tbuckley/cabot-search huggingface dataset:
Phenotyping of Disease-Initiating CD34+/CD38─ Stem Cells in BCR-ABL1─ MPN Reveals Expression of Multiple Cytokine Receptors and Resistance-Related Antigens
Authors: Daniel Ivanov, Jelena D. Milosevic Feenstra, Gregor Eisenwort, Robert Spörk, Alexandra Keller, Barbara Peter, Michael Willmann, Georg Greiner, Gabriele Stefanzl, Katharina Slavnitsch, Gregor Hoermann, Sybille Hofer, Wolfgang R. Sperr, Heinz Sill, Peter Bettelheim, Klaus Geissler, Elisabeth Koller, Michael Fillitz, Michael Pfeilstocker, Thomas Rülicke, Thamer Sliwa, Felix Keil, Robert Kralovics, Peter Valent
Journal: Blood (2020)
Lysophosphatidic Acid Receptor 4 Is Transiently Expressed during Cardiac Differentiation and Critical for Repair of the Damaged Heart
Authors: Jin-Woo Lee, Choon-Soo Lee, Yong-Rim Ryu, Jaewon Lee, HyunJu Son, Hyun-Jai Cho, Hyo-Soo Kim
Journal: Molecular Therapy (2020)

Efficient differentiation of pluripotent stem cells (PSCs) into cardiac cells is essential for the development of new therapeutic modalities to repair damaged heart tissue. We identified a novel cell surface marker, the G protein-coupled receptor lysophosphatidic acid receptor 4 (LPAR4), specific to cardiac progenitor cells (CPCs) and determined its functional significance and therapeutic potential. During in vitro differentiation of mouse and human PSCs toward cardiac lineage, LPAR4 expression peaked after 3−7 days of differentiation in cardiac progenitors and then declined. In vivo, LPAR4 was specifically expressed in the early stage of embryonal heart development, and as development progressed, LPAR4 expression decreased and was non-specifically distributed. We identified the effective agonist octadecenyl phosphate and a p38 MAPK blocker as the downstream signal blocker. Sequential stimulation and inhibition of LPAR4 using these agents enhanced the in vitro efficiency of cardiac differentiation from mouse and human PSCs. Importantly, in vivo, this sequential stimulation and inhibition of LPAR4 reduced the infarct size and rescued heart dysfunction in mice. In conclusion, LPAR4 is a novel CPC marker transiently expressed only in heart during embryo development. Modulation of LPAR4-positive cells may be a promising strategy for repairing myocardium after myocardial infarction. Efficient differentiation of pluripotent stem cells (PSCs) into cardiac cells is essential for the development of new therapeutic modalities to repair damaged heart tissue. We identified a novel cell surface marker, the G protein-coupled receptor lysophosphatidic acid receptor 4 (LPAR4), specific to cardiac progenitor cells (CPCs) and determined its functional significance and therapeutic potential. During in vitro differentiation of mouse and human PSCs toward cardiac lineage, LPAR4 expression peaked after 3−7 days of differentiation in cardiac progenitors and then declined. In vivo, LPAR4 was specifically expressed in the early stage of embryonal heart development, and as development progressed, LPAR4 expression decreased and was non-specifically distributed. We identified the effective agonist octadecenyl phosphate and a p38 MAPK blocker as the downstream signal blocker. Sequential stimulation and inhibition of LPAR4 using these agents enhanced the in vitro efficiency of cardiac differentiation from mouse and human PSCs. Importantly, in vivo, this sequential stimulation and inhibition of LPAR4 reduced the infarct size and rescued heart dysfunction in mice. In conclusion, LPAR4 is a novel CPC marker transiently expressed only in heart during embryo development. Modulation of LPAR4-positive cells may be a promising strategy for repairing myocardium after myocardial infarction.
