tbuckley/cabot-search huggingface dataset:
NHS will need 190 000 more clinicians unless productivity improves, workforce plan warns
Authors: Abi Rimmer
Journal: BMJ (2017)

The NHS will need 190 000 more clinicians by 2027 unless demand is reduced through better productivity and service transformation, Health Education England (HEE) has said.

The organisation’s workforce strategy, published on 13 December,1 is its first to look more than five years ahead. The strategy says that HEE has worked out the likely future demand for NHS staff by looking at growth projections for the economy that were more accurate than previous estimates, based on employer needs, that had underestimated future demand.

“Our ten year forward look shows that if no action is taken to reduce demand through prevention or through better productivity and service transformation, the NHS will need to grow by 190 000 clinical posts by 2027 to meet demand,” HEE said.

To plan better for the future medical workforce HEE said that …
Deconstruction of a Metastatic Tumor Microenvironment Reveals a Common Matrix Response in Human Cancers
Authors: Oliver M.T. Pearce, Robin M. Delaine-Smith, Eleni Maniati, Sam Nichols, Jun Wang, Steffen Böhm, Vinothini Rajeeve, Dayem Ullah, Probir Chakravarty, Roanne R. Jones, Anne Montfort, Tom Dowe, John Gribben, J. Louise Jones, Hemant M. Kocher, Jonathan S. Serody, Benjamin G. Vincent, John Connelly, James D. Brenton, Claude Chelala, Pedro R. Cutillas, Michelle Lockley, Conrad Bessant, Martin M. Knight, Frances R. Balkwill
Journal: Cancer Discovery (2017)

We have profiled, for the first time, an evolving human metastatic microenvironment by measuring gene expression, matrisome proteomics, cytokine and chemokine levels, cellularity, extracellular matrix organization, and biomechanical properties, all on the same sample. Using biopsies of high-grade serous ovarian cancer metastases that ranged from minimal to extensive disease, we show how nonmalignant cell densities and cytokine networks evolve with disease progression. Multivariate integration of the different components allowed us to define, for the first time, gene and protein profiles that predict extent of disease and tissue stiffness, while also revealing the complexity and dynamic nature of matrisome remodeling during development of metastases. Although we studied a single metastatic site from one human malignancy, a pattern of expression of 22 matrisome genes distinguished patients with a shorter overall survival in ovarian and 12 other primary solid cancers, suggesting that there may be a common matrix response to human cancer.Significance: Conducting multilevel analysis with data integration on biopsies with a range of disease involvement identifies important features of the evolving tumor microenvironment. The data suggest that despite the large spectrum of genomic alterations, some human malignancies may have a common and potentially targetable matrix response that influences the course of disease. Cancer Discov; 8(3); 304-19. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 253.
Nusinersen for Spinal Muscular Atrophy
Authors: Vinay Prasad
Journal: JAMA Pediatrics (2017)

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
A meta-analysis of two randomized, double-blind, placebo-controlled, phase III studies in patients (PTS) with metastatic colorectal cancer (MCRC) receiving FOLFOX4 and PTK/ZK to determine clinical benefit on progression-free survival (PFS) in high LDH PTS
Authors: T Trarbach, P Major, H J Lenz, D Kerr, K Pendergrass, J Y Douillard, B Chen, A Littlewood-Evans, D Laurent, C Jacques, E Van Cutsem
Journal: Annals of Oncology (2006)
Comparative diagnostic efficacy of biopsy strategies for prostate cancer detection: a Bayesian network meta-analysis of 24 randomised controlled trials
Authors: Lu Yang, Shi Qiu, Linghui Deng, Haiyang Bian, Ian Charles Tobias, Chengyi Huang, Liangren Liu, Zhenhua Liu, Yige Bao, Qiang Wei
Journal: The Lancet (2017)
Ensuring Patient Safety and Access in Cancer Care
Authors: Katy Winckworth-Prejsnar, Elizabeth A. Nardi, James McCanney, F. Marc Stewart, Terry Langbaum, Bruce J. Gould, C. Lyn Fitzgerald, Robert W. Carlson
Journal: Journal of the National Comprehensive Cancer Network (2017)

