tbuckley/cabot-search huggingface dataset:
ORGANIZATION OF THROMBUS CONTRIBUTES TO RAPID PROGRESSION OF CORONARY ARTERY DISEASE: A SERIAL CORONARY ANGIOGRAMS AND OPTICAL COHERENCE TOMOGRAPHY STUDY
Authors: Kenichi Fujii, Satoru Otsuji, Shin Takiuchi, Wataru Yamamoto, Kasumi Ishibuchi, Hiroto Tamaru, Katsuyuki Hasegawa, Rui Ishii, Sho Nakabayashi, Motoaki Ibuki, Shinya Nagayama, Yorihiko Higashino
Journal: Journal of the American College of Cardiology (2018)
Review: In hypertension, BP self-monitoring interventions improve BP levels and BP control at 12 months
Authors: David Siegel
Journal: Annals of Internal Medicine (2018)

Source Citation Tucker KL, Sheppard JP, Stevens R, et al. Self-monitoring of blood pressure in hypertension: a systematic review and individual patient data meta-analysis. PLoS Med. 2017;14:e1002389. 28926573
Over 5000 GPs have been prevented from returning to work, says RCGP
Authors: Abi Rimmer
Journal: BMJ (2014)

“Unnecessary and excessive bureaucratic hurdles” have prevented more than 5000 GPs from returning to work, the Royal College of General Practitioners (RCGP) has said.

The college said that, over the past five years, 5229 GPs aged under 50 had left the workforce, of whom 3151 were under 40. Of the GPs who had left, it said that many had wanted to return to the workforce but were prevented from doing so by bureaucratic requirements associated with returning to practice. 

The RCGP and the BMA have written to NHS England calling for greater flexibility in applying the regulations …
Self-questionnaire to assess patient’s preferences for participation in phase I clinical trials
Authors: B. Verret, A. Perret, S. Delaloge, B. Besse, A. Le Cesne, A. Hollebecque, C. Baldini, C. Massard, J.-C. Soria, S. Postel-Vinay
Journal: Annals of Oncology (2018)
First interim results of the Radium-223 (Ra-223) reassure observational study in metastatic castration-resistant prostate cancer (mCRPC): Safety and baseline (BL) characteristics of U.S. patients (Pts) by prior/concomitant treatment (Tx).
Authors: Lauren Christine Harshman, A. Oliver Sartor, Timothy Richardson, John Sylvester, Daniel Y. Song, Constantine Mantz, Robert K. Brookland, Mark Perlmutter, Robert Given, Jan Kalinovsky, Svetlana Babajanyan, Yoriko De Sanctis, Celestia S. Higano
Journal: Journal of Clinical Oncology (2018)

233 Background: Ra-223, a targeted alpha therapy, extended survival and had a favorable safety profile at 3 years’ follow up in pts with mCRPC in the pivotal phase 3 ALSYMPCA trial. The maturing global, prospective, single-arm, observational REASSURE study, designed to evaluate long-term safety at 7 years’ follow up, enrolled pts with mCRPC with bone metastases planned to receive Ra-223. Methods: We performed a descriptive analysis of safety and BL characteristics of US pts according to prior or concomitant abiraterone/enzalutamide (abi/enza) or prior docetaxel/cabazitaxel (chemo) using data from the first planned interim analysis (pts receiving ≥1 Ra-223 dose; median follow up 8 mo). Results: 244 US pts were included; 80% had no prior chemo. Prior abi/enza and/or chemo pts had higher median BL PSA and were less likely to complete 5-6 doses (Table). Subgroups had similar median ALP, LDH and Hb. Overall, drug-related tx-emergent AEs occurred in 71 pts (29%) and serious AEs in 9 (3.7%). Most common AEs were diarrhea, fatigue and anemia. AE incidence was numerically higher in pts who received prior chemo and/or abi/enza. Clinical trial information: NCT02141438. Conclusions: To date, REASSURE has not revealed any new safety findings and most pts complete 5-6 Ra-223 doses in routine US clinical practice. Pts with prior tx lines had lower Ra-223 tx completion and higher AE incidence, likely reflecting greater disease burden, as evidenced by higher median BL PSA.[Table: see text]
Initial experience with a sensorimotor rhythm-based brain-computer interface in a Parkinson’s disease patient
Authors: Kazumi Kasahara, Hideki Hoshino, Yoshihiko Furusawa, Charles Sayo DaSalla, Manabu Honda, Miho Murata, Takashi Hanakawa
Journal: Brain-Computer Interfaces (2018)