Real-World Treatment Patterns and Outcomes of Proteasome Inhibitor (PI: Bortezomib [V], Carfilzomib [K], or Ixazomib [I])-Lenalidomide/Dexamethasone (Rd)-Triplets By Prior Lenalidomide-Exposure in Patients with Relapsed/Refractory Multiple Myeloma (RRMM) Engaged in Routine Care in the United States (US)
Authors: Larysa Sanchez, Dasha Cherepanov, Dorothy Romanus, Aditya Raju, Marlo Blazer, Eileen Farrelly, Dawn Marie Stull, Sikander Ailawadhi
Journal: Blood (2020)
Racial and Ethnic Disparities Have a Significant Impact on the Outcomes of Patients with Myelodysplastic Syndromes: A Population-Based Study
Authors: Suleyman Y Goksu, Jude Khatib, Busra N Bacik Goksu, Rong Wang, Prapti A. Patel, Madhuri Vusirkala, Suzanne Cole, Ahmet Seyhanli, Muhammet Ozer, Robert H. Collins, Stephen Chung, Amer M. Zeidan, Yazan F. Madanat
Journal: Blood (2020)
Long-Term Efficacy of First-Line Ibrutinib Treatment for Chronic Lymphocytic Leukemia (CLL) With 4 Years of Follow-Up in Patients With <i>TP53</i> Aberrations (del(17p) or <i>TP53</i> Mutation): A Pooled Analysis From 4 Clinical Trials
Authors: John N. Allan, Tait Shanafelt, Adrian Wiestner, Carol Moreno, Susan M. O'Brien, Esteban Braggio, Emily Liu, James P. Dean, Dominic Lai, Inhye E. Ahn
Journal: Blood (2020)
Elective Care and Health Services Research in the COVID-19 Era
Authors: Elizabeth A. Jacobs, Olugbenga Ogedegbe, Stephan D. Fihn
Journal: JAMA Network Open (2020)

Christopher M. Whaley, PhD; Megan F. Pera, MS; Jonathan Cantor, PhD; Jennie Chang, BA; Julia Velasco, BS; Heather K. Hagg, PhD; Neeraj Sood, PhD; Dena M. Bravata, MD, MS
AIDS might have been tackled differently if it had presented as a disease of women
Authors: L. H Breimer
Journal: BMJ (1996)

More paediatric renal donors should be used for adult recipients EDITOR,-Appropriately, the shortage of organs for renal transplantation commands increasing space in journals.'One aspect, however, does not seem to have been adequately covered and offers the potential of increasing the number of donors for renal transplantation.Paediatric donors are used for children unless they are very small, in which case they are often rejected, particularly in Britain.The United Kingdom Transplant Support Service Authority reports that up to April this year 480 donors were offered for kidney donation but only 306 were used; this indicates underuse in 174 cases (P Pocock, personal communication).This figure is probably below the true potential number of donors because the United Network for Organ Sharing in the United States reports that about 7% of the total cadaver donors recov- ered every year are children under 5V2 Roughly one third of these are below the age of 1.In addi- tion, potential paediatric donors are probably not offered in Britain because of their perceived lack of suitability.The main reason for this underuse is the increase in technical complications resulting in vascular thrombosis and ureteric necrosis.In addition, it has generally been held that paediatric kidneys will be damaged by adult blood pressure.3There is now increasing evidence that small kidneys from donors down to the age of 6 weeks can be successfully transplanted into adult recipients, provided they are grafted as a block with the aorta and vena cava.4The kidneys sub- sequently grow normally and tolerate adult blood pressure.Most of this experience comes from the United States, Germany, and Spain, and only six recipients have received these grafts in Britain.This includes two patients from our centre, who now have creatinine concentrations of 120 and 85 jmol/l.Use of these donors should be promoted to bring Britain into line with the United States.However, because of the specific problems, which seem to be most acute at the start of such programmes, such use should be restricted to a few centres.This would allow the most efficacious techniques and immunosuppressive regimens to be arrived at.
