tbuckley/cabot-search huggingface dataset:
Human CD34+ Myeloid Leukemic Progenitor Cells Are Susceptible to Lysis by Minor Histocompatibility Antigen LRH-1-Specific Cytotoxic T Lymphocytes.
Authors: Harry Dolstra, Ingrid Overes, Inge Jedema, Annemieke Vos, Agnes van Horssen-Zoetbrood, Wieger Norde, Robbert van der Voort, J.H. Frederik Falkenburg, Anton V. Schattenberg, T.M. de Witte
Journal: Blood (2006)
Novel P38 MAP Kinase Inhibitor and Anti-P38 RNA Interference as Potential Therapeutic Approaches in Myelodysplastic Syndromes.
Authors: Mani Mohindru, Perry Pahanish, Efstratios Katsoulidis, Robert Collins, Thomas Rogers, Tony Navas, Linda Higgins, Leonidas Platanias, Amit Verma
Journal: Blood (2004)
<i>In vivo</i> liposomal delivery of PPARα/γ dual agonist tesaglitazar in a model of obesity enriches macrophage targeting and limits liver and kidney drug effects
Authors: Victoria Osinski, Dustin K. Bauknight, Siva Sai Krishna Dasa, Matthew J. Harms, Tobias Kroon, Melissa A. Marshall, James C. Garmey, Anh T. Nguyen, Julia Hartman, Aditi Upadhye, Prasad Srikakulapu, Andrea Zhou, Gavin O'Mahony, Alexander L. Klibanov, Kimberly A. Kelly, Jeremie Boucher, Coleen A. McNamara
Journal: Theranostics (2019)

