tbuckley/cabot-search huggingface dataset:
Autotitrating external positive end-expiratory airway pressure to abolish expiratory flow limitation during tidal breathing in patients with severe COPD: a physiological study
Authors: Eui-Sik Suh, Pasquale Pompilio, Swapna Mandal, Peter Hill, Georgios Kaltsakas, Patrick B. Murphy, Robert Romano, John Moxham, Raffaele Dellaca, Nicholas Hart
Journal: European Respiratory Journal (2020)

The optimal noninvasive application of external positive end-expiratory pressure (EPAP) to abolish tidal-breathing expiratory flow limitation (EFLT) and minimise intrinsic positive end-expiratory pressure (PEEPi) is challenging in COPD patients. We investigated whether auto-titrating EPAP, using the forced oscillation technique (FOT) to detect and abolish EFLT, would minimise PEEPi, work of breathing and neural respiratory drive (NRD) in patients with severe COPD.Patients with COPD with chronic respiratory failure underwent auto-titration of EPAP using a FOT-based algorithm that detected EFLT. Once optimal EPAP was identified, manual titration was performed to assess NRD (using diaphragm and parasternal intercostal muscle electromyography, EMGdi and EMGpara, respectively), transdiaphragmatic inspiratory pressure swings (ΔPdi), transdiaphragmatic pressure-time product (PTPdi) and PEEPi, between EPAP levels 2 cmH2O below to 3 cmH2O above optimal EPAP.Of 10 patients enrolled (age 65±6 years; male 60%; body mass index 27.6±7.2 kg.m-2; forced expiratory volume in 1 s 28.4±8.3% predicted), eight had EFLT, and optimal EPAP was 9 (range 4-13) cmH2O. NRD was reduced from baseline EPAP at 1 cmH2O below optimal EPAP on EMGdi and at optimal EPAP on EMGpara. In addition, at optimal EPAP, PEEPi (0.80±1.27 cmH2O versus 1.95± 1.70 cmH2O; p<0.05) was reduced compared with baseline. PTPdi (10.3±7.8 cmH2O·s-1versus 16.8±8.8 cmH2O·s-1; p<0.05) and ΔPdi (12.4±7.8 cmH2O versus 18.2±5.1 cmH2O; p<0.05) were reduced at optimal EPAP+1 cmH2O compared with baseline.Autotitration of EPAP, using a FOT-based algorithm to abolish EFLT, minimises transdiaphragmatic pressure swings and NRD in patients with COPD and chronic respiratory failure.
Emerging role of mTOR in tumor immune contexture: Impact on chemokine-related immune cells migration
Authors: Jing Jin, Qijie Zhao
Journal: Theranostics (2020)

During the last few decades, cell-based anti-tumor immunotherapy emerged and it has provided us with a large amount of knowledge.Upon chemokines recognition, immune cells undergo rapid trafficking and activation in disease milieu, with immune cells chemotaxis being accompanied by activation of diverse intercellular signal transduction pathways.The outcome of chemokines-mediated immune cells chemotaxis interacts with the cue of mammalian target of rapamycin (mTOR) in the tumor microenvironment (TME).Indeed, the mTOR cascade in immune cells involves migration and infiltration.In this review, we summarize the available mTOR-related chemokines, as well as the characterized upstream regulators and downstream targets in immune cells chemotaxis and assign potential underlying mechanisms in each evaluated chemokine.Specifically, we focus on the involvement of mTOR in chemokine-mediated immune related cells in the balance between tumor immunity and malignancy.
DR-region of Na<sup>+</sup>/K<sup>+</sup>-ATPase is a target to ameliorate hepatic insulin resistance in obese diabetic mice
Authors: Hai-Jian Sun, Lei Cao, Meng-Yuan Zhu, Zhi-Yuan Wu, Chen-You Shen, Xiao-Wei Nie, Jin-Song Bian
Journal: Theranostics (2020)

