tbuckley/cabot-search huggingface dataset:
The chromatin remodeling subunit Baf200 promotes normal hematopoiesis and inhibits leukemogenesis
Authors: Lulu Liu, Xiaoling Wan, Peipei Zhou, Xiaoyuan Zhou, Wei Zhang, Xinhui Hui, Xiujie Yuan, Xiaodan Ding, Ruihong Zhu, Guangxun Meng, Hui Xiao, Feng Ma, He Huang, Xianmin Song, Bin Zhou, Sidong Xiong, Yan Zhang
Journal: Journal of Hematology & Oncology (2018)

Adenosine triphosphate (ATP)-dependent chromatin remodeling SWI/SNF-like BAF and PBAF complexes have been implicated in the regulation of stem cell function and cancers. Several subunits of BAF or PBAF, including BRG1, BAF53a, BAF45a, BAF180, and BAF250a, are known to be involved in hematopoiesis. Baf200, a subunit of PBAF complex, plays a pivotal role in heart morphogenesis and coronary artery angiogenesis. However, little is known on the importance of Baf200 in normal and malignant hematopoiesis. Utilizing Tie2-Cre-, Vav-iCre-, and Mx1-Cre-mediated Baf200 gene deletion combined with fetal liver/bone marrow transplantation, we investigated the function of Baf200 in fetal and adult hematopoiesis. In addition, a mouse model of MLL-AF9-driven leukemogenesis was used to study the role of Baf200 in malignant hematopoiesis. We also explored the potential mechanism by using RNA-seq, RT-qPCR, cell cycle, and apoptosis assays. Tie2-Cre-mediated loss of Baf200 causes perinatal death due to defective erythropoiesis and impaired hematopoietic stem cell expansion in the fetal liver. Vav-iCre-mediated loss of Baf200 causes only mild anemia and enhanced extramedullary hematopoiesis. Fetal liver hematopoietic stem cells from Tie2-Cre + , Baf200 f/f or Vav-iCre + , Baf200 f/f embryos and bone marrow hematopoietic stem cells from Vav-iCre + , Baf200 f/f mice exhibited impaired long-term reconstitution potential in vivo. A cell-autonomous requirement of Baf200 for hematopoietic stem cell function was confirmed utilizing the interferon-inducible Mx1-Cre mouse strain. Transcriptomes analysis revealed that expression of several erythropoiesis- and hematopoiesis-associated genes were regulated by Baf200. In addition, loss of Baf200 in a mouse model of MLL-AF9-driven leukemogenesis accelerates the tumor burden and shortens the host survival. Our current studies uncover critical roles of Baf200 in both normal and malignant hematopoiesis and provide a potential therapeutic target for suppressing the progression of leukemia without interfering with normal hematopoiesis.
THE EFFECT OF OBESITY ON THE PREVALENCE OF ATRIAL FIBRILLATION: A 2014 NATIONWIDE ANALYSIS
Authors: Mariam Khandaker, Zuhair Khandker, Bing Yue, Xin Wei, Basera Sabharwal, Natasha Garg, Chayakrit Krittanawong, Eyal Herzog
Journal: Journal of the American College of Cardiology (2018)
Immune response to reovirus (REO) in phase I study with chemotherapy in patients with KRAS mutant metastatic colorectal cancer (mCRC).
Authors: Ruwan Parakrama, Imran Chaudhary, Matthew C. Coffey, Sanjay Goel, Radhashree Maitra
Journal: Journal of Clinical Oncology (2018)