Macrophages are important regulators of obesity-associated inflammation and PPARα and -γ agonism in macrophages has anti-inflammatory effects.In this study, we tested the efficacy with which liposomal delivery could target the PPARα/γ dual agonist tesaglitazar to macrophages while reducing drug action in common sites of drug toxicity: the liver and kidney, and whether tesaglitazar had anti-inflammatory effects in an in vivo model of obesity-associated dysmetabolism.Methods: Male leptin-deficient (ob/ob) mice were administered tesaglitazar or vehicle for one week in a standard oral formulation or encapsulated in liposomes.Following the end of treatment, circulating metabolic parameters were measured and pro-inflammatory adipose tissue macrophage populations were quantified by flow cytometry.Cellular uptake of liposomes in tissues was assessed using immunofluorescence and a broad panel of cell subset markers by flow cytometry.Finally, PPARα/γ gene target expression levels in the liver, kidney, and sorted macrophages were quantified to determine levels of drug targeting to and drug action in these tissues and cells.Results: Administration of a standard oral formulation of tesaglitazar effectively treated symptoms of obesity-associated dysmetabolism and reduced the number of pro-inflammatory adipose tissue macrophages.Macrophages are the major cell type that took up liposomes with many other immune and stromal cell types taking up liposomes to a lesser extent.Liposome delivery of tesaglitazar did not have effects on inflammatory macrophages nor did it improve metabolic parameters to the extent of a standard oral formulation.Liposomal delivery did, however, attenuate effects on liver weight and liver and kidney expression of PPARα and -γ gene targets compared to oral delivery.Conclusions: These findings reveal for the first time that tesaglitazar has anti-inflammatory effects on adipose tissue macrophage populations in vivo.These data also suggest that while nanoparticle delivery reduced off-target effects, yet the lack of tesaglitazar actions in non-targeted cells such (as hepatocytes and adipocytes) and the uptake of drug-loaded liposomes in many other cell types, albeit to a lesser extent, may have impacted overall therapeutic efficacy.This fulsome analysis of cellular uptake of tesaglitazar-loaded liposomes provides important lessons for future studies of liposome drug delivery.
Childhood Acute Lymphoblastic Leukemia: High Genomic Stability from Initial Diagnosis to Early Relapse.
Authors: Barbara Meissner, Cornelia Eckert, Anja Moericke, Arend von Stackelberg, Renate Kirschner-Schwabe, Gunnar Cario, André Schrauder, Martin Zimmermann, Karl Welte, Martin Schrappe, Martin Stanulla
Journal: Blood (2008)
Activated B-Cell (ABC) Profile Does Not Have An Inferior Outcome Compared to Germinal Center B-Cell (GCB) Profile Determined by Immunohistochemistry Tissue Microarray in Poor Prognosis Diffuse Large B-Cell Lymphoma (DLBCL) Treated with Rituximab and Dose- Dense and High-Dose Chemotherapy (HDC) Plus Autologous Stem Cell Transplantation (ASCT).
Authors: Annalisa Chiappella, Domenico Novero, Alessandra Tucci, Maria Giuseppina Cabras, Anna Marina Liberati, Giovannino Ciccone, Flavia Salvi, Emanuele Angelucci, Chiara Bottelli, Barbara Botto, Fabio Facchetti, Lorenzo Falchi, Chiara Frairia, Alessandro Levis, Lorella Orsucci, Tommasina Perrone, Enrico Maria Pogliani, Delia Rota-Scalabrini, Anna Tonso, Giorgio Inghirami, Umberto Vitolo
Journal: Blood (2008)
Increased Global Dispersion of Ventricular Repolarization during Left Ventricular Epicardial Pacing: In Vivo Evaluation by Monophasic Action Potential Mapping in Swine
Authors: Yunlong Xia, Ole Kongstad Rasmussen, Pyotr Platonov, Bertil Olsson, Shiwen Yuan, Yanzong Yang
Journal: Circulation (2010)
Stratification by DNA Damage-Induced Apoptotic and Transcriptional Responses Provides Insight into the Molecular Mechanisms Underlying Blast Clearance Rates in Paediatric B-Precursor ALL.
Authors: Eliot Marston, Victoria Weston, Belinda Austen, Michael Wakelam, Sarah Lawson, Phil Darbyshire, Jenny Jesson, Paul Moss, Tatjana Stankovic
Journal: Blood (2006)
Prevention of Human Interferon-alpha-Induced Thrombocytopenia by a Non-Peptidyl Human Thrombopoietin Receptor Activator, NIP-004.
Authors: Akiko Yamane, Takanori Nakamura, Mamoru Ito, Yasuyuki Ohnishi, Yasuo Ikeda, Yoshitaka Miyakawa
Journal: Blood (2006)
A Pilot Trial of Campath-1H and Dose-Adjusted EPOCH in CD52-Expressing Aggressive T-Cell Malignancies.
Authors: John E. Janik, Kieron Dunleavy, Stefania Pittaluga, Elaine S. Jaffe, Nicole Grant, Margaret Shovlin, Maryalice Stetler-Stevenson, Wyndham H. Wilson
Journal: Blood (2005)
Hematologic Improvement (HI) by TLK199 (Telintra™), a Novel Glutathione Analog, in Myelodysplastic Syndrome: Phase 2 Study Results.
Authors: Azra Raza, Natalie Callander, Leonel Ochoa, Lawrence Piro, Peter Emanuel, Susan Guba, Gabriel Shapiro, Stephanie Williams, Howard Burris, Stefan Faderl, Zeev Estrov, Peter Curtain, Richard Larson, Shelby Young, Gail L. Brown
Journal: Blood (2005)
979 IMPAIRED PRODUCTION OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS g BY LIVER AND ADIPOSE TISSUE IN ALCOHOLIC LIVER DISEASE
Authors: S. Naveau, N. Barriova, L. Bouchet-Delbos, M. Njiké-Nakseu, A. Balian, S. Maitre, S. Prévot, C. Vons, I. Dagher, H. Agostini, D. Franco, D. Emilie, A.-M. Cassard-Doulcier, G. Perlemuter
Journal: Journal of Hepatology (2009)
Abstract 17026: Effects of Supervised Exercise Therapy on Free-Living Physical Activity Among Patients With Symptomatic Peripheral Artery Disease
Authors: Erica Schorr, Mary Whipple, Diane Treat-Jacobson
Journal: Circulation (2018)

