tbuckley/cabot-search huggingface dataset:
PB1713 NEW METHODS FOR ASSESSING THE GENOTOXICITY OF CHEMOTHERAPY DRUGS IN ACUTE MYELOID LEUKEMIA
Authors: D. Zhogolev, A. Polyakov, S. Kolubaeva, Z. Alexander, Y. Noskov
Journal: HemaSphere (2019)

Background: This abstract presents the experience of cultivating the peripheral blast cells of a patient with resistant acute myeloid leukemia (AML) and testing 2 methods for assessing the effects of chemotherapy drugs on them. Aims: Suitability examination of cell sorting (CS) and micronucleus test (MT) for assessing the genotoxicity of chemotherapy drugs. Methods: Blast cells were obtained by taking blood from a patient with multi‐resistant AML. On sampling days, the percentage of blasts in the patient's peripheral blood ranged from 50% to 75%. In total, 3 in vitro experiments were conducted. In experiment №1, 520650 CD34+ cells were sorted into 2 tubes, which were incubated for 4 days (37 °C, 5% CO 2 ) in 5 ml of complete nutrient medium (CM): 80% RPMI‐1640, 10% fetal calf serum, 10% of the patient's original serum, 10 μl of phytohaemagglutinin and 100 U/ml penicillin. After the first day, decitabine was added to one of the samples at a concentration of 1160 ng/ml. To assess the genotoxicity of the drug at the end of cultivation, we determined the number of cells that retained viability by evaluating the results of labeling free DNA. In experiments №2 and №3, 0.5 ml of blood was cultured with 5 ml of CM. After 24 hours, various concentrations of decitabine (290 ng/ml, 580 ng/ml, 1160 ng/ml) were added to the samples of experiment №2. Daunorubicin (3400 ng/ml) was added to the samples of experiment №3, as well as its combination with interferon alpha‐2a in the calculation of 3600 IU/ml. Next, samples were cultured for 48 hours. To assess the genotoxicity in these experiments MT was used. Results: The results of experiment №1 are presented in Figure 1, №2 in table 1, №3 in table 2. Summary/Conclusion: 1. CS allows selection of the required number of cells with the required phenotype and assess their viability after cultivation with high accuracy. In the sample with the addition of decitabine, living blast cells turned out to be almost 2 times less than in the control sample. image image 2. MT can be used to assess the genotoxicity of chemotherapy drugs for peripheral blood blast cells. From the results of experiment №2, it follows that the concentration of the drug has a direct correlation with the level of its genotoxicity on blast cells. In experiment №3, the combination of daunorubicin with interferon showed much stronger genotoxic effects on blast cells compared to daunorubicin without interferon.
Histamine beyond its effects on allergy: Potential therapeutic benefits for the treatment of Amyotrophic Lateral Sclerosis (ALS)
Authors: Cinzia Volonté, Savina Apolloni, Mario Sabatelli
Journal: Pharmacology & Therapeutics (2019)

ALS currently remains a challenge despite many efforts in performing successful clinical trials and formulating therapeutic solutions. By learning from current failures and striving for success, scientists and clinicians are checking every possibility to search for missing hints and efficacious treatments. Because the disease is very complex and heterogeneous and, moreover, targeting not only motor neurons but also several different cell types including muscle, glial, and immune cells, the right answer to ALS is conceivably a multidrug strategy or the use of broad-spectrum molecules. The aim of the present work is to gather evidence about novel perspectives on ALS pathogenesis and to present recent and innovative paradigms for therapy. In particular, we describe how an old molecule possessing immunomodulatory and neuroprotective functions beyond its recognized effects on allergy, histamine, might have a renewed and far-reaching momentum in ALS.
Abstract 15585: Loss of Sox9 in Cardiomyocytes Delays the Onset of Cardiac Hypertrophy and Fibrosis
Authors: Antje Schauer, Volker Adams
Journal: Circulation (2018)

Introduction: The transcription factor Sox9 has been shown to be upregulated in association with cardiac injury and remodeling. Injured zebrafish hearts show a strong cardiomyocyte specific upregul...
Caring for Suicidal Patients
Authors: David A. Brent, Maria A. Oquendo, Charles F. Reynolds
Journal: JAMA Psychiatry (2019)

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 Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Psychiatry journal
Abstract 1005: Vascular Cells Derived from Mouse Embryonic Stem Cells Display a Low Inflammatory Response due to Decreased TLR4 Expression
Authors: Anna Zampetaki, Qingzhong Xiao, Lingfang Zeng, Yanhua Hu, Qingbo Xu
Journal: Circulation (2006)