Brain-computer interfaces (BCIs) show potential as neuroprosthetic and neurorehabilitative interventions for patients with motor impairments. However, recent evidence suggests that BCIs depend on cortico-striatal circuit function, implying that patients with impaired cortico-striatal circuits may have difficulty using BCIs. In this pilot study, we applied a sensorimotor rhythm (SMR)-based BCI to a patient with Parkinson's disease. The patient was required to change the path of a falling cursor to either the right or the left by generating laterality in SMRs. The patient performed the BCI in separate sessions, namely while off and on antiparkinsonian medication. The online BCI success rate was higher in the on-medication condition (65.0%) than in the off-medication condition (58.3%). Particularly, for Right trials, event-related desynchronization of SMR was also more evident in the on-medication condition than in the off-medication condition. This preliminary result suggests a possible way via which patients with dopamine deficiency could control SMR-based BCIs.
I am a doctor from the European Economic Area and am fully registered with the General Medical Council. I am interested in a career in neurosurgery. How should I go about this?
Authors: Ramesh Chelvarajah
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.
DIFFERENTIAL EFFECTS OF SIROLIMUS- AND CALCINEURIN INHIBITOR-ASSOCIATED HYPERLIPIDEMIA ON CARDIAC ALLOGRAFT VASCULOPATHY PROGRESSION AND OUTCOMES AFTER HEART TRANSPLANTATION
Authors: Rabea Asleh, Alexandros Briasoulis, Naveen Pereira, Brooks Edwards, Alfredo Clavell, Barry Boilson, Robert Frantz, John Schirger, Richard Rodeheffer, Simon Maltais, John Stulak, Richard Daly, Amir Lerman, Sudhir Kushwaha
Journal: Journal of the American College of Cardiology (2018)
Rituximab May Cause Increased Hepatitis C Virus Viremia in Rheumatoid Arthritis Patients Through Declining Exosomal MicroRNA‐155
Authors: Tsai‐Ling Liao, Shie‐Liang Hsieh, Yi‐Ming Chen, Hsin‐Hua Chen, Hung‐Jen Liu, Hsiu‐Chin Lee, Der‐Yuan Chen
Journal: Arthritis & Rheumatology (2018)

Several studies have shown that rituximab may enhance hepatitis C virus (HCV) activity. MicroRNAs (miRNAs) have been implicated in modulating the host immune response in HCV infection; miRNAs can be packaged into the exosomes and then shuttled by the exosomes to aid biologic functions. However, the role of exosomal miRNAs (exo-miRNAs) in rituximab-related HCV activity enhancement remains unclear.The association between rituximab and increased HCV activity was examined using an in vitro cell-based assay. Purified exosomes were confirmed using immunoblotting and flow cytometry and quantified using enzyme-linked immunosorbent assay. Exosomal miRNA-155 (exo-miR-155) levels were measured using quantitative reverse transcription-polymerase chain reaction.In vitro data showed that B cell-derived miR-155 could inhibit HCV replication in hepatocytes through exosome transmission. Rituximab could both induce B cell depletion and affect intracellular miR-155 production as well as exo-miR-155 transmission and then enhance HCV activity in hepatocytes (P < 0.005). Serum exosome levels were increased in rheumatoid arthritis (RA) patients with HCV infection compared with the levels in RA patients without HCV infection (P < 0.01). The exo-miR-155 levels were significantly increased in RA patients with HCV infection compared with those without infection (P < 0.01). A significantly greater decrement of exo-miR-155 expression was observed after rituximab therapy compared with those observed before therapy (P < 0.01), and hepatitis C viral loads increased simultaneously (P < 0.05).Circulating exo-miR-155 levels were negatively correlated with hepatitis C viral loads and subsequently associated with rituximab-related HCV activity enhancement in RA patients. Exo-miR-155 may become a potential diagnostic biomarker or therapeutic target.
Bile acids stimulate cholangiocyte fluid secretion by activation of transmembrane member 16A Cl− channels
Authors: Qin Li, Amal Dutta, Charles Kresge, Abhijit Bugde, Andrew P. Feranchak
Journal: Hepatology (2018)

