tbuckley/cabot-search huggingface dataset:
CD13 as a new tumor target for antibody-drug conjugates: validation with the conjugate MI130110
Authors: Juan Manuel Domínguez, Gema Pérez-Chacón, María José Guillén, María José Muñoz-Alonso, Beatriz Somovilla-Crespo, Danay Cibrián, Bárbara Acosta-Iborra, Magdalena Adrados, Cecilia Muñoz-Calleja, Carmen Cuevas, Francisco Sánchez-Madrid, Pablo Avilés, Juan M. Zapata
Journal: Journal of Hematology & Oncology (2020)

Abstract Background In the search for novel antibody-drug conjugates (ADCs) with therapeutic potential, it is imperative to identify novel targets to direct the antibody moiety. CD13 seems an attractive ADC target as it shows a differential pattern of expression in a variety of tumors and cell lines and it is internalized upon engagement with a suitable monoclonal antibody. PM050489 is a marine cytotoxic compound tightly binding tubulin and impairing microtubule dynamics which is currently undergoing clinical trials for solid tumors. Methods Anti-CD13 monoclonal antibody (mAb) TEA1/8 has been used to prepare a novel ADC, MI130110, by conjugation to the marine compound PM050489. In vitro and in vivo experiments have been carried out to demonstrate the activity and specificity of MI130110. Results CD13 is readily internalized upon TEA1/8 mAb binding, and the conjugation with PM050489 did not have any effect on the binding or the internalization of the antibody. MI130110 showed remarkable activity and selectivity in vitro on CD13-expressing tumor cells causing the same effects than those described for PM050489, including cell cycle arrest at G2, mitosis with disarrayed and often multipolar spindles consistent with an arrest at metaphase, and induction of cell death. In contrast, none of these toxic effects were observed in CD13-null cell lines incubated with MI130110. Furthermore, in vivo studies showed that MI130110 exhibited excellent antitumor activity in a CD13-positive fibrosarcoma xenograft murine model, with total remissions in a significant number of the treated animals. Mitotic catastrophes, typical of the payload mechanism of action, were also observed in the tumor cells isolated from mice treated with MI130110. In contrast, MI130110 failed to show any activity in a xenograft mouse model of myeloma cells not expressing CD13, thereby corroborating the selectivity of the ADC to its target and its stability in circulation. Conclusion Our results show that MI130110 ADC combines the antitumor potential of the PM050489 payload with the selectivity of the TEA1/8 monoclonal anti-CD13 antibody and confirm the correct intracellular processing of the ADC. These results demonstrate the suitability of CD13 as a novel ADC target and the effectiveness of MI130110 as a promising antitumor therapeutic agent.
Colistin plus meropenem for carbapenem-resistant Gram-negative infections: in vitro synergism is not associated with better clinical outcomes
Authors: Amir Nutman, Jonathan Lellouche, Elizabeth Temkin, George Daikos, Anna Skiada, Emanuele Durante-Mangoni, Yael Dishon-Benattar, Roni Bitterman, Dafna Yahav, Vered Daitch, Mariano Bernardo, Domenico Iossa, Oren Zusman, Lena E. Friberg, Johan W. Mouton, Ursula Theuretzbacher, Leonard Leibovici, Mical Paul, Yehuda Carmeli, Mical Paul, Yael Dishon Benattar, Yaakov Dickstein, Roni Bitterman, Hiba Zayyad, Fidi Koppel, Yael Zak-Doron, Sergey Altunin, Nizar Andria, Ami Neuberger, Anat Stern, Neta Petersiel, Marina Raines, Amir Karban, Leonard Leibovici, Dafna Yahav, Noa Eliakim-Raz, Oren Zusman, Michal Elbaz, Heyam Atamna, Vered Daitch, Tanya Babich, Yehuda Carmeli, Amir Nutman, Amos Adler, Inbar Levi, George L. Daikos, Anna Skiada, Ioannis Pavleas, Anastasia Antoniadou, Antigoni Kotsaki, Emanuele Durante-Mangoni, Roberto Andini, Domenico Iossa, Mariano Bernardo, Giusi Cavezza, Lorenzo Bertolino, Giuseppe Giuffre, Roberto Giurazza, Susanna Cuccurullo, Maria Galdo, Patrizia Murino, Adriano Cristinziano, Antonio Corcione, Rosa Zampino, Pia Clara Pafundi, Johan Mouton, Lena Friberg, Anders Kristoffersson, Ursula Theuretzbacher
Journal: Clinical Microbiology and Infection (2020)
Interstitial lung disease in primary immunodeficiency: towards a brighter future
Authors: John R. Hurst, Klaus Warnatz
Journal: European Respiratory Journal (2020)