Introduction: Evidence supporting the effects of supervised exercise therapy (SET) on alleviating symptoms and improving walking ability for patients with symptomatic peripheral artery disease (PAD) is robust and well recognized. However, little is known about the impact of SET on free-living physical activity (PA). The aim of this study was to examine the relationship between participation in SET and changes in free-living PA among individuals in the the EX ercise Training to Reduce Claudication: Arm ER gometry versus T readmill Walking ( EXERT ) trial. Methods: In this randomized, controlled trial, 104 participants (mean age 68±9; 29% female) were allocated to receive treadmill (TM) exercise (n=41), upper body ergometry (UBE) exercise (n=42), or usual-care (UC) (n=21) for 12 weeks. Exercise participants attended SET three times per week; UC participants met with study staff weekly. PA was measured over 7 days via waist-worn ActiGraph accelerometers at baseline, 6, and 12 weeks. Steps per day was the primary outcome. Secondary outcomes were proportion of time in light and moderate to vigorous physical activity (MVPA), and sedentary time. PA was controlled for in TM participants by using SET logs. Results were analyzed using descriptive statistics, two-sample t-tests, and analysis of variance. Results: Regardless of randomization, average daily steps were low at baseline and 6 weeks (4,013 steps, p =.72; and 3,911 steps, p =.84, respectively), and slightly higher at 12 weeks (4,307 steps; p =.93). Although not statistically significant but perhaps clinically relevant, UBE participants exhibited greater increases in MVPA over 12 weeks (0.9% to 1.3%; F =.48, p =.62) compared to TM (1.2% to 1.3%; F =.35, p =.71) and UC (1.3% to 1.5%, F =.03, p =.97); similarly all participants exhibited reductions in sedentary time and increases in free-living PA between baseline and 12 weeks. Conclusions: These data suggest individuals with PAD attending SET replace sedentary time with light or moderate intensity PA regardless of exercise modality. Despite study participants meeting the recommended daily steps for adults with chronic conditions (3,500-5,500 steps), it is suspected that they did not reach the daily goal of 30 minutes of enhanced PA to reduce health risks. Future research should incorporate activity tracking devices that can provide feedback on PA as an approach to meet daily PA goals. Activity tracking devices used in conjunction with SET may further improve walking distance, symptom management, and quality of life among patients with symptomatic PAD.
Acute Myeloid Leukemia (AML) in a 3D Bone Marrow Niche Showed High Performance for in Vitro and In Vivo Drug Screenings
Authors: Giulia Borella, Ambra Da Ros, Elena Porcù, Claudia Tregnago, Maddalena Benetton, Valeria Bisio, Elisabetta Campodoni, Silvia Panseri, Monica Sandri, Monica Montesi, Stefano Cairo, Franco Locatelli, Martina Pigazzi
Journal: Blood (2019)
T Cell Immunotherapy for Adenoviral Infections of Stem Cell Transplant Recipients.
Authors: Ann M. Leen, Gary D. Myers, Heidi Weiss, Adrian P. Gee, Kathryn S. Leung, Robert A. Krance, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop, Catherine M. Bollard
Journal: Blood (2006)
<i>Vital Signs:</i> Status of Human Immunodeficiency Virus Testing, Viral Suppression, and HIV Preexposure Prophylaxis — United States, 2013–2018
Authors: Norma S. Harris, Anna Satcher Johnson, Ya-Lin A. Huang, Dayle Kern, Paul Fulton, Dawn K. Smith, Linda A. Valleroy, H. Irene Hall
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Approximately 38,000 new human immunodeficiency virus (HIV) infections occur in the United States each year; these infections can be prevented. A proposed national initiative, Ending the HIV Epidemic: A Plan for America, incorporates three strategies (diagnose, treat, and prevent HIV infection) and seeks to leverage testing, treatment, and preexposure prophylaxis (PrEP) to reduce new HIV infections in the United States by at least 90% by 2030. Targets to reach this goal include that at least 95% of persons with HIV receive a diagnosis, 95% of persons with diagnosed HIV infection have a suppressed viral load, and 50% of those at increased risk for acquiring HIV are prescribed PrEP. Using surveillance, pharmacy, and other data, CDC determined the current status of these three initiative strategies.CDC analyzed HIV surveillance data to estimate annual number of new HIV infections (2013-2017); estimate the percentage of infections that were diagnosed (2017); and determine the percentage of persons with diagnosed HIV infection with viral load suppression (2017). CDC analyzed surveillance, pharmacy, and other data to estimate PrEP coverage, reported as a percentage and calculated as the number of persons who were prescribed PrEP divided by the estimated number of persons with indications for PrEP.The number of new HIV infections remained stable from 2013 (38,500) to 2017 (37,500) (p = 0.448). In 2017, an estimated 85.8% of infections were diagnosed. Among 854,206 persons with diagnosed HIV infection in 42 jurisdictions with complete reporting of laboratory data, 62.7% had a suppressed viral load. Among an estimated 1.2 million persons with indications for use of PrEP, 18.1% had been prescribed PrEP in 2018.Accelerated efforts to diagnose, treat, and prevent HIV infection are needed to achieve the U.S. goal of at least 90% reduction in the number of new HIV infections by 2030.
Impact of stress on epidermal barrier function
Authors: M. Maarouf, C.L. Maarouf, G. Yosipovitch, V.Y. Shi
Journal: British Journal of Dermatology (2019)