Reduced hepatic Na+/K+-ATPase (NKA) activity and NKAα1 expression are engaged in the pathologies of metabolism diseases. The present study was designed to investigate the potential roles of NKAα1 in hepatic gluconeogenesis and glycogenesis in both hepatocytes and obese diabetic mice. Methods: Insulin resistance was mimicked by glucosamine (GlcN) in either human hepatocellular carcinoma (HepG2) cells or primary mouse primary hepatocytes. Obese diabetic mice were induced by high-fat diet (HFD) feeding for 12 weeks. Results: We found that both NKA activity and NKAα1 protein level were downregulated in GlcN-treated hepatocytes and in the livers of obese diabetic mice. Pharmacological inhibition of NKA with ouabain worsened, while activation of NKAα1 with an antibody against an extracellular DR region of NKAα1 subunit (DR-Ab) prevented GlcN-induced increase in gluconeogenesis and decrease in glycogenesis. Likewise, the above results were also corroborated by the opposite effects of genetic knockout/overexpression of NKAα1 on both gluconeogenesis and glycogenesis. In obese diabetic mice, hepatic activation or overexpression of NKAα1 stimulated the PI3K/Akt pathway to suppress hyperglycemia and improve insulin resistance. More importantly, loss of NKA activities in NKAα1+/- mice was associated with more susceptibility to insulin resistance following HFD feeding. Conclusions: Our findings suggest that NKAα1 is a physiological regulator of glucose homoeostasis and its DR-region is a novel target to treat hepatic insulin resistance.
Genomic Methods Identify Homologous Recombination Deficiency in Pancreas Adenocarcinoma and Optimize Treatment Selection
Authors: Wungki Park, Jiapeng Chen, Joanne F. Chou, Anna M. Varghese, Kenneth H. Yu, Winston Wong, Marinela Capanu, Vinod Balachandran, Caitlin A. McIntyre, Imane El Dika, Danny N. Khalil, James J. Harding, Nima Ghalehsari, Zoe McKinnell, Sree B. Chalasani, Vladimir Makarov, Pier Selenica, Xin Pei, Nicolas Lecomte, David P. Kelsen, Ghassan K. Abou-Alfa, Mark E. Robson, Liying Zhang, Michael F. Berger, Nikolaus Schultz, Timothy A. Chan, Simon N. Powell, Jorge S. Reis-Filho, Christine A. Iacobuzio-Donahue, Nadeem Riaz, Eileen M. O'Reilly
Journal: Clinical Cancer Research (2020)

Genomic methods can identify homologous recombination deficiency (HRD). Rigorous evaluation of their outcome association to DNA damage response-targeted therapies like platinum in pancreatic ductal adenocarcinoma (PDAC) is essential in maximizing therapeutic outcome.
Abstract 10201: Clinical Implications of 18F-sodium Fluoride Uptake in Subclinical Aortic Valve Calcification: Its Relation to Coronary Atherosclerosis and Predictive Value
Authors: Toshiro Kitagawa, Yumiko Nakamoto, Ko Sasaki, Yutaka Hirokawa, Yasuki Kihara
Journal: Circulation (2019)

Background: 18F-sodium fluoride (18F-NaF) positron emission tomography (PET) is reported to reflect active calcification, and its application to aortic valve calcification (AVC) in the earlier phas...
Long-term efficacy of antifungals in toenail onychomycosis: a critical review
Authors: B.J. Cribier, C. Paul
Journal: British Journal of Dermatology (2008)