Lung disease is a frequent clinical manifestation in people living with primary immunodeficiency diseases, the most prevalent of which are common variable immunodeficiency disorders (CVID). CVID is primarily characterised by antibody deficiency, but recent definitions and diagnostic criteria recognise a much more complex pattern of immunological defects [1]. CVID can be classified into two major clinical phenotypes. One group experiences infection as the only major clinical manifestation, whilst the other present a variety of lymphoproliferative, inflammatory and/or autoimmune complications. The ERS eGLILDnet CRC is working for better care and research for people affected by GLILD <http://bit.ly/37WZGdd>
Epicutaneous sensitization in the development of food allergy: What is the evidence and how can this be prevented?
Authors: Helen A. Brough, Kari C. Nadeau, Sayantani B. Sindher, Shifaa S. Alkotob, Susan Chan, Henry T. Bahnson, Donald Y. M. Leung, Gideon Lack
Journal: Allergy (2020)

Abstract There is increasing evidence regarding the importance of allergic sensitization through the skin. In this review, we provide an overview of the atopic march and immune mechanism underlying the sensitization and effector phase of food allergy. We present experimental models and human data that support the concept of epicutaneous sensitization and how this forms one half of the dual‐allergen exposure hypothesis. We discuss specific important elements in the skin ( FLG and other skin barrier gene mutations, Langerhans cells, type 2 innate lymphoid cells, IL‐33, TSLP) that have important roles in the development of allergic responses as well as the body of evidence on environmental allergen exposure and how this can sensitize an individual. Given the link between skin barrier impairment, atopic dermatitis, food allergy, allergic asthma, and allergic rhinitis, it is logical that restoring the skin barrier and prevention or treating atopic dermatitis would have beneficial effects on prevention of related allergic diseases, particularly food allergy. We present the experimental and human studies that have evaluated this approach and discuss various factors which may influence the success of these approaches, such as the type of emollient chosen for the intervention, the role of managing skin inflammation, and differences between primary and secondary prevention of atopic dermatitis to achieve the desired outcome.
Validating the Importance of Positive Childhood Experiences on Adult Mental Health—Reply
Authors: Christina Bethell, Robert Sege
Journal: JAMA Pediatrics (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Association of a Simplified Finnegan Neonatal Abstinence Scoring Tool With the Need for Pharmacologic Treatment for Neonatal Abstinence Syndrome
Authors: Lori A. Devlin, Janis L. Breeze, Norma Terrin, Enrique Gomez Pomar, Henrietta Bada, Loretta P. Finnegan, Kevin E. O’Grady, Hendrée E. Jones, Barry Lester, Jonathan M. Davis
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Observer-rated scales, such as the Finnegan Neonatal Abstinence Scoring Tool (FNAST), are used to quantify the severity of neonatal abstinence syndrome (NAS) and guide pharmacologic therapy. The FNAST, a comprehensive 21-item assessment tool, was developed for research and subsequently integrated into clinical practice; a simpler tool, designed to account for clinically meaningful outcomes, is urgently needed to standardize assessment. <h3>Objectives</h3> To identify FNAST items independently associated with the decision to use pharmacologic therapy and to simplify the FNAST while minimizing loss of information for the treatment decision. <h3>Design, Setting, and Participants</h3> This multisite cohort study included 424 neonates with opioid exposure who had a gestational age of at least 36 weeks with follow-up from birth to hospital discharge in the derivation cohort and 109 neonates with opioid exposure from the Maternal Opioid Treatment: Human Experimental Research Study in the validation cohort. Neonates in the derivation cohort were included in a medical record review at the Universities of Louisville and Kentucky or in a randomized clinical trial and observational study conducted at Tufts University (2014-2018); the Maternal Opioid Treatment: Human Experimental Research was conducted from 2005 to 2008. Data analysis was conducted from May 2017 to August 2019. <h3>Exposures</h3> Prenatal opioid exposure. <h3>Main Outcomes and Measures</h3> All FNAST items were dichotomized as present or not present, and logistic regression was used to identify binary items independently associated with pharmacologic treatment. The final model was validated with an independent cohort of neonates with opioid exposure. <h3>Results</h3> Among 424 neonates (gestational age, ≥36 weeks; 217 [51%] female infants), convulsions were not observed, and high-pitched cry and hyperactive Moro reflex had extremely different frequencies across cohorts. Therefore, these 3 FNAST items were removed from further analysis. The 2 tremor items were combined, and 8 of the remaining 17 items were independently associated with pharmacologic treatment, with an area under the curve of 0.86 (95% CI, 0.82-0.89) compared with 0.90 (95% CI, 0.87-0.94) for the 21-item FNAST. External validation of the 8 items resulted in an area under the curve of 0.86 (95% CI, 0.79-0.93). Thresholds of 4 and 5 on the simplified scale yielded the closest agreement with FNAST thresholds of 8 and 12 (weighted κ = 0.55; 95% CI, 0.48-0.61). <h3>Conclusions and Relevance</h3> The findings of this study suggest that 8 signs of NAS may be sufficient to assess whether a neonate meets criteria for pharmacologic therapy. A focus on these signs could simplify the FNAST tool and may enhance its clinical utility.
Spironolactone metabolite concentrations in decompensated heart failure: insights from the ATHENA‐HF trial
Authors: Simon de Denus, Grégoire Leclair, Marie‐Pierre Dubé, Isabelle St‐Jean, Yassamin Feroz Zada, Essaïd Oussaïd, Martin Jutras, Michael M. Givertz, Robert J. Mentz, W.H. Wilson Tang, João Pedro Ferreira, Jean Rouleau, Javed Butler, Andreas P. Kalogeropoulos
Journal: European Journal of Heart Failure (2020)
Vanishing vessels aboding pulmonary disease: a role for VEGFR2
Authors: Liza Botros, Anton Vonk Noordegraaf, Jurjan Aman
Journal: European Respiratory Journal (2020)

