tbuckley/cabot-search huggingface dataset:
SARS-CoV-2 transmission via endoscopy in the COVID-19 era
Authors: Theodor Alexandru Voiosu, Claudia Irina Puscasu, Andrei Voiosu
Journal: Gut (2021)

<h3>Objectives</h3> To determine the patterns of storing, using and disposing of opioids among patients with advanced cancer followed at home. <h3>Methods</h3> Patients who were prescribed opioids were selected. Prescribed opioids and their doses used for background pain and breakthrough pain were collected, as well as CAGE (cut down, annoyed, guilty and eye opener) for alcohol and drugs, smoking and history of illicit substance use. Questions regarding the opioid use, storage and disposal were posed. <h3>Results</h3> 100 patients were surveyed. Fifty-one patients had unused opioids at home, 25 patients did not throw away the drugs, 40 patients saved opioids for future use and 35 patients were unaware of proper opioid disposal methods. A total of 28 patients reported unsafe use by sharing or losing their opioids; 12 patients were unaware that their opioid could be fatal when taken by others. Most patients acknowledged that pain medications could be dangerous when taken by others. Patients with a partner and who were married were more likely to keep their opioids locked (p=0.028 and p=0.025, respectively). <h3>Conclusion</h3> A large number of patients with advanced cancer followed at home do not store, use and dispose of opioids safely. Patient education programmes should be incorporated to decrease the availability of opioids at home for abuse, diversion, and accidental poisoning.
Hospital efficiency and quality of prostate cancer care.
Authors: Ravishankar Jayadevappa, Sumedha Chhatre, S. Bruce Malkowicz, Thomas J. Guzzo, Alan J. Wein, Jerome Sanford Schwartz
Journal: Journal of Clinical Oncology (2021)

223 Background: There is no consistent evidence with respect to the role of hospital efficiency in improving quality of prostate cancer care. Study objective was to examine the association between hospital efficiency and quality of care in African American, Hispanic, and white Medicare beneficiaries with prostate cancer. Methods: Population-based cohort study using Surveillance, Epidemiological, and End Results-Medicare (SEER-Medicare) data from 2000–2016 for prostate cancer patients aged 66 or older. SEER-Medicare data was linked to American Hospital Association data. We computed hospital technical efficiency using data envelopment analysis. Outcomes were emergency room visits, complications, hospitalizations, cost, treatment and mortality (all-cause and prostate cancer-specific). We used competing risk analysis for survival, log-link GLM models for cost, and Poisson (zero inflated) models for count data. Propensity score and instrumental variable approaches were used to minimize potential biases. Results: We identified 87,117 eligible prostate cancer patients. Of these, 86% were white, 11% were African American, and 3% were Hispanic. Table shows the association between four quartiles of efficiency and outcomes. Higher hospital efficiency was consistently associated with decreased all-cause mortality, prostate cancer-specific mortality and emergency room visits. Association between hospital efficiency and mortality varied between racial and ethnic groups. Conclusions: Increasing hospital efficiency may reduce some of the disparity in prostate cancer outcomes. Our findings indicate important racial and ethnic differences that should be considered while planning hospital efficiency models to improve quality of prostate cancer care. Policies to redirect minority patients to hospital with higher efficiency may reduce racial and ethnic disparity in quality of care and outcomes. [Table: see text]
The emerging clinical role of wearables: factors for successful implementation in healthcare
Authors: Matthew Smuck, Charles A. Odonkor, Jonathan K. Wilt, Nicolas Schmidt, Michael A. Swiernik
Journal: npj Digital Medicine (2021)

Abstract Wearable technologies promise to redefine assessment of health behaviors, yet their clinical implementation remains a challenge. To address this gap, two of the NIH’s Big Data to Knowledge Centers of Excellence organized a workshop on potential clinical applications of wearables. A workgroup comprised of 14 stakeholders from diverse backgrounds (hospital administration, clinical medicine, academia, insurance, and the commercial device industry) discussed two successful digital health interventions that involve wearables to identify common features responsible for their success. Seven features were identified including: a clearly defined problem, integration into a system of healthcare delivery, technology support, personalized experience, focus on end-user experience, alignment with reimbursement models, and inclusion of clinician champions. Health providers and systems keen to establish new models of care inclusive of wearables may consider these features during program design. A better understanding of these features is necessary to guide future clinical applications of wearable technology.
40P Phase I study of the safety, pharmacokinetics and pharmacodynamics of escalating doses followed by dose expansion of selinexor in Asian patients with advanced solid tumour malignancies
Authors: J.S. Ho, V. Heong, W.P. Yong, R. Soo, C.E. Chee, A. Wong, Y.L. Thian, R. Sundar, A. Gopinathan, S.C. Lee, B.C. Goh, H. Xu, D.S. Tan
Journal: Annals of Oncology (2021)
Novel synthetic lethality (SL) anti-cancer drug target in urothelial bladder cancer (UCB) based on <i>MTAP</i> genomic loss: Incidence and correlations in standard of care (SOC).
Authors: Gennady Bratslavsky, Joseph M Jacob, Andrea Necchi, Petros Grivas, Natalie Danziger, Ethan Sokol, Russell Madison, Shakti H. Ramkissoon, Ryon Graf, Douglas A Mata, Brennan James Decker, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2021)

