tbuckley/cabot-search huggingface dataset:
A homogenous nanoporous pulmonary drug delivery system based on metal-organic frameworks with fine aerosolization performance and good compatibility
Authors: Yixian Zhou, Boyi Niu, Biyuan Wu, Sulan Luo, Jintao Fu, Yiting Zhao, Guilan Quan, Xin Pan, Chuanbin Wu
Journal: Acta Pharmaceutica Sinica B (2020)

Pulmonary drug delivery has attracted increasing attention in biomedicine, and porous particles can effectively enhance the aerosolization performance and bioavailability of drugs. However, the existing methods for preparing porous particles using porogens have several drawbacks, such as the inhomogeneous and uncontrollable pores, drug leakage, and high risk of fragmentation. In this study, a series of cyclodextrin-based metal-organic framework (CD-MOF) particles containing homogenous nanopores were delicately engineered without porogens. Compared with commercial inhalation carrier, CD-MOF showed excellent aerosolization performance because of the homogenous nanoporous structure. The great biocompatibility of CD-MOF in pulmonary delivery was also confirmed by a series of experiments, including cytotoxicity assay, hemolysis ratio test, lung function evaluation, in vivo lung injury markers measurement, and histological analysis. The results of ex vivo fluorescence imaging showed the high deposition rate of CD-MOF in lungs. Therefore, all results demonstrated that CD-MOF was a promising carrier for pulmonary drug delivery. This study may throw light on the nanoporous particles for effective pulmonary administration.
AB0976 CAPTURING THE ENTHESITIS RELATED ARTHRITIS CONTEMPORARY PROFILE OF NORTHERN GREEK PATIENTS IN THE ERA OF BIOLOGICS
Authors: D. Deligeorgakis, M. Trachana, P. Pratsidou-Gertsi, D. Dimopoulou, A. B. Haidich, A. Garyfallos
Journal: Annals of the Rheumatic Diseases (2020)

Background: Enthesitis-Related Arthritis (ERA) is a subtype of Juvenile Idiopathic Arthritis (JIA) subtype with an estimated prevalence ranging from 8% to 37.4%. The improvement of the disease course and outcome has been related with the introduction of biologic Disease-Modifying Antirheumatic Drugs (bDMARDs) and the uninterrupted monitoring following the transition of young patients to adult rheumatology settings. Objectives: To capture the contemporary ERA profile in Northern Greek patients by analyzing the characteristics and treatment outcome in the era of bDMARDs. Methods: This retrospective cohort study included patients who had been monitored on a 3-month schedule for ≥12 months, from 2000 to 2017. The periodic metric assessment included the disease status and burden by applying contemporary tools in respect to activity, clinical remission (CR) and damage (cJADAS, JSpADA, Wallace criteria for CR and JADI, respectively). Results: Forty-three patients, mainly male (60%) with a mean age at disease onset of 10.75 (SD:2.75) years were enrolled. The predominant joints were the hip, ankle and sacroiliac (56%, 49% and 46%, respectively). Median lag time from diagnosis to bDMARDs initiation was 8.5 months. Patients with sacroiliitis were more likely to receive bDMARDs (hazard ratio [HR]:3.26, 95% confidence interval [CI]: 1.35, 7.88). Thirty six patients (84%) achieved clinical remission (CR) on medication (CRONM), within a median time of 11 months and correlated with compliance (HR:3.62, 95%CI: 1.34, 9.76). Twenty patients (47%) experienced a flare following CR, mainly as a single episode (75%). The median flare-free survival following remission on and off medication (CROFFM) was 42 and 34 months, respectively. At the last evaluation, both median baseline cJADAS (8), and JSpADA (2) dropped to 0, while 13 patients (30%) were in CROFFM, 17 (40%) in CRONM, and 13 (30%) had persistent disease activity. The median percentage of CR per patient was 54% and no patient had JADI &gt;0. Conclusion: Early administration of bDMARDs and compliance to monitoring and treatment improved the long-term outcome in ERA. Axial involvement emerged as a negative prognostic factor with an increased need for bDMARDs and diminished rates of CR. Disclosure of Interests: Dimitrios Deligeorgakis: None declared, Maria Trachana: None declared, Polyxeni Pratsidou-Gertsi: None declared, Despoina Dimopoulou: None declared, Anna Bettina Haidich: None declared, Alexandros Garyfallos Grant/research support from: MSD, Aenorasis SA, Speakers bureau: MSD, Novartis, gsk
Priority Rankings of Patient-Reported Outcomes for Pancreatic Ductal Adenocarcinoma: A Comparison of Patient and Physician Perspectives
Authors: Michelle Guan, Gillian Gresham, Arvind Shinde, Isaac Lapite, Jun Gong, Veronica R. Placencio-Hickok, Christopher B. Forrest, Andrew E. Hendifar
Journal: Journal of the National Comprehensive Cancer Network (2020)