The skin is made up of three layers. They are the epidermis, dermis and subcutaneous fat. The epidermis is the outermost layer which gives your skin its colour, regulates water loss through the skin and protects the body from bacteria and substances that irritate the skin. Plenty of research shows that stress that comes from crowding, isolation, cigarette smoke, lack of sleep, pain and marital strain can cause this layer to lose its function in both the short‐term and long‐term. This study aimed to review the relationship between stress and the loss of function of the epidermis. The results of 21 studies that looked into this relationship were analysed. They were all in English language and ranged from small to large‐scale studies. The stimulation of stress hormone release comes from a circuit in the brain. This study found that emotional stressors boost this circuit therefore increasing the amount of stress hormone released into the blood. This reduces production of the components that make up the epidermal layer, which leads to greater water loss. In conclusion, this review of 21 studies showed that there were negative effects of emotional stressors on the epidermal barrier function. It is recommended that future studies look into more real‐life stressors to further investigate the effect on skin. It also advises researching practical stress‐relieving therapies that can help minimise and restore the epidermal function, particularly in high‐risk people.
Outcomes of invasive fungal infections in hematopoietic stem cell transplant patients.
Authors: Shagufta Shaheen, Shivanck Upadhyay, Creticus Petrov Marak, Gagan Kumar, Achuta Kumar Guddati
Journal: Journal of Clinical Oncology (2013)

