tbuckley/cabot-search huggingface dataset:
Characterization and prognosis of temozolomide-induced aplastic anemia in patients with central nervous system malignancies
Authors: Albert K Park, Anem Waheed, Deborah A Forst, Hanny Al-Samkari
Journal: Neuro-Oncology (2021)

Abstract Background Temozolomide-induced aplastic anemia (TIAA) is a rare but highly challenging complication of temozolomide (TMZ) therapy. Evidence describing prognosis, clinical characteristics, and treatment of this entity is very limited. Methods We performed a multicenter, 22-year observational cohort study of patients with central nervous system (CNS) malignancies treated with temozolomide who developed TIAA, retrospectively analyzing prognosis, complications, and recovery. TIAA was defined using adapted evidence-based severe aplastic anemia criteria incorporating profound cytopenias and a minimum duration (4 weeks) without hematologic recovery. Results Of 3821 patients with CNS malignancies receiving TMZ, 34 patients (0.89%) met criteria for TIAA. Onset was rapid, with 29 patients (85.3%) developing TIAA before completing a second TMZ cycle. 23 patients (67.6%) ultimately achieved a hematologic recovery. Patients without recovery were more likely to develop febrile neutropenia (72.7% vs. 30.4%, P = .03), infectious complications (45.5% vs. 8.7%, P = .02), require hospitalization (81.8% vs. 43.5%, P = .04), and die (100.0% vs. 60.9%, P = .02). Median overall survival from TIAA diagnosis was 752 days in patients achieving a partial hematologic recovery versus 28 days in those who did not (P &amp;lt; .0001). 29 patients (85.3%) received one or more hematopoietic growth factors; hematologic recovery rates were higher in patients receiving thrombopoietin receptor agonists (81.8% vs. 60.9%) but were not higher in patients receiving granulocyte colony-stimulating factors. Conclusions TIAA occurs in &amp;lt;1% of patients receiving TMZ for CNS malignancies, but is highly morbid when it occurs and frequently fatal in the one-third of patients not achieving hematologic recovery. Thrombopoietin receptor agonists may improve the likelihood of a hematologic recovery.
Photoactivatable Biomedical Materials Based on Luminogens with Aggregation‐Induced Emission (AIE) Characteristics
Authors: Jiangman Sun, Hui Li, Xinggui Gu, Ben Zhong Tang
Journal: Advanced Healthcare Materials (2021)

Fluorescence probes with aggregation-induced emission (AIE) property are fascinating and vital in biological fields due to their bright fluorescence in the solid state. In contrast, traditional AIE materials are obscured by the off-target effects and lack of spatial and temporal control. Photoactivatable materials with AIE characteristics, whose physicochemical behaviors can be remotely activated by light, provide great potential in biochemical information acquisition with high spatial and temporal resolution. By using AIE-featured photoactivatable fluorescence probes, accurate analysis of the targets of interest is possible. For example, where, when, and to what extent a process is started or stopped by manipulating the non-invasive light accurately. Thus, many researchers are enthusiastic about developing AIE-featured photoactivatable materials and mainly focus on developing novel molecules by rational molecular structure design, and exploring advanced applications by appropriate molecular functionalization. In this review, the recent achievements of photoactivatable materials with AIE characteristics from the aspects involving inherent mechanism of photoactivity, molecular design strategy, and the corresponding applications in biological fields, are summarized. The biological applications are highlighted and discussed, including photoactivatable bioimaging, diagnosis, and photo-controlled therapy. Finally, the challenges and prospects of the AIE-featured photoactivatable materials are also outlined and discussed.
Quality and Safety in Healthcare, Part XCI
Authors: Jay A. Harolds
Journal: Clinical Nuclear Medicine (2021)

Abstract Lean thinking refers to the thought processes utilizing the main characteristics of Lean to improve processes, reduce waste, and increase value to the customer. Lean thinking can be used to improve health care organizations using such tools as the A3 form, root-cause analysis, value stream maps, Gemba walks, kaizen events, and defining standard work. Examples are given about how Lean thinking improved scheduling and productivity, as well as better compliance regarding core measures and adherence to best practices. Lean thinking examples are also given which resulted in less need for space, inventory, and personnel, and a decrease in hospital-acquired infections.
Recent advances in engineering iron oxide nanoparticles for effective magnetic resonance imaging
Authors: Zhenghuan Zhao, Muyao Li, Jie Zeng, Linlin Huo, Kun Liu, Ruixue Wei, Kaiyuan Ni, Jinhao Gao
Journal: Bioactive Materials (2021)

