tbuckley/cabot-search huggingface dataset:
Maternal smoking during pregnancy affects adult onset of asthma in offspring: a follow up from birth to age 46 years
Authors: Sanna Toppila-Salmi, Annika T. Luukkainen, Baizhuang Xu, Jussi Lampi, Juha Auvinen, Kishor Dhaygude, Marjo-Riitta Järvelin, Juha Pekkanen
Journal: European Respiratory Journal (2020)

Rationale Environmental tobacco smoke (ETS) exposure increases asthma risk in children. There is limited knowledge of prenatal ETS for adult-onset asthma. Objectives To determine the association between prenatal ETS and adult onset asthma. Measurements and main results The questionnaire and clinical data of 5200 people, free of physician-diagnosed asthma by 31 years of age, who were included in the Northern Finland Birth Cohort 1966 Study was used. The association of maternal smoking during the last 3 months of pregnancy with onset of physician-diagnosed asthma and with lung function in adult offspring was studied using adjusted multivariate regression analyses. The cumulative incidence of physician-diagnosed asthma between the ages of 31 and 46 years was 5.1% among men and 8.8% among women. Gestational smoke exposure was associated with adult-onset asthma among offspring (adjusted OR 1.54, 95% CI 1.04–2.29), namely among offspring who reported either past non-diagnosed asthma (OR 9.63, 95% CI 2.28–40.67) or past cough with wheeze (3.21, 95% CI 1.71–6.05). A significant association was detected between gestational smoke exposure and the offspring's forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) ratio at 31 years of age. In offspring with the haplotype rs11702779-AA of RUNX1 , gestational smoke exposure was associated with adult-onset asthma (5.53, 95% CI 2.11–14.52, adjusted p-value for interaction 0.10). Conclusion Maternal smoking during pregnancy is associated with the cumulative incidence of asthma in offspring between the ages of 31 and 46 years. The association was accentuated in offspring who at age 31, reported having past respiratory problems and/or who had haplotype rs11702779-AA. A reduction in FEV 1 /FVC ratio was also observed at age 31 years in offspring with gestational smoke exposure. These results could reflect the early vulnerability of offspring's airways to ETS and its putative long-term effects.
The role of renal hypoxia in the pathogenesis of diabetic kidney disease: a promising target for newer renoprotective agents including SGLT2 inhibitors?
Authors: Anne C. Hesp, Jennifer A. Schaub, Pottumarthi V. Prasad, Volker Vallon, Gozewijn D. Laverman, Petter Bjornstad, Daniël H. van Raalte
Journal: Kidney International (2020)
Assessment of Interlaboratory Variation in the Interpretation of Genomic Test Results in Patients With Epilepsy
Authors: Jeffrey A. SoRelle, Juan M. Pascual, Garrett Gotway, Jason Y. Park
Journal: JAMA Network Open (2020)

Discordance in the interpretations of genetic test results has occurred with the increased number of laboratories that are performing testing. Differences in diagnostic interpretations may have implications for the treatment of patients.To assess the interlaboratory variation in the interpretations of genetic test results with potential therapeutic implications.In this cross-sectional study, 70 genes that are commonly tested in patients with epilepsy were examined to identify 22 676 genetic variants from an unknown number of patients using the ClinVar public database of clinically annotated variants. Variant annotations submitted to ClinVar (data set version 2019-05) between November 16, 2012, and May 3, 2019, were included in the analysis. Conflicting interpretations of the genetic variants associated with epilepsy were analyzed for clinically substantial discrepancies between May 7 and June 29, 2019. Variants were examined only if they had been interpreted by 2 or more clinical laboratories. A variant with a clinically substantial difference in interpretation was defined as a variant that crossed the threshold between a likely pathogenic variant and a variant of uncertain significance.The frequency and types of variant interpretation conflicts were analyzed when a conflict was identified.A total of 6292 of 22 676 variants related to epilepsy (27.7%) were interpreted by 2 or more clinical laboratories. Many variants (3307 of 6292 [52.6%]) had interpretations that were fully concordant. However, 2985 variants (47.4%) had conflicting interpretations. A clinically substantial conflict was identified in 201 of 6292 variants (3.2%). Furthermore, 117 of 201 variants (58.2%) with differences in interpretation occurred in genes with therapeutic implications.In this cross-sectional study, most interpretations of genetic variants associated with epilepsy were concordant among laboratories, but more than half of the variants with conflicting interpretations occurred in genes that have therapeutic implications. It would be helpful for genetic laboratories to report known diagnostic discordance with other clinical laboratories.
Abstract 462: Medical Emergency Team Replaces Code Blue Activations at Pediatric Hospital
Authors: Elizabeth Masse, Joan S Roberts
Journal: Circulation (2019)