217 Background: Viruses are well known immune sensitizing agents. The therapeutic efficacy of oncolytic reovirus in combination with chemotherapy is underway in a phase 1 study of mCRC. This study evaluates the nature of immune response by determining the distribution of antigen presenting cells (APCs) and activated T lymphocytes along with the cytokine expression pattern in peripheral circulation. Methods: REO was administered as a 60-minute intravenous infusion for 5 consecutive days every 28 days, at a tissue culture infective dose (TCID 50 ) of 3x10 6 . Serum was collected pre- and post- REO on days 1, pre REO on days 2-5, and days 8, 15, 22, and 29. Peripheral blood mononuclear cells (PBMC) were isolated and stained with fluorophore labelled antibodies against CD4, CD8, CD56, CD70, and CD123. Stained cells were fixed and evaluated by flow cytometry. The expression profile of 25 cytokines in plasma was assessed (post PBMC isolation) on an EMD Millipore multiplex Luminex platform. Results: Patients mount a robust immune response with dendritic cell maturation at 48 hrs (p &lt; 0.01) followed by activation of cytotoxic T (CD8+) cells at Day 8 (p &lt; 0.01). Cytokine assay indicated upregulation of Interleukin 1 beta (IL-1β; p = 0.004), Granulocyte-macrophage colony-stimulating factor (GM-CSF; p = 0.05), the chemokine Macrophage Inflammatory Proteins (MIP-1β; p = 0.05) at day 15. Furthermore, consistent upregulation of inflammatory cytokine IL-6 was seen from days 3 through 8 (p &lt; 0.05), and decrease in IL-8 at 72 hrs (p = 0.03) was observed. Conclusions: REO induces strong immune response in patients with mCRC. APCs are stimulated within 48 hrs and activated (CD8+ CD70+) T cells within 168 hrs. Cytokine profiling indicates stimulation for maturation of APCs, chemotactic induction for macrophages and activation of T cells as highlighted by release of IL-1β, GM-CSF and MIP-1β respectively. Sustained increased expression of IL-6 (triggering lymphocyte maturation) and downregulation of IL-8 (pro-angiogenic cytokine) is also observed. REO thus functions bimodally as an oncolytic agent causing lysis of tumor cells, and facilitator of immune-mediated recognition and destruction of tumor cells. Clinical trial information: NCT01274624.
I am currently applying for SHO posts starting in August 2005. I would like to become a GP. Should I apply directly for a VTS post or should I consider doing one of the new F2 posts first?
Authors: Bill Irish
Journal: BMJ (2005)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone (www.bmjcareers.com/advicezone) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.
Disconnection vs excision? A ten year review of hypothalamic hamartomas
Authors: Ribhav Pasricha, Saquib Azad Siddiqui, Ashish Suri, Sachin Borkar, Ashok K Mahapatra
Journal: Neuro-Oncology (2018)

Hypothalamic hamartomas (HH) are rare tumors of childhood. They are usually associated with gelastic seizures. The optimal management of these tumors lacks a consensus. We present our experience with hypothalamic hamartomas over a ten year period. This study presents a retrospective review of 16 patients with HH’s treated between 2002 and 2012 at the All India Institute of Medical Sciences (AIIMS), New Delhi, India, a tertiary care neurosurgical centre. There were 16 patients with an age ranging from 1.5 years to 20 years and included 9 males and 7 females. The most common symptom was seizures (81%; gelastic seizures-62.5%) followed by precocious puberty (56.2%). The median tumor volume was 5.9 cc (range 1.3 to 108 cc). Fourteen patients underwent surgery while two were managed conservatively. Three patients received secondary Gamma Knife therapy. A good seizure outcome (Engel class I and II) post surgery was seen in 8 (50%) patients. The median follow up period was 39 months (range 1 to 114 months). The odds ratio for a better seizure outcome was 2.5 times more in disconnection than for excision. The symptoms of precocious puberty had resolved in 7 of the 9 affected patients (78%). Transient diabetes insipidus was seen in one (6.2%) patient postoperatively while hyperphagia was noted in four (25%) patients. Hyperphagia persisted in all four patients until last follow up. HHs present with gelastic seizures or precocious puberty. Disconnection of the HH is more effective and a safer procedure vis-a-vis excision for controlling seizures.
Improved Risk Stratification by Circulating Tumor Cell Counts in Pancreatic Cancer
Authors: Katharina E. Effenberger, Cornelia Schroeder, Annkathrin Hanssen, Stefan Wolter, Christine Eulenburg, Michael Tachezy, Florian Gebauer, Jacob R. Izbicki, Klaus Pantel, Maximilian Bockhorn
Journal: Clinical Cancer Research (2018)