e18008 Background: Invasive fungal infections are associated with higher mortality in hematopoietic stem cell transplant (HSCT) recipients despite the use of broad spectrum antifungal agents. With the increase in the number of patients undergoing HSCT and a newer array of immunosuppressants, it is necessary to examine the incidence and outcomes of fungal infection in this population. Methods: We used Nationwide Inpatient Sample from years 2000 to 2008 to examine the trends and outcomes of fungal infections in patients admitted for HSCT. We used ICD-9-CM codes to identify those with HSCT. Similarly we identified invasive fungal infection using ICD-9-CM codes. The engraftment period and subsequent admissions were examined separately. Outcomes studied were in-hospital mortality and length of hospital stay. Logistic regression analysis was used to identify independent association of fungal infection with mortality. The model was adjusted for demographic and hospital characteristics, Charlson's co-morbidity index and severity of sepsis using number of organ failures. Results: There were 291,182 admissions with HSCT from 2000 to 2008. Of these, 3.4% patients had invasive fungal infections. They were more frequent in allogenic transplant during the engraftment period (4.2%) and in those with graft versus host disease (GVHD) in subsequent admission (7.1%). The unadjusted in-hospital mortality was significantly higher in those with invasive fungal infection (28% vs. 7%, p&lt;0.001). On adjusted analysis, the odds of mortality were highest for those with mucor (OR 4.3;95%CI 2.5-7.5) and aspergillus (OR 3.7; 95%CI 3.1-4.5) infections while the results did not reach significance for candidemia. The length of hospital stay was significantly longer in those with invasive fungal infections (median 19 days vs. 7 days, p&lt;0.001). Conclusions: Fungal infections are common in HSCT recipients - especially in those with allografts and with GVHD. Mortality is high and is mostly associated with aspergillus and mucor. A higher index of suspicion for fungal infections in HSCT patients, strict isolation precautions and increased surveillance for aspergillus and mucor in HSCT patients may help decrease the length of hospital stay and mortality.
Phase 2 Study of Voreloxin (Formerly Known as SNS-595) as Single Agent Therapy for Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia (AML): Preliminary Safety and Clinical Responses (The REVEAL-1 Study).
Authors: Michael Maris, Larry D. Cripe, Robert K Stuart, Farhad Ravandi, Glenn C Michelson, Rachel E. Hawtin, Lyra E Ericson, Craig J. Berman
Journal: Blood (2008)
Trends in HbA1c and LDL Cholesterol in Patients With Type 2 Diabetes Receiving First-Time Treatment in Northern Denmark, 2000–2017: Population-Based Sequential Cross-Sectional Analysis
Authors: Jakob S. Knudsen, Adam Hulman, Pernille F. Rønn, Torsten Lauritzen, Henrik T. Sørensen, Daniel R. Witte, Reimar W. Thomsen
Journal: Diabetes Care (2019)

The evolving evidence base for early diabetes detection and intensive treatment over the recent decades has likely led to a change in the profile of patients initiating type 2 diabetes treatment (1–3). Knowing in which direction the clinical profile of patients with diabetes is moving is important because treatment guidelines rely on the generalizability of clinical trials to contemporary populations (3). Many of these trials were conducted when both the diagnostic criteria and treatment targets were quite different than today (1–3). Population-based data investigating long-term trends in diabetes management and treatment targets are scarce. We aimed to examine 18-year changes in HbA1c and lipid testing and control among people initiating glucose-lowering drugs (GLDs) for type 2 diabetes. We performed one of the first population-based studies, using laboratory and health care databases covering the entire population of Northern Denmark (∼1.8 million people) (4).

We identified people redeeming their first-ever GLD prescription at age ≥30 years. For all 94,175 GLD initiators 2000–2017, we examined pretreatment HbA1c and lipid levels and proportions of testing. For initiators 2000–2016, we assessed 12 months posttreatment lipid-lowering therapy and achievement of glycemic and LDL cholesterol targets. Mean HbA1c and LDL levels and reductions were plotted with 95% CIs.

Median age at first GLD treatment fell from 64 years in 2000 to 61 in 2017; 56% of the study population were men. The proportion of patients with at least one HbA1c test within 12 months after GLD initiation increased from 53% (2000) to 95% (2016) (Fig. 1 A ). Concurrently, mean pretreatment HbA1c decreased from 9.2% (77 mmol/mol) (2000) to 7.9% (63 mmol/mol) (2017), with a nadir occurring in 2011 (7.3% [56 mmol/mol]). For mean posttreatment HbA1c, a smaller decline was seen from 7.1% …
Newly developed myocardial imaging by using single photon emission computed tomography (SPECT).
Authors: Tsunehiko Nishimura, Toshihisa Uehara, Kohei Hayashida, Isao Mitani, Kazuo Haze, Hiroyuki Noda, Hisateru Takano
Journal: Circulation (1990)