Embryonic stem (ES) cells and ES cell-derived differentiated vascular cells represent a promising potential in cardiovascular diseases as they can be used in tissue regeneration approaches. However...
A Multifunctional Nanotherapy for Targeted Treatment of Colon Cancer by Simultaneously Regulating Tumor Microenvironment
Authors: Qixiong Zhang, Fuzhong Zhang, Shanshan Li, Renfeng Liu, Taotao Jin, Yin Dou, Zhenhua Zhou, Jianxiang Zhang
Journal: Theranostics (2019)

Colitis-associated colon cancer (CAC) is a widely recognized cancer, while treatment with the existing chemotherapeutic drugs affords limited clinical benefits. Herein we proposed a site-specific, combination nanotherapy strategy for targeted treatment of CAC by the oral route. Methods: A reactive oxygen species (ROS)-responsive and hydrogen peroxide-eliminating material OCD was synthesized, which was further produced into a functional nanoparticle (OCD NP). The antioxidative stress and anti-inflammatory effects of OCD NP were examined by in vitro and in vivo experiments. By packaging an anticancer drug camptothecin-11 (CPT-11) into OCD NP, a ROS-responsive nanotherapy CPT-11/OCD NP was obtained, and its antitumor activity was evaluated by both in vitro and in vivo studies. Preliminary safety studies were also performed for CPT-11/OCD NP in mice. Results: OCD NP significantly attenuated oxidative stress and inhibited inflammatory response in different cells and mice with induced colitis. CPT-11/OCD NP could selectively release drug molecules under intestinal pH conditions and at high levels of ROS. In C26 murine colon carcinoma cells, this nanotherapy showed significantly higher antitumor activity compared to free CPT-11 and a non-responsive CPT-11 nanotherapy. Correspondingly, oral delivery of CPT-11/OCD NP notably inhibited tumorigenesis and tumor growth in mice with induced CAC. By combination therapy with the nanovehicle OCD NP in the inflammatory phase, more desirable therapeutic effects were achieved. Furthermore, CPT-11/OCD NP displayed excellent safety profile for oral administration at a dose that is 87.3-fold higher than that employed in therapeutic studies. Conclusions: Anticancer nanotherapies derived from intrinsic anti-inflammatory nanocarriers are promising for targeted combination treatment of inflammation-associated tumors by simultaneously shaping pro-inflammatory microenvironment toward a relatively normal niche sensitive to chemotherapy.
PS1487 EFFECT OF PLASMA EXCHANGE ON THE PHARMACOKINETICS AND PHARMACODYNAMICS OF CAPLACIZUMAB
Authors: L. Sargentini, E. Hansson, M. Bergstrand, F. Callewaert, R. Sousa
Journal: HemaSphere (2019)