Pancreatic ductal adenocarcinoma (PDAC) is associated with high symptom burden. However, treatment decisions currently depend heavily on physician interpretation of clinical parameters and may not consider patients' health preferences. The NIH Patient-Reported Outcomes Measurement Information System (PROMIS) initiative standardized a set of patient-reported outcomes for use in chronic diseases. This study identifies preference rankings among patients with PDAC and physicians for PROMIS domains and compares the priorities of patients and their providers.We condensed the 96 NIH PROMIS adult domains into 31 domains and created a Maximum Difference Scaling questionnaire. Domain preference scores were generated from the responses of patients with PDAC and physicians, which were compared using Maximum Difference Scaling software across demographic and clinical variables.Participants included 135 patients with PDAC (53% male; median age, 68 years) and 54 physicians (76% male; median years of experience, 10). Patients selected physical functioning (PF) as their top priority, whereas physicians identified pain as most important. PF, ability to perform activities of daily living, and symptom management were within the top 5 domains for both patients and physicians, and varied only slightly across age, sex, and ethnicity. However, several domains were ranked significantly higher by patients than by physicians, including but not limited to PF; ability to do things for yourself, family, and friends; ability to interact with others to obtain help; and sleep quality. Physicians ranked pain, anxiety, and depression higher than patients did.Our findings suggest that patients with PDAC value PF and engaging in daily and social activities the most, whereas physicians prioritize symptoms such as pain. Patient-reported outcomes need to become more integrated into PDAC care and research to better identify unmet patient needs, inform treatment decisions, and develop therapies that address outcomes valued by patients.
Lung Screen Uptake Trial: results from a single lung cancer screening round
Authors: Mamta Ruparel, Samantha L Quaife, Jennifer L Dickson, Carolyn Horst, Sophie Tisi, Helen Hall, Magali Taylor, Asia Ahmed, Penny Shaw, Stephen Burke, May-Jan Soo, Arjun Nair, Anand Devaraj, Karen Sennett, Stephen W Duffy, Neal Navani, Angshu Bhowmik, David R Baldwin, Sam M Janes
Journal: Thorax (2020)

The Lung Screen Uptake Trial tested a novel invitation strategy to improve uptake and reduce socioeconomic and smoking-related inequalities in lung cancer screening (LCS) participation. It provides one of the first UK-based ‘real-world’ LCS cohorts. Of 2012 invited, 1058 (52.6%) attended a ‘lung health check’. 768/996 (77.1%) in the present analysis underwent a low-dose CT scan. 92 (11.9%) and 33 (4.3%) participants had indeterminate pulmonary nodules requiring 3-month and 12-month surveillance, respectively; 36 lung cancers (4.7%) were diagnosed (median follow-up: 1044 days). 72.2% of lung cancers were stage I/II and 79.4% of non-small cell lung cancer had curative-intent treatment.
Nanopore metagenomic sequencing of influenza virus directly from respiratory samples: diagnosis, drug resistance and nosocomial transmission
Authors: Y Xu, K Lewandowski, L O Downs, J Kavanagh, T Hender, S Lumley, K Jeffery, D Foster, N Sanderson, A Vaughan, M Morgan, R Vipond, M Carroll, T Peto, D Crook, A S Walker, P Matthews, Pullan
Journal: Eurosurveillance (2020)

