tbuckley/cabot-search huggingface dataset:
Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immunotherapy for the treatment of breast cancer
Authors: Leisha A Emens, Sylvia Adams, Ashley Cimino-Mathews, Mary L Disis, Margaret E Gatti-Mays, Alice Y Ho, Kevin Kalinsky, Heather L McArthur, Elizabeth A Mittendorf, Rita Nanda, David B Page, Hope S Rugo, Krista M Rubin, Hatem Soliman, Patricia A Spears, Sara M Tolaney, Jennifer K Litton
Journal: Journal for ImmunoTherapy of Cancer (2021)

Breast cancer has historically been a disease for which immunotherapy was largely unavailable. Recently, the use of immune checkpoint inhibitors (ICIs) in combination with chemotherapy for the treatment of advanced/metastatic triple-negative breast cancer (TNBC) has demonstrated efficacy, including longer progression-free survival and increased overall survival in subsets of patients. Based on clinical benefit in randomized trials, ICIs in combination with chemotherapy for the treatment of some patients with advanced/metastatic TNBC have been approved by the United States (US) Food and Drug Administration (FDA), expanding options for patients. Ongoing questions remain, however, about the optimal chemotherapy backbone for immunotherapy, appropriate biomarker-based selection of patients for treatment, the optimal strategy for immunotherapy treatment in earlier stage disease, and potential use in histological subtypes other than TNBC. To provide guidance to the oncology community on these and other important concerns, the Society for Immunotherapy of Cancer (SITC) convened a multidisciplinary panel of experts to develop a clinical practice guideline (CPG). The expert panel drew upon the published literature as well as their clinical experience to develop recommendations for healthcare professionals on these important aspects of immunotherapeutic treatment for breast cancer, including diagnostic testing, treatment planning, immune-related adverse events (irAEs), and patient quality of life (QOL) considerations. The evidence-based and consensus-based recommendations in this CPG are intended to give guidance to cancer care providers treating patients with breast cancer.
Year 1 of the Bundled Payments for Care Improvement–Advanced Model
Authors: Karen E. Joynt Maddox, E. John Orav, Jie Zheng, Arnold M. Epstein
Journal: New England Journal of Medicine (2021)

The Center for Medicare and Medicaid Innovation launched the Medicare Bundled Payments for Care Improvement-Advanced (BPCI-A) program for hospitals in October 2018. Information is needed about the effects of the program on health care utilization and Medicare payments.We conducted a modified segmented regression analysis using Medicare claims and including patients with discharge dates from January 2017 through September 2019 to assess differences between BPCI-A participants and two control groups: hospitals that never joined the BPCI-A program (nonjoining hospitals) and hospitals that joined the BPCI-A program in January 2020, after the conclusion of the intervention period (late-joining hospitals). The primary outcomes were the differences in changes in quarterly trends in 90-day per-episode Medicare payments and the percentage of patients with readmission within 90 days after discharge. Secondary outcomes were mortality, volume, and case mix.A total of 826 BPCI-A participant hospitals were compared with 2016 nonjoining hospitals and 334 late-joining hospitals. Among BPCI-A hospitals, the mean baseline 90-day per-episode Medicare payment was $27,315; the change in the quarterly trends in the intervention period as compared with baseline was -$78 per quarter. Among nonjoining hospitals, the mean baseline 90-day per-episode Medicare payment was $25,994; the change in quarterly trends as compared with baseline was -$26 per quarter (difference between nonjoining hospitals and BPCI-A hospitals, $52 [95% confidence interval {CI}, 34 to 70] per quarter; P<0.001; 0.2% of the baseline payment). Among late-joining hospitals, the mean baseline 90-day per-episode Medicare payment was $26,807; the change in the quarterly trends as compared with baseline was $4 per quarter (difference between late-joining hospitals and BPCI-A hospitals, $82 [95% CI, 41 to 122] per quarter; P<0.001; 0.3% of the baseline payment). There were no meaningful differences in the changes with regard to readmission, mortality, volume, or case mix.The BPCI-A program was associated with small reductions in Medicare payments among participating hospitals as compared with control hospitals. (Funded by the National Heart, Lung, and Blood Institute.).
Functional siRNA Delivery by Extracellular Vesicle–Liposome Hybrid Nanoparticles
Authors: Martijn J. W. Evers, Simonides I. van de Wakker, Ellis M. de Groot, Olivier G. de Jong, Jerney J. J. Gitz‐François, Cor S. Seinen, Joost P. G. Sluijter, Raymond M. Schiffelers, Pieter Vader
Journal: Advanced Healthcare Materials (2021)

