tbuckley/cabot-search huggingface dataset:
PROGNOSTIC SIGNIFICANCE OF SERUM CHOLINESTERASE IN PATIENTS ADMITTED FOR ACUTE DECOMPENSATED HEART FAILURE
Authors: Masahiro Seo, Takahisa Yamada, Takashi Morita, Yoshio Furukawa, Shunsuke Tamaki, Yusuke Iwasaki, Masato Kawasaki, Atsushi Kikuchi, Tsutomu Kawai, Eiji Fukuhara, Iyo Ikeda, Jun Nakamura, Makoto Abe, Kiyomi Kayama, Masatsugu Kawahira, Kazuya Tanabe, Masatake Fukunami
Journal: Journal of the American College of Cardiology (2018)
DE-ESCALATION OF ANTIANGINAL MEDICATIONS AFTER SUCCESSFUL CHRONIC TOTAL OCCLUSION PCI: FREQUENCY AND RELATIONSHIP WITH HEALTH STATUS
Authors: Mohammed Qintar, Taishi Hirai, Justin Sheehy, James Sapontis, Philip Jones, Yuanyuan Tang, William L. Lombardi, Dimitrios I. Karmpaliotis, Jeffrey Moses, David Cohen, John Spertus, James Aaron Grantham, Suzanne Arnold, Adam Salisbury
Journal: Journal of the American College of Cardiology (2018)
Emergency admissions rise 24% in past decade, costing almost £14bn a year
Authors: Adrian O’Dowd
Journal: BMJ (2018)

Emergency admissions to hospitals in England are still a significant drain on NHS resources—costing around 10% of the entire annual NHS budget—despite efforts to reduce them, according to the public spending watchdog.

In a report1 published on 2 March, the National Audit Office (NAO) said that the average annual cost of dealing with such emergency admissions had reached £13.7bn (€15.4bn; $18.9bn) in 2015-16.

Doctors’ leaders have said the situation is symptomatic of an “entirely congested and underfunded health system.”

The watchdog said that emergency admissions were a serious challenge to both the service and financial position of the NHS, despite the fact that progress had been made in some areas in the past four years in managing the impact on …
Early long-term administration of the CSF1R inhibitor PLX3397 ablates microglia and reduces accumulation of intraneuronal amyloid, neuritic plaque deposition and pre-fibrillar oligomers in 5XFAD mouse model of Alzheimer’s disease
Authors: Justyna Sosna, Stephan Philipp, Ricardo Albay, Jorge Mauricio Reyes-Ruiz, David Baglietto-Vargas, Frank M. LaFerla, Charles G. Glabe
Journal: Molecular Neurodegeneration (2018)

Besides the two main classical features of amyloid beta aggregation and tau-containing neurofibrillary tangle deposition, neuroinflammation plays an important yet unclear role in the pathophysiology of Alzheimer's disease (AD). Microglia are believed to be key mediators of neuroinflammation during AD and responsible for the regulation of brain homeostasis by balancing neurotoxicity and neuroprotective events. We have previously reported evidence that neuritic plaques are derived from dead neurons that have accumulated intraneuronal amyloid and further recruit Iba1-positive cells, which play a role in either neuronal demise or neuritic plaque maturation or both. To study the impact of microglia on neuritic plaque development, we treated two-month-old 5XFAD mice with a selective colony stimulation factor 1 receptor (CSF1R) inhibitor, PLX3397, for a period of 3 months, resulting in a significant ablation of microglia. Directly after this treatment, we analyzed the amount of intraneuronal amyloid and neuritic plaques and performed behavioral studies including Y-maze, fear conditioning and elevated plus maze. We found that early long-term PLX3397 administration results in a dramatic reduction of both intraneuronal amyloid as well as neuritic plaque deposition. PLX3397 treated young 5XFAD mice also displayed a significant decrease of soluble fibrillar amyloid oligomers in brain lysates, a depletion of soluble pre-fibrillar oligomers in plasma and an improvement in cognitive function measured by fear conditioning tests. Our findings demonstrate that CSF1R signaling, either directly on neurons or mediated by microglia, is crucial for the accumulation of intraneuronal amyloid and formation of neuritic plaques, suggesting that these two events are serially linked in a causal pathway leading to neurodegeneration and neuritic plaque formation. CSF1R inhibitors represent potential preventative or therapeutic approach that target the very earliest stages of the formation of intraneuronal amyloid and neuritic plaques.
What is the average week for a clinical oncologist like?
Authors: Justin Stebbing
Journal: BMJ (2005)