485 Background: When UCB presents or progresses to chemorefractory metastatic disease, the search for new therapy targets is paramount. Targeting PRMT5 arginine methyltransferase accumulation in tumors with MTAP (methylthioadenosine Phosphorylase) genomic loss has been proposed as a new SL based anti-tumor strategy and under consideration for development for UCB. We sought to evaluate the incidence of patients with candidate SL and correlate to treatment-guiding biomarkers currently evaluated in SOC. Methods: 2,683 cases of clinically advanced UCB underwent hybrid-capture based comprehensive genomic profiling in a standard of care setting using the F1CDx FDA-approved assay to evaluate all classes of genomic alterations (GA) among 324 genes. Tumor mutational burden (TMB) was determined on 0.8 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 95 loci. PD-L1 expression was determined by IHC (Dako 22C3). Results: 650 (24%) of UCB feature MTAP loss (MTAP-) (Table). The gene and age distributions were similar MTAP intact (MTAP+) and MTAP- UCB. The GA/tumor was higher in MTAP- UCB likely reflecting the significant GA co-deletions of CDKN2A/ B at the 9p21 locus. Of potential therapeutic targets, FGFR3 and PTEN GA were more frequent in the MTAP- UCB. In contrast, biomarkers of immunotherapy (IO) response included higher frequencies of high TMB and high PD-L1 IHC staining in the MTAP+ UCB. Conclusions: When compared with MATP+ UCB, MTAP- UCB differs in genomic signatures including an increase in potential for targeted therapies but a lower potential for IO drug benefit. Thus, the genomic landscape in MTAP- UCB may play a significant role in the design of clinical trials incorporating SL strategies when targeting PRMT5 in MTAP deficient tumors. [Table: see text]
Nivolumab and Ipilimumab as Maintenance Therapy in Extensive-Disease Small-Cell Lung Cancer: CheckMate 451
Authors: Taofeek K. Owonikoko, Keunchil Park, Ramaswamy Govindan, Neal Ready, Martin Reck, Solange Peters, Shaker R. Dakhil, Alejandro Navarro, Jerónimo Rodríguez-Cid, Michael Schenker, Jong-Seok Lee, Vanesa Gutierrez, Ivor Percent, Daniel Morgensztern, Carlos H. Barrios, Laurent Greillier, Sofia Baka, Miten Patel, Wen Hong Lin, Giovanni Selvaggi, Christine Baudelet, Jonathan Baden, Dimple Pandya, Parul Doshi, Hye Ryun Kim
Journal: Journal of Clinical Oncology (2021)

