tbuckley/cabot-search huggingface dataset:
A PET imaging approach for determining EGFR mutation status for improved lung cancer patient management
Authors: Xilin Sun, Zunyu Xiao, Gongyan Chen, Zhaoguo Han, Yang Liu, Chongqing Zhang, Yingying Sun, Yan Song, Kai Wang, Fang Fang, Xiance Wang, Yanhong Lin, Lili Xu, Liming Shao, Jin Li, Zhen Cheng, Sanjiv Sam Gambhir, Baozhong Shen
Journal: Science Translational Medicine (2018)

Tumor heterogeneity and changes in epidermal growth factor receptor (EGFR) mutation status over time challenge the design of effective EGFR tyrosine kinase inhibitor (TKI) treatment strategies for non-small cell lung cancer (NSCLC). Therefore, there is an urgent need to develop techniques for comprehensive tumor EGFR profiling in real time, particularly in lung cancer precision medicine trials. We report a positron emission tomography (PET) tracer, N-(3-chloro-4-fluorophenyl)-7-(2-(2-(2-(2-18F-fluoroethoxy) ethoxy) ethoxy) ethoxy)-6-methoxyquinazolin-4-amine (18F-MPG), with high specificity to activating EGFR mutant kinase. We evaluate the feasibility of using 18F-MPG PET for noninvasive imaging and quantification of EGFR-activating mutation status in preclinical models of NSCLC and in patients with primary and metastatic NSCLC tumors. 18F-MPG PET in NSCLC animal models showed a significant correlation (R2 = 0.9050) between 18F-MPG uptake and activating EGFR mutation status. In clinical studies with NSCLC patients (n = 75), the concordance between the detection of EGFR activation by 18F-MPG PET/computed tomography (CT) and tissue biopsy reached 84.29%. There was a greater response to EGFR-TKIs (81.58% versus 6.06%) and longer median progression-free survival (348 days versus 183 days) in NSCLC patients when 18F-MPG PET/CT SUVmax (maximum standard uptake value) was ≥2.23 versus <2.23. Our study demonstrates that 18F-MPG PET/CT is a powerful method for precise quantification of EGFR-activating mutation status in NSCLC patients, and it is a promising strategy for noninvasively identifying patients sensitive to EGFR-TKIs and for monitoring the efficacy of EGFR-TKI therapy.
Adrenal Hemangioma Definite Diagnosis on CT, MRI, and FDG PET in a Patient With Primary Lung Cancer
Authors: Benjamin Wilson, Allison Becker, Thomas Estes, Jayanth Keshavamurthy, Darko Pucar
Journal: Clinical Nuclear Medicine (2018)

Distinguishing adrenal incidentalomas (5% of all abdominal CT scans) from metastasis is a frequent diagnostic challenge in primary malignancies with a propensity for adrenal spread, such as lung cancer. Adrenal myelolipoma and adenoma can be definitively characterized as benign by demonstrating gross and microscopic fat, respectively, on CT and MRI and an absence of abnormal uptake on PET. Unfortunately, adrenal sampling is frequently necessary in indeterminate cases for adequate staging of extra-adrenal primary malignancy. We present a lung cancer case in which definite characterization of a rare adrenal hemangioma with CT, PET, and MRI avoided unnecessary adrenal sampling.
Smooth muscle cells of intracranial vessels: from development to disease
Authors: Juhana Frösen, Anne Joutel
Journal: Cardiovascular Research (2018)

Cerebrovascular diseases that cause ischaemic or haemorrhagic stroke with subsequent loss of life or functional capacity due to damage of the brain tissue are among the leading causes of human suffering and economic burden inflicted by diseases in the developed world. Diseases affecting intracranial vessels are significant contributors to ischaemic and haemorrhagic strokes. Brain arteriovenous malformations, which are a collection of abnormal blood vessels connecting arteries to veins, are the most common cause of intracranial haemorrhage in children and young adults. Saccular intracranial aneurysms, which are pathological saccular dilations mainly occurring at bifurcations of the large intracranial arteries near the circle of Willis, are highly prevalent in the middle-aged population, causing significant anxiety and concern; their rupture, although rare, is a significant cause of intracranial haemorrhage in those past middle age that is associated with a very sinister prognosis. Cerebral small-vessel disease, which comprise all pathological processes affecting vessels <500 microns in diameter, account for the majority of intracerebral haemorrhages and ∼25% of ischaemic strokes and 45% of dementias in the elderly. In this review, we summarize the developmental, structural, and functional features of intracranial vessels. We then describe the role of smooth muscle cells in brain arteriovenous malformations, intracranial aneurysms, and small-vessel diseases, and discuss how the peculiar ontogeny, structure, and function of intracranial vessels are related to the development of these diseases.
Idalopirdine: another disappointment for people with dementia
Authors: David G Le Couteur, Brace Bateman, Carol Brayne
Journal: BMJ (2018)