Iron oxide nanoparticle (IONP) with unique magnetic property and high biocompatibility have been widely used as magnetic resonance imaging (MRI) contrast agent (CA) for long time. However, a review which comprehensively summarizes the recent development of IONP as traditional T2 CA and its new application for different modality of MRI, such as T1 imaging, simultaneous T2/T1 or MRI/other imaging modality, and as environment responsive CA is rare. This review starts with an investigation of direction on the development of high-performance MRI CA in both T2 and T1 modal based on quantum mechanical outer sphere and Solomon-Bloembergen-Morgan (SBM) theory. Recent rational attempts to increase the MRI contrast of IONP by adjusting the key parameters, including magnetization, size, effective radius, inhomogeneity of surrounding generated magnetic field, crystal phase, coordination number of water, electronic relaxation time, and surface modification are summarized. Besides the strategies to improve r2 or r1 values, strategies to increase the in vivo contrast efficiency of IONP have been reviewed from three different aspects, those are introducing second imaging modality to increase the imaging accuracy, endowing IONP with environment response capacity to elevate the signal difference between lesion and normal tissue, and optimizing the interface structure to improve the accumulation amount of IONP in lesion. This detailed review provides a deep understanding of recent researches on the development of high-performance IONP based MRI CAs. It is hoped to trigger deep thinking for design of next generation MRI CAs for early and accurate diagnosis.
Assessment of the Feasibility and Safety of Durvalumab for Treatment of Solid Tumors in Patients With HIV-1 Infection
Authors: Maria Gonzalez-Cao, Teresa Morán, Judith Dalmau, Javier Garcia-Corbacho, Jillian W. P. Bracht, Reyes Bernabe, Oscar Juan, Javier de Castro, Remei Blanco, Ana Drozdowskyj, Jordi Argilaguet, Andreas Meyerhans, Julia Blanco, Julia G. Prado, Jorge Carrillo, Bonaventura Clotet, Bartomeu Massuti, Mariano Provencio, Miguel A. Molina-Vila, Clara Mayo de las Casa, Monica Garzon, Peng Cao, Chung-Ying Huang, Javier Martinez-Picado, Rafael Rosell
Journal: JAMA Oncology (2020)

<h3>Importance</h3> Therapies targeting the programmed cell death 1 (PD-1) receptor or its ligand (PD-L1), such as the humanized monoclonal antibody durvalumab, have shown durable clinical responses in several tumor types. However, concerns about the safety and feasibility of PD-1/PD-L1 blockade in HIV-1–infected individuals have led to the exclusion of these patients from clinical trials on cancer immunotherapies. <h3>Objective</h3> To evaluate the feasibility and safety of durvalumab treatment in patients with advanced cancer and virologically controlled HIV-1 infection. <h3>Design, Setting, and Participants</h3> The DURVAST study was a nonrandomized, open-label, phase 2 clinical trial in patients with any solid tumor type in which anti–PD-1 or anti–PD-L1 antibodies have approved indications or for which there are data of antitumoral activity with no other available curative therapy. All patients had basal undetectable plasma viremia while undergoing combination antiretroviral therapy. <h3>Interventions</h3> Treatment consisted of intravenous infusion of durvalumab (1500 mg every 4 weeks) until disease progression or unacceptable toxic effects. <h3>Main Outcomes and Measures</h3> Adverse events were graded with the use of the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03. Tumor response was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1. <h3>Results</h3> A total of 20 HIV-1–infected patients with advanced cancer were enrolled; 16 (80%) were male, the median (range) age was 54 (30-73) years, and 12 (60%) had progressed with previous cancer treatment lines. A median (range) of 4 (1-16) cycles of durvalumab were administered. Drug-related adverse events were observed in 50% of patients, and all were grade 1 and 2 (mainly diarrhea, asthenia, and arthromyalgia). Four of 16 response-evaluable patients (25%) had a partial response. Five patients (31%) had stable disease, including 4 with durable stable disease (disease control rate of 50%). CD4<sup>+</sup>and CD8<sup>+</sup>T-cell counts and plasma HIV-1 viremia remained stable throughout the study. <h3>Conclusions and Relevance</h3> Durvalumab treatment was feasible and safe in HIV-1–infected patients with cancer receiving combination antiretroviral therapy. HIV-1–infected patients on suppressive antiretroviral therapy with advanced cancer should have access to cancer immunotherapy treatments. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT03094286
Self-Management Education Class Attendance and Health Care Provider Counseling for Physical Activity Among Adults with Arthritis — United States, 2019
Authors: Lindsey M. Duca, Charles G. Helmick, Kamil E. Barbour, Dana Guglielmo, Louise B. Murphy, Michael A. Boring, Kristina A. Theis, Erica L. Odom, Yong Liu, Janet B. Croft
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Arthritis is a highly prevalent and disabling condition among U.S. adults (1); arthritis-attributable functional limitations and severe joint pain affect many aspects of health and quality of life (2). Self-management education (self-management) and physical activity can reduce pain and improve the health status and quality of life of adults with arthritis; however, in 2014, only 11.4% and 61.0% of arthritis patients reported engaging in each, respectively. To assess self-reported self-management class attendance and health care provider physical activity counseling among adults with doctor-diagnosed arthritis, CDC analyzed 2019 Behavioral Risk Factor Surveillance System (BRFSS) data. In 2019, an age-standardized state median of one in six (16.2%) adults with arthritis reported ever attending a self-management class, and 69.3% reported ever receiving health care provider counselling to be physically active. Prevalences of both differed by state and sociodemographic characteristics; decreased with lower educational attainment, joint pain severity, and urbanicity; and were lower in men than in women. Health care providers can play an important role in promoting self-management class attendance and physical activity by counseling arthritis patients about their benefits and referring patients to evidence-based programs (3).
Re-operation for recurrent intracranial meningioma – is it worth it?
Authors: George Richardson, Conor Gillespie, Mohammad Mustafa, Basel Taweel, Christopher Millward, Abdurrahman Islim, Michael Jenkinson
Journal: Neuro-Oncology (2021)

