tbuckley/cabot-search huggingface dataset:
Single-cell profiling of human megakaryocyte-erythroid progenitors identifies distinct megakaryocyte and erythroid differentiation pathways
Authors: Bethan Psaila, Nikolaos Barkas, Deena Iskander, Anindita Roy, Stacie Anderson, Neil Ashley, Valentina S. Caputo, Jens Lichtenberg, Sandra Loaiza, David M. Bodine, Anastasios Karadimitris, Adam J. Mead, Irene Roberts
Journal: Genome biology (2016)

Recent advances in single-cell techniques have provided the opportunity to finely dissect cellular heterogeneity within populations previously defined by "bulk" assays and to uncover rare cell types. In human hematopoiesis, megakaryocytes and erythroid cells differentiate from a shared precursor, the megakaryocyte-erythroid progenitor (MEP), which remains poorly defined.To clarify the cellular pathway in erythro-megakaryocyte differentiation, we correlate the surface immunophenotype, transcriptional profile, and differentiation potential of individual MEP cells. Highly purified, single MEP cells were analyzed using index fluorescence-activated cell sorting and parallel targeted transcriptional profiling of the same cells was performed using a specifically designed panel of genes. Differentiation potential was tested in novel, single-cell differentiation assays. Our results demonstrate that immunophenotypic MEP comprise three distinct subpopulations: "Pre-MEP," enriched for erythroid/megakaryocyte progenitors but with residual myeloid differentiation capacity; "E-MEP," strongly biased towards erythroid differentiation; and "MK-MEP," a previously undescribed, rare population of cells that are bipotent but primarily generate megakaryocytic progeny. Therefore, conventionally defined MEP are a mixed population, as a minority give rise to mixed-lineage colonies while the majority of cells are transcriptionally primed to generate exclusively single-lineage output.Our study clarifies the cellular hierarchy in human megakaryocyte/erythroid lineage commitment and highlights the importance of using a combination of single-cell approaches to dissect cellular heterogeneity and identify rare cell types within a population. We present a novel immunophenotyping strategy that enables the prospective identification of specific intermediate progenitor populations in erythro-megakaryopoiesis, allowing for in-depth study of disorders including inherited cytopenias, myeloproliferative disorders, and erythromegakaryocytic leukemias.
Survival and cardiovascular events in men treated with testosterone replacement therapy: an intention-to-treat observational cohort study
Authors: Christopher J D Wallis, Kirk Lo, Yuna Lee, Yonah Krakowsky, Alaina Garbens, Raj Satkunasivam, Sender Herschorn, Ronald T Kodama, Patrick Cheung, Steven A Narod, Robert K Nam
Journal: The Lancet Diabetes & Endocrinology (2016)
Carcinogenic Activity of Analogues of <italic>p</italic>-Dimethylaminoazobenzene. VI. Activity of the Methyl-5′-Quinoline Analogues<xref ref-type="fn" rid="FN2">2</xref>
Authors: Ellis V. Brown, James J. Duffy
Journal: JNCI Journal of the National Cancer Institute (1968)

Seven compounds, which are monomethyl derivatives of the previously tested 5′-(p-dimethylaminophenylazo)quinoline (Q5′), have now been prepared and tested for hepatocarcinogenic action in rats. The one omission is the 4′-methyl, which has not as yet been prepared. The compounds were tested in rats at the 0.03% level and compared with p-dimethylaminoazobenzene (DAB). The order is Q5′, 2′-methylQ5′, 7′-methylQ5′, 8′-methylQ5′⋙ 2-methylQ5′, 3-methylQ5′≫3′-methylQ5′>DAB >6′-methylQ5′. 8′-MethylQ5′ was also tested at 0.01% because of its great toxicity.
The burden of cancer in Japan, the United States, France, Germany, Italy, Spain, Sweden, and the United Kingdom.
Authors: N. Koinuma, N. E. Wilking, B. Jonsson, D. Hogberg
Journal: Journal of Clinical Oncology (2011)