This has already been a disheartening year for research into drug treatments for dementia and Alzheimer’s disease, especially for people affected by dementia. Negative results have been posted for phase III clinical trials of two 5-hydroxytryptamine-6 receptor (5-HT6) antagonists for the symptomatic treatment of moderate dementia,12 as well as for a trial of an amyloid β antibody as a disease modifying treatment in mild dementia.3 Pfizer announced that it will end its neuroscience and related dementia investments in drug development, removing a major industry partner from the field.4

These developments follow a long period of negative drug trials in dementia. In recent decades the failure rate has been nearly 100%,5 and the only registered medicines are the cholinesterase inhibitors and memantine, which at best generate modest symptomatic improvement in cognitive testing among some patients and for only a limited period.

Drug development has often been associated with great excitement generated by the so called breakthroughs seen in animal models of dementia, followed by uncertain results in early human studies and then the certainty of …
Prostate Cancer Lytic Bone Metastases Imaged With 18F-Fluorocholine PET/CT
Authors: Yazan Z. Alabed
Journal: Clinical Nuclear Medicine (2018)

A 76-year-old man with metastatic prostate cancer and back pain was referred for palliative radiotherapy. Staging F-fluorocholine PET/CT scan revealed fluorocholine-avid prostate mass, extensive lymphadenopathy, lung nodules, and extensive osteolytic lesions throughout the axial skeleton. Prostate cancer bone metastases are predominantly sclerotic in nature. We present F-fluorocholine PET/CT imaging of prostate cancer with very rare lytic bone metastases.
Iodine/FDG “Flip-Flop” Phenomenon Inside a Large Metastatic Thyroid Cancer Lesion Better Characterized on SPECT/CT and PET/CT Studies
Authors: Paulo Schiavom Duarte, José Flávio Gomes Marin, José Willegaignon de Amorim de Carvalho, Marcelo Tatit Sapienza, Carlos Alberto Buchpiguel
Journal: Clinical Nuclear Medicine (2018)

Iodine/FDG "flip-flop" phenomenon inside large metastatic thyroid cancer lesions has been rarely described. We present a case of this phenomenon better characterized using SPECT/CT and PET/CT studies.
Doctors could face “trial by media” under new GMC sanctions, BMA warns
Authors: Abi Rimmer
Journal: BMJ (2014)

Doctors could face a “trial by media” if proposed changes to the General Medical Council’s guidance on sanctions go ahead, the BMA has warned.

The association raised the concern in response to a GMC consultation on the way that the regulator deals with concerns about doctors through its guidance for the panels that investigate doctors’ fitness to practise. The Medical Defence Union has also raised concerns about the guidance …
GLA:D to have a high-value option for patients with knee and hip arthritis across four continents: Good Life with osteoArthritis from Denmark
Authors: Ewa M Roos, Christian J Barton, Aileen M Davis, Rhona McGlasson, Joanne L Kemp, Kay M Crossley, Qiang Liu, Jianhao Lin, Søren T Skou
Journal: British Journal of Sports Medicine (2018)

We know that we should be providing patient education, exercise and weight management for people with knee and hip osteoarthritis, but do we know what to do? GLA:D may provide an answer, and train clinicians worldwide to deliver high-value treatments.