Bile acids stimulate a bicarbonate-rich choleresis, in part, through effects on cholangiocytes. Because Cl- channels in the apical membrane of cholangiocytes provide the driving force for secretion and transmembrane member 16A (TMEM16A) has been identified as the Ca2+ -activated Cl- channel in the apical membrane of cholangiocytes, the aim of the present study was to determine whether TMEM16A is the target of bile-acid-stimulated Cl- secretion and to identify the regulatory pathway involved. In these studies of mouse, rat, and human biliary epithelium exposure to ursodeoxycholic acid (UDCA) or tauroursodeoxycholic acid (TUDCA) rapidly increased the rate of exocytosis, ATP release, [Ca2+ ]i , membrane Cl- permeability, and transepithelial secretion. Bile-acid-stimulated Cl- currents demonstrated biophysical properties consistent with TMEM16A and were inhibited by pharmacological or molecular (small-interfering RNA; siRNA) inhibition of TMEM16A. Bile acid-stimulated Cl- currents were not observed in the presence of apyrase, suramin, or 2-aminoethoxydiphenyl borate (2-APB), demonstrating that current activation requires extracellular ATP, P2Y, and inositol 1,4,5-trisphosphate (IP3) receptors. TUDCA did not activate Cl- currents during pharmacologic inhibition of the apical Na+ -dependent bile acid transporter (ASBT), but direct intracellular delivery of TUDCA rapidly activated Cl- currents.Bile acids stimulate Cl- secretion in mouse and human biliary cells through activation of membrane TMEM16A channels in a process regulated by extracellular ATP and [Ca2+ ]i . These studies suggest that TMEM16A channels may be targets to increase bile flow during cholestasis. (Hepatology 2018;68:187-199).
Radiation dose to the thoracic vertebral bodies and impact on hematologic toxicity in patients receiving concurrent chemoradiation for esophageal cancer.
Authors: Denise Fabian, Dominic J. DiCostanzo, Christian Barney, Jihad Aljabban, Evan John Wuthrick, Terence Marques Williams, Jose G. Bazan
Journal: Journal of Clinical Oncology (2018)

