tbuckley/cabot-search huggingface dataset:
Age-associated distribution of normal B-cell and plasma cell subsets in peripheral blood
Authors: Elena Blanco, Martín Pérez-Andrés, Sonia Arriba-Méndez, Teresa Contreras-Sanfeliciano, Ignacio Criado, Ondrej Pelak, Ana Serra-Caetano, Alfonso Romero, Noemí Puig, Ana Remesal, Juan Torres Canizales, Eduardo López-Granados, Tomas Kalina, Ana E. Sousa, Menno van Zelm, Mirjam van der Burg, Jacques J.M. van Dongen, Alberto Orfao
Journal: Journal of Allergy and Clinical Immunology (2018)

<h3>Background</h3> Humoral immunocompetence develops stepwise throughout life and contributes to individual susceptibility to infection, immunodeficiency, autoimmunity, and neoplasia. Immunoglobulin heavy chain (IgH) isotype serum levels can partly explain such age-related differences, but their relationship with the IgH isotype distribution within memory B-cell (MBC) and plasma cell (PCs) compartments remains to be investigated. <h3>Objective</h3> We studied the age-related distribution of MBCs and PCs expressing different IgH isotypes in addition to the immature/transitional and naive B-cell compartments. <h3>Methods</h3> B-cell and PC subsets and plasma IgH isotype levels were studied in cord blood (n = 19) and peripheral blood (n = 215) from healthy donors aged 0 to 90 years by using flow cytometry and nephelometry, respectively. <h3>Results</h3> IgH-switched MBCs expressing IgG<sub>1</sub>, IgG<sub>2</sub>, IgG<sub>3</sub>, IgA<sub>1</sub>, and IgA<sub>2</sub> were already detected in cord blood and newborns at very low counts, whereas CD27<sup>+</sup>IgM<sup>++</sup>IgD<sup>+</sup> MBCs only became detectable at 1 to 5 months and remained stable until 2 to 4 years, and IgD MBCs peaked at 2 to 4 years, with both populations decreasing thereafter. MBCs expressing IgH isotypes of the second immunoglobulin heavy chain constant region <i>(IGHC)</i> gene block (IgG<sub>1</sub>, IgG<sub>3</sub>, and IgA<sub>1</sub>) peaked later during childhood (2-4 years), whereas MBCs expressing third <i>IGHC</i> gene block immunoglobulin isotypes (IgG<sub>2</sub>, IgG<sub>4</sub>, and IgA<sub>2</sub>) reached maximum values during adulthood. PCs were already detected in newborns, increasing in number until 6 to 11 months for IgM, IgG<sub>1</sub>, IgG<sub>2</sub>, IgG<sub>3</sub>, IgA<sub>1</sub>, and IgA<sub>2</sub>; until 2 to 4 years for IgD; and until 5 to 9 years for IgG<sub>4</sub> and decreasing thereafter. For most IgH isotypes (except IgD and IgG<sub>4</sub>), maximum plasma levels were reached after PC and MBC counts peaked. <h3>Conclusions</h3> PC counts reach maximum values early in life, followed by MBC counts and plasma IgH isotypes. Importantly, IgH isotypes from different <i>IGHC</i> gene blocks show different patterns, probably reflecting consecutive cycles of IgH isotype switch recombination through life.
Editor’s Choice: Shackles and shields
Authors: Tom Moberly
Journal: BMJ (2015)

The world has changed a great deal since 1993, when the European Working Time Directive was originally negotiated. But one thing that hasn’t changed is the health service’s reliance on stressed and fatigued doctors.

Despite placing strict limits on the hours that doctors can work, the Working Time Directive has not removed the stress and fatigue facing the medical workforce. The directive has instead …
Amino Acid Uptake Measured by [<sup>18</sup>F]AFETP Increases in Response to Arginine Starvation in ASS1-Deficient Sarcomas
Authors: Bethany Cheree Prudner, Fangdi Sun, Jeffrey Charles Kremer, Jinbin Xu, Chaofeng Huang, Kiran Kumar Solingapuram Sai, Zachary Morgan, Hayden Leeds, Jonathan McConathy, Brian Andrew Van Tine
Journal: Theranostics (2018)