Abstract Aims Meningioma is the commonest primary brain tumour. Despite surgery, meningiomas can recur. Surgery is usually the first line treatment for recurrent meningioma. The aim was to determine the risk factors associated with clinical outcomes (performance status, morbidity, mortality, recurrence) following re-operation for recurrence of intracranial meningioma. Method Retrospective cohort study (1998-2018). Eligible patients had re-operation for local recurrence of a previously operated meningioma. Collected data included baseline clinical and imaging characteristic. Primary outcome measure was performance status after each re-operation. Secondary outcome measures were medical and surgical morbidity, recurrence-free survival (RFS) and overall survival (OS). Results Fifty-eight patients were eligible (38 female, mean age at 1st re-operation 56 years (SD=11.4)). Eleven patients (18.9%) had 2 re-operations and 3 patients (3.4%) had 3 re-operations. Median follow up was 125.5 months (IQR 73-191.5). Median time to 1st recurrence and 1st re-operation were 36.5 (IQR 24.2–79.1) and 43.8 months (IQR 22.9–102.7), respectively. Fifteen patients (25.9%) had worse performance status after 1st re-operation, compared to 6.9% (n=4) after the primary operation (Figure 1). Complication rate was 32.8% (n=19) after the primary operation compared to 46.6% (n=27) after 1st re-operation. At primary operation, there were 29 (50%) grade 1, 26 (44.8%) grade 2, and 1 (1.7%) grade 3 tumours. Median RFS after first re-operation was 68 months (95% CI 45.5-90.5) (figure 2). Median OS was 312 months (95% CI 236.9-387.1) (Figure 3). Post-operative complications were a risk factor for worsened performance status following re-operation (OR 4.91, 95% CI 1.3-18.4). Conclusion Re-operation is associated with a worse performance status and increased risk of complications. Re-operating meningiomas for radiological recurrence without symptoms increases patient morbidity. Shared-care management decision should be made with patients when considering operating for radiological recurrence only.
Abstract 15307: The Effect of Healthy Diets on Subclinical Cardiac Injury and Inflammation: Results From the OmniHeart Trial
Authors: Lara C Kovell, Edwina Yeung, Edgar R Miller, Lawrence J Appel, Robert H Christenson, Heather Rebuck, Steven P Schulman, Stephen P Juraschek
Journal: Circulation (2018)

Background: Cardiovascular disease (CVD) is pervasive, and dietary interventions are the first line approach to reducing CVD risk factors. The effects of dietary interventions on subclinical cardio...
Predicted Cure and Survival Among Transplant Recipients With a Previous Cancer Diagnosis
Authors: Eric A. Engels, Gregory Haber, Allyson Hart, Charles F. Lynch, Jie Li, Karen S. Pawlish, Baozhen Qiao, Kelly J. Yu, Ruth M. Pfeiffer
Journal: Journal of Clinical Oncology (2021)