Introduction: In free-standing pediatric hospitals, the Code Blue team may be activated for events in adults to provide triage, resuscitation, medical screening exams, EMTALA documentation and disposition decisions. However, activation of the Code Blue team can require significant time and critical care resources and may delay patient care if the activation is external to the building. Hypothesis: Development of a small triage team focused on specific adult triage algorithms will provide a safe, effective and efficient alternative to Code Blue team response. Methods: 407 bed tertiary pediatric hospital, within metropolitan area. Collaborative multi-disciplinary QI process to design and simulate the roles, workflow and documentation of the Medical Emergency Team (MET). Education and communication to hospital-wide staff on MET, as well as MET responders completion of Advanced Cardiac Life Support course. Collaboration with local EMS leadership to coordinate transfer of patient was also undertaken. Results: MET roles were developed and two configurations of the MET team were implemented July 2018: one inside the footprint of the building and anther outside the footprint of the building, including the hospital grounds. The teams consisted of a mid-level provider, charge nurse, two security officers and a shift administrator: inside team relied on ICU provider and charge nurse, while outside team led by Emergency Medicine provider and charge nurse. Each team had a backpack with supplies, and transport gurney. Since inception, 199 activations occurred, 191 inside and 8 outside the facility. The activations included 45 staff or volunteers, 84 adult visitors, 75 pediatric visitors. Outcome for the activations: 57 transported to the hospital ED, 47 transported to another facility, 21 refused treatment and 68 had resolution of concerns. EMTALA documentation was complete in 112/137 (82%). Conclusions: Pediatric hospitals have substantial adult populations, where medical emergencies that arise rely on Code Blue in medical emergencies for simplicity. Development of a response team for nonpatients allows specific training, triage, and processes to improve care and reduce drain on ICU resources.
Comparative seasonalities of influenza A, B and ‘common cold’ coronaviruses – setting the scene for SARS-CoV-2 infections and possible unexpected host immune interactions
Authors: Yang Liu, Tommy T.Y. Lam, Florence Y.L. Lai, Mel Krajden, Steven J. Drews, Todd F. Hatchette, Pieter L.A. Fraaij, Jeroen J.A. van Kampen, Darmaa Badarch, Pagbajabyn Nymadawa, Kok Keng Tee, Hong Kai Lee, Evelyn S.C. Koay, Lance Jennings, Marion Koopmans, Julian W. Tang
Journal: Journal of Infection (2020)
Analysis of the susceptibility of lung cancer patients to SARS-CoV-2 infection
Authors: Qi Kong, Zhiguang Xiang, Yue Wu, Yu Gu, Jianguo Guo, Fei Geng
Journal: Molecular Cancer (2020)

Abstract Recent studies have reported that COVID-19 patients with lung cancer have a higher risk of severe events than patients without cancer. In this study, we investigated the gene expression of angiotensin I-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) with prognosis in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Lung cancer patients in each age stage, subtype, and pathological stage are susceptible to SARS-CoV-2 infection, except for the primitive subtype of LUSC. LUAD patients are more susceptible to SARS-CoV-2 infection than LUSC patients. The findings are unanimous on tissue expression in gene and protein levels.
Glioblastoma in adults: a Society for Neuro-Oncology (SNO) and European Society of Neuro-Oncology (EANO) consensus review on current management and future directions
Authors: Patrick Y Wen, Michael Weller, Eudocia Quant Lee, Brian M Alexander, Jill S Barnholtz-Sloan, Floris P Barthel, Tracy T Batchelor, Ranjit S Bindra, Susan M Chang, E Antonio Chiocca, Timothy F Cloughesy, John F DeGroot, Evanthia Galanis, Mark R Gilbert, Monika E Hegi, Craig Horbinski, Raymond Y Huang, Andrew B Lassman, Emilie Le Rhun, Michael Lim, Minesh P Mehta, Ingo K Mellinghoff, Giuseppe Minniti, David Nathanson, Michael Platten, Matthias Preusser, Patrick Roth, Marc Sanson, David Schiff, Susan C Short, Martin J B Taphoorn, Joerg-Christian Tonn, Jonathan Tsang, Roel G W Verhaak, Andreas von Deimling, Wolfgang Wick, Gelareh Zadeh, David A Reardon, Kenneth D Aldape, Martin J van den Bent
Journal: Neuro-Oncology (2020)