Rational:In a subset of cancers, arginine auxotrophy occurs due to the loss of expression of argininosuccinate synthetase 1 (ASS1).This loss of ASS1 expression makes cancers sensitive to arginine starvation that is induced by PEGylated arginine deiminase (ADI-PEG20).Although ADI-PEG20 treatment is effective, it does have important limitations.Arginine starvation is only beneficial in patients with cancers that are ASS1-deficient.Also, these tumors may metabolically reprogram to express ASS1, transforming them from an auxotrophic phenotype to a prototrophic phenotype and thus rendering ADI-PEG20 ineffective.Due to these limitations of ADI-PEG20 treatment and the potential for developing resistance, non-invasive tools to monitor sensitivity to arginine starvation are needed.Methods: Within this study, we assess the utility of a novel positron emission tomography (PET) tracer to determine sarcomas reliant on extracellular arginine for survival by measuring changes in amino acid transport in arginine auxotrophic sarcoma cells treated with ADI-PEG20.The uptake of the 18 F-labeled histidine analogue, (S)-2-amino-3-[1-(2-[ 18 F]fluoroethyl)-1H-[1,2,3]triazol-4-yl]propanoic acid (AFETP), was assessed in vitro and in vivo using human-derived sarcoma cell lines.In addition, we examined the expression and localization of cationic amino acid transporters in response to arginine starvation with ADI-PEG20. Results:In vitro studies revealed that in response to ADI-PEG20 treatment, arginine auxotrophs increase the uptake of L-[ 3 H]arginine and [ 18 F]AFETP due to an increase in the expression and localization to the plasma membrane of the cationic amino acid transporter CAT-1.Furthermore, in vivo PET imaging studies in mice with arginine-dependent osteosarcoma xenografts showed increased [ 18 F]AFETP uptake in tumors 4 days after ADI-PEG20 treatment compared to baseline. Conclusion:CAT-1 transporters localizes to the plasma membrane as a result of arginine starvation with ADI-PEG20 in ASS1-deficient tumor cells and provides a mechanism for using cationic amino acid transport substrates such as [ 18 F]AFETP for identifying tumors susceptible to ADI-PEG20 treatment though non-invasive PET imaging techniques.These findings indicate that [ 18 F]AFETP-PET may be suitable for the early detection of tumor response to arginine depletion due to ADI-PEG20 treatment.
What is a career in dance medicine like, and what opportunities exist for graduates?
Authors: Peter Skew
Journal: BMJ (2004)

Got 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.
A coordinate deregulation of microRNAs expressed in mucosa adjacent to tumor predicts relapse after resection in localized colon cancer
Authors: Angela Grassi, Lisa Perilli, Laura Albertoni, Sofia Tessarollo, Claudia Mescoli, Emanuele D. L. Urso, Matteo Fassan, Massimo Rugge, Paola Zanovello
Journal: Molecular Cancer (2018)

Up to 20% of colorectal cancer (CRC) node-negative patients develop loco-regional or distant recurrences within 5 years from surgery. No predictive biomarker able to identify the node-negative subjects at high risk of relapse after curative treatment is presently available. Forty-eight localized (i.e. stage I-II) colon cancer patients who underwent radical tumor resection were considered. The expression of five miRNAs, involved in CRC progression, was investigated by qRT-PCR in both tumor tissue and matched normal colon mucosa. Interestingly, we found that the coordinate deregulation of four miRNAs (i.e. miR-18a, miR-21, miR-182 and miR-183), evaluated in the normal mucosa adjacent to tumor, is predictive of relapse within 55 months from curative surgery. Our results, if confirmed in independent studies, may help to identify high-risk patients who could benefit most from adjuvant therapy. Moreover, this work highlights the importance of extending the search for tissue biomarkers also to the tumor-adjacent mucosa.
Integrated SPECT-MRI for enhanced stratification and early treatment response assessment in glioma
Authors: Susan Short, Brian Hutton, Luisa Ottobrini, Irene De Francesco, Carlo Fiorini:
Journal: Neuro-Oncology (2018)