PURPOSE A previous cancer diagnosis is a negative consideration in evaluating patients for possible solid organ transplantation. Statistical models may improve selection of patients with cancer evaluated for transplantation. METHODS We fitted statistical cure models for patients with cancer in the US general population using data from 13 cancer registries. Patients subsequently undergoing solid organ transplantation were identified through the Scientific Registry of Transplant Recipients. We estimated cure probabilities at diagnosis (for all patients with cancer) and transplantation (transplanted patients). We used Cox regression to assess associations of cure probability at transplantation with subsequent cancer-specific mortality. RESULTS Among 10,524,326 patients with 17 cancer types in the general population, the median cure probability at diagnosis was 62%. Of these patients, 5,425 (0.05%) subsequently underwent solid organ transplantation and their median cure probability at transplantation was 94% (interquartile range, 86%-98%). Compared with the tertile of transplanted patients with highest cure probability, those in the lowest tertile more frequently had lung or breast cancers and less frequently colorectal, testicular, or thyroid cancers; more frequently had advanced-stage cancer; were older (median 57 v 51 years); and were transplanted sooner after cancer diagnosis (median 3.6 v 8.6 years). Patients in the low-cure probability tertile had increased cancer-specific mortality after transplantation (adjusted hazard ratio, 2.08; 95% CI, 1.48 to 2.93; v the high tertile), whereas those in the middle tertile did not differ. CONCLUSION Patients with cancer who underwent solid organ transplantation exhibited high cure probabilities, reflecting selection on the basis of existing guidelines and clinical judgment. Nonetheless, there was a range of cure probabilities among transplanted patients and low probability predicted increased cancer-specific mortality after transplantation. Cure probabilities may facilitate guideline development and evaluating individual patients for transplantation.
A Continuously Benchmarked and Crowdsourced Challenge for Rapid Development and Evaluation of Models to Predict COVID-19 Diagnosis and Hospitalization
Authors: Yao Yan, Thomas Schaffter, Timothy Bergquist, Thomas Yu, Justin Prosser, Zafer Aydin, Amhar Jabeer, Ivan Brugere, Jifan Gao, Guanhua Chen, Jason Causey, Yuxin Yao, Kevin Bryson, Dustin R. Long, Jeffrey G. Jarvik, Christoph I. Lee, Adam Wilcox, Justin Guinney, Sean Mooney, Chethan Jujjavarapu, jason thomas, Martin Gunn, YiFan Wu, Nicholas Dobbins, Vikas O'Reilly-Shah, Andrew Teng, Noah Hammarlund, Graham Nichol, Pascal Brandt, Vikas Pejaver, Beth Britt, Yuanfang Guan, Lingrui Cai, Kaiman Zeng, Bruce Cragin, Shirya Kaul, Jennifer Fowler, Oznur Tastan, Vladimir Kovacevic, Ege Alpay, Luiza Romanovskii-Chernik, Aleksandr Romanovskii-Chernik, Alper Bingol, Sema Yılmazer, Shankai Yan, Santina Lin, Ege Arıkan, Lav Varshney, Jimmy Phuong
Journal: JAMA Network Open (2021)

Machine learning could be used to predict the likelihood of diagnosis and severity of illness. Lack of COVID-19 patient data has hindered the data science community in developing models to aid in the response to the pandemic.
Modulation of Cardiac Arrhythmogenesis by Epicardial Adipose Tissue
Authors: Auriane C. Ernault, Veronique M.F. Meijborg, Ruben Coronel
Journal: Journal of the American College of Cardiology (2021)

Obesity is a significant risk factor for arrhythmic cardiovascular death. Interactions between epicardial adipose tissue (EAT) and myocytes are thought to play a key role in the development of arrhythmias. In this review, the authors investigate the influence of EAT on arrhythmogenesis. First, they summarize electrocardiographic evidence showing the association between increased EAT volume and atrial and ventricular conduction delay. Second, they detail the structural cross talk between EAT and the heart and its arrhythmogenicity. Adipose tissue infiltration within the myocardium constitutes an anatomical obstacle to cardiac excitation. It causes activation delay and increases the risk of arrhythmias. Intercellular electrical coupling between cardiomyocytes and EAT can further slow conduction and increase the risk of block, favoring re-entry and arrhythmias. Finally, EAT secretes multiple substances that influence cardiomyocyte electrophysiology either by modulating ion currents and electrical coupling or by stimulating fibrosis. Thus, structural and paracrine cross talk between EAT and cardiomyocytes facilitates arrhythmias.
The novel hypoxia-targeted anticancer agent AQ4N is not subject to multi-drug resistance mediated by PGP/MDR1
Authors: Mark R. Albertella, Wendy V. Grocock, Graeme C. M. Smith, Chris R. Dunk, Peter A. Harris
Journal: Cancer Research (2005)