Background: During clinical trials in patients with acquired thrombotic thrombocytopenic purpura, caplacizumab was administered as a 10 mg intravenous (iv) bolus prior to plasma exchange (PE), followed by 10 mg daily subcutaneous (sc) doses during the daily PE period and at least 30 days thereafter. Aims: The potential effect of different time intervals between the first iv bolus and the subsequent PE, and the effect of different PE schedules, have been investigated. Methods: An integrated pharmacokinetic (PK)/pharmacodynamic (PD) model was developed to describe the interaction between caplacizumab and vWF using non‐linear mixed effects modeling and used to simulate the resulting PK and PD for different predetermined scenarios: 1) PE start 3, 5, 11, 23 h post‐caplacizumab 10 mg iv bolus 2) PE schedule: daily and twice per day (bid) at the first day or during 7 days Results: Data from clinical trials indicate complete neutralization of vWF activity for caplacizumab peak plasma concentrations ≥500ng/mL. Simulations suggest that median caplacizumab peak plasma levels would remain above this threshold if the PE starts up to 5 h post‐caplacizumab iv bolus. For longer delays median caplacizumab peak plasma levels can fall below 500ng/mL, and an additional 10 mg sc dose prior to PE can maintain an effective drug exposure. Simulations of the effect of a bid PE for 7 days, suggest that the sc dosing schedule of caplacizumab during the PE period could be adjusted with bid 10 mg caplacizumab sc dosing after each PE treatment during the time of bid PE treatment. Summary/Conclusion: Effective drug levels are expected if PE is started up to 5 h following the first iv dose of caplacizumab. For longer delays, an additional 10 mg sc dose prior to PE can be envisaged. In case of bid PE for 7 days, the sc administration schedule of caplacizumab could be adjusted with bid caplacizumab after each PE treatment.
AB1239 GENDER DIFFERENCE IN PULMONARY ARTERIAL HYPERTENSION, ASSOCIATED WITH CONNECTIVE TISSUE DISEASES
Authors: Alexander Volkov, Natalia Yudkina, Ekaterina Nikolaeva, Evgeny Nasonov
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Pulmonary arterial hypertension (PAH) is a progressive fatal disease with a known gender dimorphism. However, data on gender differences at patients with pulmonary arterial hypertension, associated with connective tissue diseases (PAH-CTD), currently not enough. <h3>Objectives:</h3> Therefore, this study aimed to investigate the role of gender in clinical future, hemodynamic data and survival PAH-CTD. <h3>Methods:</h3> We examined the long-term prognosis of 97 consecutive PAH-CTD patients, mean age 49 years (7 males and 90 females) diagnosed in our Institute from January 2009 to December 2018. The primary outcome was death. We used nonparametric analysis, Cox regression and the Kaplan-Meier method to assess variables obtained at baseline. All patients received PAH-specific therapy according to the current recommendations. <h3>Results:</h3> We found that male patients had differences in diagnosis duration, level of creatinine, uric acid, RAP. We did not reveal differences in age, a functional class, a risk scale, and the majority clinical, tool and hemodynamic indicators. However, there were significant differences in survival. So, in male group survival was 21 [12; 51] months, in comparison in female group 74 [48; 119] months, p&lt;0,02. Thus, the male sex was an independent predictor of poor prognosis (HR 2.92 [95%CI 1.21; 7.03], p = 0.018) of PAH-CTD. <h3>Conclusion:</h3> These results indicate that female PAH-CTD patients have better long-term prognosis than male, despite lack of many distinctions. It needs to be considered at outcome assessment. <h3>Disclosure of Interests:</h3> Alexander Volkov : None declared, Natalia Yudkina: None declared, Ekaterina Nikolaeva: None declared, Evgeny Nasonov Speakers bureau: Pfizer, Inc., MSD, Novartis, AbbVie Inc., Celgen Corporation, Biocad, Janssen, UCB, Inc.
PB1839 SUCCESSFUL PERIOPERATIVE HEMOSTATIC MANAGEMENT FOR SURGERY IN PATIENTS WITH CONGENITAL FACTOR IX DEFICIENCY: A SINGLE CENTER EXPERIENCE
Authors: Y.S. Park
Journal: HemaSphere (2019)