The inability to obtain the right high-quality cancer care in a timely and safe manner can have devastating results for patients. As cancer care becomes inundated with cutting edge and novel treatments, such as personalized medicine, oral chemotherapy, biosimilars, and immunotherapy, new safety challenges are emerging at increasing speed and complexity. Moreover, shifting federal healthcare policies could have significant implications for the safety and access to high-quality and effective cancer care for millions of patients with cancer. Challenges and opportunities in ensuring patient access to safe, affordable, and high-quality cancer care remain significant within the policy landscape. To address these concerns, NCCN hosted the Ensuring Safety and Access in Cancer Care Policy Summit in June 2017 to discuss pertinent patient safety issues and access implications under the Trump administration, as well as policy and advocacy strategies to address these gaps and build on opportunities moving forward.
Is continuous electronic fetal monitoring useful for all women in labour?
Authors: Edward Mullins, Christoph Lees, Peter Brocklehurst
Journal: BMJ (2017)

Routine monitoring of all women would prevent much neonatal morbidity, argue <b>Edward Mullins </b>and <b>Christoph Lees</b>, but <b>Peter Brocklehurst</b> believes that it will increase the risk of harm from unnecessary caesarean sections
Adoption of hypofractionated radiotherapy (HyRT) for ductal carcinoma in situ (DCIS): A SEER-Medicare study.
Authors: Aaron David Falchook, Laura H. Hendrix, Noam Avraham VanderWalde, Timothy M. Zagar, Ellen Jones, Reshma Jagsi, Ronald C. Chen
Journal: Journal of Clinical Oncology (2014)

1006 Background: Multiple randomized trials published in 2008-2010 demonstrated that for women with early-stage invasive breast cancer receiving adjuvant radiotherapy (RT) after a lumpectomy, shorter course (hypofractionated) RT is non-inferior to conventionally fractionated RT (CRT). However, the role of HyRT has not been evaluated prospectively for DCIS. The purpose of this study is to examine adoption of HyRT in DCIS. Methods: DCIS patients diagnosed from 2004-9 in the Surveillance Epidemiology and End Results (SEER)-Medicare database were included, with Medicare claims data available through 2010. A total of 4,459 women received lumpectomy followed by external beam RT. The number of RT treatments received by each patient was determined from Medicare claims, and grouped into: accelerated partial breast irradiation (APBI, ≤12 treatments), HyRT (13-24), or CRT (≥25). Proportions of women receiving different fractionation schemes were described per year of RT, and in subgroups based on patient and disease factors. Multivariate logistic regression was used to examine factors associated with receipt of HyRT (vs. CRT). Results: Utilization of HyRT increased from ~4% to 8.8% in 2008 and 11.2% in 2009-10, with corresponding decreases in CRT (Table); external beam APBI utilization was low and stable during the study years. HyRT was more common in older women. On multivariate analysis, older age (OR 1.8 for age 80+ vs. age 66-69, p=.002), later RT years (OR 2.8 for 2009-10 vs. 2005, p<.001) and higher regional education were significantly associated with increased utilization of HyRT, while higher grade was associated with less HyRT (OR .8 for Grade 3 vs. Grade 1, p=.06). Race, marital status, comorbidity, and laterality (left vs. right) were not significantly associated with HyRT. Conclusions: Utilization of HyRT increased after 2008 coinciding with trial publications for invasive cancer, even though the efficacy of this treatment for DCIS has not been clearly established. APBI (%) HyRT (%) CRT (%) Univariate p RT year 2004 2.7 4.3 93.0 <.001 2005 2.0 3.8 94.3 2006 4.0 4.0 92.0 2007 3.3 4.2 92.5 2008 2.6 8.8 88.6 2009-10 2.5 11.2 86.3 Age (yrs) 66-69 3.6 4.7 91.7 <.001 70-75 2.1 6.1 91.7 76-79 2.4 8.6 89.1 80+ 3.1 8.1 88.8
Transduction Methods for Cytosolic Delivery of Proteins and Bioconjugates into Living Cells
Authors: Manuela Chiper, Karen Niederreither, Guy Zuber
Journal: Advanced Healthcare Materials (2017)