In extensive-disease small-cell lung cancer (ED-SCLC), response rates to first-line platinum-based chemotherapy are robust, but responses lack durability. CheckMate 451, a double-blind phase III trial, evaluated nivolumab plus ipilimumab and nivolumab monotherapy as maintenance therapy following first-line chemotherapy for ED-SCLC.Patients with ED-SCLC, Eastern Cooperative Oncology Group performance status 0-1, and no progression after ≤ 4 cycles of first-line chemotherapy were randomly assigned (1:1:1) to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg once every 3 weeks for 12 weeks followed by nivolumab 240 mg once every 2 weeks, nivolumab 240 mg once every 2 weeks, or placebo for ≤ 2 years or until progression or unacceptable toxicity. Primary end point was overall survival (OS) with nivolumab plus ipilimumab versus placebo. Secondary end points were hierarchically tested.Overall, 834 patients were randomly assigned. The minimum follow-up was 8.9 months. OS was not significantly prolonged with nivolumab plus ipilimumab versus placebo (hazard ratio [HR], 0.92; 95% CI, 0.75 to 1.12; P = .37; median, 9.2 v 9.6 months). The HR for OS with nivolumab versus placebo was 0.84 (95% CI, 0.69 to 1.02); the median OS for nivolumab was 10.4 months. Progression-free survival HRs versus placebo were 0.72 for nivolumab plus ipilimumab (95% CI, 0.60 to 0.87) and 0.67 for nivolumab (95% CI, 0.56 to 0.81). A trend toward OS benefit with nivolumab plus ipilimumab was observed in patients with tumor mutational burden ≥ 13 mutations per megabase. Rates of grade 3-4 treatment-related adverse events were nivolumab plus ipilimumab (52.2%), nivolumab (11.5%), and placebo (8.4%).Maintenance therapy with nivolumab plus ipilimumab did not prolong OS for patients with ED-SCLC who did not progress on first-line chemotherapy. There were no new safety signals.
N-Terminal Fragment of the Type-B Natriuretic Peptide (NT-proBNP) Is an Independent Prognostic Factor for Overall Survival in Patients with Monoclonal Gammopathy of Undetermined Significance (MGUS)
Authors: Paolo Milani, Morie A. Gertz, Giampaolo Merlini, Giovanni Palladini, Martha Q Lacy, Francis K Buadi, Shaji K Kumar, Suzanne R. Hayman, Nelson Leung, David Dingli, John A. Lust, Yi Lin, Prashant Kapoor, Ronald S. Go, Yi L. Hwa, Steven Zeldenrust, Robert A Kyle, S. Vincent Rajkumar, Angela Dispenzieri
Journal: Blood (2017)
Abstract 14968: A Double Blind, Randomized, Controlled Pharmacokinetic and Pharmacodynamics Trial of Ambrisentan After Fontan Surgery
Authors: Kevin D Hill, Anil Maharaj, Elizabeth Thompson, Jennifer S Li, Elliott Pearson, Christoph Hornik
Journal: Circulation (2018)

Introduction: Ambrisentan is a hepatically metabolized endothelin receptor antagonist (ERA) that induces pulmonary vasodilation, which may be beneficial after Fontan surgery. Ambrisentan’s hepatic ...
Insight into chemical basis of traditional Chinese medicine based on the state-of-the-art techniques of liquid chromatography−mass spectrometry
Authors: Yang Yu, Changliang Yao, De-an Guo
Journal: Acta Pharmaceutica Sinica B (2021)

Traditional Chinese medicine (TCM) has been an indispensable source of drugs for curing various human diseases. However, the inherent chemical diversity and complexity of TCM restricted the safety and efficacy of its usage. Over the past few decades, the combination of liquid chromatography with mass spectrometry has contributed greatly to the TCM qualitative analysis. And novel approaches have been continuously introduced to improve the analytical performance, including both the data acquisition methods to generate a large and informative dataset, and the data post-processing tools to extract the structure-related MS information. Furthermore, the fast-developing computer techniques and big data analytics have markedly enriched the data processing tools, bringing benefits of high efficiency and accuracy. To provide an up-to-date review of the latest techniques on the TCM qualitative analysis, multiple data-independent acquisition methods and data-dependent acquisition methods (precursor ion list, dynamic exclusion, mass tag, precursor ion scan, neutral loss scan, and multiple reaction monitoring) and post-processing techniques (mass defect filtering, diagnostic ion filtering, neutral loss filtering, mass spectral trees similarity filter, molecular networking, statistical analysis, database matching, etc.) were summarized and categorized. Applications of each technique and integrated analytical strategies were highlighted, discussion and future perspectives were proposed as well.
Enhancement of acellular cartilage matrix scaffold by Wharton's jelly mesenchymal stem cell-derived exosomes to promote osteochondral regeneration
Authors: Shuangpeng Jiang, Guangzhao Tian, Zhen Yang, Xiang Gao, Fuxin Wang, Juntan Li, Zhuang Tian, Bo Huang, Fu Wei, Xinyu Sang, Liuqi Shao, Jian Zhou, Zhenyong Wang, Shuyun Liu, Xiang Sui, Quanyi Guo, Weimin Guo, Xu Li
Journal: Bioactive Materials (2021)