The therapeutic use of RNA interference is limited by the inability of siRNA molecules to reach their site of action, the cytosol of target cells. Lipid nanoparticles, including liposomes, are commonly employed as siRNA carrier systems to overcome this hurdle, although their widespread use remains limited due to a lack of delivery efficiency. More recently, nature's own carriers of RNA, extracellular vesicles (EVs), are increasingly being considered as alternative siRNA delivery vehicles due to their intrinsic properties. However, they are difficult to load with exogenous cargo. Here, EV-liposome hybrid nanoparticles (hybrids) are prepared and evaluated as an alternative delivery system combining properties of both liposomes and EVs. It is shown that hybrids are spherical particles encapsulating siRNA, contain EV-surface makers, and functionally deliver siRNA to different cell types. The functional behavior of hybrids, in terms of cellular uptake, toxicity, and gene-silencing efficacy, is altered as compared to liposomes and varies among recipient cell types. Moreover, hybrids produced with cardiac progenitor cell (CPC) derived-EVs retain functional properties attributed to CPC-EVs such as activation of endothelial signaling and migration. To conclude, hybrids combine benefits of both synthetic and biological drug delivery systems and might serve as future therapeutic carriers of siRNA.
Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial
Authors: Bernhard Ludvik, Francesco Giorgino, Esteban Jódar, Juan P Frias, Laura Fernández Landó, Katelyn Brown, Ross Bray, Ángel Rodríguez
Journal: The Lancet (2021)
AIFNet: Automatic vascular function estimation for perfusion analysis using deep learning
Authors: Ezequiel de la Rosa, Diana M. Sima, Bjoern Menze, Jan S. Kirschke, David Robben
Journal: Medical Image Analysis (2021)

Perfusion imaging is crucial in acute ischemic stroke for quantifying the salvageable penumbra and irreversibly damaged core lesions. As such, it helps clinicians to decide on the optimal reperfusion treatment. In perfusion CT imaging, deconvolution methods are used to obtain clinically interpretable perfusion parameters that allow identifying brain tissue abnormalities. Deconvolution methods require the selection of two reference vascular functions as inputs to the model: the arterial input function (AIF) and the venous output function, with the AIF as the most critical model input. When manually performed, the vascular function selection is time demanding, suffers from poor reproducibility and is subject to the professionals' experience. This leads to potentially unreliable quantification of the penumbra and core lesions and, hence, might harm the treatment decision process. In this work we automatize the perfusion analysis with AIFNet, a fully automatic and end-to-end trainable deep learning approach for estimating the vascular functions. Unlike previous methods using clustering or segmentation techniques to select vascular voxels, AIFNet is directly optimized at the vascular function estimation, which allows to better recognise the time-curve profiles. Validation on the public ISLES18 stroke database shows that AIFNet almost reaches inter-rater performance for the vascular function estimation and, subsequently, for the parameter maps and core lesion quantification obtained through deconvolution. We conclude that AIFNet has potential for clinical transfer and could be incorporated in perfusion deconvolution software.
Shear Wave Elastography of the Diaphragm: Good Vibrations?
Authors: Annemijn H. Jonkman, Chris L. de Korte
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

exposures in our cities, the findings from Wright and colleagues highlight how important it is to understand disproportionate impacts on lifelong health outcomes from exposures even before the first breath.We need policies aimed at the most important exposures impacting lifelong health, including UFPs, and to promote transportation and environmental justice so that everyone has the same opportunity for a long and healthy life, regardless of where they are born.
Characteristics, Management and Outcome of DLBCL Patients Presenting with Simultaneous Systemic and CNS Disease at Diagnosis - a Retrospective Multicenter Study
Authors: Sharon Ben Barouch, Yair Herishanu, Nadav Sarid, Chava Perry, Irit Avivi, Lev Shvidel, Osnat Bairey, Noa Lavi, Netanel A Horowitz, Abraham Avigdor, Neta Goldschmidt, Eyal Lebel, Orit Sofer
Journal: Blood (2017)
Abstract 14629: Electrocardiographic Atrial Cardiomyopathy Markers and Risk of Atrial Fibrillation After Cardiac Surgery
Authors: Ilkka O Ruohonen, Antti Eranti, Arto Relander, Sami Sinisilta, Veikko Lahtinen, Juho M Jalkanen, Sirpa Jalkanen, Maija Hollmen, Juhani Airaksinen, Fausto Biancari, Jarmo Gunn, Tuomas O Kiviniemi
Journal: Circulation (2019)