105 Background: Concurrent chemotherapy and radiation (CRT) for the treatment of esophageal cancer (EC) is associated with acute hematologic toxicity (HT). There are few data evaluating the relationship between radiation dose (RT) to the thoracic vertebral bodies (TVB) and the development of HT in EC patients receiving CRT. We hypothesized that increasing RT to the TVB contributes to the development of HT in EC patients receiving CRT. Methods: We identified cases of EC treated with curative intent CRT from 2007-2016. We retrospectively contoured the thoracic vertebral bodies (TVB). The TVB-mean dose and the TVB V5-V50 were calculated from the dose volume histogram. HT was graded according to the Common Terminology Criteria for Adverse Events, v4 based on leukocyte, neutrophil, and platelet nadirs during CRT. Grade≥3 HT (HT3+) was the primary endpoint. Logistic regression was used to test associations between HT3+ and dosimetric/clinical parameters. Results: We included 137 cases: 115 males (84%); median age 61 years (Interquartile range [IQR], 55-67); predominantly stage III (54%). Most patients received concurrent carboplatin/paclitaxel (N = 83). Median RT dose was 50.4 (IQR = 50.4-50.4) Gy, and the majority underwent surgery (60.6%). The rate of HT3+ was 39.4% (N = 54) at a median of 28 (IQR = 21-32) days after CRT start. On univariate analysis, a 5% increase in TVB-V40 was associated with increased odds of HT3+ (OR = 1.13, 95% CI 1.04-1.23, p = 0.0004). TVB-mean and TVB V30-V50, age (OR = 1.04, p = 0.03), males (OR = 0.38, p = 0.04), and carboplatin/paclitaxel vs. other regimen (OR = 2.66, p = 0.01) were significantly associated with HT3+, while BMI was not (OR = 1.00, p = 0.94). On multivariate analysis, TVB-V40 (OR = 1.20, p = 0.0004), carboplatin/paclitaxel (OR = 4.84, p = 0.0007), and age (OR = 1.04, p = 0.03) were independently associated with HT3+ while male gender (OR = 0.48, p = 0.16) was not. The results were similar for TVB-mean and TVB V30-V50. Conclusions: We found that increasing TVB dose was associated with HT3+ in EC patients treated with CRT. This suggests that efforts to spare RT to the TVB may reduce rates of HT3+ and prospective evaluation of these results is needed.
HEE plans to embed patient safety into training
Authors: Abi Rimmer
Journal: BMJ (2014)

Health Education England (HEE) has established a board to ensure that medical education and training focus on the importance of patient safety.

The HEE safety board will be chaired by Norman Williams, past president of the Royal College of Surgeons, with Keith Pearson, chair of HEE, acting as vice chair. They will seek additional members to join the board, set out a work programme, and invite evidence in the …
Harnessing biochemical and structural cues for tenogenic differentiation of adipose derived stem cells (ADSCs) and development of an in vitro tissue interface mimicking tendon-bone insertion graft
Authors: Sajeesh Kumar Madhurakkat Perikamana, Jinkyu Lee, Taufiq Ahmad, Eun Mi Kim, Hayeon Byun, Sangmin Lee, Heungsoo Shin
Journal: Biomaterials (2018)
Regional variation in the costs of treating curative gastric cancer.
Authors: Yunni Jeong, Alyson L. Mahar, Brandon Zagorski, Natalie Coburn
Journal: Journal of Clinical Oncology (2018)

165 Background: Gastric cancer is a highly morbid and fatal disease. While the clinical challenge with gastric cancer is widely described, little is known about the economic burden of the disease. Many guidelines outline the curative treatment for gastric cancer and in a universal healthcare system, equal access and uniform healthcare delivery is predicted. Yet, regional variation in practice exists and may result in increased healthcare costs. We therefore aimed to investigate of the costs of treating curative gastric cancer, explore regional variation in costs, and to identify the factors which drive these costs. Methods: We conducted a patient-level cost analysis of curative-intent stage I-III gastric cancer diagnosed between 2005 and 2008 from the perspective of a universal healthcare system, using a 26-month time horizon. Clinical and stage data were abstracted from a provincial chart review. Costs associated with physician billings, same day surgery, hospitalization, drug benefits, emergency department visits, continuing care, and long-term care were derived using administrative healthcare databases and compared among healthcare regions. Costs were inflated to 2017 United States dollars (USD). We used a linear regression model to identify factors predictive of these treatment costs. Results: A total of 722 patients with Stage I-III gastric cancer were identified. Mean costs per region ranged from $55,650 to $92,852 (USD) across 14 health regions. The lowest contributing cost sector was long-term care and the highest contributing proportion of costs was from hospital admissions. A laparoscopic surgical approach was predictive of lower costs while age over 70 years and death at one year from diagnosis was predictive of higher costs. Conclusions: Regional variation exists in the treatment costs for patients with curative gastric cancer despite guidelines directing appropriate care and healthcare delivery in a universal healthcare system. Governmental intervention to ensure quality care delivery is necessary for improved and sustainable curative gastric cancer care across regions.
Pay proposals may penalise consultants who don’t comply with management goals, BMA warns
Authors: Helen Jaques
Journal: BMJ (2013)

Proposed changes to the clinical excellence awards and to consultants’ pay scales could allow organisations to financially penalise consultants who did not comply with managers’ objectives, the BMA has warned.