BACKGROUNDPersonalised treatment based on individual tumour biology tracked over time is an important goal to improve outcomes in glioma. Imaging biomarkers have the potential to permit individualization by defining heterogeneous biology in 3D space and tracking response. To optimize application of this approach, biological readouts need to be aligned with high quality anatomical information. The INSERT consortium seeks to address this unmet need using simultaneous multi-tracer SPECT and MRI.
Artificial intelligence powers digital medicine
Authors: Alexander L. Fogel, Joseph C. Kvedar
Journal: npj Digital Medicine (2018)

Artificial intelligence (AI) has recently surpassed human performance in several domains, and there is great hope that in healthcare, AI may allow for better prevention, detection, diagnosis, and treatment of disease. While many fear that AI will disrupt jobs and the physician-patient relationship, we believe that AI can eliminate many repetitive tasks to clear the way for human-to-human bonding and the application of emotional intelligence and judgment. We review several recent studies of AI applications in healthcare that provide a view of a future where healthcare delivery is a more unified, human experience.
Managing low risk prostate cancer: A cost analysis.
Authors: Franklin Gaylis, Kevin McGill, Susan S Levy, Catherine E Ball, Hillary Prime, Paul Dato, Edward Cohen
Journal: Journal of Clinical Oncology (2018)

50 Background: Healthcare costs in the US continue to rise at an unsustainable rate. Prostate cancer (PCa) accounts for 21% of all new cancer cases in men and is predicted to incur a cost of $18.53 billion in the next few years. In this study we examined the costs associated with managing low-risk PCa with traditional treatment options compared to Active Surveillance. Methods: One hundred ninety-five patients were identified as NCCN defined low-risk PCa (Gleason score ≤ 6, PSA &lt; 10, clinical stage T1c to T2a) between January 1, 2012 to June 30, 2013 at Genesis Healthcare Partners (GHP). Ninety three (48.7%) patients had at least 3 years of follow-up care and formed the cohort for analysis. Treatment paths analyzed included active surveillance (AS), radical prostatectomy (RP), stereotactic body radiation therapy (SBRT) and intensity-modulated radiation therapy/image-guided radiation therapy (IMRT/IGRT). Patients’ charts were examined for all episodes of care during the three-year period subsequent to their first positive biopsy and cost attribution to each episode was based on a cost-to-Medicare perspective using the Medicare Physician Fee Schedule (MPFS) for GHP. Total and annual costs of care were compared for patients followed for a 3-year period using one-way analysis of covariance (ANCOVA), covarying for patient age and Charlson Comorbidity Index (CCI). Results: Active surveillance ($4,072 ± $1354) compared to RP ($9,972 ± $1571), SBRT ($26,294 ± $2049), and IMRT/IGRT ($40,438 ± $2091) had significantly lower total 3-year costs ( p &lt; .001, ɳ² = .44) compared to those in the other treatments group. Specific characteristics of the AS cohort’s treatment path included an average number of biopsies of 2.0 ± 0.8 and only six (21%) patients had at least one MRI performed during their treatment path. Active surveillance with a more costly genomic study (n = 4) incurred a cost of $9,475 ± $1456 over three years. Conclusions: Active surveillance may be considered a beneficial management strategy for low-risk PCa from a cost perspective. The cost effective benefit as well as the avoidance of treatment (surgery, radiation therapy) related side effects, support its consideration as a value-based care model, the primary goal of the Medicare Access and Chip Reauthorization Act.
Is there any special interest training in mental health for GPs?
Authors: Rahul Rao
Journal: BMJ (2006)

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 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. <b>www.bmjcareers.com/advicezone</b>
Rituximab (RTX) plus Methotrexate (MTX) prevents bone erosion and joint-space narrowing (JSN) and reduces synovitis, osteitis as shown on MRI: Results from a randomised, placebo-controlled trial in patients (PTS) with rheumatoid arthritis (RA-score)
Authors: C. Peterfy, P. Emery, P.-P. Tak, Mikkel Østergaard, J. DiCarlo, K. Otsa, F. Navarro Sarabia, K. Pavelka, K. Preston, T. Shaw, M.-A. Bagnard, A. Gabriele
Journal: Annals of the Rheumatic Diseases (2011)
GMC will formally recognise all medical trainers by July 2016
Authors: Abi Rimmer
Journal: BMJ (2015)

The General Medical Council aims to fully recognise all medical trainers by July next year, Vicky Osgood, the GMC’s director of education and standards, has said. 

