceros and pig. Our findings reveal a unique landscape of "gene vestiges" in the Cetacea sebum-producing compartment, with limited gene loss observed in other mammalian lineages: suggestive of specific adaptations or specializations of skin lipids.