Background Modern antifungal drugs achieve high mycological and clinical cure rates in onychomycosis of the toes, but little is known about the long-term evolution of the treated patients. Objectives The aim of this review was to analyse the therapeutic results recorded more than 1 year after initiation of therapy. Methods We used two endpoints for the analysis: EP1 (the number of patients with negative mycology after follow-up, divided by the number of patients included at day 0, including all patients lost to follow-up), and EP2 (the number of patients with negative mycology after follow-up divided by the number of patients with negative mycology at week 48). Clinical cure rate (EPclin) was the number of patients clinically cured or with minimal residual lesions divided by the number of patients included at day 0. Results From a Medline search we identified 17 studies providing results beyond 48 weeks. Ketoconazole 200 mg d−1 up to 1 year resulted in EP1 of 11% at 18 months, and EP2 of 43%. Griseofulvin 1 g d−1 for 1 year allowed an EP1 of 43% at 18 months, and EP2 of 71%. The mean EP1 after fluconazole once weekly up to 1 year was 49% at 18 months, and EP2 was 91%. With itraconazole 200 mg d−1 or 400 mg d−1 for 1 week each month for 3–4 months, EP1 was 37% at 18 months, and 53% at 2 years; EP2 was 76% at 4 years. Terbinafine 250 mg d−1 for 12–16 weeks achieved an EP1 of 62% at 18 months, 72% at 2 years, and 60% at 4 years; EP2 was 80% at 18 months, 81% at 2 years, and 71% at 4 years. In the only study planned to compare the long-term efficacy of terbinafine and itraconazole, EP1 at 18 months was significantly higher with continuous terbinafine than with intermittent itraconazole (66% vs. 37%, P < 0·001). The clinical cure rates were 21% at 60 weeks and 37% at 72 weeks with fluconazole. EPclin was 27% at 18 months and 35% at 2 years with itraconazole. EPclin was 48% at 18 months, 69% at 2 years and 50% at 4 years with terbinafine. Conclusions Considering the stringency of the criteria we used, this critical review suggests that the long-term efficacy achieved with terbinafine is superior to that obtained with griseofulvin, ketoconazole, fluconazole or itraconazole.
Correction: Hdac3 is an epigenetic inhibitor of the cytotoxicity program in CD8 T cells
Authors: Rong En Tay, Olamide Olawoyin, Paloma Cejas, Yingtian Xie, Clifford A. Meyer, Yoshinaga Ito, Qing Yu Weng, David E. Fisher, Henry W. Long, Myles Brown, Hye-Jung Kim, Kai W. Wucherpfennig
Journal: The Journal of Experimental Medicine (2020)
Erratum: Regulator of G-protein signaling-2 mediates vascular smooth muscle relaxation and blood pressure (Nature Medicine (2003) 9 (1506-1512))
Authors: K. Mary Tang, Guang Rong Wang, Ping Lu, Richard H. Karas, Mark Aronovitz, Scott P. Heximer, Kevin M. Kaltenbronn, Kendall J. Blumer, David P. Siderovski, Yan Zhu, Michael E. Mendelsohn
Journal: Nature Medicine (2004)
Joint AAD-NPF Guidelines of Care for the Management of Psoriasis With Systemic Non-Biological Therapies
Authors: Alan Menter, Joel M Gelfand, Cody Connor, April W Armstrong, Kelly M Cordoro, Dawn Mr Davis, Boni E Elewski, Kenneth B Gordon, Alice B Gottlieb, Daniel H Kaplan, Arthur Kavanaugh, Matthew Kiselica, Dario Kivelevitch, Neil J Korman, Daniela Kroshinsky, Mark Lebwohl, Craig L Leonardi, Jason Lichten, Henry W Lim, Nehal N Mehta, Amy S Paller, Sylvia L Parra, Arun L Pathy, Elizabeth F Prater, Robert S Rahimi, Reena N Rupani, Michael Siegel, Benjamin Stoff, Bruce E Strober, Elliot B Tapper, Emily B Wong, Jashin J Wu, Vidhya Hariharan, Craig A Elmets
Journal: Journal of the American Academy of Dermatology (2020)
Physician’s global assessment is often useful in SLE, but not always: the case of clinical remission
Authors: Margherita Zen, Francesca Saccon, Mariele Gatto, Andrea Doria
Journal: Annals of the Rheumatic Diseases (2020)

We read with interest the paper by Aranow et al 1 where physician’s global assessment (PGA) displayed excellent inter-rater reliability, which could rely on the inclusion of highly selected lupus experts, as stated by the authors themselves. Indeed, in previous studies, PGA showed a high intra-rater and inter-rater variability,2 3 consistently with PGA being a subjective measure.

The high inter-rater reliability observed by the authors is surprising considering that the timeframe for assessing disease activity significantly varied among respondents: 36.7% scored PGA over the previous 7–10 days, 36.7% over the previous month, the remainder over shorter or longer periods of time. Additionally, in almost one-third of respondents, lupus damage was considered when scoring PGA.