Risk of cognitive impairment in children after maternal exposure to the 1998 Yangtze River flood during pregnancy: analysis of data from China's second National Sample Survey on Disability
Authors: Chao Guo, Gong Chen, Ping He, Lei Zhang, Xiaoying Zheng
Journal: The Lancet Planetary Health (2020)

More research is needed to understand the long-term effects of prenatal exposure to adverse events, such as floods and other natural disasters, on cognitive outcomes in childhood. We aimed to explore the risk of cognitive impairment in children following maternal exposure to the 1998 Yangtze River flood in China during pregnancy.For this study we obtained and analysed individual-level data from the second China National Sample Survey on Disability (CNSSD), which was done in 2006. We defined the flood period as June-August, 1998. The analytical sample comprised children from four birth cohorts, defined according to their month of birth: the post-partum exposed cohort (children born between June, 1997, and May, 1998), the prenatal exposed cohort (children born between June, 1998, and May, 1999), the preconception exposed cohort (children born between June 1999, and May, 2000), and the unexposed cohort (children born between June, 2000, and May, 2001). In the CNSSD, cognitive impairment was assessed and diagnosed by validated screening tools and procedures. Difference-in-difference models were used to examine variations in the effects of maternal flood exposure on cognitive impairment in childhood across the different birth cohorts and regions.108 175 children born between June, 1997, and May, 2001, and aged 4-8 years at the time of the survey, were included in our analysis. 1131 children had a cognitive impairment; the prevalence of cognitive impairment was 1·05% (95% CI 0·99-1·11). Maternal exposure to flood during pregnancy increased the risk of cognitive impairment among children (adjusted odds ratio [OR] 2·18 [95% CI 1·54-3·08]; p<0·0001). No significant sex-specific differences were observed, and the risk of cognitive impairment was especially high when maternal flood exposure occurred during the first trimester of pregnancy (adjusted OR 5·05 [95% CI 3·88-6·58]; p<0·0001). The risk of cognitive impairment also increased with longer durations of maternal flood exposure and with increasing severity of flooding; the risk was highest in the prenatal exposed cohort with 3 months of flood exposure in the most severely affected area (adjusted OR 5·56 [95% CI 1·58-19·54]; p=0·007).Prenatal flood exposure had a long-term negative effect on cognitive development of children. Greater maternal support and public health interventions during pregnancy and early life after a natural disaster are warranted to facilitate healthy cognitive development in later life.National Social Science Foundation of China.
Tumor Lysis Syndrome Risk in Outpatient Versus Inpatient Administration of Venetoclax and Hypomethlators for Acute Myeloid Leukemia
Authors: Aryeh Pelcovits, Brianna Bakow, Jozal Waroich, Pamela C Egan, Rabin Niroula, Adam J Olszewski, John L Reagan
Journal: Blood (2020)
Cardiac Involvement After Recovering From COVID-19
Authors: Lukasz A. Malek
Journal: JAMA Cardiology (2020)

Valentina O. Puntmann, MD, PhD; M. Ludovica Carerj, MD; Imke Wieters, MD; Masia Fahim; Christophe Arendt, MD; Jedrzej Hoffmann, MD; Anastasia Shchendrygina, MD, PhD; Felicitas Escher, MD; Mariuca Vasa-Nicotera, MD; Andreas M. Zeiher, MD; Maria Vehreschild, MD; Eike Nagel, MD
Incidence and Causes of Prolonged Hematologic Toxicity after Chimeric Antigen Receptor T Cell Therapy: A City of Hope (COH) Experience
Authors: Geoffrey Shouse, Thai Cao, Jianying Zhang, Matthew Mei, Alex F. Herrera, Liana Nikolaenko, Jasmine Zain, Tanya Siddiqi, Leslie L. Popplewell, Stephen J. Forman, Lihua E Budde
Journal: Blood (2020)
The contribution of HIV point-of-care tests in early HIV diagnosis: community-based HIV testing monitoring in Catalonia, 1995 to 2018
Authors: Laura Fernàndez-López, Juliana Reyes-Urueña, Anna Conway, Jorge Saz, Adriana Morales, Jaime Quezadas, Jordi Baroja, Anna Rafel, Ander Pazos, Anna Avellaneda, Mercè Meroño, Lorena Andreo, Lluís Romero, Anna Lara, Araceli Otón, Benet Rifà, Rosa Mansilla, Joan Colom, Jordi Casabona
Journal: Eurosurveillance (2020)

BackgroundCommunity-based HIV testing services combined with the use of point-of-care tests (POCT) have the potential to improve early diagnosis through increasing availability, accessibility and uptake of HIV testing.AimTo describe community-based HIV testing activity in Catalonia, Spain, from 1995 to 2018, and to evaluate the impact of HIV POCT on the HIV continuum of care.MethodsA community-based network of voluntary counselling and testing services in Catalonia, Spain has been collecting systematic data on activity, process and results since 1995. A descriptive analysis was performed on pooled data, describing the data in terms of people tested and reactive screening test results.ResultsBetween 1995 and 2018, 125,876 HIV tests were performed (2.1% reactive). Since the introduction of HIV POCT in 2007, a large increase in the number of tests performed was observed, reaching 14,537 tests alone in 2018 (1.3% reactive). Men who have sex with men (MSM), as a proportion of all people tested, has increased greatly over time reaching 74.7% in 2018. The highest percentage of reactive tests was found in people who inject drugs followed by MSM. The contribution of community-based HIV testing to the overall total notified cases in the Catalonia HIV registry has gradually increased, reaching 37.9% in 2018, and 70% of all MSM cases. In 2018, the percentage of individuals with a reactive screening test who were linked to care was 89.0%.ConclusionOur study reinforces the important role that community-based HIV POCT has on the diagnosis of HIV in key populations.