Articular cartilage defect repair is a problem that has long plagued clinicians. Although mesenchymal stem cells (MSCs) have the potential to regenerate articular cartilage, they also have many limitations. Recent studies have found that MSC-derived exosomes (MSC-Exos) play an important role in tissue regeneration. The purpose of this study was to verify whether MSC-Exos can enhance the reparative effect of the acellular cartilage extracellular matrix (ACECM) scaffold and to explore the underlying mechanism. The results of in vitro experiments show that human umbilical cord Wharton's jelly MSC-Exos (hWJMSC-Exos) can promote the migration and proliferation of bone marrow-derived MSCs (BMSCs) and the proliferation of chondrocytes. We also found that hWJMSC-Exos can promote the polarization of macrophages toward the M2 phenotype. The results of a rabbit knee osteochondral defect repair model confirmed that hWJMSC-Exos can enhance the effect of the ACECM scaffold and promote osteochondral regeneration. We demonstrated that hWJMSC-Exos can regulate the microenvironment of the articular cavity using a rat knee joint osteochondral defect model. This effect was mainly manifested in promoting the polarization of macrophages toward the M2 phenotype and inhibiting the inflammatory response, which may be a promoting factor for osteochondral regeneration. In addition, microRNA (miRNA) sequencing confirmed that hWJMSC-Exos contain many miRNAs that can promote the regeneration of hyaline cartilage. We further clarified the role of hWJMSC-Exos in osteochondral regeneration through target gene prediction and pathway enrichment analysis. In summary, this study confirms that hWJMSC-Exos can enhance the effect of the ACECM scaffold and promote osteochondral regeneration.
Patterns and predictors of oral anticancer agent utilization in diverse metastatic renal cell carcinoma patients.
Authors: Stephanie B. Wheeler, Lisa Spees, Bradford E Jackson, Christopher Baggett, Lauren E Wilson, Melissa A. Greiner, Daniel J. George, Charles D. Scales, Jessica Pritchard, Michaela Ann Dinan
Journal: Journal of Clinical Oncology (2021)

279 Background: Availability of targeted oral anti-cancer agents (OAA) has transformed care delivery for metastatic renal cell carcinoma (RCC) patients. Our objective was to identify patterns and predictors of OAA use within the 12 months after metastatic RCC was detected to understand the extent of real-world adoption of these treatment advances. Methods: We used a novel, North Carolina, registry-linked multi-payer claims data resource to examine patterns of use of sorafenib, sunitinib, pazopanib, everolimus, axitinib, cabozantinib, and levantinib in a cohort of metastatic RCC patients diagnosed over 10 years (2006-2015, with claims through 2016). Patients were required to have 12 months of pre- and post-metastatic-index-date continuous enrollment. Log-Poisson models estimated unadjusted and adjusted risk ratios (RRs) and 95% confidence limits (CLs) for associations between patient characteristics and OAA use. In sensitivity analyses, we used a competing risk framework to estimate adjusted risk differences (RD) in OAA use. Results: Our population-based study of 713 patients demonstrated relatively low (37%) OAA use at any time during the 12 months post-metastatic-index date among publicly and privately insured patients, with shifting patterns of use consistent with regulatory approvals over time. Lower OAA use was observed among patients who were older, frailer, and with greater comorbidity burden. Other patient-level characteristics, such as sex, race, rurality and type of insurance were not significant predictors of OAA use. Conclusions: These data underscore the importance of distinguishing clinically appropriate from potentially poor-quality care and warrant additional studies to understand in more depth the system, provider and patient level drivers of these patterns.
Helen Salisbury: Stepping back from vaccination priorities and focusing on minimising the risk of exposure
Authors: Helen Salisbury
Journal: BMJ (2021)

In the last week, many GPs have been trying to make sense of new lists of patients coded as being at high risk of complications from covid-19 who are therefore a priority for vaccination. We’ve been weeding out cases in which a typo has resulted in a body mass index of 25 000 or an innocent childhood heart murmur has been translated into congenital heart disease. Are women with a previous history of gestational diabetes, but five years of normal blood sugars since then, really at increased risk? Should an incidental ultrasonography finding of fatty liver, with completely normal liver function tests, gain you a place on the list? As we …
Antidrug Antibodies and Drug Development: Challenges in the Immunotherapy Era
Authors: Bernard Doger de Spéville, Victor Moreno
Journal: Clinical Cancer Research (2021)