Introduction: Performance of electrocardiography markers of atrial cardiomyopathy in post-operative atrial fibrillation prediction remains unknown in patients undergoing open-heart surgery. Hypothe...
Ibritumomab tiuxetan (Zevalin(TM)) therapy is feasible and safe for the treatment of patients with advanced B-cell follicular NHL in first remission.: Interim analysis for safety of a multicenter, phase III clinical trial.
Authors: JA Radford, N Ketterer, C Sebban, PL Zinzani, AB Delaloye, A Rohatiner, GA Salles, J Kuhlmann, A Chlistalla, A Hagenbeek
Journal: Blood (2003)
Infections
Authors: L. Holzapfel, Cl. Chastang, Ph. Carme, T. Joffre, G. Demingeon, C. Clément, S. Chevret, P. Lestavel, D. Poulain, F. Fourrier, J. Fruit, H. Medhaoui, C. Chopin, R. Jordá, J. Serra, J. Nava, E. Maraví, F. Alvarez, F. Salord, N. Eynard, J. Grando, R. Chacornac, M. van Deuren, R. van Dalen, R. W. Sauerwein, A. K. M. Bartelink, J. W. M. van der Meer, B. Guidet, I. Nicola, F. Staikowsky, V. Barakett, J. C. Petit, G. Offenstadt
Journal: Intensive Care Medicine (1992)
Training in infectious diseases across Europe in 2021 – a survey on training delivery, content and assessment
Authors: Ronja A. Brockhoff, Scott R. Hicks, Jon Salmanton-García, Davorka Dušek, Jean-Paul Stahl, Nick J. Beeching, Oliver A. Cornely, Jonas Ahl, Arvydas Ambrozaitis, Alpay Azap, Bojana Beović, Francesco Castelli, José Miguel Cisneros, Costas Constantinou, Christian Van Delden, Eoghan De Barra, Paul De Munter, Olga Džupová, Gerd Fätkenheuer, Robert Flisiak, Simin Aysel Florescu, Claudia Fsadni, Ville Holmberg, Søren Jensen-Fangel, Philipp Koehler, Már Kristjánsson, Andreas Lind, Athanasios Michos, Alastair Miller, Zsofia Muller, Joaquim Oliveira, Mical Paul, Ertan Sal, Marija Santini, Narina Sargsyants, L'ubomir Soják, Pilleriin Soodla, Therese Staub, Florian Thalhammer, Annelies Verbon, Renaud Verdon, Zbigniew Wegrzyn
Journal: Clinical Microbiology and Infection (2021)

To define the status of infectious diseases (ID) as an approved specialty in Europe; to enumerate the number of specialists (in general and in relation to the overall population) and specialist trainees and describe the content, delivery and evaluation of postgraduate training in ID in different countries.Structured web-based questionnaire surveys in March 2021 of responsible national authorities, specialist societies and individual country representatives to the Section of Infectious Diseases of the European Union for Medical Specialties. Descriptive analysis of quantitative and qualitative responses.In responses received from 33/35 (94.3%) countries, ID is recognized as a specialty in 24 and as a subspecialty of general internal medicine (GIM) in eight, but it is not recognized in Spain. The number of ID specialists per country varies from <5 per million inhabitants to 78 per million inhabitants. Median length of training is 5 years (interquartile range 4.0-6.0 years) with variable amounts of preceding and/or concurrent GIM. Only 21.2% of countries (7/33) provide the minimum recommended training of 6 months in microbiology and 30% cover competencies such as palliative care, team working and leadership, audit, and quality control. Training is monitored by personal logbook or e-portfolio in 75.8% (25/33) and assessed by final examinations in 69.7% (23/33) of countries, but yearly reviews with trainees only occur in 54.5% (18/33) of countries.There are substantial gaps in modernization of ID training in many countries to match current European training requirements. Joint training with clinical microbiology (CM) and in multidisciplinary team working should be extended. Training/monitoring trainers should find greater focus, together with regular feedback to trainees within many national training programmes.
Basal epithelial stem cells cross an alarmin checkpoint for postviral lung disease
Authors: Kangyun Wu, Kenji Kamimoto, Yong Zhang, Kuangying Yang, Shamus P. Keeler, Benjamin J. Gerovac, Eugene V. Agapov, Stephen P. Austin, Jennifer Yantis, Kelly A. Gissy, Derek E. Byers, Jennifer Alexander-Brett, Christy M. Hoffmann, Matthew Wallace, Michael E. Hughes, Erika C. Crouch, Samantha A. Morris, Michael J. Holtzman
Journal: Journal of Clinical Investigation (2021)