The Review Body on Doctors’ and Dentists’ Remuneration (DDRB) has suggested that local clinical excellence and distinction awards for NHS consultants should be awarded on the basis of job performance.1 The DDRB proposed that this should include doctors’ contribution to their employing organisation’s objectives.

Under the plans, employers would review doctors’ performance annually. They would …
IMPACT OF BASELINE THROMBOCYTOPENIA ON IN-HOSPITAL OUTCOMES AFTER PERCUTANEOUS CORONARY INTERVENTIONS: ANALYSIS OF OVER 70,000 PATIENTS
Authors: Karam Ayoub, Gbolahan Ogunbaya, Meera Marji, Bassam Ayoub, Ahmed Abdel-Latif, Khaled Ziada, Srikanth Vallurupalli
Journal: Journal of the American College of Cardiology (2018)
Osteoblast-Secreted Factors Mediate Dormancy of Metastatic Prostate Cancer in the Bone via Activation of the TGFβRIII–p38MAPK–pS249/T252RB Pathway
Authors: Li-Yuan Yu-Lee, Guoyu Yu, Yu-Chen Lee, Song-Chang Lin, Jing Pan, Tianhong Pan, Kai-Jie Yu, Bin Liu, Chad J. Creighton, Jaime Rodriguez-Canales, Pamela A. Villalobos, Ignacio I. Wistuba, Eulalia de Nadal, Francesc Posas, Gary E. Gallick, Sue-Hwa Lin
Journal: Cancer Research (2018)

Abstract Bone metastasis from prostate cancer can occur years after prostatectomy, due to reactivation of dormant disseminated tumor cells (DTC) in the bone, yet the mechanism by which DTCs are initially induced into a dormant state in the bone remains to be elucidated. We show here that the bone microenvironment confers dormancy to C4-2B4 prostate cancer cells, as they become dormant when injected into mouse femurs but not under the skin. Live-cell imaging of dormant cells at the single-cell level revealed that conditioned medium from differentiated, but not undifferentiated, osteoblasts induced C4-2B4 cellular quiescence, suggesting that differentiated osteoblasts present locally around the tumor cells in the bone conferred dormancy to prostate cancer cells. Gene array analyses identified GDF10 and TGFβ2 among osteoblast-secreted proteins that induced quiescence of C4-2B4, C4-2b, and PC3-mm2, but not 22RV1 or BPH-1 cells, indicating prostate cancer tumor cells differ in their dormancy response. TGFβ2 and GDF10 induced dormancy through TGFβRIII to activate phospho-p38MAPK, which phosphorylates retinoblastoma (RB) at the novel N-terminal S249/T252 sites to block prostate cancer cell proliferation. Consistently, expression of dominant-negative p38MAPK in C4-2b and C4-2B4 prostate cancer cell lines abolished tumor cell dormancy both in vitro and in vivo. Lower TGFβRIII expression in patients with prostate cancer correlated with increased metastatic potential and decreased survival rates. Together, our results identify a dormancy mechanism by which DTCs are induced into a dormant state through TGFβRIII–p38MAPK–pS249/pT252–RB signaling and offer a rationale for developing strategies to prevent prostate cancer recurrence in the bone. Significance: These findings provide mechanistic insights into the dormancy of metastatic prostate cancer in the bone and offer a rationale for developing strategies to prevent prostate cancer recurrence in the bone. Cancer Res; 78(11); 2911–24. ©2018 AACR.
Current Challenges and Opportunities in the Prevention and Management of Diabetic Foot Ulcers
Authors: William J. Jeffcoate, Loretta Vileikyte, Edward J. Boyko, David G. Armstrong, Andrew J.M. Boulton
Journal: Diabetes Care (2018)