1569 Background: Cancer causes a significant burden to society in terms of human suffering and costs. We analyzed the burden of cancer in Japan, the US, France, Germany, Italy, Spain, Sweden and the UK. Methods: We reviewed the incidence, mortality and costs in Japan and compared with other countries. We also conducted survey of the actual economic burden of cancer patients in Japan. Results: The overall incidence in Japan is lower than other countries. Only in stomach cancer is the incidence in Japan higher. The incidence in Japan has been increasing in the past decades for the major cancers, except stomach cancer. Similar trends are found in the US and the European countries, although some countries show declining long trends in male lung cancer (US, Germany, Italy, Sweden and UK), colorectal cancer (US and Germany), breast cancer (US) and in prostate cancer (US). The overall cancer mortality and that of all the five major cancer types are increasing in Japan, but declining in other countries. The direct cost of cancer treatment in Japan amounts to US$23 billion. Indirect costs of morbidity and mortality amount to $65 billion. The cost of cancer per capita in Japan is $691, which is lower than in the US ($784) but higher than in France ($582) and in Sweden ($504). The annual out-of-pocket expenses are $11,000 on average in Japan (n=6,604). 7.3% of all health care resources are spent on cancer treatment In Japan, which is higher than in other countries. The expenditure on cancer drugs in Japan is $57 per capita, which is lower than in the US ($64) and France ($69), but higher than in the remaining countries. Conclusions: The trend in cancer mortality in Japan is, in contrast to the US and Europe, increasing. A more systematic use of economic evaluations of new cancer treatments in Japan would also support the use of the most cost effective alternatives. It is important to discuss the cost with patients and to minimize the economic burden of patients in clinical settings and in policy making.
Health activists join forces in bid to reform Medical Council of India
Authors: Dinsa Sachan
Journal: BMJ (2016)

Public health activists in India have launched a coalition to try to reform the Medical Council of India, the often criticised and controversial regulator of medical education and ethics.

The council has been under scrutiny since the arrest in 2010 of a former chair, Ketan Desai, on corruption charges. In March a parliamentary committee condemned the council on several grounds in a report submitted to the Indian parliament. It said that the regulator could no longer be trusted with its responsibilities because of its “massive failures.”1

On 2 May the Supreme Court of India appointed a three member panel, headed by a former chief justice of India, …
Counterpoint: Chemosensitivity Assays for Recurrent Ovarian Cancer
Authors: Maurie Markman
Journal: Journal of the National Comprehensive Cancer Network (2011)

Unfortunately, no reliable evidence-based data have shown any in vitro chemosensitivity assay strategy to be clinically useful in the management of recurrent ovarian cancer, despite frequent use. Several clinical trials have been proposed with the potential to support or refute the relevance of these approaches.
External contingency management for chronic pain: critical review of the evidence
Authors: P R Latimer
Journal: American Journal of Psychiatry (1982)

The use of operant conditioning to treat chronic pain has grown rapidly in the past 10 years. It usually occurs in a multidisciplinary inpatient setting with patients for whom nearly everything else has failed. The author reviews the theoretical rationale for this application of contingency management and evaluates the evidence for its efficacy. Although the evidence indicates considerable promise, particularly in improving physical functioning and reducing analgesic use, more definitive conclusions about the role of these methods in treatment of chronic pain are precluded by the methodological limitations of research in this area.
Segmental Jejunal Stenosis of Ischemic Origin
Authors: Melvin Greenblatt, Harry Goodman
Journal: New England Journal of Medicine (1959)

INCREASING awareness of the varied clinical manifestations of chronic ischemia of the gastrointestinal tract1 , 2 prompts this report of an unusual case of segmental jejunal stenosis produced by thrombotic occlusion of the regional mesenteric arteries. The etiology of this lesion is well documented by the pathological findings. The clinical and roentgenographic findings are presented. The relation to, and differentiation from, stenosing intestinal disorders of more obscure origin are discussed.Case ReportA 47-year-old male office worker complained of sudden, severe epigastric and substernal pain radiating to both shoulders and arms. An electrocardiogram taken shortly after admission to the hospital showed changes . . .
The Number Of Peripheral Blood CD4+CD25+FOXP3+ Regulatory T-Cells Is a Marker Of Response In Patients With JAK2 V617F Positive Myeloproliferative Neoplasms Treated With Pegylated-Interferon-α
Authors: Todd W. Kelley, Sabina Swierczek, Olga Efimova, Andrew R. Wilson, Soo Jin Kim, Josef Prchal
Journal: Blood (2013)
Identifying existing Choosing Wisely recommendations of high relevance and importance to hematology
Authors: Lisa K. Hicks, Anita Rajasekhar, Harriet Bering, Kenneth R. Carson, Judith Kleinerman, Vishal Kukreti, Alice Ma, Brigitta U. Mueller, Sarah H. O'Brien, Julie A. Panepinto, Marcelo C. Pasquini, Ravi Sarode, William A. Wood
Journal: American Journal of Hematology (2016)