Epithelial cells are charged with protection at barrier sites, but whether this normally beneficial response might sometimes become dysfunctional still needs definition. Here, we recognized a pattern of imbalance marked by basal epithelial cell growth and differentiation that replaced normal airspaces in a mouse model of progressive postviral lung disease due to the Sendai virus. Single-cell and lineage-tracing technologies identified a distinct subset of basal epithelial stem cells (basal ESCs) that extended into gas-exchange tissue to form long-term bronchiolar-alveolar remodeling regions. Moreover, this cell subset was selectively expanded by crossing a cell-growth and survival checkpoint linked to the nuclear-localized alarmin IL-33 that was independent of IL-33 receptor signaling and instead connected to autocrine chromatin accessibility. This mechanism creates an activated stem-progenitor cell lineage with potential for physiological or pathological function. Thus, conditional loss of Il33 gene function in basal epithelial cells disrupted the homeostasis of the epithelial barrier at skin and gut sites but also markedly attenuated postviral disease in the lung based on the downregulation of remodeling and inflammation. Thus, we define a basal ESC strategy to deploy innate immune machinery that appears to overshoot the primordial goal of self-defense. Our findings reveal new targets to stratify and correct chronic and often deadly postviral disease.
Effects of liraglutide on visceral and ectopic fat in adults with overweight and obesity at high cardiovascular risk: a randomised, double-blind, placebo-controlled, clinical trial
Authors: Ian J Neeland, Steven P Marso, Colby R Ayers, Bienka Lewis, Robert Oslica, Wynona Francis, Susan Rodder, Ambarish Pandey, Parag H Joshi
Journal: The Lancet Diabetes & Endocrinology (2021)
Join us at The Lancet Clinic
Authors: Sabine Kleinert, Richard Horton, Elena Becker-Barroso, Niall Boyce, David Collingridge, Justine Davies, Emma Grainger, Peter Hayward, John McConnell, Zoë Mullan, Lan-Lan Smith
Journal: The Lancet Global Health (2015)

On Oct 5, 2015, we launch the first 45 disease-specific pages of a major new online initiative involving all Lancet journals that will bring together an overview Seminar and relevant Reviews, Clinical Series, Commissions, research, Case Reports, and Clinical Pictures. Over the next 18 months or so when The Lancet Clinic is complete, there will be online pages for 135 diseases, which we have identified by a combination of global burden of disease data and clinical practice needs. We hope that The Lancet Clinic will help practising doctors make better informed decisions that ultimately lead to better lives of people worldwide, and help others who want to educate or update themselves keep abreast of the evolving evidence base. Importantly, these pages will be updated at regular intervals. The authors of newly commissioned Seminars have agreed to provide regular summaries of important new evidence for 4 years. Individual clinical editors will pull together newly published material from across the Lancet journals and post links to these on the page regularly. In addition, we are continuing our regular editorial policies of commissioning more specialised Clinical Reviews and Series across The Lancet Group to provide a more focused and in-depth assessment for key diseases. And beyond providing knowledge and information, we want to encourage academic and practising clinicians to use this knowledge for advocacy and change. In 2014, The Lancet published the first Clinical Commission on liver disease in the UK and in February, 2015, we launched our first Clinical Campaign based on this Commission. A Cancer Campaign as a joint effort between The Lancet and The Lancet Oncology followed in April. Clinical Campaigns aim to effect change based on data, knowledge, and expert interpretation in partnership with others. Further Clinical Commissions on asthma, hypertension, dementia, tuberculosis, traumatic brain injury, psychotherapy, chronic obstructive pulmonary disease, and others are underway across all Lancet journals. With these Clinical Commissions and Campaigns, we hope to extend our goal to publish the best science for better lives to being an active partner in using this science for actual change. Commissions and Campaigns will be part of the disease pages to encourage engagement and actions. The Lancet Clinic invites you to be part of this endeavour.
心筋細胞におけるインターロイキン-18(IL-18)誘導遺伝子発現ならびにPPARγ作動薬,ピオグリタゾンによるアポトーシスの二重阻害機構
Authors: Sakoda Tsuyoshi, Naka Toshio, Doi Takashi, Tsujino Takeshi, Masuyama Tohru, Ohyanagi Mitsumasa
Journal: Circulation (2006)
The upregulated intestinal folate transporters direct the uptake of ligand-modified nanoparticles for enhanced oral insulin delivery
Authors: Jingyi Li, Yaqi Zhang, Miaorong Yu, Aohua Wang, Yu Qiu, Weiwei Fan, Lars Hovgaard, Mingshi Yang, Yiming Li, Rui Wang, Xiuying Li, Yong Gan
Journal: Acta Pharmaceutica Sinica B (2021)