Notably, the authors suggest that PGA should be scored after considering laboratory results, owing to a better correlation with systemic lupus erythematosus (SLE) disease activity index-2000 (SLEDAI-2K) of postlaboratory versus prelaboratory PGA. …
Large community-acquired Legionnaires’ disease outbreak caused by Legionella pneumophila serogroup 1, Italy, July to August 2018
Authors: Marino Faccini, Antonio Giampiero Russo, Maira Bonini, Sara Tunesi, Rossella Murtas, Monica Sandrini, Sabrina Senatore, Anna Lamberti, Giorgio Ciconali, Serafina Cammarata, Eros Barrese, Valentina Ceriotti, Sonia Vitaliti, Marina Foti, Gabriella Gentili, Elisabetta Graziano, Emerico Panciroli, Marco Bosio, Maria Gramegna, Danilo Cereda, Carlo Federico Perno, Ester Mazzola, Daniela Campisi, Gianuario Aulicino, Silvana Castaldi, Antonietta Girolamo, Maria Grazia Caporali, Maria Scaturro, Maria Cristina Rota, Maria Luisa Ricci
Journal: Eurosurveillance (2020)

In July 2018, a large outbreak of Legionnaires' disease (LD) caused by Legionella pneumophila serogroup 1 (Lp1) occurred in Bresso, Italy. Fifty-two cases were diagnosed, including five deaths. We performed an epidemiological investigation and prepared a map of the places cases visited during the incubation period. All sites identified as potential sources were investigated and sampled. Association between heavy rainfall and LD cases was evaluated in a case-crossover study. We also performed a case-control study and an aerosol dispersion investigation model. Lp1 was isolated from 22 of 598 analysed water samples; four clinical isolates were typed using monoclonal antibodies and sequence-based typing. Four Lp1 human strains were ST23, of which two were Philadelphia and two were France-Allentown subgroup. Lp1 ST23 France-Allentown was isolated only from a public fountain. In the case-crossover study, extreme precipitation 5-6 days before symptom onset was associated with increased LD risk. The aerosol dispersion model showed that the fountain matched the case distribution best. The case-control study demonstrated a significant eightfold increase in risk for cases residing near the public fountain. The three studies and the matching of clinical and environmental Lp1 strains identified the fountain as the source responsible for the epidemic.
Contempo '81. Nuclear medicine. The internist's view
Authors: M. L. Lecklitner
Journal: JAMA (1981)

<h3>Hepatobiliary Scanning</h3> In recent years, the development of technetium Tc 99m iminodiacetic acid derivatives (<sup>99m</sup>Tc-IDA derivatives) and similar compounds for scintigraphic evaluation of the hepatobiliary system has constituted one of the most important contributions of nuclear medicine to clinical practice. Heretofore, only rose bengal sodium I 131 was available for scintigraphic evaluation of the hepatobiliary system, but dosimetry considerations precluded administration of sufficient quantities to enable satisfactory visualization. The<sup>99m</sup>Tc-IDA derivatives have altered this situation, and hepatobiliary scintigraphy has its prime use in the exclusion of acute cholecystitis as the cause of acute intra-abdominal pain, tenderness, and muscular rigidity, which necessitates surgery.<sup>1</sup>Scintigraphic visualization of the gallbladder following intravenous administration of the radiopharmaceutical virtually excludes acute cholecystitis as the diagnosis, because almost all cases are associated with cystic-duct obstruction, preventing ingress of material to the gallbladder. Nonvisualization of the gallbladder when liver function is normal is compatible
Deep Learning Automated Detection of Reticular Pseudodrusen from Fundus Autofluorescence Images or Color Fundus Photographs in AREDS2
Authors: Tiarnan D.L. Keenan, Qingyu Chen, Yifan Peng, Amitha Domalpally, Elvira Agrón, Christopher K. Hwang, Alisa T. Thavikulwat, Debora H. Lee, Daniel Li, Wai T. Wong, Zhiyong Lu, Emily Y. Chew
Journal: Ophthalmology (2020)
Beyond the Apnea Test: An Argument to Broaden the Requirement for Consent to the Entire Brain Death Evaluation
Authors: Erin Paquette, Joel Frader, Seema Shah, Robert C. Tasker, Robert Truog
Journal: The American Journal of Bioethics (2020)