Speaking at a conference on professionalism and excellence in Edinburgh last month, Osgood said that the regulator was in the final stages of its work on the formal recognition and …
Infrequent occurrence of TET1, TET3, and ASXL2 mutations in myelodysplastic/myeloproliferative neoplasms
Authors: Terra L. Lasho, Rangit Vallapureddy, Christy M. Finke, Abhishek Mangaonkar, Naseema Gangat, Rhett Ketterling, Ayalew Tefferi, Mrinal M. Patnaik
Journal: Blood Cancer Journal (2018)
GPs report “unsustainable” workload and funding pressures
Authors: Helen Jaques
Journal: BMJ (2013)

Two thirds of GPs in southwest England believe that their current working pattern is not sustainable, according to an online survey. 

The poll, conducted by local medical committees in the region, received responses from 2745 of around 6000 GPs in the area. More than half (59.2%) said that they would struggle to keep their practices viable should the government’s planned changes to the GP contract go ahead. 

More than two thirds (70.6%) said that their working …
Indirect treatment comparison (ITC) of abiraterone acetate (AA) plus prednisone (P) and docetaxel (DOC) on patient-reported outcomes (PROs) in metastatic castration-naïve prostate cancer (mCNPC).
Authors: Susan Feyerabend, Fred Saad, Tracy Li, Tetsuro Ito, Joris Diels, Suzy Van Sanden, Peter De Porre, Seye Abogunrin, Maria Koufopoulou, Karim Fizazi
Journal: Journal of Clinical Oncology (2018)

200 Background: AA + P added to androgen deprivation therapy (ADT) improved overall survival among newly diagnosed mCNPC patients (pts) with high-risk disease (HRD) vs placebos (PBOs) + ADT in the phase 3 LATITUDE study. Although ADT with or without chemotherapy is recommended in clinical guidelines as the mainstay of management for mCNPC, adding DOC to ADT does not consistently improve health-related quality of life (HRQoL). We performed an ITC to understand the relative impact of AA + P vs DOC on PROs in mCNPC pts. Methods: PROs were assessed using the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and Brief Pain Inventory (BPI). Mean change from baseline (BL) was based on differences in FACT-P and BPI scores between active vs control arms in LATITUDE (intention-to-treat [ITT] population) and CHAARTED (available data included mCNPC pts with high-volume disease [HVD] and low-volume disease [LVD]). Higher FACT-P score indicates better outcome/function; lower BPI score indicates better outcome/less pain. The probability of AA + P being better than DOC at 3, 6, 9, and 12 mos after treatment was based on fixed-effects Bayesian network meta-analysis. Results: Benefits in PROs with AA + P vs DOC were observed from 3 mos and sustained at least 1 year after treatment. Bayesian probability of AA + P being the better treatment for PROs ranged from 92.3% to 100%. Conclusions: Results from a Bayesian ITC suggest that AA + P was superior to DOC in improving PROs for at least 1 year after initiating treatment in men with mCNPC. In the absence of head-to-head trials, these analyses can provide useful insights on the relative impact of treatment options on HRQoL in mCNPC pts. Clinical trial information: NCT01715285. [Table: see text]
Where should I look for jobs in anatomy?
Authors: Paul M Rea
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 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. <b>www.bmjcareers.com/advicezone</b>
I am interested in training in reconstructive surgery. How can I find specialist consultants or reconstructive units in the UK, Ireland, or Australasia?
Authors: Jain Abhilash
Journal: BMJ (2004)

<i>Got 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.</i>
Variable Rates of Simple Satellite Gains across the Drosophila Phylogeny
Authors: Kevin H -C Wei, Sarah E Lower, Ian V Caldas, Trevor J S Sless, Daniel A Barbash, Andrew G Clark
Journal: Molecular Biology and Evolution (2018)