GLA:D is a new evidence-based solution in the toolbox for clinicians who manage middle-aged and older people with painful knees and hips. The programme is a not-for-profit initiative hosted by the University of Southern Denmark, and has a registered trademark to help maintain programme quality. GLA:D provides an effective, high-value alternative to current standard of care in patients not needing total joint replacement: prescription of pain killers and low-value referral (imaging and knee arthroscopy).1

GLA:D is a standardised, but individualised, treatment consisting of 2 patient education sessions and 12 neuromuscular exercise therapy sessions.2 All sessions are group-based and supervised by a certified clinician with expertise in osteoarthritis and exercise therapy. GLA:D is most commonly provided by a physiotherapist, but can be provided by other health practitioners if required by the healthcare system of the specific country or region.

After 3 years of unsuccessful discussions with …
Hunt says there are no preconditions to junior contract negotiations
Authors: Abi Rimmer
Journal: BMJ (2015)

Jeremy Hunt has said in a letter to the BMA that there are no preconditions to negotiations on the junior doctor contract in England.

In a letter sent to Johann Malawana, chair of the BMA’s Junior Doctors Committee, on 17 November the health secretary for England said “there are no preconditions to talks whatsoever.”1

Malawana had previously said that the BMA wanted the government to withdraw preconditions to contract negotiations.2 A spokeswoman …
Differential Control of Axonal and Somatic Resting Potential by Voltage-Dependent Conductances in Cortical Layer 5 Pyramidal Neurons
Authors: Wenqin Hu, Bruce P. Bean
Journal: Neuron (2018)

Highlights•Axonal resting potential is negative to that of the soma in pyramidal neurons•The difference results from Kv7 channels localized in the axon•Multiple voltage-dependent channels regulate axonal and somatic resting potential•Somatic HCN current is necessary for resting activation of axonal Kv7 channelsSummaryVoltage-dependent conductances not only drive action potentials but also help regulate neuronal resting potential. We found differential regulation of resting potential in the proximal axon of layer 5 pyramidal neurons compared to the soma. Axonal resting potential was more negative than the soma, reflecting differential control by multiple voltage-dependent channels, including sodium channels, Cav3 channels, Kv7 channels, and HCN channels. Kv7 current is highly localized to the axon and HCN current to the soma and dendrite. Because of impedance asymmetry between the soma and axon, axonal Kv7 current has little effect on somatic resting potential, while somatodendritic HCN current strongly influences the proximal axon. In fact, depolarizing somatodendritic HCN current is critical for resting activation of all the other voltage-dependent conductances, including Kv7 in the axon. These experiments reveal complex interactions among voltage-dependent conductances to control region-specific resting potential, with somatodendritic HCN channels playing a critical enabling role.Graphical abstract
A genomic classifier for identifying a neuroendocrine-like bladder cancer subtype.
Authors: Jonathan L. Wright, Marc Dall'era, Trinity Bivalacqua, Roland Seiler, Yang Liu, Ewan Gibb, Natalie Qiqi Wang, Nicholas Erho, Mohammed Alshalalfa, Elai Davicioni, Jason A. Efstathiou, James G. Douglas, Joost L Boormans, Michiel Simon Van Der Heijden, Yair Lotan, Peter C. Black
Journal: Journal of Clinical Oncology (2018)

440 Background: Neuroendocrine (NE) carcinoma is a rare and aggressive variant of muscle invasive bladder cancer (MIBC). Molecular subtyping studies found 5-15% of bladder tumors had transcriptome profiles consistent with NE carcinoma but lacked NE histology (Robertson 2017, Sjödahl 2017). Identifying NE variants may have prognostic implications and modify treatment recommendations. In this study, we present a robust genomic classifier trained to identify NE carcinoma. Methods: Transcriptome-wide expression profiles were generated for 576 MIBC patients collected from seven institutions. Model training included profiles generated from TURBT and RC specimens from 320 patients prior to treatment with NAC or chemo-radiation. The validation cohort consisted of 256 RC specimens (no prior systemic treatment). Using 10 MIBC-related gene sets, a GLMNET model was built to predict patients with a NE carcinoma expression profile. Uni- and multi-variable survival analyses were used to characterize outcomes of the predicted NE tumors. Results: In the training set, hierarchical clustering using a panel of 54 genes showed a cluster of 17 patients (5.3%) with a NE carcinoma expression profile. These patients had significantly worse 1 year progression free survival (65% vs 82% for NE vs overall; p = 0.046). In the validation set, 7 tumors were classified (2.7%) as NE with 4 (57%) patients dying from the disease at 1 year after RC. Within 3 years of RC, 100% (7/7) of patients with NE tumors had died. After adjusting for various clinical and pathological factors, patients with predicted NE tumors had a 6.40 increased risk of all-cause mortality (p = 0.001). Conclusions: We have developed a gene expression signature that predicts a particularly high-risk group that may need treatment intensification, alternative chemotherapy or clinical trials. Validation will be required to assess the potential clinical utility of this NE carcinoma classifier.
Workplace Bullying in the NHS
Authors: Rachel Hooke
Journal: BMJ (2006)