Myocardial Gene Expression Signatures in Human Heart Failure With Preserved Ejection Fraction
Authors: Virginia S. Hahn, Hildur Knutsdottir, Xin Luo, Kenneth Bedi, Kenneth B. Margulies, Saptarsi M. Haldar, Marina Stolina, Jun Yin, Aarif Y. Khakoo, Joban Vaishnav, Joel S. Bader, David A. Kass, Kavita Sharma
Journal: Circulation (2020)

Background: Heart failure (HF) with preserved ejection fraction (HFpEF) constitutes half of all HF but lacks effective therapy. Understanding of its myocardial biology remains limited because of a paucity of heart tissue molecular analysis. Methods: We performed RNA sequencing on right ventricular septal endomyocardial biopsies prospectively obtained from patients meeting consensus criteria for HFpEF (n=41) contrasted with right ventricular septal tissue from patients with HF with reduced ejection fraction (HFrEF, n=30) and donor controls (n=24). Principal component analysis and hierarchical clustering tested for transcriptomic distinctiveness between groups, effect of comorbidities, and differential gene expression with pathway enrichment contrasted HF groups and donor controls. Within HFpEF, non–negative matrix factorization and weighted gene coexpression analysis identified molecular subgroups, and the resulting clusters were correlated with hemodynamic and clinical data. Results: Patients with HFpEF were more often women (59%), African American (68%), obese (median body mass index 41), and hypertensive (98%), with clinical HF characterized by 65% New York Heart Association Class III or IV, nearly all on a loop diuretic, and 70% with a HF hospitalization in the previous year. Principal component analysis separated HFpEF from HFrEF and donor controls with minimal overlap, and this persisted after adjusting for primary comorbidities: body mass index, sex, age, diabetes, and renal function. Hierarchical clustering confirmed group separation. Nearly half the significantly altered genes in HFpEF versus donor controls (1882 up, 2593 down) changed in the same direction in HFrEF; however, 5745 genes were uniquely altered between HF groups. Compared with controls, uniquely upregulated genes in HFpEF were enriched in mitochondrial adenosine triphosphate synthesis/electron transport, pathways downregulated in HFrEF. HFpEF-specific downregulated genes engaged endoplasmic reticulum stress, autophagy, and angiogenesis. Body mass index differences largely accounted for HFpEF upregulated genes, whereas neither this nor broader comorbidity adjustment altered pathways enriched in downregulated genes. Non–negative matrix factorization identified 3 HFpEF transcriptomic subgroups with distinctive pathways and clinical correlates, including a group closest to HFrEF with higher mortality, and a mostly female group with smaller hearts and proinflammatory signaling. These groupings remained after sex adjustment. Weighted gene coexpression analysis yielded analogous gene clusters and clinical groupings. Conclusions: HFpEF exhibits distinctive broad transcriptomic signatures and molecular subgroupings with particular clinical features and outcomes. The data reveal new signaling targets to consider for precision therapeutics.