Choosing Wisely (CW) is a medical stewardship initiative led by the American Board of Internal Medicine Foundation in collaboration with professional medical societies in the United States. In an effort to learn from and leverage the work of others, the American Society of Hematology CW Task Force developed a method to identify and prioritize CW recommendations from other medical societies of high relevance and importance to patients with blood disorders and their physicians. All 380 CW recommendations were reviewed and assessed for relevance and importance. Relevance was assessed using the MORE(TM) relevance scale. Importance was assessed with regard to six guiding principles: harm avoidance, evidence, aggregate cost, relevance, frequency and impact. Harm avoidance was considered the most important principle. Ten highly relevant and important recommendations were identified from a variety of professional societies. Recommendations focused on decreasing unnecessary imaging, blood work, treatments and transfusions, as well as on increasing collaboration across disciplines and considering value when recommending treatments. Many CW recommendations have relevance beyond the society of origin. The methods developed by the ASH CW Task Force could be easily adapted by other Societies to identify additional CW recommendations of relevance and importance to their fields. Am. J. Hematol. 91:787-792, 2016. © 2016 Wiley Periodicals, Inc.
Genomic screens identify a new phytobacterial microbe-associated molecular pattern and the cognate Arabidopsis receptor-like kinase that mediates its immune elicitation
Authors: G. Adam Mott, Shalabh Thakur, Elwira Smakowska, Pauline W. Wang, Youssef Belkhadir, Darrell Desveaux, David S. Guttman
Journal: Genome biology (2016)

The recognition of microbe-associated molecular patterns during infection is central to the mounting of an effective immune response. In spite of their importance, it remains difficult to identify these molecules and the host receptors required for their perception, ultimately limiting our understanding of the role of these molecules in the evolution of host-pathogen relationships. We employ a comparative genomics screen to identify six new immune eliciting peptides from the phytopathogenic bacterium Pseudomonas syringae. We then perform a reverse genetic screen to identify Arabidopsis thaliana leucine-rich repeat receptor-like kinases required for the recognition of these elicitors. We test the six elicitors on 187 receptor-like kinase knock-down insertion lines using a high-throughput peroxidase-based immune assay and identify multiple lines that show decreased immune responses to specific peptides. From this primary screen data, we focused on the interaction between the xup25 peptide from a bacterial xanthine/uracil permease and the Arabidopsis receptor-like kinase xanthine/uracil permease sensing 1; a family XII protein closely related to two well-characterized receptor-like kinases. We show that xup25 treatment increases pathogenesis-related gene induction, callose deposition, seedling growth inhibition, and resistance to virulent bacteria, all in a xanthine/uracil permease sensing 1-dependent manner. Finally, we show that this kinase-like receptor can bind the xup25 peptide directly. These results identify xup25 as a P. syringae microbe-associated molecular pattern and xanthine/uracil permease sensing 1 as a receptor-like kinase that detects the xup25 epitope to activate immune responses. The present study demonstrates an efficient method to identify immune elicitors and the plant receptors responsible for their perception. Further exploration of these molecules will increase our understanding of plant-pathogen interactions and the basis for host specificity.
US military investigation of hospital bombing insufficient, says MSF
Authors: Owen Dyer
Journal: BMJ (2016)

Medecins Sans Frontieres (MSF) has repeated its call for an independent investigation into last October’s attack on the charity’s hospital in Kunduz, Afghanistan, after a US military investigation ended with recommendations for administrative punishments against 16 unnamed servicemen, but no charges.1

“The investigation found that the incident resulted from a combination of unintentional human errors, process errors, and equipment failures, and that none of the personnel knew that they were striking a hospital,” said General Joseph Votel, who heads US Central Command and presented the report at a Pentagon press conference.