Jacqueline Randle

Radcliffe Medical Press, 2006, £19.95, 120 pages

ISBN 1 857 75783 1

Rating: ★★★★★/5



Two main types of people would be interested in this book. One is staff wondering if they are being bullied and what constitutes that kind of behaviour. The other is policymakers who want to draft guidance for their own organisations. Some people might say it seems strange to use the term “bullying” because it is more commonly associated with the playground. Physical abuse and outright name calling are rare in the workplace, but the more …
Nonfatal Assaults Among Persons Aged 10–24 Years — United States, 2001–2015
Authors: Corinne F. David-Ferdon, Tadesse Haileyesus, Yang Liu, Thomas R. Simon, Marcie-jo Kresnow
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

In 2015, persons aged 10-24 years who were treated for nonfatal assault injuries in emergency departments (EDs) in the United States accounted for 32% of the approximately 1.5 million patients of all ages that EDs treated for nonfatal assault injuries (1). CDC analyzed data from the National Electronic Injury Surveillance System-All Injury Program (NEISS-AIP) to examine 2001-2015 trends in nonfatal assault injuries among youths treated in EDs, by sex and age group, and to assess current rates by sex, age group, mechanism of injury, and disposition (1). Rates for 2001-2015 were significantly higher among males than among females and among young adults aged 20-24 years than among youths aged 10-14 and 15-19 years. During 2011-2015, rates declined for all groups. The 2015 rate among persons aged 10-24 years was 753.2 per 100,000 population, the lowest in the 15-year study period. Despite encouraging trends, the assault rate among young persons remains high. Rates in 2015 were higher among males, persons aged 20-24 years, and those who incurred intentional strike or hit injuries. Nearly one in 10 patients were admitted to the hospital, transferred to another hospital, or held for observation. Youth violence prevention strategies, including primary prevention approaches that build individual skills, strengthen family relationships, or connect young persons treated in EDs to immediate and ongoing support, can be implemented to decrease injuries and fatalities (2).
Immunological changes during intraperitoneal growth of colorectal cancer.
Authors: Seung Chul Heo, Jie-Eun Kim, Rumi Shin
Journal: Journal of Clinical Oncology (2018)