Abstract The human organism and its constituting cells rely on interplay between multiple proteins exerting specific functions. Progress in molecular biotechnologies has facilitated the production of recombinant proteins. When administrated to patients, recombinant proteins can provide important healthcare benefits. To date, most therapeutic proteins must act from the extracellular environment, with their targets being secreted modulators or extracellular receptors. This is because proteins cannot passively diffuse across the plasma membrane into the cytosol. To expand the scope of action of proteins for cytosolic targets (representing more than 40% of the genome) effective methods assisting protein cytosolic entry are being developed. To date, direct protein delivery is extremely tedious and inefficient in cultured cells, even more so in animal models of pathology. Novel techniques are changing this limitation, as recently developed in vitro methods can robustly convey large amount of proteins into cell cultures. Moreover, advances in protein formulation or protein conjugates are slowly, but surely demonstrating efficiency for targeted cytosolic entry of functional protein in vivo in tumor xenograft models. In this review, various methods and recently developed techniques for protein transport into cells are summarized. They are put into perspective to address the challenges encountered during delivery.
Combination Immunotherapy of MUC1 mRNA Nano-vaccine and CTLA-4 Blockade Effectively Inhibits Growth of Triple Negative Breast Cancer
Authors: Lina Liu, Yuhua Wang, Lei Miao, Qi Liu, Sara Musetti, Jun Li, Leaf Huang
Journal: Molecular Therapy (2017)

Triple negative breast cancer (TNBC), which constitutes 10%-20% of all breast cancers, is associated with aggressive progression, a high rate of metastasis, and poor prognosis. The treatment of patients with TNBC remains a great clinical challenge. Preclinical reports support the combination immunotherapy of cancer vaccines and immune checkpoint blockades in non-immunogenic tumors. In this study, we constructed nanoparticles (NPs) to deliver an mRNA vaccine encoding tumor antigen MUC1 to dendritic cells (DCs) in lymph nodes to activate and expand tumor-specific T cells. An anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) monoclonal antibody was combined with the mRNA vaccine to enhance the anti-tumor benefits. In vivo studies demonstrated that the NP-based mRNA vaccine, targeted to mannose receptors on DCs, could successfully express tumor antigen in the DCs of the lymph node; that the NP vaccine could induce a strong, antigen-specific, in vivo cytotoxic T lymphocyte response against TNBC 4T1 cells; and that combination immunotherapy of the vaccine and anti-CTLA-4 monoclonal antibody could significantly enhance anti-tumor immune response compared to the vaccine or monoclonal antibody alone. These data support both the NP as a carrier for delivery of mRNA vaccine and a potential combination immunotherapy of the NP-based mRNA vaccine and the CTLA-4 inhibitor for TNBC.
Abstract 12935: Age Related Cardiac Dysfunction and Pancreatic β-cell Function in Diabetes Were Improved by P53 Inhibition Through Parkin-mediated Mitophagy
Authors: Makoto Ariyoshi, Atsushi Hoshino, Yoshifumi Okawa, Syuhei Tateishi, Daichi Hato, Ryoetsu Yamanaka, Sakiko Honda, Yohei Fushimura, Eri Iwai-Kanai, Satoaki Matoba
Journal: Circulation (2016)