Have a career or related problem that needs answering? Can't find the right person to point you in the right direction? Log on to the Advice Zone 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. [www.bmjcareers.com/advicezone][1] [1]: http://www.bmjcareers.com/advicezone
Confabulation and epistemic authority
Authors: Sarah Robins
Journal: Behavioral and Brain Sciences (2018)

Abstract Mahr &amp; Csibra (M&amp;C) claim that episodic remembering's autonoetic character serves as an indicator of epistemic authority. This proposal is difficult to reconcile with the existence of confabulation errors – where participants fabricate memories of experiences that never happened to them. Making confabulation errors damages one's epistemic authority, but these false memories have an autonoetic character.
von Willebrand factor.
Authors: Z M Ruggeri
Journal: Journal of Clinical Investigation (1997)

The adhesive protein von Willebrand factor contributes to platelet function by mediating the initiation and progression of thrombus formation at sites of vascular injury. In the last 2 years, there has been considerable progress in explaining the biologic properties of von Willebrand factor. The three-dimensional structure of specific domains has been explained, with the demonstration of distinct conformational changes in the A1 domain caused by single amino acid substitutions associated with enhanced binding to platelets. The structural and functional properties of the interaction between the von Willebrand factor A1 domain and glycoprotein Ibalpha have also been elucidated in greater detail, bringing researchers closer to understanding how this adhesive bond can oppose the fluid dynamic effects of rapidly flowing blood to initiate thrombus formation and, concurrently, contribute to platelet activation. Because hemodynamic forces greatly influence platelet responses to vascular injury in stenosed and partially occluded arteries, a detailed description of how von Willebrand factor interacts with tissues and platelets may help in the design of more specific therapeutic inhibitors of arterial thrombosis. Moreover, enlightening findings have been obtained on the link between regulation of von Willebrand factor multimer size and microvascular thrombosis. This progress in basic research has provided critical information to define with greater precision the role of von Willebrand factor in vascular biology and pathology.
Activation of an unconventional meroterpenoid gene cluster in Neosartorya glabra leads to the production of new berkeleyacetals
Authors: Tao Zhang, Jun Wan, Zhajun Zhan, Jian Bai, Bingyu Liu, Youcai Hu
Journal: Acta Pharmaceutica Sinica B (2018)

Fungal genomes carry many gene clusters seemingly capable of natural products biosynthesis, yet most clusters remain cryptic or down-regulated. Genome mining revealed an unconventional paraherquonin-like meroterpenoid biosynthetic gene cluster in the chromosome of
PRL-3 is a potential glioblastoma prognostic marker and promotes glioblastoma progression by enhancing MMP7 through the ERK and JNK pathways
Authors: Nan Mu, Jintao Gu, Nannan Liu, Xiaochang Xue, Zhen Shu, Kuo Zhang, Tonglie Huang, Chu Chu, Wangqian Zhang, Li Gong, Huadong Zhao, Bo Jia, Dakuan Gao, Lei Shang, Wei Zhang, Qingdong Guo
Journal: Theranostics (2018)

Purpose: Glioblastoma is the most common and aggressive type of primary brain malignancy and is associated with a poor prognosis. Previously, we found that phosphatase of regenerating liver-3 (PRL-3) was significantly up-regulated in glioblastoma as determined by a microarray analysis. However, the function of PRL-3 in glioblastoma remains unknown. We aimed to investigate the clinical relationship between PRL-3 and glioblastoma, and uncover the mechanisms of PRL-3 in the process of glioblastoma. Methods: PRL-3 expression was evaluated in 61 glioblastoma samples and 4 cell lines by RT-qPCR and immunohistochemistry. Kaplan-Meier analysis was performed to evaluate the prognostic value of PRL-3 for overall survival (OS) and progression-free survival (PFS) for glioblastoma patients. Proliferation was evaluated by Cell Counting Kit-8 (CCK-8) assay and EdU proliferation assay, migration and invasion by wound-closure/Transwell assays, and qRT-PCR/immunoblotting/IHC were used for both in vivo and in vitro investigations. Result: A high PRL-3 expression level was closely correlated with unfavorable OS and PFS for glioblastoma patients, and was also significantly correlated with Ki-67 expression. Down-regulation of PRL-3 inhibited glioma cell proliferation, invasion and migration through ERK/JNK/matrix metalloproteinase 7 (MMP7) in vitro and in vivo. Conclusions: PRL-3 expression enhances the invasion and proliferation of glioma cells, highlighting this phosphatase as a novel prognostic candidate and an attractive target for future therapy in glioblastoma.
English patients are mostly positive about their GPs
Authors: Helen Jaques
Journal: BMJ (2012)

Most patients in England are happy with the way their GP handles consultations and trust their doctor, the annual GP patient survey for 2011-12 has found.