Transporters are traditionally considered to transport small molecules rather than large-sized nanoparticles due to their small pores. In this study, we demonstrate that the upregulated intestinal transporter (PCFT), which reaches a maximum of 12.3-fold expression in the intestinal epithelial cells of diabetic rats, mediates the uptake of the folic acid-grafted nanoparticles (FNP). Specifically, the upregulated PCFT could exert its function to mediate the endocytosis of FNP and efficiently stimulate the traverse of FNP across enterocytes by the lysosome-evading pathway, Golgi-targeting pathway and basolateral exocytosis, featuring a high oral insulin bioavailability of 14.4% in the diabetic rats. Conversely, in cells with relatively low PCFT expression, the positive surface charge contributes to the cellular uptake of FNP, and FNP are mainly degraded in the lysosomes. Overall, we emphasize that the upregulated intestinal transporters could direct the uptake of ligand-modified nanoparticles by mediating the endocytosis and intracellular trafficking of ligand-modified nanoparticles via the transporter-mediated pathway. This study may also theoretically provide insightful guidelines for the rational design of transporter-targeted nanoparticles to achieve efficient drug delivery in diverse diseases.
1-step screening approach detected more GDM than 2-step approach but did not improve clinical outcomes
Authors: Robert P. Kauffman
Journal: Annals of Internal Medicine (2021)

ACP Journal ClubAugust 20211-step screening approach detected more GDM than 2-step approach but did not improve clinical outcomesRobert P. Kauffman, MDRobert P. Kauffman, MDTexas Tech University School of Medicine, Amarillo, Texas, USA (R.P.K.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJ202108170-093 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationHillier TA, Pedula KL, Ogasawara KK, et al. A pragmatic, randomized clinical trial of gestational diabetes screening. N Engl J Med. 2021;384:895-904. https://pubmed.ncbi.nlm.nih.gov/33704936Clinical Impact RatingsGIM/FP/GP: Endocrinology: References1 Bogdanet D, O’Shea P, Lyons C et al. The oral glucose tolerance test—is it time for a change?—a literature review with an emphasis on pregnancy. J Clin Med. 2020;9:3451. [PMID: 33121014] Google Scholar2 American Diabetes Association. Management of diabetes in pregnancy: standards of medical care in diabetes–2021. Diabetes Care. 2021;44:S200-10. [PMID: 33298425] Google Scholar3 ACOG practice bulletin no. 190: gestational diabetes mellitus. Obstet Gynecol. 2018;131:e49-64. [PMID: 29370047] Google Scholar Author, Article, and Disclosure InformationAffiliations: Texas Tech University School of Medicine, Amarillo, Texas, USA (R.P.K.)Disclosures: The commentator has reported no disclosures of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M20-7319.This article was published at Annals.org on 3 August 2021. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics August 2021Volume 174, Issue 8Page: JC93KeywordsClinical trialsDisclosureGestational diabetesGlucoseHematologic testsObesityOral glucose tolerance testPregnancyRacial and ethnic issuesShoulders ePublished: 3 August 2021 Issue Published: August 2021 Copyright & PermissionsCopyright © 2021 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Hemodialysis Patients Make Long-Lived Antibodies against SARS-CoV-2 that May Be Associated with Reduced Reinfection
Authors: Gemma D. Banham, Alexandra Godlee, Sian E. Faustini, Adam F. Cunningham, Alex Richter, Lorraine Harper
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections have a devastating effect on patients receiving hemodialysis. To what extent infection-induced antibody responses are maintained, or protective, is unknown. This study describes the evolution of antibodies against the SARS-CoV-2 spike protein in a cohort of 990 patients on hemodialysis. During the first wave of the pandemic, 26% of patients had developed antispike SARS-CoV-2 antibodies. Fewer PCR-confirmed second-wave infections were observed in patients with pre-existing antibodies (4.2%) than those without antibodies (11.4%). This study shows that SARS-CoV-2 antibodies in patients on hemodialysis are well maintained and associate with reduced risk of subsequent SARS-CoV-2 infection.