Previous studies have demonstrated mitochondrial dysfunction has roles in the progression of several diseases and tumor suppressor p53 has a boarder role that extends to the modulation of mitochondrial homeostasis. Here we show that cytosolic p53 impairs autophagic degradation of damaged mitochondria and facilitates mitochondrial dysfunction during the development of heart failure and diabetes, and that cytosolic p53 binds to Parkin and disturbs its translocation to damaged mitochondria and their subsequent clearance by mitophagy. In heart, prevalence and induction of mitochondrial autophagy is attenuated by senescence or doxorubicin (DOX) treatment. And p53-deficient mice show less decline of mitochondrial integrity and cardiac function reserve with increasing age or after treatment with DOX. And, overexpression of Parkin improves the functional decline in aged heart, and is accompanied by decreased senescence-associated β-galactosidase activity and proinflammatory phenotypes. Furthermore, regarding diabetes, p53 deficiency protects against the development of diabetes in streptozotocin (STZ)-induced type 1 and db/db mouse models of type 2 diabetes. Glucolipotoxicity stimulates NADPH oxidase via RAGE and TLR4. This oxidative stress induces the accumulation of p53 in the cytosolic compartment of pancreatic β cells in concert with ER stress. The occurrence of mitophagy is maintained in STZ-treated p53–/– mice that exhibit preserved glucose oxidation capacity and subsequent insulin secretion signaling, leading to better glucose tolerance. These protective effects are not observed when Parkin is deleted. Besides, pifithrin-α improves mitochondrial dysfunction and glucose intolerance in both STZ-treated and db/db mice. Thus, p53-mediated inhibition of mitophagy modulates dysfunction of heart and islet, raising the possibility that therapeutic activation of mitophagy by inhibiting cytosolic p53 may ameliorate heart failure and diabetes.
Radiofrequency Denervation for Chronic Low Back Pain—Reply
Authors: Esther Maas, Johan Juch, Frank Huygen
Journal: JAMA (2017)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Bottom‐up Nanoencapsulation from Single Cells to Tunable and Scalable Cellular Spheroids for Hair Follicle Regeneration
Authors: Jin Wang, Yong Miao, Yong Huang, Bojie Lin, Xiaomin Liu, Shune Xiao, Lijuan Du, Zhiqi Hu, Malcolm Xing
Journal: Advanced Healthcare Materials (2017)

Abstract Cell surface engineering technology advances cell therapeutics and tissue engineering by accurate micro/nanoscale control in cell–biomaterial ensembles and cell spheroids formation. By tailoring cell surface, microgels can encapsulate cells for versatile uses. However, microgels are coated in a thick layer to house multiple cells together but not a single cell based. Besides, excessive deposition on cell surface is detrimental to cellular functions. Herein, layer‐by‐layer (LbL) self‐assembly to encapsulate single cell using nanogel is reported, owing to its security and tunable thickness at nanoscale, and further forms cell spheroids by physical cross‐linking on nanogel‐coated cells for delivery. A hair follicle (HF) regeneration model where the dermal papilla cells (DPCs) are given a 3D installation to maintain its ability of HF induction during in vitro culture is studied. Dermal papilla (DP) spheroids are optimized and that LbL‐DPCs aggregation is akin to primary DP is demonstrated. The markers ALP, Versican, and NCAM are examined to investigate that high‐passaged (P8) DP spheroids can restore the hair induction potential, which are lost in 2D culture. New HFs are regenerated successfully by implantation of DP spheroids in vivo.
Proposal to disregard athletics world records prior to 2005: a radical and misjudged initiative
Authors: Andrew Mark Edwards, Andrew M Jones, David B Pyne
Journal: British Journal of Sports Medicine (2017)

The recent announcement that the European Athletics Council has proposed to disregard all athletics world records set prior to 20051 has caused considerable controversy and debate among the athletics community. It is a radical initiative with commendable aims to redress the consequences of past undetected doping violations that may have led to some of the least attainable world records. This proposal has now been put to the world governing body, the International Amateur Athletics Federation (IAAF), and its merits require discussion.