<b>VEGFR2 has a pivotal and specific role in vascular homeostasis and VEGFR2 mutations provide robust clinical evidence for direct involvement of a disturbed vasculature in a wide variety of lung diseases</b>http://bit.ly/383ixTb
Abstract 11783: Diagnostic Yield of Customized Exercise Provocation After Graded Exercise Testing
Authors: Timothy W Churchill, Michael Disanto, Tamanna K Singh, Erich Groezinger, Garrett Loomer, Miranda Contursi, Jennifer Michaud-Finch, Katie M Stewart, Adolph M Hutter, Gregory D Lewis, Rory B Weiner, Aaron L Baggish, Meagan M Wasfy
Journal: Circulation (2018)

Introduction: Guidelines advocate for individualized exercise testing (IET) to address patient-specific diagnostic goals, including reproduction of presenting exertional symptoms, as standardized g...
Inhaled aztreonam improves symptoms of cough and sputum production in patients with bronchiectasis: a <i>post hoc</i> analysis of the AIR-BX studies
Authors: Megan L. Crichton, Mike Lonergan, Alan F. Barker, Oriol Sibila, Pieter Goeminne, Amelia Shoemark, James D. Chalmers
Journal: European Respiratory Journal (2020)

Introduction Inhaled antibiotics may improve symptom scores, but it is not known which specific symptoms improve with therapy. Item-level analysis of questionnaire data may allow us to identify which specific symptoms respond best to treatment. Methods Post hoc analysis of the AIR-BX1 studies and two trials of inhaled aztreonam versus placebo in bronchiectasis. Individual items from the quality of life bronchiectasis (QOL-B) respiratory symptom scale, were extracted as representing severity of nine distinct symptoms. Generalised linear models were used to evaluate changes in symptoms with treatment versus placebo from baseline to end of first on-treatment cycle and mixed models were used to evaluate changes across the full 16-week trial. Results Aztreonam improved cough (difference 0.22, 95% CI 0.08–0.37; p=0.002), sputum production (0.30, 95% CI 0.15–0.44; p&lt;0.0001) and sputum colour (0.29, 95% CI 0.15–0.43; p&lt;0.0001) versus placebo equating to a 20% improvement in cough and 25% improvement in sputum production and colour. Similar results were observed for cough, sputum production and sputum purulence across the trial duration (all p&lt;0.05). Patients with higher sputum production and sputum colour scores had a greater response on the overall QOL-B (difference 4.82, 95% CI 1.12–8.53; p=0.011 for sputum production and 5.02, 95% CI 1.19–8.86; p=0.01 for sputum colour). In contrast, treating patients who had lower levels of bronchitic symptoms resulted in shorter time to next exacerbation (hazard ratio 1.83, 95% CI 1.02–3.28; p=0.042). Conclusion Baseline bronchitic symptoms predict response to inhaled aztreonam in bronchiectasis. More sensitive tools to measure bronchitic symptoms may be useful to better identify inhaled antibiotic responders and to evaluate patient response to treatment.
Antimicrobial Resistance — The Glass Is Half Full
Authors: Ferric C. Fang, Robert T. Schooley
Journal: New England Journal of Medicine (2020)