Simple satellites are tandemly repeating short DNA motifs that can span megabases in eukaryotic genomes. Because they can cause genomic instability through nonallelic homologous exchange, they are primarily found in the repressive heterochromatin near centromeres and telomeres where recombination is minimal, and on the Y chromosome, where they accumulate as the chromosome degenerates. Interestingly, the types and abundances of simple satellites often vary dramatically between closely related species, suggesting that they turn over rapidly. However, limited sampling has prevented detailed understanding of their evolutionary dynamics. Here, we characterize simple satellites from whole-genome sequences generated from males and females of nine Drosophila species, spanning 40 Ma of evolution. We show that PCR-free library preparation and postsequencing GC-correction better capture satellite quantities than conventional methods. We find that over half of the 207 simple satellites identified are species-specific, consistent with previous descriptions of their rapid evolution. Based on a maximum parsimony framework, we determined that most interspecific differences are due to lineage-specific gains. Simple satellites gained within a species are typically a single mutation away from abundant existing satellites, suggesting that they likely emerge from existing satellites, especially in the genomes of satellite-rich species. Interestingly, unlike most of the other lineages which experience various degrees of gains, the lineage leading up to the satellite-poor D. pseudoobscura and D. persimilis appears to be recalcitrant to gains, providing a counterpoint to the notion that simple satellites are universally rapidly evolving.
David Oliver: The Bawa-Garba case, doctors, and the GMC—what next?
Authors: David Oliver
Journal: BMJ (2018)

Since the High Court ruled in January that the trainee paediatrician Hadiza Bawa-Garba must be struck off the UK medical register, much has happened that may change how NHS doctors work, how we’re regulated, and how we raise concerns.

The General Medical Council (GMC) and the government have both announced reviews of how gross negligence manslaughter is applied to medical practice.12 Both reviews will make recommendations, but neither will have the power to make coroners’ decision making fairer to doctors. Nor can these reviews alter the common law tests for gross negligence or the fact that such cases are tried by juries without medical experience or expertise.

The GMC has put out a “frequently asked questions” document in response to …
Geographic Variations in Arthritis Prevalence, Health-Related Characteristics, and Management — United States, 2015
Authors: Kamil E. Barbour, Susan Moss, Janet B. Croft, Charles G. Helmick, Kristina A. Theis, Teresa J. Brady, Louise B. Murphy, Jennifer M. Hootman, Kurt J. Greenlund, Hua Lu, Yan Wang
Journal: MMWR Surveillance Summaries (2018)

Doctor-diagnosed arthritis is a common chronic condition affecting an estimated 23% (54 million) of adults in the United States, greatly influencing quality of life and costing approximately $300 billion annually. The geographic variations in arthritis prevalence, health-related characteristics, and management among states and territories are unknown. Therefore, public health professionals need to understand arthritis in their areas to target dissemination of evidence-based interventions that reduce arthritis morbidity.2015.The Behavioral Risk Factor Surveillance System is an annual, random-digit-dialed landline and cellular telephone survey of noninstitutionalized adults aged ≥18 years residing in the United States. Self-reported data are collected from the 50 states, the District of Columbia, Guam, and Puerto Rico. Unadjusted and age-standardized prevalences of arthritis, arthritis health-related characteristics, and arthritis management were calculated. County-level estimates were calculated using a validated statistical modeling method.In 2015, in the 50 states and the District of Columbia, median age-standardized prevalence of arthritis was 23.0% (range: 17.2%-33.6%). Modeled prevalence of arthritis varied considerably by county (range: 11.2%-42.7%). In 13 states that administered the arthritis management module, among adults with arthritis, the age-standardized median percentage of participation in a self-management education course was 14.5% (range: 9.1%-19.0%), being told by a health care provider to engage in physical activity or exercise was 58.5% (range: 52.3%-61.9%), and being told to lose weight to manage arthritis symptoms (if overweight or obese) was 44.5% (range: 35.1%-53.2%). Respondents with arthritis who lived in the quartile of states with the highest prevalences of arthritis had the highest percentages of negative health-related characteristics (i.e., arthritis-attributable activity limitations, arthritis-attributable severe joint pain, and arthritis-attributable social participation restriction; ≥14 physically unhealthy days during the past 30 days; ≥14 mentally unhealthy days during the past 30 days; obesity; and leisure-time physical inactivity) and the lowest percentage of leisure-time walking.The prevalence, health-related characteristics, and management of arthritis varied substantially across states. The modeled prevalence of arthritis varied considerably by county.The findings highlight notable geographic variability in prevalence, health-related characteristics, and management of arthritis. Targeted use of evidence-based interventions that focus on physical activity and self-management education can reduce pain and improve function and quality of life for adults with arthritis and thus might reduce these geographic disparities.