Abstract Glioblastomas are the most common form of malignant primary brain tumor and an important cause of morbidity and mortality. In recent years there have been important advances in understanding the molecular pathogenesis and biology of these tumors, but this has not translated into significantly improved outcomes for patients. In this consensus review from the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO), the current management of isocitrate dehydrogenase wildtype (IDHwt) glioblastomas will be discussed. In addition, novel therapies such as targeted molecular therapies, agents targeting DNA damage response and metabolism, immunotherapies, and viral therapies will be reviewed, as well as the current challenges and future directions for research.
Long-Term Follow-up of the ALLG CML8 Twister Study of Treatment-Free Remission (TFR) in Patients with Chronic Myeloid Leukemia (CML)
Authors: David M Ross, Ilaria S Pagani, Naranie Shanmuganathan, John F Seymour, Anthony K Mills, Robin J Filshie, Christopher K Arthur, Phuong Dang, Verity A Saunders, Jody Braley, David T Yeung, Deborah L White, Andrew P Grigg, Anthony P Schwarer, Susan Branford, Timothy P. Hughes
Journal: Blood (2017)
Recent advances of antibody drug conjugates for clinical applications
Authors: Pengxuan Zhao, Yuebao Zhang, Wenqing Li, Christopher Jeanty, Guangya Xiang, Yizhou Dong
Journal: Acta Pharmaceutica Sinica B (2020)

Antibody drug conjugates (ADCs) normally compose of a humanized antibody and small molecular drug via a chemical linker. After decades of preclinical and clinical studies, a series of ADCs have been widely used for treating specific tumor types in the clinic such as brentuximab vedotin (Adcetris®) for relapsed Hodgkin's lymphoma and systemic anaplastic large cell lymphoma, gemtuzumab ozogamicin (Mylotarg®) for acute myeloid leukemia, ado-trastuzumab emtansine (Kadcyla®) for HER2-positive metastatic breast cancer, inotuzumab ozogamicin (Besponsa®) and most recently polatuzumab vedotin-piiq (Polivy®) for B cell malignancies. More than eighty ADCs have been investigated in different clinical stages from approximately six hundred clinical trials to date. This review summarizes the key elements of ADCs and highlights recent advances of ADCs, as well as important lessons learned from clinical data, and future directions.
David Oliver: What the pandemic measures reveal about ageism
Authors: David Oliver
Journal: BMJ (2020)