This article refers to:Legal and Ethical Considerations for Requiring Consent for Apnea Testing in Brain Death Determination
15P The CelTIL score as an early predictor of anti-tumour response following neoadjuvant therapy (NAT): A SOLTI biomarker analysis
Authors: B. González-Farré, P. Nuciforo, L. Pare Brunet, J. Cortés, A. Llombart Cussac, J. Gavila Gregori, E. Sanfeliu, N. Chic, M. Vidal, B. Adamo, M. Muñoz, P. Galván, D. Martínez, P. Villagrasa, T. Pascual, A. Prat
Journal: Annals of Oncology (2020)
Cellulitis and Soft Tissue Infections (Japanese Version)
Authors: Rachel Bystritsky, Henry Chambers
Journal: Annals of Internal Medicine (2018)

In the Clinic6 February 2018Cellulitis and Soft Tissue Infections (Japanese Version)Correction(s) for this article:CorrectionsNov 2022Correction: Japanese Translations of In the ClinicFREERachel Bystritsky, MD and Henry Chambers, MDRachel Bystritsky, MDUniversity of California, San Francisco, California (R.B., H.C.) and Henry Chambers, MDUniversity of California, San Francisco, California (R.B., H.C.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/IsTranslatedFrom_AITC201802060_Japanese SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Editors' Note: This article (available in PDF format) is the translated Japanese version of In the Clinic: Cellulitis and Soft Tissue Infections (Bystritsky R, Chambers H. Cellulitis and Soft Tissue Infections. Ann Intern Med. 2018;168:ITC17-ITC32. doi:10.7326/AITC201802060). Author, Article, and Disclosure InformationAffiliations: University of California, San Francisco, California (R.B., H.C.)Correction: This article was updated on 1 November 2022 to remove the glossary of terms, which was not present on the original publication, and to indicate the translators of the article.Funding Source: American College of Physicians.Disclosures: Dr. Chambers, ACP Contributing Author, reports grants and other from Allergan and grants from The Medicines Company outside the submitted work. Dr. Bystritsky, ACP Contributing Author, has nothing to disclose. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-2613.Acknowledgment: The authors thank Lawrence J. Eron, author of the previous version of this In the Clinic.With the assistance of additional physician writers, the editors of Annals of Internal Medicine develop In the Clinic using MKSAP and other resources of the American College of Physicians.In the Clinic does not necessarily represent official ACP clinical policy. For ACP clinical guidelines, please go to https://www.acponline.org/clinical_information/guidelines/. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoCellulitis and Soft Tissue Infections Rachel Bystritsky and Henry Chambers Correction: Japanese Translations of In the Clinic Metrics Cited byCorrection: Japanese Translations of In the ClinicCellulitis and Its Mimickers: an Approach to Diagnosis and Management 6 February 2018Volume 168, Issue 3Page: JITC17-JITC32 ePublished: 19 May 2020 Issue Published: 6 February 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Diffuse pneumonitis from coronavirus HKU1 on checkpoint inhibitor therapy
Authors: Michael T Serzan, Princy N Kumar, Michael B Atkins
Journal: Journal for ImmunoTherapy of Cancer (2020)