Abstract Novel antibody formats such as bispecifics have increased risk of immunogenicity, impacting safety and efficacy. LY3415244, a novel T-cell immunoglobulin and mucin-domain-containing molecule-3 (TIM3)-PDL1 (programmed death (ligand) 1) bispecific caused neutralizing antibody–drug antibodies (ADA) in 12 of 12 patients and required study termination. Novel approaches are needed to ameliorate and manage this undesirable effect of therapeutic antibodies. See related article by Hellmann et al., p. 2773
Abstract IA008: Age-related stromal changes drive tumorigenesis
Authors: Sheila A Stewart
Journal: Cancer Research (2021)

Abstract The stromal compartment plays a pivotal role in tumor progression. This is best illustrated in breast cancer bone metastases, where the stromal compartment supports tumor growth, albeit through poorly defined mechanisms. p38MAPKa is frequently expressed in tumor cells and surrounding stromal cells and its expression levels correlate with poor prognosis. Using a clinically relevant breast cancer metastasis model, we show that orally administered, small-molecule inhibitors of p38MAPKa or its downstream kinase, MK2, each limited outgrowth of metastatic breast cancer cells in the bone and visceral organs. Further we find that this effect is primarily mediated by inhibition of the p38MAPKa pathway within the stromal compartment. Beyond effectively limiting metastatic tumor growth, we also find that these inhibitors reduce tumor-associated and chemotherapy-induced bone loss, which is a devastating comorbidity for cancer patients that drastically impact their quality of life. Interestingly we find that p38MAPKa’s ability to limit tumor growth within the bone is dependent on CD4 T cells while MK2 does not require these cells to limit tumor progression, demonstrating that it is not a straightforward pathway. To determine which cell types within the bone contribute to tumor growth and bone loss, we have carried out single cell RNA-sequencing of stromal cells located within the bone metastatic lesion and cells outside the lesion. We find numerous differences that could explain how the stromal compartment contributes to tumor progression and bone loss and how inhibition of p38MAPKa or MK2 contribute. These data underscore the vital role stromal-derived factors play in tumor progression and identify the p38MAPK-MK2 pathway as a promising therapeutic target for metastatic disease and prevention of tumor-induced bone loss. Citation Format: Sheila A Stewart. Age-related stromal changes drive tumorigenesis [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr IA008.
Abstract 284: The Fibroblast Growth Factor System Regulates Vascular Integrity and Permeability
Authors: Masahiro Murakami, Loc T Nguyen, Zhen W Zhuang, Karen L Moodie, Radu V Stan, Michael Simons
Journal: Circulation (2007)

Background: Despite its versatile action on a wide variety of biological processes, the precise role of the fibroblast growth factor (FGF) family in the vascular system is under-characterized. We h...
SARM1 is a metabolic sensor activated by an increased NMN/NAD+ ratio to trigger axon degeneration
Authors: Matthew D. Figley, Weixi Gu, Jeffrey D. Nanson, Yun Shi, Yo Sasaki, Katie Cunnea, Alpeshkumar K. Malde, Xinying Jia, Zhenyao Luo, Forhad K. Saikot, Tamim Mosaiab, Veronika Masic, Stephanie Holt, Lauren Hartley-Tassell, Helen Y. McGuinness, Mohammad K. Manik, Todd Bosanac, Michael J. Landsberg, Philip S. Kerry, Mehdi Mobli, Robert O. Hughes, Jeffrey Milbrandt, Bostjan Kobe, Aaron DiAntonio, Thomas Ve
Journal: Neuron (2021)
The safety of asthma medications during pregnancy and lactation: Clinical management and research priorities
Authors: Christina D. Chambers, Jerry A. Krishnan, Lorene Alba, Jessica D. Albano, Allison S. Bryant, Melanie Carver, Lee S. Cohen, Elena Gorodetsky, Sonia Hernandez-Diaz, Margaret A. Honein, Bridgette L. Jones, Richard K. Murray, Jennifer A. Namazy, Leyla Sahin, Catherine Y. Spong, Kaveeta P. Vasisht, Kevin Watt, Keele E. Wurst, Lynne Yao, Michael Schatz
Journal: Journal of Allergy and Clinical Immunology (2021)
Abstract 17038: Volume of Coronary Artery Bypass Surgery and Risk of 30-Day Readmissions (Analysis From the Nationwide Readmissions Database)
Authors: Alejandro Lemor, Gabriel A Hernandez, Nish Patel, Mauricio G Cohen, Carlos E Alfonso, Eduardo De Marchena
Journal: Circulation (2017)

Background: The rate of coronary artery bypass graft (CABG) surgery has decreased in the past years as a consequence of an increase in percutaneous coronary interventions (PCI). The association bet...