BerkshireOlder age and a range of underlying medical conditions mean a higher risk of serious illness, admission, and death from covid-19 than in younger or fitter groups.Over 70s have been advised to avoid unnecessary social contact, remain largely indoors, and to do any outdoor exercise at a safe distance from others.The reaction of some older citizens to this announcement shone a light on some wider attitudes towards ageing-not least from older people themselves.
AB0091 SYNDECAN-4 IS INCREASED IN OSTEOARTHRITIC KNEE, BUT NOT HIP OR SHOULDER, ARTICULAR HYPERTROPHIC CHONDROCYTES
Authors: Christelle Sanchez, Cécile Lambert, Jean-Emile Dubuc, Jessica Bertrand, Thomas Pap, Yves Henrotin
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Syndecan-4 plays a critical role in cartilage degradation during osteoarthritis (OA). <h3>Objectives</h3> To investigate the expression and localization of syndecan-4 in different OA joint tissues. <h3>Methods</h3> Syndecan-4 mRNA levels were quantified by RT-PCR in human OA primary cells to compare non-hypertrophic vs hypertrophic articular chondrocytes, non-sclerotic vs sclerotic subchondral osteoblasts and normal/reactive vs inflamed fibroblasts-like synoviocytes. Syndecan-4 was localized by immunohistochemistry in knee, hip or shoulder OA bone/cartilage biopsies. Syndecan-4 was quantified by immmunoassay in chondrocytes culture supernatant and cell fraction. <h3>Results</h3> By immunohistochemistry, syndecan-4 was observed in chondrocytes clusters in the superficial zone of OA knee, but not in OA hip or shoulder cartilage. No staining was observed in the deep zone of cartilage and in subchondral bone. No difference between syndecan-4 expression level in sclerotic and non-sclerotic osteoblasts was observed. Syndecan-4 tended to be increased in inflamed synoviocytes compared to normal/reactive ones but difference was not significant. Differentiated hypertrophic chondrocytes from knee, but not from hip cartilage, expressed more syndecan-4 than non-hypertrophic cells. Using an immunoassay for the extracellular domain of syndecan-4, we found 68% of the syndecan-4 in the culture supernatant of OA chondrocytes culture, suggesting that a large majority of the syndecan-4 is shed and released in the extracellular medium. The shedding rate was not affected by hypertrophic differentiation state of the chondrocytes or their joint origin. <h3>Conclusion</h3> Syndecan-4 could be related to the hypertrophic differentiation of the OA chondrocytes, but the pathway seems to be knee specific. Even if chondrocytes clusters are seen in OA knee, hip and shoulder cartilage and hypertrophic differentiation appears in knee and hip OA articular chondrocytes, syndecan-4 synthesis only increased in knee. These findings suggests the presence of biochemical difference between articular cartilage according to their location and that syndecan-4 could be a biochemical marker specific for knee OA. <h3>Disclosure of Interests</h3> None declared
Efficacy of dupilumab in atopic comorbidities associated with moderate‐to‐severe adult atopic dermatitis
Authors: Eustachio Nettis, Vincenzo Patella, Carla Lombardo, Aikaterini Detoraki, Luigi Macchia, Elisabetta Di Leo, Monica Carbonara, Giorgio W. Canonica, Laura Bonzano
Journal: Allergy (2020)

Abstract Background Dupilumab is an anti‐IL‐4Rα antibody used in the treatment of patients with moderate‐to‐severe atopic dermatitis (msAD). This study explored the potential benefit of dupilumab in perennial allergic rhinoconjunctivitis (PAR) and perennial allergic asthma (PAA) caused by indoor allergens in adults with msAD. Methods This multicentric, prospective, observational, real‐life study included adult patients with msAD who had been treated with dupilumab in 16 Italian care centres. Efficacy outcomes regarding AD, PAR and PAA were collected at baseline and 16 weeks. Safety was also assessed. Results We enrolled 123 patients with msAD. Between baseline and 16 weeks of treatment, the following measurements decreased statistically significantly: Eczema Area and Severity Index, SCOring AD, Patient‐Oriented Eczema Measure, pruritus score, sleep score, Dermatology Life Quality Index and IgE. Dupilumab treatment in patients with comorbid PAR (n = 41) was associated with significant improvements in PAR disease control (measured using a Rhinitis Control Scoring System) and in PAR Quality of life (QoL) (measured using the Rhinoconjunctivitis QoL Questionnaire scores). In 32 patients with comorbid PAA, dupilumab significantly improved PAA control (measured using the Asthma Control Test and five‐item Asthma Control Questionnaire scores) and disease‐related QoL (measured using the Asthma QoL Questionnaire scores). Thirty‐five patients (28.5%) developed conjunctivitis during the study period. Conclusion These results support the benefits of dupilumab for adult patients with PAR and/or PAA associated with msAD.
68Ga-FAPI PET/CT in Assessment of Liver Nodules in a Cirrhotic Patient
Authors: Liang Zhao, Jianwei Gu, Kaili Fu, Qin Lin, Haojun Chen
Journal: Clinical Nuclear Medicine (2020)

Abstract 68 Ga-FAPI PET/CT was performed in a 56-year-old cirrhotic patient with multiple liver nodules, which were suspected of hepatocellular carcinoma by contrast-enhanced magnetic resonance but were not visualized by 18 F-FDG PET/CT. Increased 68 Ga-FAPI liver uptake was observed in this cirrhotic patient. However, the nodules had no pathological 68 Ga-FAPI uptake and were clearly visualized due to the low activity compared with surrounding liver parenchyma. The 68 Ga-FAPI PET/CT features, suggestive of benign nodules, have been later confirmed by histopathological examination. This case suggested that 68 Ga-FAPI PET/CT may be useful in the differentiation between benign nodules and hepatocellular carcinoma in the patient with liver cirrhosis.
Thresholds and Mortality Associations of Paraspinous Muscle Sarcopenia in Older Trauma Patients
Authors: Stephen J. Kaplan, K. Lynn Zhao, Melanie Koren, Itay Bentov, May J. Reed, Tam N. Pham
Journal: JAMA Surgery (2020)