SP0015 The detection of microbial dna in the joint
Authors: J Gaston
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> Lyme disease, Whipple's disease and reactive arthritis are clear examples of forms of arthritis caused by bacterial infection, but the idea that infection might be involved in diseases like rheumatoid arthritis (RA) has a long history. Although joints in all of these conditions are usually "sterile" (i.e. no bacteria can be cultured from the joint), molecular methods of detection have demonstrated the presence of bacterial nucleic acids. The fact that ribosomal RNA (rRNA) genes from all bacteria have highly conserved sequences interspersed with species-specific sequences makes it possible to use polymerase chain reaction (PCR) techniques to detect any bacteria present in synovium and synovial fluid by amplification using "universal" primers which identify the conserved sequences, and then sequencing the products to determine the bacteria from which they arises. When this technique has been applied to synovium from RA patients, multiple species of bacteria have been identified, both by PCR (showing the presence of bacterial DNA) and RT-PCR; the latter implies the presence of live bacteria since bacterial rRNA is unstable, unlike DNA. These results cannot be accounted for by artefactual contamination, and suggest that resident bacteria such as gut and skin-derived organisms can find their way to the joint, most probably within phagocytes which have previously engulfed them and then been recruited to the inflamed joint. The same results were obtained when synovial fluid from reactive arthritis patients was tested. However in reactive arthritis, by using species-specific primers, it was also possible to detect the arthritis-triggering organism (Chlamydia, Yersinia) in a proportion of cases. The specific organism was not detected simply by sequencing the product obtained using universal primers, which suggests that the specific organism is a minor component of the total bacterial colonisation of the joint. Bacterial products such as DNA, LPS and protein antigens may contribute to joint inflammation both as targets of specific immune responses and as adjuvants. Nevertheless, reactive arthritis and RA differ in that the former usually resolves spontaneously; thus the presence of bacteria is not sufficient to cause chronic inflammation and other mechanisms which engender chronicity must be important in RA. Against a background of commensal bacteria it may be difficult to detect specific disease-associated organisms in RA, since specific organisms are in a minority in the joint even in diseases such as reactive arthritis in which they are clearly important in pathogenesis.
Comparison of Gilteritinib and Salvage Chemotherapy in <i>FLT3</i>-Mutated Acute Myeloid Leukemia on the Number Needed to Treat for Various Clinical Outcomes: A Secondary Analysis of the Admiral Trial
Authors: Bhavik J. Pandya, Cynthia Z. Qi, Hongbo Yang, Andy Garnham, Manasee V. Shah, Amer M. Zeidan
Journal: Blood (2020)
Phase I Clinical Trial of Combination Propranolol and Pembrolizumab in Locally Advanced and Metastatic Melanoma: Safety, Tolerability, and Preliminary Evidence of Antitumor Activity
Authors: Shipra Gandhi, Manu R. Pandey, Kristopher Attwood, Wenyan Ji, Agnieszka K. Witkiewicz, Erik S. Knudsen, Cheryl Allen, Joseph D. Tario, Paul K. Wallace, Carlos D. Cedeno, Maria Levis, Suzanne Stack, Pauline Funchain, Joseph J. Drabick, Mark J. Bucsek, Igor Puzanov, Hemn Mohammadpour, Elizabeth A. Repasky, Marc S. Ernstoff
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Increased β-adrenergic receptor (β-AR) signaling has been shown to promote the creation of an immunosuppressive tumor microenvironment (TME). Preclinical studies have shown that abrogation of this signaling pathway, particularly β2-AR, provides a more favorable TME that enhances the activity of anti–PD-1 checkpoint inhibitors. We hypothesize that blocking stress-related immunosuppressive pathways would improve tumor response to immune checkpoint inhibitors in patients. Here, we report the results of dose escalation of a nonselective β-blocker (propranolol) with pembrolizumab in patients with metastatic melanoma. Patients and Methods: A 3 + 3 dose escalation study for propranolol twice a day with pembrolizumab (200 mg every 3 weeks) was completed. The primary objective was to determine the recommended phase II dose (RP2D). Additional objectives included safety, antitumor activity, and biomarker analyses. Responders were defined as patients with complete or partial response per immune-modified RECIST at 6 months. Results: Nine patients with metastatic melanoma received increasing doses of propranolol in cohorts of 10, 20, and 30 mg twice a day. No dose-limiting toxicities were observed. Most common treatment-related adverse events (TRAEs) were rash, fatigue, and vitiligo, observed in 44% patients. One patient developed two grade ≥3 TRAEs. Objective response rate was 78%. While no significant changes in treatment-associated biomarkers were observed, an increase in IFNγ and a decrease in IL6 was noted in responders. Conclusions: Combination of propranolol with pembrolizumab in treatment-naïve metastatic melanoma is safe and shows very promising activity. Propranolol 30 mg twice a day was selected as RP2D in addition to pembrolizumab based on safety, tolerability, and preliminary antitumor activity.