A major suggested justification for the proposal is that the IAAF has stored blood and urine samples only since 2005. As a consequence, there is limited recourse to disprove the legitimacy of performances prior to 2005 unless compelling new corroborative evidence emerges, as was the case for the cyclist Lance Armstrong. This seems unlikely when conclusive evidence of doping and admissions of guilt are not forthcoming despite widely known practices of state-sponsored doping.2 Therefore, the proposal has some merit for expunction of world records that may have been set with the aid of illegal performance-enhancing drugs. Nevertheless, there are many …
FRI0246 The impact social, labour and psychological of the chronic low back pain
Authors: FP Torres, D Ybañez-García, P Pérez-Caballero, M Morales, A Llópis
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To determine the social and psychological impact that exercises the chronic lumbar pain on the affected population. <h3>Methods</h3> We carry out a longitudinal study with patients that demand attendance for low back pain (LBP). The selected patients were interviewed to determine if the pain exercised influences on their work, familiar life, sports, their economy and their social life. To determine the psychological impact it was valued which was the most important concern for the patient, the originated pain, the lesion or disablement, taking an abnormal life, the progressive worsening, the deformity, the lost of work or he didn't have concern. <h3>Results</h3> They were carried out a total of 485 interviews. They presented repercussion on their job 377 patient (77.7%), family repercussion 218 (44.9%), social repercussion 154 (31.8%), economic repercussion 107 (22.1%) and sport 309 (63.7%). Psychologically they had some type of concern 340 cases (70.3%) and they didn't have any concern 145 (29.7%), it was the pain what more worried to a total of 125 (25.8%), not being able to carry out a normal life at 92 (19%); the progressive worsening and the disability worried to 10% of cases each one of them, being the deformity and the work loss what less worried 0.6% and 4.5% respectively. <h3>Conclusion</h3> The most important repercussion in the LBP is the labour one and the less important one is the economic repercussion. The DLC worries majority of patients. The most important concerns for the patients were the own pain and not being able to carry out a normal life: what less worried it was the work loss and the acquisition of a deformity. <h3>References</h3> Silman AL, Papageorgin AC, Thomas E, Croft PR, Jayson M, Mcfarlane GJ. Work activities and psycologycal factors as prodictors of future back pain. <i>Arthritis Rheum.</i> 1996;<b>39</b>:1.694 Reumatos 90?. Estudio sociosanitario sobre las enfermedades reumáticas en España. Gabinete de estudios Pfizer y Liga Reumatologica Española, 1992
Characterization of the Interactions of Arg-Gly-Asp- and Ala-Gly-Asp-Val-Containing Peptides with the Platelet Integrin αIIbβ3
Authors: Rustem I. Litvinov, Olga Kononova, Dmitry S. Blokhin, Vladimir V. Klochkov, John W. Weisel, Valeri Barsegov, Joel S. Bennett
Journal: Blood (2016)
EXEL-0862, a novel tyrosine kinase inhibitor, inhibits KIT activation and induces apoptosis in human mast cells bearing mutated codon 816 c-kit in vitro and ex vivo: Therapeutic implications
Authors: Jingxuan Pan, Hagop M. Kantarjian, Manshouri Taghi, Cem Akin, Peter Lamb, Jorge E. Cortes, Francis J. Giles, Srdan Verstovsek
Journal: Cancer Research (2006)

4039   Systemic mastocytosis is characterized by a clonal accumulation of mast cells in bone marrow and other tissues. The proto-oncogene  c-kit , which encodes a transmembrane tyrosine kinase, is thought to play an important role in mastocytosis. Kinase inhibitors in clinical use, such as imatinib mesylate, failed to inhibit the growth of HMC1.2 cells bearing a codon 816 mutation of  c-kit  in laboratory testing. Consequently, there is a need for development of new effective therapeutic modalities. In this investigation, we determined the effect of exEL-0862, a novel tyrosine kinase inhibitor, on human mast cells. Two human mast cell lines, HMC1.1 carrying juxtamembrane domain mutation in codon 560 and HMC1.2 carrying both codon 560 mutation and tyrosine kinase mutation in codon 816 of  c-kit , were used. We found that EXEL-0862 inhibited the phosphorylation of KIT in a dose-dependent manner. In MTS assay, EXEL-0862 decreased viability in both mast cell lines with a more potent inhibitory effect on HMC1.2 cells (IC50 was 510 nM in HMC1.1, and 350 nM in HMC1.2 cells, p ex vivo  antineoplastic effect of EXEL-0862 on mast cells from bone marrow samples from patients with mastocytosis. Treatment with 0.1 to 1.0 μM EXEL-0862 for 7 days resulted in a significant reduction in the mast cell percentage determined by flow cytometry (n=3). Taken together, our results demonstrated EXEL-0862 to be a potent mutated KIT inhibitor, which warrants clinical investigation of this compound in systemic mastocytosis.