Despite strict adherence to prevention guidelines, this study shows that CAUTIs still occur.This suggests that risk factors exist that may make certain patients more susceptible to CAUTI that are not currently addressed.Future studies are warranted in patient groups that develop CAUTIs despite guideline adherence to determine other risk factors for CAUTIs that should be addressed during patient treatment.Risk determination would also allow for a risk-adjusted rate of CAUTIs to be developed and reported rather than an absolute rate, which would better represent the occurrence of CAUTIs within specific patient subpopulations.
30 Years of Biotherapeutics Development—What Have We Learned?
Authors: Nico Ghilardi, Rajita Pappu, Joseph R. Arron, Andrew C. Chan
Journal: Annual Review of Immunology (2020)

Since the birth of biotechnology, hundreds of biotherapeutics have been developed and approved by the US Food and Drug Administration (FDA) for human use. These novel medicines not only bring significant benefit to patients but also represent precision tools to interrogate human disease biology. Accordingly, much has been learned from the successes and failures of hundreds of high-quality clinical trials. In this review, we discuss general and broadly applicable themes that have emerged from this collective experience. We base our discussion on insights gained from exploring some of the most important target classes, including interleukin-1 (IL-1), tumor necrosis factor α (TNF-α), IL-6, IL-12/23, IL-17, IL-4/13, IL-5, immunoglobulin E (IgE), integrins and B cells. We also describe current challenges and speculate about how emerging technological capabilities may enable the discovery and development of the next generation of biotherapeutics.
Primary Care Interventions for Prevention and Cessation of Tobacco Use in Children and Adolescents
Authors: Douglas K. Owens, Karina W. Davidson, Alex H. Krist, Michael J. Barry, Michael Cabana, Aaron B. Caughey, Susan J. Curry, Katrina Donahue, Chyke A. Doubeni, John W. Epling, Martha Kubik, Gbenga Ogedegbe, Lori Pbert, Michael Silverstein, Melissa A. Simon, Chien-Wen Tseng, John B. Wong
Journal: JAMA (2020)

<h3>Importance</h3> Tobacco use is the leading cause of preventable death in the US. An estimated annual 480 000 deaths are attributable to tobacco use in adults, including from secondhand smoke. It is estimated that every day about 1600 youth aged 12 to 17 years smoke their first cigarette and that about 5.6 million adolescents alive today will die prematurely from a smoking-related illness. Although conventional cigarette use has gradually declined among children in the US since the late 1990s, tobacco use via electronic cigarettes (e-cigarettes) is quickly rising and is now more common among youth than cigarette smoking. e-Cigarette products usually contain nicotine, which is addictive, raising concerns about e-cigarette use and nicotine addiction in children. Exposure to nicotine during adolescence can harm the developing brain, which may affect brain function and cognition, attention, and mood; thus, minimizing nicotine exposure from any tobacco product in youth is important. <h3>Objective</h3> To update its 2013 recommendation, the USPSTF commissioned a review of the evidence on the benefits and harms of primary care interventions for tobacco use prevention and cessation in children and adolescents. The current systematic review newly included e-cigarettes as a tobacco product. <h3>Population</h3> This recommendation applies to school-aged children and adolescents younger than 18 years. <h3>Evidence Assessment</h3> The USPSTF concludes with moderate certainty that primary care–feasible behavioral interventions, including education or brief counseling, to prevent tobacco use in school-aged children and adolescents have a moderate net benefit. The USPSTF concludes that there is insufficient evidence to determine the balance of benefits and harms of primary care interventions for tobacco cessation among school-aged children and adolescents who already smoke, because of a lack of adequately powered studies on behavioral counseling interventions and a lack of studies on medications. <h3>Recommendation</h3> The USPSTF recommends that primary care clinicians provide interventions, including education or brief counseling, to prevent initiation of tobacco use among school-aged children and adolescents. (B recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of primary care–feasible interventions for the cessation of tobacco use among school-aged children and adolescents. (I statement)