With news on many fronts seeming to get inexorably worse, it is worth pausing to raise our glasses to celebrate some recent evidence of progress. In this issue of the Journal, Jernigan and colleagues1 report the results of a survey involving multidrug-resistant (MDR) organisms at 890 hospitals representing more than 20% of the hospitalizations in the United States in the period from 2012 through 2017. Of course, there is some bad news to go with the good. The bad news, which comes as no surprise, is that infections with antimicrobial-resistant organisms continue to place a considerable burden on patients in . . .
Extraordinary Sequence Diversity and Promiscuity of Centromeric Satellites in the Legume Tribe Fabeae
Authors: Laura Ávila Robledillo, Pavel Neumann, Andrea Koblížková, Petr Novák, Iva Vrbová, Jiří Macas
Journal: Molecular Biology and Evolution (2020)

Satellite repeats are major sequence constituents of centromeres in many plant and animal species. Within a species, a single family of satellite sequences typically occupies centromeres of all chromosomes and is absent from other parts of the genome. Due to their common origin, sequence similarities exist among the centromere-specific satellites in related species. Here, we report a remarkably different pattern of centromere evolution in the plant tribe Fabeae, which includes genera Pisum, Lathyrus, Vicia, and Lens. By immunoprecipitation of centromeric chromatin with CENH3 antibodies, we identified and characterized a large and diverse set of 64 families of centromeric satellites in 14 species. These families differed in their nucleotide sequence, monomer length (33-2,979 bp), and abundance in individual species. Most families were species-specific, and most species possessed multiple (2-12) satellites in their centromeres. Some of the repeats that were shared by several species exhibited promiscuous patterns of centromere association, being located within CENH3 chromatin in some species, but apart from the centromeres in others. Moreover, FISH experiments revealed that the same family could assume centromeric and noncentromeric positions even within a single species. Taken together, these findings suggest that Fabeae centromeres are not shaped by the coevolution of a single centromeric satellite with its interacting CENH3 proteins, as proposed by the centromere drive model. This conclusion is also supported by the absence of pervasive adaptive evolution of CENH3 sequences retrieved from Fabeae species.
Organ-specific isoform selection of fatty acid–binding proteins in tissue-resident lymphocytes
Authors: H. Frizzell, R. Fonseca, S. N. Christo, M. Evrard, S. Cruz-Gomez, N. G. Zanluqui, B. von Scheidt, D. Freestone, S. L. Park, H. E. G. McWilliam, J. A. Villadangos, F. R. Carbone, L. K. Mackay
Journal: Science Immunology (2020)

Tissue-resident cells exhibit tissue-specific overlays to the T RM cell residency program that includes flexible FABP isoform selection tailored to the tissue of lodgment.
On Leaving Clinical Medicine
Authors: Kyan Lynch
Journal: Annals of Internal Medicine (2020)