Thallium myocardial imaging is a useful technique to evaluate myocardial perfusion and myocardial viability in ischemic heart disease. However, myocardial imaging using single photon emission computed tomography (SPECT) and gamma-emitting radiopharmaceuticals has been recently developed for more precise evaluation of myocardial infarction and ischemia. The present study evaluates animal experiments and the clinical applications of these new myocardial imaging techniques. Areas considered on 1) myocardial necrosis assessed using 111In-antimyosin, 2) myocardial fatty acid metabolism assessed using 123I-beta-methyl-iodophenyl pentadecanoic acid (BMIPP) and 3) myocardial sympathetic neural activity assessed using 123I-metaiodobenzyl guanidine (MIBG). Dual energy SPECT using these new agents and thallium gives precise characterization of the myocardial tissue in the infarcted and ischemic area.
PSMP/MSMP promotes hepatic fibrosis through CCR2 and represents a novel therapeutic target
Authors: Shaoping She, Xiaoning Wu, Danfeng Zheng, Xiaolei Pei, Jing Ma, Yameng Sun, Jialing Zhou, Lin Nong, Changyuan Guo, Ping Lv, Quansheng Song, Can Zheng, Weiwei Liang, Shiyang Huang, Qingqing Li, Zhongtian Liu, Zhanming Song, Yuzi Li, Yu Zhang, Wei Kong, Hong You, Jianzhong Xi, Ying Wang
Journal: Journal of Hepatology (2019)
Redefining the research hospital
Authors: Parashkev Nachev, Daniel Herron, Nick McNally, Geraint Rees, Bryan Williams
Journal: npj Digital Medicine (2019)

All medicine was innovation, once. Yet the contemporary notion of medical research is remarkably narrow. While every clinician is encouraged to be aware of the latest advances, only a few are expected to contribute to them. Anyone may be a patient, yet clinical practice is determined by the minority included in research studies. The aim of medicine is to improve the lives of patients, yet knowledge of disease is arbitrarily prioritised as its primary means. The agents of medicine are clinicians, yet new interventions are mostly created by others, within corporate enterprise deliberately kept at arm’s length. We treat the specific, individual patient in front of us, now, yet most research is addressed to faceless, generic groups, to be realised deep into an ill-defined, hypothetical future.

These constraints arise from assumptions too widely held to be self-evident for anyone seriously to question them. It is commonly assumed, at least by those who secure funding, that clinical research must be separate from service delivery, that limited samples adequately illuminate the wider population, that improving care is conditional on enhancing explicit knowledge of biology, that translation should be devolved to industry, that a patient’s individuality is random deviation from the population mean, and that the tree of innovation bears fruit long after it blooms, if it bears any fruit at all.

Were medical research clearly successful, the fidelity of these assumptions would be merely academic. But measured by what really counts—the creation of real-world interventions—its productivity has been strikingly poor. The number of drugs receiving regulatory approval per billion dollars of investment has been consistently halving every nine years, while the number of medical publications has been doubling with the same periodicity (Fig. ​(Fig.11).1,2 A disinterested auditor would justifiably have shut us down a long time ago.






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Fig. 1

The translational crisis in medicine.
Common log scale plot of the annual number of drugs approved by the FDA per billion US$ spending adjusted for inflation (in red, left y axis) and the annual number of articles indexed on PubMed (in black, right y axis) over the interval 1950–20101 and 20132. Note logarithmic decline of the former despite an equal and opposite rise of the latter, consistently over more than half a century.
Mortality of Patients with Multiple Myeloma after the Introduction of Novel Therapies in the United States
Authors: Moritz Binder, Bharat Nandakumar, Morie A Gertz, Angela Dispenzieri, Martha Q. Lacy, Matthew J. Maurer, Suzanne R. Hayman, Francis K. Buadi, David Dingli, Prashant Kapoor, Ronald S. Go, Yi L. Hwa, Amie Fonder, Miriam A. Hobbs, Yi Lin, Nelson Leung, Taxiarchis Kourelis, Rahma Warsame, Robert A. Kyle, S. Vincent Rajkumar, Shaji K. Kumar
Journal: Blood (2019)