Background: Influenza virus presents a significant challenge to public health by causing seasonal epidemics and occasional pandemics. Nanopore metagenomic sequencing has the potential to be deployed for near-patient testing, providing rapid diagnosis of infection, rationalising antimicrobial therapy, and supporting interventions for infection control. This study aimed to evaluate the applicability of this sequencing approach as a routine laboratory test for influenza in clinical settings. Methods: We conducted Nanopore metagenomic sequencing for 180 respiratory samples from a UK hospital during the 2018/19 influenza season, and compared results to routine molecular diagnostic testing. We investigated drug resistance, genetic diversity, and nosocomial transmission using influenza sequence data. Results: Metagenomic sequencing was 83% (75/90) sensitive and 93% (84/90) specific for detecting influenza A viruses compared with the diagnostic standard (Cepheid Xpress/BioFire FilmArray Respiratory Panel). We identified a H3N2 genome with the oseltamivir resistant S331R mutation in the NA protein, potentially associated with the emergence of a distinct intra-subtype reassortant. Whole genome phylogeny refuted suspicions of a transmission cluster in the infectious diseases ward, but identified two other clusters that likely reflected nosocomial transmission, associated with a predominant strain circulating in the community. We also detected a range of other potentially pathogenic viruses and bacteria from the metagenome. Conclusion: Nanopore metagenomic sequencing can detect the emergence of novel variants and drug resistance, providing timely insights into antimicrobial stewardship and vaccine design. Generation of full genomes can contribute to the investigation and management of nosocomial outbreaks.
Response to: ‘Association of subcutaneous belimumab and long-term antimalarial treatment reduces antiphospholipid antibodies levels in systemic lupus erythematosus: post-hoc analysis of a randomised placebo-controlled trial–comment on: ‘Effect of belimumab treatment on antiphospholipid antibody levels: post-hoc analysis based on two randomised placebo-controlled trials in systemic lupus erythematosus’ by Chatzidionysiou<i>et al</i>’ by Bettiol<i>et al</i>
Authors: Katerina Chatzidionysiou, Evangelia Samoli, Petros P Sfikakis, Maria G Tektonidou
Journal: Annals of the Rheumatic Diseases (2020)

We thank Dr Bettiol et al 1 for their interest in our article.2 Dr Bettiol et al performed a post-hoc analysis on a different randomised controlled trial of subcutaneous belimumab in systemic lupus erythematosus (SLE). The authors evaluated the effect of treatment with belimumab on the levels of anticardiolipin antibodies (aCL) (IgG, IgM and IgA) but also of anti-β2-glycoprotein I (antiβ2GPI) antibodies. The latter was unfortunately not available in BLISS-76 and BLISS-52 trials, as acknowledged in the limitations of our post-hoc analysis. The authors have also extended our observation about the effect of co-treatment with antimalarials on antiphospholipid antibody (aPL) titres in the belimumab versus the placebo group, by examining the duration of their use. We agree with the authors that the duration of antimalarials is of high clinical significance. In addition to previous retrospective studies,3 we have recently shown in …
Abstract A54: Parallel targeting of RAF/MEK/ERK pathway in RAS-mutant embryonal rhabdomyosarcoma
Authors: Angelina V. Vaseva, Abhik Bandyopadhyay, Vanessa Del Pozo, Craig M. Goodwin, Prson Gautam, Krister Wennerberg, Kris C. Wood, Yidong Chen, Channing J. Der, Peter J. Houghton
Journal: Cancer Research (2020)

Abstract RAS pathway mutations are found in nearly 75% of high-risk embryonal rhabdomyosarcoma (ERMS). While RAS oncoproteins are well-established therapeutic targets for many adult human cancers, still very little is known about the role of RAS mutations in the development and maintenance of ERMS. By sequencing, we identified cell lines and PDX tumors harboring activating mutations in H- or NRAS. Further, we showed that mutant H- or NRAS was critical for the growth of all RAS-mutant ERMS cell lines and that RAF/MEK/ERK signaling pathway, but not PI3K/AKT, was mediator of RAS dependency in these cells. However, in vivo treatment of RAS-mutant ERMS xenografts with the MEK inhibitor trametinib showed modest response as compared to BRAF-mutant astrocytoma xenografts. We reasoned that similarly to other RAS-driven cancers, ERMS cells and tumors are able to acquire resistance to inhibitors of the RAF/MEK/ERK pathway. We performed drug-sensitizing pooled CRISPR library screen and identified that inhibition of ERK2 potentiated trametinib treatment. We show that combining trametinib with ERK1/2 inhibitor leads to potent synergistic ERK inhibition and ERMS tumor growth suppression. Citation Format: Angelina V. Vaseva, Abhik Bandyopadhyay, Vanessa Del Pozo, Craig M. Goodwin, Prson Gautam, Krister Wennerberg, Kris C. Wood, Yidong Chen, Channing J. Der, Peter J. Houghton. Parallel targeting of RAF/MEK/ERK pathway in RAS-mutant embryonal rhabdomyosarcoma [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A54.
Abstract 16676: Prognostic Significance of Isolated Hypertension During the Alerting Reaction to Predict 10-Year Risk of Cardiovascular Events in the Dallas Heart Study
Authors: Alejandro Velasco, Colby Ayers, Sandeep R Das, James A De Lemos, Wanpen Vongpatanasin
Journal: Circulation (2014)