The survey of more than a million patients in England (38% response rate), conducted by Ipsos Mori on behalf of the Department of Health, found that most respondents thought their GP was good at listening (88%), gave them enough time for their consultation (87%), treated them with care and concern (84%), explained tests and treatments (83%), and involved them in decisions about their care (76%). …
Building an evidence base for the primary care workforce
Authors: Vari M Drennan, Simon de Lusignan, Heather Gage, Jon Gabe, Mary Halter
Journal: BMJ (2018)

Building an evidence base for the effects of different types of staff in general practice is challenging and takes time. McCartney is right to say that no evidence shows that physician associates make a difference to clinician stress and burnout.1 But more evidence is available than she suggests, which may be important at a time of considerable vacancies for …
Response to platinum-based therapy (PBT) and immune checkpoint inhibitors (ICI) in metastatic urothelial carcinoma (mUC) patients (pts) with genomic alterations (GA) in homologous recombination repair (HRR) genes.
Authors: Prateek Mendiratta, Andrea Loehr, Andrew Simmons, Pedro C. Barata, Stefan Klek, Amy Pritchard, Hamid Emamekhoo, Pauline Funchain, Davendra Sohal, Siraj Mahamed Ali, Timothy D. Gilligan, Moshe Chaim Ornstein, Jorge A. Garcia, Brian I. Rini, Petros Grivas
Journal: Journal of Clinical Oncology (2018)

447 Background: Deleterious GA in genes of the HRR pathway and tumor mutational load (TML; mutations/Mb) were shown to predict response to PBT and ICI; further validation can be informative. We assessed the predictive role of such GA in mUC. Methods: Tissue from mUC pts treated with PBT or ICI in the 1 st line setting underwent genomic profiling (GP) via FoundationOne. Pts were analyzed in 2 groups based on the presence of potentially function-impairing GA (using classification criteria) in any of 15 pre-selected HRR genes. Exploratory assessment of overall response rate (ORR; RECIST v1.1), progression-free and overall survival (PFS, OS) based on presence of relevant GA was performed using Cox proportional hazards model, Kaplan Meier estimates, and Fisher’s exact test. Results: GA were noted in 22% of 88 identified mUC pts with available GP from 2012 to 2017. The most common deleterious GA were BRCA1/2 (n=6), ATM (n=6), CDK12 (n=2), BRIP1 (n=2), BARD1 (n=1), RAD51 (n=1), and CHEK2 (n=1). Of 88 pts, 62 were treated in the 1 st line setting (median age 69; 27% women; 42% never smokers). Of these 62 pts, 42 received PBT and 20 ICI. Deleterious GAs were noted in ≥1 HR gene in 24% and 10% of pts in each group, respectively. The ORR was 40% and 43% in PBT pts with and without GA in any HRR gene, respectively. Analysis showed a median OS (10.6 vs 14.3 months, p=0.11), median PFS (6.1 vs 7.9 months, p=0.05), and no difference in the rate of responders vs non-responders (p=0.53) to PBT in pts with vs without GA in HRR genes. Analysis of ICI treated pts was not feasible (only 2 had GA in HRR genes). Median TML was 8 and 10 in pts with available data treated with PBT and ICI, respectively. There was no correlation between TML and response to either 1 st line therapy (analysis underpowered). Of pts with GA in HR genes, the one with the longest OS had 2 GA (CDK12; FANCA). Conclusions: Deleterious GAs in genes of HRR pathway are frequent in mUC supporting TCGA and other datasets but did not confer sensitivity to 1 st line PBT in our relatively small cohort. Further biomarker validation combined with LOH assessment can inform decision making and clinical trial designs.
PROCEDURAL AND ONE-YEAR OUTCOMES IN PATIENTS TREATED WITH ROTATIONAL VERSUS ORBITAL ATHERECTOMY WITH MECHANISTIC INSIGHTS USING OPTICAL COHERENCE TOMOGRAPHY
Authors: Naotaka Okamoto, Hiroshi Ueda, Samit Bhatheja, Yuliya Vengrenyuk, Melissa Aquino, Samaneh Rabiei, Nitin Barman, Joseph Sweeny, Vishal Kapur, Choudhury Hasan, Javed Suleman, Roxana Mehran, Usman Baber, Annapoorna Subhash Kini, Samin K. Sharma
Journal: Journal of the American College of Cardiology (2018)
Prognostic significance of circulating plasma cells by multi-parametric flow cytometry in light chain amyloidosis
Authors: Surbhi Sidana, Nidhi Tandon, Angela Dispenzieri, Morie A. Gertz, David Dingli, Dragan Jevremovic, William G. Morice, Prashant Kapoor, Taxiarchis V. Kourelis, Martha Q. Lacy, Suzanne R. Hayman, Francis K. Buadi, Nelson Leung, Ronald S. Go, Yi Lin, Stephen J. Russell, John A. Lust, Steven R. Zeldenrust, Rahma Warsame, Yi L. Hwa, Miriam Hobbs, Amie Fonder, Robert A. Kyle, S. Vincent Rajkumar, Shaji K. Kumar, Wilson I. Gonsalves
Journal: Leukemia (2018)
The Medic's Guide to Work and Electives around the World
Authors: Nick Banatvala
Journal: BMJ (2005)