Purpose: Pancreatic cancer is one of the most devastating diseases with a 5-year survival rate of 3% to 5%. Here, we investigated whether circulating tumor cells (CTC) may predict metastatic spread and survival in pancreatic cancer patients.Experimental Design: In a prospective study, we enrolled 69 pancreatic cancer patients. In peripheral blood, CTCs were identified by MACS enrichment (anti-cytokeratin/anti-EpCam) and subsequent automated analysis after combined anti-cytokeratin/anti-CD45/DAPI staining. CTC results were correlated to established clinicopathologic risk factors, detection of disseminated tumor cells (DTC) in bone marrow, and clinical outcome (follow-up time: 48 months).Results: Median patient survival was 11 months (0-48 months). Thirty-eight patients were male and 31 were female, and the majority received gemcitabine (58/69). CTCs were present in 23 of 69 patients (33.3%) ranging from 1 to 19 cells (17 with >1 CTC). Although clinicopathologic parameters and DTC status did not correlate with CTC incidence, progression-free survival (PFS) and overall survival (OS) were significantly reduced in CTC-positive patients in univariate (P = 0.009, PFS; P = 0.030, OS, both log rank) and multivariate analysis [HR = 4.543; confidence interval (CI), 1.549-13.329; P = 0.006, PFS; HR = 2.093; CI, 1.081-4.050; P = 0.028, OS, both Cox regression). Also within patients receiving chemotherapy, PFS was significantly reduced in CTC-positive patients in univariate (P = 0.013) and multivariate (HR = 4.203; CI, 1.416-12.471; P = 0.010) analysis.Conclusions: CTCs affect the outcome of patients with pancreatic cancer independent from other risk factors, including patients receiving (adjuvant) cytotoxic therapy. CTC stratification may allow a better upfront identification of patients with a longer lifespan who might profit from new adjuvant therapies. Clin Cancer Res; 24(12); 2844-50. ©2018 AACR.
A model for clinical attachments to support international medical graduates
Authors: Jessica Webb, Anna Marciniak, Camila Cabral, Roberta Lima Brum, Ronak Rajani
Journal: BMJ (2014)

Clinical attachments are the port of entry into the NHS for many international medical graduates, but there is wide heterogeneity in the provision of these attachments. <b>Jessica Webb and colleagues</b> argue that the system of providing and applying for these attachments needs revision, and they propose a novel model for clinical attachments
Global Prevalence of Fetal Alcohol Spectrum Disorder in Italy—Reply
Authors: Shannon Lange, Jürgen Rehm, Svetlana Popova
Journal: JAMA Pediatrics (2018)

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 Pediatrics 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 Pediatrics journal
The Osteopath's Guide to Keeping Out of Trouble
Authors: Bill Irish
Journal: BMJ (2005)

Paul Lambden

Radcliffe, 2005, £29.95, 199 pages ISBN 1 85775 737 8

Rating: ⋆/5



I have always been pretty impressed by osteopaths. Although I have never quite understood how they can realign vertebrae and discs with just a couple of deft tweaks I can't help but notice that the guy down the road drives the biggest BMW that I have ever seen. I always used to think that our physiotherapist was terrific at backs but she only gets to drive a Ford Focus.

Better still, while …
Re-programming immunosurveillance in persistent non-infectious ocular inflammation
Authors: Simon J. Epps, Joanne Boldison, Madeleine L. Stimpson, Tarnjit K. Khera, Philippa J.P. Lait, David A. Copland, Andrew D. Dick, Lindsay B. Nicholson
Journal: Progress in Retinal and Eye Research (2018)

Ocular function depends on a high level of anatomical integrity. This is threatened by inflammation, which alters the local tissue over short and long time-scales. Uveitis due to autoimmune disease, especially when it involves the retina, leads to persistent changes in how the eye interacts with the immune system. The normal pattern of immune surveillance, which for immune privileged tissues is limited, is re-programmed. Many cell types, that are not usually present in the eye, become detectable. There are changes in the tissue homeostasis and integrity. In both human disease and mouse models, in the most extreme cases, immunopathological findings consistent with development of ectopic lymphoid-like structures and disrupted angiogenesis accompany severely impaired eye function. Understanding how the ocular environment is shaped by persistent inflammation is crucial to developing novel approaches to treatment.
PROSPECTIVE EVALUATION OF CIRCULATING BIOMARKERS AS PREDICTORS OF CARDIOTOXICITY IN PATIENTS WITH HER2-POSITIVE BREAST CANCER RECEIVING ANTHRACYCLINES AND TRASTUZUMAB
Authors: Anthony F. Yu, Andrea Knezevic, Chaya Moskowitz, Chau Dang, Lakshmi Ramanathan, Kevin Oeffinger, Jennifer Liu, Richard Steingart
Journal: Journal of the American College of Cardiology (2018)
Exploiting an Asp-Glu “switch” in glycogen synthase kinase 3 to design paralog-selective inhibitors for use in acute myeloid leukemia
Authors: Florence F. Wagner, Lina Benajiba, Arthur J. Campbell, Michel Weïwer, Joshua R. Sacher, Jennifer P. Gale, Linda Ross, Alexandre Puissant, Gabriela Alexe, Amy Conway, Morgan Back, Yana Pikman, Ilene Galinsky, Daniel J. DeAngelo, Richard M. Stone, Taner Kaya, Xi Shi, Matthew B. Robers, Thomas Machleidt, Jennifer Wilkinson, Olivier Hermine, Andrew Kung, Adam J. Stein, Damodharan Lakshminarasimhan, Michael T. Hemann, Edward Scolnick, Yan-Ling Zhang, Jen Q. Pan, Kimberly Stegmaier, Edward B. Holson
Journal: Science Translational Medicine (2018)