Measurement of BP in the office often induces a transient rise in BP, known as an alerting reaction. A recent analysis from the National Health and Nutrition Examination Survey (NHANES) indicated t...
Health systems as venture capital investors in digital health: 2011–2019
Authors: Kyan C. Safavi, Adam B. Cohen, David Y. Ting, Sreekanth Chaguturu, Jack S. Rowe
Journal: npj Digital Medicine (2020)

Provider health systems as venture capital investors in digital health are uniquely positioned in the industry. Little is known about the volume or characteristics of their investments and how these compare to other investors. From 2011 to 2019, we found that health systems made 184 investments in 105 companies. Compared with other investors, they were more likely to invest in companies focused on workflow, on-demand health services, and data infrastructure/interoperability.
Metabolic conditioning of CD8+ effector T cells for adoptive cell therapy
Authors: Ramon I. Klein Geltink, Joy Edwards-Hicks, Petya Apostolova, David O’Sullivan, David E. Sanin, Annette E. Patterson, Daniel J. Puleston, Nina A. M. Ligthart, Joerg M. Buescher, Katarzyna M. Grzes, Agnieszka M. Kabat, Michal Stanczak, Jonathan D. Curtis, Fabian Hässler, Franziska M. Uhl, Mario Fabri, Robert Zeiser, Edward J. Pearce, Erika L. Pearce
Journal: Nature Metabolism (2020)
Research and Development Costs of New Drugs—Reply
Authors: Olivier J. Wouters, Martin McKee, Jeroen Luyten
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Stabilization of Metastatic Uterine Leiomyosarcoma Using Pembrolizumab
Authors: Katherine Cotangco, Mary Meram, M. Patrick Lowe
Journal: Journal of the National Comprehensive Cancer Network (2020)

The estimated 5-year survival rate for patients with stage IV uterine leiomyosarcoma is 29%, with a median survival of &lt;1 year. This report describes a patient with stage IVB leiomyosarcoma who experienced stable disease for 15 months on pembrolizumab. A woman aged 62 years, gravida 2 para 2, with postmenopausal bleeding and a necrotic uterine fibroid underwent a dilation and curettage and was diagnosed with uterine leiomyosarcoma. CT imaging showed pulmonary and bony metastasis. She underwent surgical staging with biopsy-proved stage IVB disease. A mixed partial response was noted using first- and second-line chemotherapy. Molecular tumor profiling confirmed PD-L1 expression. The patient was started on pembrolizumab, and at the time of writing she is status post 23 cycles with stable disease. Pembrolizumab was well tolerated and aided prolonged disease stabilization.
<i>Notes from the Field</i>: Characteristics of Meat Processing Facility Workers with Confirmed SARS-CoV-2 Infection — Nebraska, April–May 2020
Authors: Matthew Donahue, Nandini Sreenivasan, Derry Stover, Anu Rajasingham, Joanna Watson, Andreea Bealle, Natasha Ritchison, Thomas Safranek, Michelle A. Waltenburg, Bryan Buss, Jennita Reefhuis
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Coronavirus disease 2019 (COVID-19) has been reported nationwide among meat processing facility workers (1).In late April 2020, through flyers and text messages, workers at a Nebraska meat processing facility were invited by the facility, in partnership with the Nebraska Department of Health and Human Services, to be tested for current SARS-CoV-2, the virus that causes COVID-19, at their worksite, free of charge.Specimens were analyzed using reverse transcription-polymerase chain reaction (RT-PCR) by a contracting laboratory.This investigation was determined by CDC to be public health surveillance.*Among 1,216 Nebraska-resident meat processing facility workers tested, 375 (31%) had positive results.During May 8-25, case investigators attempted to interview the 349 workers who had positive test results and available phone numbers; five refused, 99 were not reached after five attempts, and four did not report symptom status, leaving 241 (69%) of the attempted interviews for analysis.Among the 241 interviewed workers, 57% were male, the median age was 41 years (range = 18-76 years), and 46% were Hispanic (Table ).Approximately one third (78; 32%) of respondents reported no symptoms.Among the 163 symptomatic respondents, two were hospitalized, and no deaths were identified.Workers were queried about exposures during the 14 days before symptom onset (2) or before testing if they were asymptomatic.Close contact † with a visibly ill person (or person with diagnosed COVID-19) at work was reported by 70 (29%) workers; the most frequently reported close contact locations were production areas (74%) and cafeteria/ break areas (51%).Among 167 persons who worked in the 14 days preceding symptom onset or testing, approximately half (46%) worked on the conveyor belt in harvesting (i.e., stunning, slaughtering, eviscerating, and halving), processing (i.e., cutting, preparing, and packaging), and rendering (i.e., converting waste animal materials into usable products),
Relevance of Higher-Order Epistasis in Drug Resistance
Authors: Elena R Lozovsky, Rachel F Daniels, Gavin D Heffernan, David P Jacobus, Daniel L Hartl
Journal: Molecular Biology and Evolution (2020)