Immune checkpoint inhibitors (ICIs) can produce specific immune-related adverse events including pneumonitis. The impact of ICI therapy on the severity of acute coronavirus infection symptomatology warrants further exploration.We report a 65-year-old man diagnosed with stage IV melanoma who developed pulmonary and brain metastases and was treated with bilateral craniotomies followed by combined nivolumab and ipilimumab immunotherapy. He developed early-onset severe dyspnea associated with acute coronavirus HKU1 (non-COVID-19) infection, with diffuse pneumonitis evidenced by ground glass opacification on CT scan. He was treated with steroids leading to resolution of pneumonitis on repeat imaging, suggesting an exacerbated immune-mediated toxicity.We report the first case of a patient with melanoma with severe and reversible diffuse pneumonitis in association with coronavirus HKU1 following combined nivolumab and ipilimumab immunotherapy. Although we do not have data on the impact of ICI therapy on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) symptomatology, a possible interaction should be considered when deciding on dosing in patients with possible SARS-CoV-2 exposure or when evaluating patients with presumed ICI-related pneumonitis during the COVID-19 pandemic.
Interplay between MycN and c-Myc regulates radioresistance and cancer stem cell phenotype in neuroblastoma upon glutamine deprivation
Authors: Marion Le Grand, Anna Mukha, Jakob Püschel, Emanuele Valli, Alvin Kamili, Orazio Vittorio, Anna Dubrovska, Maria Kavallaris
Journal: Theranostics (2020)

Targeting glutamine metabolism has emerged as a potential therapeutic strategy for Myc overexpressing cancer cells.Myc proteins contribute to an aggressive neuroblastoma phenotype.Radiotherapy is one of the treatment modalities for high-risk neuroblastoma patients.Herein, we investigated the effect of glutamine deprivation in combination with irradiation in neuroblastoma cells representative of high-risk disease and studied the role of Myc member interplay in regulating neuroblastoma cell radioresistance.Methods: Cell proliferation and viability assays were used to establish the effect of glutamine deprivation in neuroblastoma cells expressing c-Myc or MycN.Gene silencing and overexpression were used to modulate the expression of Myc genes to determine their role in neuroblastoma radioresistance.qPCR and western blot investigated interplay between expression of Myc members.The impact of glutamine deprivation on cell response following irradiation was explored using a radiobiological 3D colony assay.DNA repair gene pathways as well as CSC-related genes were studied by qPCR array.Reactive Oxygen Species (ROS) and glutathione (GSH) levels were detected by fluorescence and luminescence probes respectively.Cancer-stem cell (CSC) properties were investigated by sphere-forming assay and flow cytometry to quantify CSC markers.Expression of DNA repair genes and CSC-related genes was analysed by mining publicly available patient datasets.Results: Our results showed that glutamine deprivation decreased neuroblastoma cell proliferation and viability and modulated Myc member expression.We then demonstrated for the first time that combined glutamine deprivation with irradiation led to a selective radioresistance of MYCN-amplified neuroblastoma cells.By exploring the underlying mechanism of neuroblastoma radioresistance properties, our results highlight interplay between c-Myc and MycN expression suggesting compensatory mechanisms in Myc proteins leading to radioresistance in MYCN-amplified cells.This result was associated with the ability of MYCN-amplified cells to dysregulate the DNA repair gene pathway, maintain GSH and ROS levels and to increase the CSC-like population and properties.Conversely, glutamine deprivation led to radiosensitization in non-MYCN amplified cell lines through a disruption of the cell redox balance and a trend to decrease in the CSC-like populations.Mining publicly available gene expression dataset obtained from pediatric neuroblastoma patients, we identified a correlation pattern between Myc members and CSC-related genes as well as a specific group of DNA repair gene pathways. Ivyspring
Clinical decision making: from theory to practice. Guidelines for policy statements: the explicit approach
Authors: D M Eddy
Journal: JAMA (1990)

THE FIRST obligation of a policymaker is to design a policy that, if accepted and applied correctly, will improve patients' lives. The second obligation is to present the policy in a way that ensures it will be accepted and applied correctly. The first obligation is addressed through the choice of methods for designing a policy.<sup>1</sup>The second obligation is addressed through the policy statement. <h3>Objectives</h3> The objectives for policy statements are similar to the objectives for methods: accuracy, accountability, predictability, defensibility, and usability.<sup>1</sup>The pertinence of these objectives to policy statements can be appreciated by viewing the policy statement from the perspective of the people who will be affected by it—practitioners, patients, and payers. Begin with the primary audience of a policy statement— practitioners. The purpose of a practice policy is to modify the behavior of practitioners to steer their decisions toward actions that the policymakers consider desirable.