Paralog-selective inhibitors of GSK3 kinases were designed by exploiting a single amino acid difference in their ATP-binding domains and studied in AML.
A proper job⇓
Authors: Nicola Sharp
Journal: BMJ (2004)

“That's him. Over there. Just wait till I get my hands on him.” Martha stood outside her bell tent with her hands on her hips.

“Who?” Janet stood by the remains of the campfire and combed out her long golden hair.

“Douglas, of course,” said Martha.

“Where?” Janet peered out from underneath her hair.

“Over there, by the main entrance.”

“It can't be Douglas,” said Janet. “That man's wearing a suit; Douglas never does. Also it's too early for Douglas; he's never up at seven thirty.”

\* * *|

David Millstone sat in the boardroom at the Turchester Royal with four other men, all dressed in dark grey suits.

David scratched his head. “But you said the finances were finalised.”

“They were.”

“And now you say the money isn't there.”

“That's the NHS for you. Eats money. Disappears through the floorboards, down the drains.”

“So there aren't going to be any new buildings?”

“Not for mental health.”

“What about the other departments?”

“The situation is very similar.”

“How will I run my service?”

“There are the two existing wards and the outpatient department.”

“But they are for the population of Turchester. How can we expand the service to meet the …
Correlation of MTOR protein expression in the tumor and its microenvironment with more aggressive pathology at cystectomy.
Authors: Brian Winters, Funda Vakar-Lopez, MD, Lisha Brown, BS, Robert B. Montgomery, Roland Seiler, Andrew Caleb Hsieh, Jonathan L. Wright, Hung-Ming Lam
Journal: Journal of Clinical Oncology (2018)

438 Background: The mechanistic target of rapamycin (mTOR) has been implicated in driving tumor biology in multiple malignancies, including urothelial carcinoma (UC). We investigate how mTOR and phosphorylated mTOR (pmTOR) protein expression in both the tumor, and the tumor microenvironment, correlate with final pathologic stage at cystectomy after neoadjuvant chemotherapy (NAC). Methods: A single-institution retrospective analysis was performed on 62 patients with cT2-4Nany UC undergoing NAC followed by radical cystectomy. Diagnostic (transurethral resection specimens, TURBT) and post-NAC radical cystectomy specimens were evaluated for mTOR and pmTOR protein expression using immunohistochemistry of the tumor, peritumoral stroma, and normal surrounding tissue. Protein expression levels were compared between TURBT and cystectomy samples. Whole transcriptome analysis was performed to evaluate mRNA expression relative to mTOR pathway activation. Results: Baseline levels of mTOR and pmTOR within TURBT specimens were not associated with clinical stage or response to NAC overall. Non-responder patients, defined as pT2-T4/pTanyN+, had significantly elevated mTOR tumor staining (p = 0.006) and sustained mTOR and pmTOR staining in the peritumoral and surrounding normal stroma of cystectomy specimens compared with baseline TURBT samples (NS). In contrast, complete responders (pT0), had significant decreases in tumoral mTOR and pmTOR protein expression at cystectomy (p = 0.01-0.03). Several genes relevant to mTOR activity were found to be overexpressed in post-NAC cystectomy samples (compared with TURBT) of non-responder patients (THBS1, FN1, FOS, CNN1, COL1A2). Conclusions: Our results suggest that mTOR pathway activity is increased in the tumor and sustained the tumor microenvironment of patients with adverse pathologic findings at cystectomy after NAC. These findings suggest the relevance of targeting the mTOR pathway in bladder cancer.
The art of efficiency
Authors: Graham Easton
Journal: BMJ (2004)

One of the most useful and enduring skills for a doctor to master is efficiency. Clinical brilliance counts for little if you can't find your patients, haven't got your pathology results, or turn up an hour late for clinic. This week we have some suggestions for mastering the art.