I 'd recommend this book—a Lonely Planet guide, if you like, for healthcare workers, with many of the same strengths and limitations of that series.

A second edition always has the advantage of having been tried and tested; initial teething problems will hopefully have been ironed out. A great deal more information has been added to this edition. The book is divided into three sections: Getting Ready, Destinations, and Adventure Medicine (expedition, diving, mountain medicine, and so on). An appendix includes details on nongovernmental agencies, travel bursaries, vaccine requirements, and embassies and …
PROGNOSTIC VALUE OF DIMENSIONLESS INDEX IN PATIENTS WITH BIOLOGICAL HEART VALVE PROSTHESES
Authors: Issa Farah Issa, Steen Poulsen, Farhad Waziri, Christian Torp-Pedersen, Lars Riber, Jordi Dahl, Peter Søgaard, Jacob Møller
Journal: Journal of the American College of Cardiology (2018)
Comparative effectiveness of a patient-centered prostate biopsy report in clinical prostate cancer practice.
Authors: Jasmir G. Nayak, Nicholas Scalzo, Alice Chu, Geolani Dy, Liam Connor Macleod, James T Kearns, Matthew Mossanen, William J. Ellis, Daniel W. Lin, Lawrence D. True, John L. Gore
Journal: Journal of Clinical Oncology (2018)

145 Background: The prostate biopsy pathology report is a critical decision-making document for men newly-diagnosed with prostate cancer, yet the content may be beyond the health literacy of most patients. We compare the effectiveness of a patient-centered prostate biopsy report developed through patient-centered outcomes research methods with standard synoptic reports. Methods: Using a modified Delphi approach, a multidisciplinary group of prostate cancer experts provided consensus for the critical components of a prostate biopsy report for treatment decision-making. Patient focus groups provided input for syntax and formatting to inform the design of a patient-centered pathology report. 94 patients with recent prostate biopsies were block randomized to receive the standard report with or without the patient-centered report. We evaluated patient self-efficacy, provider communication and empathy, and prostate cancer knowledge at pathology disclosure. We compared study groups with descriptive statistics. Results: Experts selected primary and secondary Gleason score and number of positive cores as the important elements of a prostate biopsy report. Patients prioritized a narrative word structure, clear language, a tabular format for histologic grade, and information on risk classification. Initial assessments were completed by 84% (79/94) of participants including 40/46 in the standard report group and 39/48 in the patient-centered report group. Patients who received the patient-centered report had significantly improved ability to recall their Gleason score (100% vs. 85%, p = 0.03) and number of positive cores (90% vs. 65%, p = 0.01). Provider communication and patient self-efficacy were uniformly high and did not differ between groups. 88% of patients who received the patient-centered report felt that it helped them better understand their pathology results. Conclusions: A patient-centered prostate biopsy pathology report is associated with significantly higher knowledge about a new prostate cancer diagnosis. These health information documents may help facilitate shared decision-making among patients newly diagnosed with prostate cancer.
NATIONWIDE TRENDS AND OUTCOMES OF TEMPORARY MECHANICAL CIRCULATORY SUPPORT FOR CARDIOGENIC SHOCK AFTER LEFT VENTRICULAR ASSIST DEVICE IMPLANTATION
Authors: Saraschandra Vallabhajosyula, Shilpkumar Arora, Ankit Sakhuja, Sopan Lahewala, Varun Kumar, Ghanshyam P.S. Shantha, Bernard J. Gersh, Rajiv Gulati, Abhiram Prasad, Abhishek J. Deshmukh
Journal: Journal of the American College of Cardiology (2018)
Diary of a major incident
Authors: Kaji Sritharan, Vivian A Elwell
Journal: BMJ (2005)