循環器病の診断と治療に関するガイドライン(2006-2007年度合同研究班報告)心房細動治療(薬物)ガイドライン(2008年改訂版)
Authors: 年度合同研究班報告, 義房 相澤, 博次 新, 博 井上, 謙 奥村, 史郎 鎌倉, 浩一郎 熊谷, 之宏 是恒, 秀雄 三田村, 正弘 矢坂, 武志 山下, 透 大江, 逸雄 児玉, 一昌 比江嶋, 捷介 矢野
Journal: Circulation (2008)
Integrative Transcriptome and Quantitative Proteome Analyses Identify METTL3 As a Key Regulator for Aberrant RNA Processing in Chronic Lymphocytic Leukemia
Authors: Yiming Wu, Meiling Jin, Kevyn Hart, Aijun Liao, Stacey M. Fernandes, Tinisha McDonald, Lucy Brown, Daniel Roeth, Markus Kalkum, Raju Pillai, Jianjun Chen, Jennifer R Brown, Steven T. Rosen, Tanya Siddiqi, Lili Wang
Journal: Blood (2020)
Efficacy, Safety, and Pharmacokinetics (PK) of Azacitidine (AZA) in Children and Young Adults with Acute Myeloid Leukemia (AML) in the Phase 2 AZA-AML-004 Trial
Authors: Dirk Reinhardt, Henrik Hasle, Karsten Nysom, André Baruchel, Franco Locatelli, Bouchra Benettaib, Noha Biserna, Meera Patturajan, Mathew Simcock, Allison Gaudy, C. Michel Zwaan
Journal: Blood (2020)
Dosing, Patient Satisfaction and Other Patient-Reported Outcomes after Switching to Rurioctocog Alfa Pegol in Athn 2: A Longitudinal, Observational Study of Previously Treated Hemophilia Patients Switching Coagulation Replacement Factor Products
Authors: Janna M. Journeycake, Michael Recht, Christine Guelcher, Ellis J. Neufeld, Margaret V. Ragni, Robert F. Sidonio, Cliff Takemoto, Michael D Tarantino, Dunlei Cheng, Susan U. Lattimore, Jorge Caicedo, Michael Denne
Journal: Blood (2020)
Engineered Memory-like NK Cars Targeting a Neoepitope Derived from Intracellular NPM1c Exhibit Potent Activity and Specificity Against Acute Myeloid Leukemia
Authors: Han Dong, Guozhu Xie, Yong Liang, James Dongjoo Ham, Juliana Vergara, Jianzhu Chen, Jerome Ritz, Rizwan Romee
Journal: Blood (2020)
Comprehensive Profiling of the Epitranscriptomic N6-Methyladenosine RNA Methylation in Chronic Lymphocytic Leukemia
Authors: Ya Zhang, Xinting Hu, Hongzhi Xu, Ying Li, Lingyan Zhang, Lili Feng, Xiangxiang Zhou, Xiaosheng Fang, Yujie Jiang, Mei Ding, Jianhong Wang, Xin Wang
Journal: Blood (2020)
Exploration of Bacterial Bottlenecks and Streptococcus pneumoniae Pathogenesis by CRISPRi-Seq
Authors: Xue Liu, Jacqueline M. Kimmey, Laura Matarazzo, Vincent de Bakker, Laurye Van Maele, Jean-Claude Sirard, Victor Nizet, Jan-Willem Veening
Journal: Cell Host & Microbe (2020)