Embracing diversity might help. Diversity has become a bit of a buzzword in the NHS and, …
Histopathological tumor regression or ypN: Which better predicts survival of patients who received neoadjuvant chemotherapy and surgery for non-type 4 locally advanced gastric cancer?
Authors: Kazumasa Fujitani, Kenichi Nakamura, Junki Mizusawa, Takeshi Kuwata, Tadakazu Shimoda, Hiroshi Katayama, Ryoji Kushima, Hirokazu Taniguchi, Takaki Yoshikawa, Narikazu Boku, Masanori Terashima, Haruhiko Fukuda
Journal: Journal of Clinical Oncology (2018)

114 Background: Histopathological tumor regression with &lt; 10% residual tumor is a globally accepted prognostic factor in gastric cancer patients who received neoadjuvant chemotherapy (NAC) and curative surgery, however, impact of ypN remains unclear. Methods: Previously, Japan Clinical Oncology Group (JCOG) had conducted 3 phase II trials to evaluate NAC with irinotecan/CDDP (JCOG0001) and S-1/CDDP (JCOG0405) for extensive nodal disease, and with S-1/CDDP (JCOG0210) for large type 3 and type 4 (linitis plastica) disease. Prognostic factors, including ypN and histopathological tumor regression with &lt; 10% residual tumor, were analyzed in patients with curative resection excluding type 4 advanced gastric cancer in these trials by univariable and multivariable analyses using the Cox proportional hazards model. Results: Among 85 patients, 5-year OS was 46.0% (95% CI, 35.0-56.4). Median OS was not reached in patients with &lt; 10% residual tumor (n = 26), whereas that was 2.7 years (95% CI, 1.4-4.5) in patients with &gt; 10% residual tumor (n = 59) (p = 0.008). Median OS was not reached in patients with ypN0-1 (n = 25), whereas that was 2.6 years (95% CI, 1.5-4.0) in patients with ypN2-3 (n = 60) (p = 0.003). On multivariable analysis, only ypN2-3 was an independent predictor of OS (hazard ratio, 3.67; 95% CI, 1.55 to 8.69), whereas &lt; 10% residual tumor was not (hazard ratio, 2.24; 95% CI, 0.98 to 5.10). Conclusions: It is suggested that ypN may have greater impact on the survival than histopathological tumor regression in patients who received NAC and surgery for AGC.
Abstract ES11-1: Luminal ABC: optimal use of all available options?
Authors: AM DeMichele
Journal: Cancer Research (2018)

Abstract Despite advanced in early detection and aggressive adjuvant endocrine therapy, recurrence and metastasis of estrogen-receptor (ER)- positive breast cancer remains a problem, with a substantial proportion of patients relapsing years after diagnosis. Biologically, these tumors are primarily of the luminal subtype, amenable to anti-estrogen strategies that can control disease growth and limit metastatic spread. However, resistance and progression are universal, and patients will eventually stop responding to endocrine approaches. Advances in our understanding of luminal breast cancer biology, metastatic progression and endocrine resistance have led to new approaches and additional targets for intervention. Most important among these are interactions between ER signaling pathways and cell cycle control mechanisms or PI3K/mTor signaling, leading to new strategies incorporating cyclin-dependent kinase (cdk) and mTOR inhibitors, respectively, into endocrine therapy. While successful, many questions remain unanswered regarding optimal combinations and sequencing of these agents in specific populations, and management at the time of progression. This session will address (1) the evidence supporting the use of cdk 4/6 and mTOR inhibitors in standard practice for luminal advanced breast cancer, including agent selection and management of toxicity, (2) current understanding of resistance mechanisms and (3) next generation clinical trials designed to address resistance and improve outcomes in women with luminal advanced breast cancer. Citation Format: DeMichele AM. Luminal ABC: optimal use of all available options? [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES11-1.
Biocompatible and biodegradable zeolitic imidazolate framework/polydopamine nanocarriers for dual stimulus triggered tumor thermo-chemotherapy
Authors: Qiong Wu, Meng Niu, Xiaowei Chen, Longfei Tan, Changhui Fu, Xiangling Ren, Jun Ren, Laifeng Li, Ke Xu, Hongshan Zhong, Xianwei Meng
Journal: Biomaterials (2018)
Intraoperative cholangiography during cholecystectomy in sequential treatment of cholecystocholedocholithiasis: To be, or not to be, that is the question A cohort study
Authors: Antonia Rizzuto, Massimiliano Fabozzi, Anna Settembre, Stefano Reggio, Ernesto Tartaglia, Salomone Di Saverio, Piero Angelini, Vania Silvestri, Chiara Mignogna, Raffaele Serra, Stefano De Franciscis, Leonardo De Luca, Diego Cuccurullo, Francesco Corcione
Journal: International Journal of Surgery (2018)