525  AQ4N (banoxantrone; 1,4-Bis{[2-(dimethylamino)ethyl]amino}-5,8-dihydroxyanthracene-9,10-dione bis-N-oxide) is a novel therapeutic agent that targets the treatment-resistant hypoxic fraction of tumors. AQ4N is a highly soluble and penetrating prodrug that is enzymatically reduced to a cytotoxic DNA-binding agent, AQ4, preferentially in conditions of low oxygen tension. Combination therapy using AQ4N in addition to radiation and/or chemotherapy targets both the oxygenated and hypoxic regions of tumors, increasing effectiveness of treatment in preclinical models. AQ4N is well-tolerated in man and is currently in Phase I clinical trial. A major contributor to acquired drug resistance is the multi-drug resistance phenotype (MDR) caused by overexpression of ABC family transmembrane protein pumps. Substrates for MDR include anthracyclines (eg daunorubicin) and anthracenediones (eg mitoxantrone). We have investigated whether AQ4N and AQ4, which are structurally related to mitoxantrone, are substrates for the prototypical MDR protein PGP/MDR1. The intrinsic fluorescence of these molecules was used to directly evaluate transport by PGP using flow cytometry. The measurement of steady state levels in MDR1-positive cell lines revealed no sensitivity to the PGP inhibitor verapamil for AQ4, in contrast to a 3-5-fold increase for mitoxantrone (indicative of cellular accumulation). Direct measurements of efflux from isogenically matched PGP-overexpressing cells confirmed no verapamil-dependent efflux of AQ4, contrasting sharply with a dramatic efflux of mitoxantrone and daunorubicin. Survival assays using the MDR1-positive cells revealed no differential toxicity of AQ4 or AQ4N compared to the control parental cell lines, whereas mitoxantrone showed reduced sensitivity in the PGP-overexpressing line, demonstrating a functional relevance of the efflux observations. The potential roles of other transmembrane pumps in transport of AQ4, and the significance of these findings in in vivo models are also under further investigation. These data suggest that AQ4N is not a substrate for MDR, which is one of the major barriers to the effectiveness of anthraquinones and other agents. AQ4N is also effective under conditions of hypoxia, another well-known characteristic of treatment resistant tumours. Taken together, these features indicate significant clinical potential, and the utility of AQ4N, both as monotherapy and in combination with established regimes, is under evaluation in a range of Phase I trials.
Preterm Delivery and Long-term Risk of Hypertension in Women
Authors: Casey Crump, Jan Sundquist, Kristina Sundquist
Journal: JAMA Cardiology (2021)

Preterm delivery has been associated with future cardiometabolic disorders in women. However, the long-term risks of chronic hypertension associated with preterm delivery and whether such risks are attributable to familial confounding are unclear. Such knowledge is needed to improve long-term risk assessment, clinical monitoring, and cardiovascular prevention strategies in women.
Dual‐target inhibitors of bromodomain and extra‐terminal proteins in cancer: A review from medicinal chemistry perspectives
Authors: Lu Feng, Guan Wang, Yi Chen, Gu He, Bo Liu, Jie Liu, Cheng‐Ming Chiang, Liang Ouyang
Journal: Medicinal Research Reviews (2021)

Abstract Bromodomain‐containing protein 4 (BRD4), as the most studied member of the bromodomain and extra‐terminal (BET) family, is a chromatin reader protein interpreting epigenetic codes through binding to acetylated histones and non‐histone proteins, thereby regulating diverse cellular processes including cell cycle, cell differentiation, and cell proliferation. As a promising drug target, BRD4 function is closely related to cancer, inflammation, cardiovascular disease, and liver fibrosis. Currently, clinical resistance to BET inhibitors has limited their applications but synergistic antitumor effects have been observed when used in combination with other tumor inhibitors targeting additional cellular components such as PLK1, HDAC, CDK, and PARP1. Therefore, designing dual‐target inhibitors of BET bromodomains is a rational strategy in cancer treatment to increase potency and reduce drug resistance. This review summarizes the protein structures and biological functions of BRD4 and discusses recent advances of dual BET inhibitors from a medicinal chemistry perspective. We also discuss the current design and discovery strategies for dual BET inhibitors, providing insight into potential discovery of additional dual‐target BET inhibitors.