Diabetic foot ulcers remain a major health care problem. They are common, result in considerable suffering, frequently recur, and are associated with high mortality, as well as considerable health care costs. While national and international guidance exists, the evidence base for much of routine clinical care is thin. It follows that many aspects of the structure and delivery of care are susceptible to the beliefs and opinion of individuals. It is probable that this contributes to the geographic variation in outcome that has been documented in a number of countries. This article considers these issues in depth and emphasizes the urgent need to improve the design and conduct of clinical trials in this field, as well as to undertake systematic comparison of the results of routine care in different health economies. There is strong suggestive evidence to indicate that appropriate changes in the relevant care pathways can result in a prompt improvement in clinical outcomes.
The Association between Lifelong Greenspace Exposure and 3-Dimensional Brain Magnetic Resonance Imaging in Barcelona Schoolchildren
Authors: Payam Dadvand, Jesus Pujol, Dídac Macià, Gerard Martínez-Vilavella, Laura Blanco-Hinojo, Marion Mortamais, Mar Alvarez-Pedrerol, Raquel Fenoll, Mikel Esnaola, Albert Dalmau-Bueno, Mónica López-Vicente, Xavier Basagaña, Michael Jerrett, Mark J. Nieuwenhuijsen, Jordi Sunyer
Journal: Environmental Health Perspectives (2018)

Background: Proponents of the biophilia hypothesis believe that contact with nature, including green spaces, has a crucial role in brain development in children. Currently, however, we are not aware of evidence linking such exposure with potential effects on brain structure. Objective: We determined whether lifelong exposure to residential surrounding greenness is associated with regional differences in brain volume based on 3-dimensional magnetic resonance imaging (3D MRI) among children attending primary school. Methods: We performed a series of analyses using data from a subcohort of 253 Barcelona schoolchildren from the Brain Development and Air Pollution Ultrafine Particles in School Children (BREATHE) project. We averaged satellite-based normalized difference vegetation index (NDVI) across 100-m buffers around all residential addresses since birth to estimate each participant's lifelong exposure to residential surrounding greenness, and we used high-resolution 3D MRIs of brain anatomy to identify regional differences in voxel-wise brain volume associated with greenness exposure. In addition, we performed a supporting substudy to identify regional differences in brain volume associated with measures of working memory (d′ from computerized n-back tests) and inattentiveness (hit reaction time standard error from the Attentional Network Task instrument) that were repeated four times over one year. We also performed a second supporting substudy to determine whether peak voxel tissue volumes in brain regions associated with residential greenness predicted cognitive function test scores. Results: Lifelong exposure to greenness was positively associated with gray matter volume in the left and right prefrontal cortex and in the left premotor cortex and with white matter volume in the right prefrontal region, in the left premotor region, and in both cerebellar hemispheres. Some of these regions partly overlapped with regions associated with cognitive test scores (prefrontal cortex and cerebellar and premotor white matter), and peak volumes in these regions predicted better working memory and reduced inattentiveness. Conclusion: Our findings from a study population of urban schoolchildren in Barcelona require confirmation, but they suggest that being raised in greener neighborhoods may have beneficial effects on brain development and cognitive function. https://doi.org/10.1289/EHP1876
Nurses show less opposition to pension deal than doctors do
Authors: Ingrid Torjesen
Journal: BMJ (2012)

The Royal College of Nursing has formally held back from rejecting the government’s proposals on pensions after a poor response to a ballot of its members on the deal.

The ballot indicates that the strength of feeling against the pensions deal is much greater among doctors than nurses.

Nearly two thirds (62%) of members of the college who responded to the ballot, which closed on Monday, voted against the government’s pensions proposals, but only 65 759 votes were cast—a turnout …