We studied five chemically distinct but related 1,3,5-triazine antifolates with regard to their effects on growth of a set of mutants in dihydrofolate reductase. The mutants comprise a combinatorially complete data set of all 16 possible combinations of four amino acid replacements associated with resistance to pyrimethamine in the malaria parasite Plasmodium falciparum. Pyrimethamine was a mainstay medication for malaria for many years, and it is still in use in intermittent treatment during pregnancy or as a partner drug in artemisinin combination therapy. Our goal was to investigate the extent to which the alleles yield similar adaptive topographies and patterns of epistasis across chemically related drugs. We find that the adaptive topographies are indeed similar with the same or closely related alleles being fixed in computer simulations of stepwise evolution. For all but one of the drugs the topography features at least one suboptimal fitness peak. Our data are consistent with earlier results indicating that third order and higher epistatic interactions appear to contribute only modestly to the overall adaptive topography, and they are largely conserved. In regard to drug development, our data suggest that higher-order interactions are likely to be of little value as an advisory tool in the choice of lead compounds.
Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data (vol 11, 34, 2019)
Authors: F. Finotello, C. Mayer, C. Plattner, G. Laschober, D. Rieder, H. Hackl, A. Krogsdam, Z. Loncova, W. Posch, D. Wilflingseder, S. Sopper, M. Ijsselsteijn, T.P. Brouwer, D. Johnson, Y.M. Xu, Y. Wang, M.E. Sanders, M.V. Estrada, P. Ericsson-Gonzalez, P. Charoentong, J. Balko, N.F.D.C. de Miranda, Z. Trajanoski
Journal: Genome Medicine (2019)
Lupus-like autoimmunity and increased interferon response in patients with STAT3-deficient hyper-IgE syndrome
Authors: Rishi R. Goel, Shuichiro Nakabo, Brian L.P. Dizon, Amanda Urban, Meryl Waldman, Lillian Howard, Dirk Darnell, Munir Buhaya, Carmelo Carmona-Rivera, Sarfaraz Hasni, Mariana J. Kaplan, Alexandra F. Freeman, Sarthak Gupta
Journal: Journal of Allergy and Clinical Immunology (2020)
Analysis of Baseline Clinical Characteristics and Disease Burden in Patients Enrolled in the International Paroxysmal Nocturnal Hemoglobinuria Registry
Authors: Hubert Schrezenmeier, Jaroslaw P. Maciejewski, Alexander Roeth, David J. Araten, Yuzuru Kanakura, Loree Larratt, Jamile M. Shammo, Amanda Wilson, Gilda Shayan, Peter Hillmen
Journal: Blood (2017)
Comparison of clinical and molecular characteristics of patients with acute myeloid leukemia and either TP73 or TP53 mutations
Authors: Alice S. Mims, Jessica Kohlschmidt, Ann-Kathrin Eisfeld, Krzysztof Mrόzek, James S. Blachly, Shelley Orwick, Dimitrios Papaioannou, Deedra Nicolet, Deepa Sampath, Richard M. Stone, Bayard L. Powell, Jonathan E. Kolitz, John C. Byrd, Clara D. Bloomfield
Journal: Leukemia (2020)