Background: Hemophilia B is an X‐linked recessive bleeding disorder resulting from factor IX (FIX) deficiency. Prevalence of hemophilia B is one in 20,000 live male births, a quarter that of hemophilia A. While coagulation factor replacement is essential in surgical intervention in hemophilia B patients, evidence in support of the perioperative management is more lacking than hemophilia A. Aims: This study provides an updated evaluation of the safety and effectiveness of coagulation FIX concentrates in treating perioperative bleeding. Methods: We reviewed the records of hemophilia B patients without inhibitors who underwent surgery between June 2006 and May 2017 using coagulation FIX concentrates at a single center. The first bolus of [80 IU/kg X 1.2‐1.4] was given 30 min before surgery to achieve a preoperative FIX level of 80 % under the supervision of a multidisciplinary hemophilia team of our institute. Approximately 50% of the initial dose was administered every 12 h and the dosing intervals were increased to 24 h. Results: In total, 109 surgeries (93 orthopedic, 16 other) were conducted in 70 hemophilia B patients. The median age of the patients was 35.5 years (range, 6–78). The median duration of hospitalization was 14.3 days (range, 2–47), and median duration from operation to discharge was 11.5 days (1‐42). Recombinant FIX concentrates were administered in all cases except 2 patients. The major surgical procedures, that were defined as one that required hemostatic support for periods exceeding 5 consecutive days, were 94 cases (89.5%). Median difference between preoperative and postoperative hemoglobin was 2.35 g/dL (range, 0‐7.7). Total 18 cases of patients required packed RBC transfusion after surgery. In most cases, bleeding stopped or was well controlled; however, one patient expired after emergent surgery for intracranial hemorrhage. No thromboembolic event and development of antibody to FIX were observed in any case. Summary/Conclusion: Good control of hemostasis can be achieved using FIX concentrates in hemophilia B patients who are undergoing surgery. Thorough planning is needed before elective surgery and more active and aggressive management may be needed for emergency surgery.
AB1213 PATIENTS’ PERSPECTIVES OF OUTCOMES AFTER TOTAL KNEE AND TOTAL HIP ARTHROPLASTY: A NOMINAL GROUP STUDY
Authors: Susan Goodman, Bella Mehta, Serene Mirza, Mark Figgie, Peter Sculco, Michael Parks, Jasvinder Singh
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Utilization rates of total joint replacements (TJR) are high and rising to treat advanced symptomatic arthritis, but there is little qualitative research to define the most important outcomes from the patient perspective. <h3>Objectives</h3> To assess the most important outcomes of TJR from the patients' perspective using nominal group technique (NGT). <h3>Methods</h3> Recruited patients were ≥18 and had received total hip (THR) or total knee replacements (TKR). Participants completed a questionnaire including demographics and pain and function measures, and answered "What result/results matter the most to a patient undergoing/having a knee or hip replacement?". Outcomes were independently selected, listed in a round robin, and ranked by the group using NGT. <h3>Results</h3> 36 patients participated in 6 nominal groups in January 2019. 42% were men <b>(Table 1</b>). For THR, 94% reported no/mild pain. For TKR, 81% reported no/mild pain pivoting or on stairs, 1 patient reported severe pain. Satisfaction was high, 97% reported very/somewhat satisfied with pain relief. Of 216 total votes, A) pain received 98 votes, B) function 52; C) quality of life 40; D) adverse events 16 votes and E) revision 2 votes, the remainder 8 votes were distributed to post-op concerns including access to rehabilitation or education <b>(Table 2)</b>. <h3>Conclusion</h3> Pain, function, quality of life, and adverse events are the outcomes ranked highest by patients, supporting their inclusion in TJR clinical trials. <h3>Disclosure of Interests</h3> Susan Goodman Grant/research support from: Novartis: research support, Consultant for: Novartis, UCB, Pfizer: consulting, Bella Mehta: None declared, Serene Mirza: None declared, Mark Figgie: None declared, Peter Sculco: None declared, Michael Parks Grant/research support from: Zimmer Biomet, Employee of: Zimmer Biomet, jasvinder singh Shareholder of: Amarin pharmaceuticals and Viking therapeutics, Consultant for: Crealta/Horizon, Fidia, UBM LLC, Medscape, WebMD, the National Institutes of Health and the American College of Rheumatology
FRI0395 SWITCHING RATE OF ANTI-TNF AGENTS IN SPONDYLOARTHRITIS PATIENTS: TREASURE – REAL LIFE DATA
Authors: Umut Kalyoncu, Sedat Kiraz, Abdulsamet Erden, Orhan Küçükşahin, Timuçin Kaşifoğlu, Ediz Dalkılıç, Cemal Bes, Nilüfer Alpay Kanıtez, Hakan Emmungil, Pamir Atagündüz, Belkıs Nihan Coşkun, Burcu Yağız, Süleyman Serdar Koca, Muhammet Çınar, Aşkın Ateş, Servet Akar, Onay Gercik, Duygu Ersözlü, Veli Yazısız, Gezmiş Kimyon, Müge Aydın, Rıdvan Mercan, Burak Öz, Nazife Sule Yasar Bilge, Zeynel Abidin Akar, Omer Karadag, Ayse Bahar Kelesoglu Dincer, Sedat Yilmaz, Ufuk İlgen, Yavuz Pehlivan, Ender Terzioğlu, Levent Kılıç, Şükran Erten, Ali İhsan Ertenli
Journal: Annals of the Rheumatic Diseases (2019)