“The label ‘war crimes’ is typically reserved for intentional acts—intentionally targeting civilians or intentionally targeting protected objects or locations,” …
Suicidal Attempts in Children
Authors: R H LAWLER, W NAKIELNY, N A WRIGHT
Journal: JAMA (1963)

Psychiatric assessment and management of 22 suicidal attempts in children are reviewed. Intrapsychic and interpersonal conflicts of a serious nature were present in all cases. Most patients demonstrated longstanding, unrecognized disturbed mental states. These were associated with disturbed family relationships in the majority of cases. The child's position in sibling order appeared to be of some significance. It was of interest to find the presence of superior intelligence in all but one patient. Various types of loss were significant precipitating factors. All patients demonstrated a need for hospitalization and immediate treatment based on a thorough assessment of underlying dynamic factors.
The Undiagnosed Diseases Program
Authors: Brian C. Drolet, Jonathan P. Brower
Journal: JAMA (2016)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Prevention of active multiple myeloma (MM) using IL-1 receptor antagonist (IL-1ra) and low-dose dexamethasone (Dex) and monitoring the high sensitivity C-reactive protein (hsCRP)
Authors: J. A. Lust, M. Q. Lacy, S. R. Zeldenrust, A. Dispenzieri, M. A. Gertz, P. R. Greipp, T. E. Witzig, S. Kumar, S. M. Geyer, K. A. Donovan
Journal: Journal of Clinical Oncology (2007)

8105 Background: IL-6 is the central myeloma growth factor and we have shown that abnormal production of IL-1beta in the myeloma microenvironment stimulates the generation of paracrine IL-6. A Phase II trial was completed using IL-1ra, which inhibits paracrine IL-6 production, and low dose Dexamethasone (Dex), which decreases IL-1 levels through myeloma cell apoptosis, in patients with smoldering/indolent MM (SMM/IMM). These patients are at the greatest risk for progression to active MM and most likely to benefit from anti- cytokine therapy. Methods: Patients that had ≥ 10% bone marrow plasma cells and/or an IgG or IgA M-spike ≥ 3 g/dL and did not require immediate chemotherapy were eligible. A total of 47 patients received 100 mg of IL-1ra SQ qd for 6 months unless clinical progression occurred. Responding patients were allowed to continue on therapy with IL-1ra alone. Low dose Dex (20 mg qweek) was added after 6 months of IL-1ra in non-responding patients. The primary endpoint was progression-free survival (PFS). Results: The 47 patients were at high risk for progression to active MM with 98% having ≥ 10% plasma cells, 89% generating IL-1 levels consistent with myeloma (≥ 1.0), and 32% having bone lesions. All 47 patients received IL-1ra initially and 25/47 subsequently received IL-1Ra/Dex. For the group of 47 patients, the median overall progression-free survival was 37.5 months. Three patients achieved a minor response (MR) to Anakinra alone; 5 pts achieved a PR and 4 patients an MR after addition of Dex. Seven patients had a decrease in the plasma cell labeling index (PCLI; a marker of myeloma cell growth) on Anakinra alone which paralleled a decrease in the high sensitivity CRP (a marker of serum IL-6 levels). The median PFS for patients without (n=12) and with (n=35) a ≥ 15% decrease in their baseline hsCRP was 6 months and &gt; 3 yrs, respectively (p=0.002). Conclusions: In SMM/IMM patients at high risk for progression to active myeloma, treatment with IL-1 inhibitors (IL-1ra ± Dex) results in an increased PFS in patients that demonstrate a ≥15% reduction in the baseline CRP compared to those that do not respond. No significant financial relationships to disclose.
A phase III protocol of androgen suppression (AS) and 3DCRT/IMRT versus AS and 3DCRT/IMRT followed by chemotherapy (CT) with docetaxel and prednisone for localized, high-risk prostate cancer (RTOG 0521).
Authors: Howard M. Sandler, Chen Hu, Seth A. Rosenthal, Oliver Sartor, Leonard G. Gomella, Mahul Amin, James Purdy, Jeff M. Michalski, Mark Garzotto, Nadeem Pervez, Alexander G. Balogh, George Rodrigues, Luis Souhami, M. Neil Reaume, Scott G. Williams, Raquibul Hannan, Eric M. Horwitz, Adam Raben, Rebecca Paulus, William U. Shipley
Journal: Journal of Clinical Oncology (2015)