On Being a Doctor7 April 2020On Leaving Clinical MedicineKyan Lynch, MD, MAKyan Lynch, MD, MAUniversity of Rochester Medical Center, Rochester, New York (K.L.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/M19-2666 Audio Reading - "On Leaving Clinical Medicine" Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads "On Leaving Clinical Medicine" by Kyan Lynch, MD, MA Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail When I graduated from medical school, I was on top of the world. I delivered the graduation address in which I compared my marriage to medicine with my 5-day-old marriage to the girl of my dreams. I had reached a peak most would never see, and it was only up from there.Five months later, I was in crisis. Sitting on the floor of my apartment with an unending tightness in my chest, I was barely able to organize my thoughts long enough to brush my teeth and get dressed. I was in the midst of an ugly divorce from ... Author, Article, and Disclosure InformationAffiliations: University of Rochester Medical Center, Rochester, New York (K.L.)Corresponding Author: Kyan Lynch, MD, MA, Department of Obstetrics and Gynecology, University of Rochester Medical Center, 601 Elmwood Avenue, Box 668, Rochester, NY 14642; e-mail, [email protected]rochester.edu. PreviousarticleNextarticle Advertisement Audio Reading - "On Leaving Clinical Medicine" Audio. Michael A. Lacombe, MD, Annals Associate Editor, reads "On Leaving Clinical Medicine" by Kyan Lynch, MD, MA Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics Cited byPhysician Suicide: A Scoping Literature Review to Highlight Opportunities for Prevention 7 April 2020Volume 172, Issue 7Page: 497-498KeywordsAnxietyDisabilitiesHealth careObstetrics and gynecologyPopulation statisticsPrevention, policy, and public healthPsychiatry and mental healthResidencySleepThorax ePublished: 7 April 2020 Issue Published: 7 April 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 13053: CRyo Ablation of Septal Hypertrophy (CRASH) in HOCM
Authors: Aharon Medina, Michael Ilan, Adi Butnaru, Arik Wolak, Rafael Wolff, Marc Klutstein, Moshe Rav Acha, David Meerkin, Yaron Almagor, Dan Tzivoni, Michael Glikson
Journal: Circulation (2019)

Introduction: Current interventions in HOCM include surgical myectomy and trans-catheter alcohol septal ablation, albeit coronary anatomy is not always suitable for this approach. Dual chamber paci...
Chronic liver disease negatively affects outcome in hospitalised patients with community-acquired pneumonia
Authors: Carla Bellinghausen, Mathias W Pletz, Jan Rupp, Martin Witzenrath, Christoph Welsch, Stefan Zeuzem, Jonel Trebicka, Gernot G U Rohde
Journal: Gut (2020)

We read with great interest the article by Fernandez and colleagues1 which identifies bacterial infections, including pneumonia, not only as a trigger, but also as a common complication of acute-on-chronic liver failure with severe consequences. Moreover, in this and other studies the role of respiratory infections and failure has been shown to be detrimental in patients with chronic liver disease (CLD).2–4 While it is well established that respiratory infections aggravate the clinical outcome and increase mortality in CLD, there are little to no data from large cohorts analysing the role of CLD in patients with community-acquired pneumonia (CAP). This prompted us to analyse the impact of CLD on the severity of CAP using data from the German Competence Network for Community-acquired pneumonia (CAPNETZ) study, a large multicentre study on CAP conducted between 2001 and 2017.5 6 The CAPNETZ study included a total of 11 832 patients with episodes of CAP, of whom 5449 hospitalised patients had information available on the presence or absence of CLD. In this cohort, 289 patients with CAP (5.3%; online supplementary figure S1) were identified with CLD. CAP patients with CLD were significantly younger than those without; their median age (IQR) was 64 years (50–73) vs 73 years (64–80) (p<0.001). Possibly due to the lower age in this patient group, cardiac disease, cerebrovascular disease and diabetes mellitus were less frequent in CAP patients with CLD than in those without. By contrast, chronic respiratory diseases were more common …
OLGenie: Estimating Natural Selection to Predict Functional Overlapping Genes
Authors: Chase W Nelson, Zachary Ardern, Xinzhu Wei
Journal: Molecular Biology and Evolution (2020)

Purifying (negative) natural selection is a hallmark of functional biological sequences, and can be detected in protein-coding genes using the ratio of nonsynonymous to synonymous substitutions per site (dN/dS). However, when two genes overlap the same nucleotide sites in different frames, synonymous changes in one gene may be nonsynonymous in the other, perturbing dN/dS. Thus, scalable methods are needed to estimate functional constraint specifically for overlapping genes (OLGs). We propose OLGenie, which implements a modification of the Wei-Zhang method. Assessment with simulations and controls from viral genomes (58 OLGs and 176 non-OLGs) demonstrates low false-positive rates and good discriminatory ability in differentiating true OLGs from non-OLGs. We also apply OLGenie to the unresolved case of HIV-1's putative antisense protein gene, showing significant purifying selection. OLGenie can be used to study known OLGs and to predict new OLGs in genome annotation. Software and example data are freely available at https://github.com/chasewnelson/OLGenie (last accessed April 10, 2020).