Background: switching from reference infliximab (RI) to biosimilar infliximab (BI) had no detrimental effects on efficacy and safety compared to continuous RI.However, long-term follow-up data is missing.Objectives: the aim of this study was to evaluate if BI is equivalent to RI to maintain patients with Ankylosing Spondylitis (AS) in clinical remission, in a long-term fashion.Methods: one hundred and nine consecutive unselected AS patients were investigated.All, followed-up at predefined times receiving RI (5mg/kg/8 weeks) and were naïve to other biologics.Patients who were in clinical remission were asked to switch from RI to BI using the same therapeutic dose.Patients switched to BI were compared with a match control group receiving continuous RI.During follow-up the demographic, clinical, laboratory parameters and comorbidities were all recorded for at least 18 months.Disease activity was measured using the Bath Ankylosing Spondylitis activity index (BASDAI), and the Ankylosing Spondylitis disease activity score (ASDAS), using the C-reactive protein.Remission was defined if patients achieved BASDAI <4 and ASDAS <1.3.Results: twenty-one patients were excluded, nine because had no clinical remission and twelve because refused to switch.Thus, 88 were evaluated.From those, 45 switched to BI, while 43 continued receiving RI.There were no differences between groups regarding demographic, clinical and laboratory parameters.All patients were in clinical remission (BASDAI <4 and ASDAS <1.3).During follow-up, five patients from the switched group and three from the maintenance group discontinued the study.Four patients receiving BI presented nocebo effects and were switched back to the RI.Three responded well, while the fourth did not.After 18 months of treatment, all patients in both groups remained in clinical remission.No significant adverse events were noted between groups.Conclusion: BI is equivalent to RI in maintaining AS in clinical remission for at least 18 months.
Millstone: software for multiplex microbial genome analysis and engineering
Authors: Daniel B. Goodman, Gleb Kuznetsov, Marc J. Lajoie, Brian W. Ahern, Michael G. Napolitano, Kevin Y. Chen, Changping Chen, George M. Church
Journal: Genome biology (2017)

Inexpensive DNA sequencing and advances in genome editing have made computational analysis a major rate-limiting step in adaptive laboratory evolution and microbial genome engineering. We describe Millstone, a web-based platform that automates genotype comparison and visualization for projects with up to hundreds of genomic samples. To enable iterative genome engineering, Millstone allows users to design oligonucleotide libraries and create successive versions of reference genomes. Millstone is open source and easily deployable to a cloud platform, local cluster, or desktop, making it a scalable solution for any lab.
Updates in the management of intradural spinal cord tumors: a radiation oncology focus
Authors: Rupesh Kotecha, Minesh P Mehta, Eric L Chang, Paul D Brown, John H Suh, Simon S Lo, Sunit Das, Haider H Samawi, Julia Keith, James Perry, Arjun Sahgal
Journal: Neuro-Oncology (2019)

Primary spinal cord tumors represent a hetereogeneous group of central nervous system malignancies whose management is complex given the relatively uncommon nature of the disease and variety of tumor subtypes, functional neurologic deficits from the tumor, and potential morbidities associated with definitive treatment. Advances in neuroimaging; integration of diagnostic, prognostic, and predictive molecular testing into tumor classification; and developments in neurosurgical techniques have refined the current role of radiotherapy in the multimodal management of patients with primary spinal cord tumors, and corroborated the need for prospective, multidisciplinary discussion and treatment decision making. Radiotherapeutic technological advances have dramatically improved the entire continuum from treatment planning to treatment delivery, and the development of stereotactic radiosurgery and proton radiotherapy provides new radiotherapy options for patients treated in the definitive, adjuvant, or salvage setting. The objective of this comprehensive review is to provide a contemporary overview of the management of primary intradural spinal cord tumors, with a focus on radiotherapy.
Global impact of rotavirus vaccine introduction on rotavirus hospitalisations among children under 5 years of age, 2008–16: findings from the Global Rotavirus Surveillance Network
Authors: Negar Aliabadi, Sébastien Antoni, Jason M Mwenda, Goitom Weldegebriel, Joseph N M Biey, Dah Cheikh, Kamal Fahmy, Nadia Teleb, Hossam Abdelrahman Ashmony, Hinda Ahmed, Danni S Daniels, Dovile Videbaek, Annemarie Wasley, Simarjit Singh, Lucia Helena de Oliveira, Gloria Rey-Benito, N Jennifer Sanwogou, Pushpa Ranjan Wijesinghe, Jayantha B L Liyanage, Batmunkh Nyambat, Varja Grabovac, James D Heffelfinger, Kimberley Fox, Fem Julia Paladin, Tomoka Nakamura, Mary Agócs, Jillian Murray, Thomas Cherian, Catherine Yen, Umesh D Parashar, Fatima Serhan, Jacqueline E Tate, Adam L Cohen
Journal: The Lancet Global Health (2019)

Rotavirus vaccine use in national immunisation programmes has led to declines in hospital admissions for rotavirus gastroenteritis among children; however, the global impact of rotavirus vaccine introduction has not been described using primary data. We describe the impact of rotavirus vaccine introduction on admissions for acute rotavirus gastroenteritis in primarily low-income and middle-income countries, using 9 years of data from the WHO-coordinated Global Rotavirus Surveillance Network (GRSN).