LBA5002 Background: High-risk, localized prostate cancer (PCa) patients have a relatively poor prognosis. We hypothesized that the addition of adjuvant docetaxel and prednisone to long-term (24 month) AS and radiation therapy (RT) would improve overall survival (OS). Methods: RTOG 0521 opened December 2005 and closed August 2009 with targeted accrual of 600 cases. It was designed to detect improvement in 4-year OS from 86% to 93% with a 51% hazard reduction (HR = 0.49). Under a 0.05 1-sided type I error and 90% power, at least 78 deaths were required to analyze the OS endpoint. Patients had 1) Gleason (Gl) 7-8, any T-stage, and PSA &gt; 20, or 2) Gl 8, ≥ T2, any PSA, or 3) Gl 9-10, any T-stage, any PSA. All had PSA ≤ 150. RT dose was 75.6 Gy. CT consisted of 6, 21-day cycles of docetaxel + prednisone starting 28 days after RT. Results: Of 612 enrolled, 50 were excluded for eligibility issues, leaving 562 evaluable. Median age = 66, median PSA = 15.1, 53% had Gl 9-10, 27% had cT3-4. Median follow-up = 5.5 yrs. 4-yr OS rates were 89% [95% CI: 84-92%] for the AS+RT arm and 93% [95% CI: 90-96%] for the AS+RT+CT arm (1-sided p = 0.03, HR = 0.68 [95% CI: 0.44, 1.03]). There were 52 centrally-reviewed deaths in the AS+RT arm and 36 in the AS+RT+CT arm, with fewer deaths both due to PCa/treatment (20 vs 16) and due to other causes/unknown (32 vs 20) in the AS+RT+CT arm. 5-yr disease-free survival rates were 66% for AS+RT and 73% for AS+RT+CT (2-sided p = 0.05, HR = 0.76 [95% CI: 0.57, 1.00]). There was 1, Gr 5 unlikely-related adverse event (AE) in the AS+RT arm and 2, Gr 5 possibly/probably-related AEs with AS+RT+CT. Conclusions: For high-risk, localized PCa, adjuvant CT improved the OS from 89% to 93% at 4 years. Toxicity was acceptable. This trial was designed with a short OS assessment period and additional follow-up is warranted to determine the long-term benefit of CT to the current standard of care of long-term AS+RT. This project was supported by grants U10CA21661, U10CA180868, U10CA180822, from the National Cancer Institute and Sanofi with additional support from AstraZeneca for Australian site participation. Clinical trial information: NCT00288080.
Myeloid cell transmigration across the CNS vasculature triggers IL-1β–driven neuroinflammation during autoimmune encephalomyelitis in mice
Authors: Sébastien A. Lévesque, Alexandre Paré, Benoit Mailhot, Victor Bellver-Landete, Hania Kébir, Marc-André Lécuyer, Jorge Ivan Alvarez, Alexandre Prat, Juan Pablo de Rivero Vaccari, Robert W. Keane, Steve Lacroix
Journal: The Journal of Experimental Medicine (2016)

Growing evidence supports a role for IL-1 in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), but how it impacts neuroinflammation is poorly understood. We show that susceptibility to EAE requires activation of IL-1R1 on radiation-resistant cells via IL-1β secreted by bone marrow–derived cells. Neutrophils and monocyte-derived macrophages (MDMs) are the main source of IL-1β and produce this cytokine as a result of their transmigration across the inflamed blood–spinal cord barrier. IL-1R1 expression in the spinal cord is found in endothelial cells (ECs) of the pial venous plexus. Accordingly, leukocyte infiltration at EAE onset is restricted to IL-1R1+ subpial and subarachnoid vessels. In response to IL-1β, primary cultures of central nervous system ECs produce GM-CSF, G-CSF, IL-6, Cxcl1, and Cxcl2. Initiation of EAE or subdural injection of IL-1β induces a similar cytokine/chemokine signature in spinal cord vessels. Furthermore, the transfer of Gr1+ cells on the spinal cord is sufficient to induce illness in EAE-resistant IL-1β knockout (KO) mice. Notably, transfer of Gr1+ cells isolated from C57BL/6 mice induce massive recruitment of recipient myeloid cells compared with cells from IL-1β KO donors, and this recruitment translates into more severe paralysis. These findings suggest that an IL-1β–dependent paracrine loop between infiltrated neutrophils/MDMs and ECs drives neuroinflammation.