On the morning of Thursday 7 July 2005, London was the target of a long-predicted terrorist attack. Junior doctors <i>Kaji Sritharan</i> and <i>Vivian Elwell</i> have been finding out how the major incident response unfolded from key players on the day
Natural History of Chronic Obstructive Pulmonary Disease Exacerbations in a General Practice–based Population with Chronic Obstructive Pulmonary Disease
Authors: Kieran J. Rothnie, Hana Müllerová, Liam Smeeth, Jennifer K. Quint
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) are important adverse events in the natural history of chronic obstructive pulmonary disease (COPD).To investigate the natural history of AECOPDs over 10 years of follow-up.We identified 99,574 patients with COPD from January 1, 2004, to March 31, 2015, from the UK Clinical Practice Research Datalink. We defined moderate AECOPDs as those managed outside hospital and severe as those requiring hospitalization. During the baseline period (first year of follow-up), patients were grouped according to the number and severity of AECOPDs and then followed for a maximum of 10 years (mean, 4.9 yr). We investigated the effect of baseline AECOPD number and severity on risk of further events and death.Around one-quarter of the patients with COPD did not exacerbate during follow-up. Compared with no AECOPDs in the baseline period, AECOPD number predicted the future long-term rate of AECOPDs in a graduated fashion, ranging from hazard ratio (HR) of 1.71 (1.66-1.77) for one event to HR of 3.41 (3.27-3.56) for five or more events. Two or more moderate AECOPDs were also associated with an increased risk of death in a graduated fashion, ranging from HR of 1.10 (1.03-1.18) for two moderate AECOPDs to HR of 1.57 (1.45-1.70) for five or more moderate AECOPDs, compared with those with no AECOPDs at baseline. Severe AECOPDs were associated with an even higher risk of death (HR, 1.79; 1.65-1.94).A large proportion of patients with COPD do not exacerbate over a maximum 10 years of follow-up. AECOPD frequency in a single year predicts long-term AECOPD rate. Increasing frequency and severity of AECOPDs is associated with risk of death and highlights the importance of preventing AECOPDs.
Clinical Evolution in Patients With New‐Onset Inflammatory Back Pain
Authors: Runsheng Wang, Cynthia S. Crowson, Kerry Wright, Michael M. Ward
Journal: Arthritis & Rheumatology (2018)

Objective Inflammatory back pain ( IBP ) is often an early manifestation of spondyloarthritis (SpA), but the prognosis of patients with incident IBP is unknown. This study was undertaken to investigate long‐term outcomes in patients with IBP , and predictors of progression to SpA, in a population‐based cohort. Methods We conducted a retrospective, longitudinal study using the Rochester Epidemiology Project, a longstanding population‐based cohort of residents of Olmsted County, MN . Patients ages 16–35 years with clinical visits for back pain from 1999 to 2003 were identified, and we screened these patients for the presence of new‐onset IBP and performed medical record reviews to collect data on clinical, laboratory, and imaging features of SpA. Outcomes in these patients were followed up until July 2016. We used survival analysis for competing risks to examine progression to either SpA, a non‐SpA diagnosis, or resolution of back pain. Recursive partitioning was used to identify predictors of progression to SpA. Results Among 5,304 patients with back pain, we identified 124 patients with new‐onset IBP . After a median follow‐up of 13.2 years, IBP had progressed to SpA in 39 patients, 15 patients developed a non‐SpA diagnosis, and 58 patients had resolution of IBP . At 10 years, the probability of having SpA was 30%, while the probability of resolution of IBP was 43%. The most important predictors for progression to SpA were uveitis, male sex, and family history of SpA. Conclusion In a minority of patients, new‐onset IBP progresses to SpA, while IBP resolves in many. That IBP often resolves may explain the difference between the prevalence of IBP (3–6%) and the prevalence of SpA (0.4–1.3%).