97 Background: Immunoediting other than PD-1 works in colorectal cancer (CRC), except for some MSI high tumors. Study of immune response to cancers in the primary CRC is difficult due to interference by the colonic microorganisms. If a clinical model reflecting tumor progression, free from microbial antigens and characterizing the microenvironment is developed it will help us understand the immunoediting of CRC. We studied immunologic changes, according to the peritoneal tumor progression, in ascites and peritoneal immune cells of CRC patients. These results will provide clues to the immunoediting of CRC and to immunotherapy of peritoneal carcinomatosis. Methods: Ascites and peritoneal cells were collected from CRCs during surgery or malignant ascites drainage. Forty-two immune molecules and ratios of immune cells were assayed. Patients with intestinal perforation or leukocytosis were excluded to remove interference by the foreign antigens. Patients were grouped according to the peritoneal tumor progression (PC stages) as follows; SE-: without peritoneal exposure of cancer cells (T3 or lower T stage, no tumor cells in peritoneal cavity); SE+: with peritoneal exposure without peritoneal seeding (T4, microscopic tumor cells in peritoneal cavity); l-PC: localized peritoneal seeding; g-PC: generalized peritoneal seeding. Molecular and cellular changes were evaluated according to PC stages. Results: Of the 42, five (IL-10, IL-6, VEGF, CCL20 and TGF-b) increased with the PC stage progression, meanwhile IL-18 decreased. CXCL8 was elevated in only g-PC. However, 14 molecules could not be assayed due to lower level than the references and other 3 could be assayed in only some g-PCs. The other 18 were not different among PC stages. Especially, IL-10 is a prognostic factor of peritoneal recurrence in SE+. IL-10 and IL-6 are highly correlated. The ratio of CD56+ cells, but not the others, increased according to PC stages. Conclusions: Intraperitoneal CRC growth accompanied IL-10, IL-6, VEGF, CCL20, TGF-b and NK cell increase, meanwhile IL-18 decrease. IL-10 is a prognostic factor of peritoneal recurrence. Identification of secreting and targeting cells of each molecules as well as immune network will provide the clues to immunoediting of CRC.
PREVALENCE OF CORONARY MICROVASCULAR DYSFUNCTION IN PATIENTS WITH STABLE CORONARY ARTERY DISEASE: THE CE-MARC 2 CORONARY PHYSIOLOGY SUB-STUDY
Authors: David Corcoran, Robin Young, David Adlam, Alex McConnachie, Kenneth Mangion, David RIpley, David Cairns, Julia Brown, Chiara Bucciarelli-Ducci, Rajesh Kharbanda, Keith Oldroyd, Gerry McCann, John Greenwood, Colin Berry
Journal: Journal of the American College of Cardiology (2018)
Tenofovir versus Placebo to Prevent Perinatal Transmission of Hepatitis B
Authors: Gonzague Jourdain, Nicole Ngo-Giang-Huong, Linda Harrison, Luc Decker, Woottichai Khamduang, Camlin Tierney, Nicolas Salvadori, Tim R. Cressey, Wasna Sirirungsi, Jullapong Achalapong, Prapap Yuthavisuthi, Prateep Kanjanavikai, Orada P. Na Ayudhaya, Thitiporn Siriwachirachai, Sinart Prommas, Prapan Sabsanong, Aram Limtrakul, Supang Varadisai, Chaiwat Putiyanun, Pornnapa Suriyachai, Prateung Liampongsabuddhi, Suraphan Sangsawang, Wanmanee Matanasarawut, Sudanee Buranabanjasatean, Pichit Puernngooluerm, Chureeratana Bowonwatanuwong, Thanyawee Puthanakit, Virat Klinbuayaem, Satawat Thongsawat, Sombat Thanprasertsuk, George K. Siberry, Diane H. Watts, Nahida Chakhtoura, Trudy V. Murphy, Noele P. Nelson, Raymond T. Chung, Stanislas Pol, Nantasak Chotivanich
Journal: New England Journal of Medicine (2018)

Pregnant women with an elevated viral load of hepatitis B virus (HBV) have a risk of transmitting infection to their infants, despite the infants' receiving hepatitis B immune globulin.
Without state funded care patients’ genes may determine how much they pay, NHS chief warns
Authors: Abi Rimmer
Journal: BMJ (2014)

If the health service does not remain state funded, patients’ genes could dictate how much they pay for healthcare, NHS England’s national medical director has said.

Addressing junior doctors at an Agents for Change event in London, Bruce Keogh said that future discussions about the NHS’s affordability needed to take into account the implications of future technology and the use of genomics. “We’re going to go into a period over the next few years, I think, where there is going to be serious debate about whether the health service is affordable or not—whether …
LETTER OF THE MONTH Is greed good?
Authors: Mark L Jones
Journal: BMJ (2007)

We welcome your rapid responses, whether in direct response to an article in Career Focus or as a way of sharing your own ideas. As long as it isn9t libellous or offensive, we9ll post it on our website. We print a selection of rapid reponses here and the writer of the best each month wins an <i>Oxford Handbook</i> of their choice. Letter of the month prize is donated by OUP.
Women's empowerment in India: assessment of women's confidence before and after training as a lay provider
Authors: Megan Storm, Alan Xi, Ayesha Khan
Journal: The Lancet Global Health (2018)

BackgroundGender is the main social determinant of health in India and affects women's health outcomes even before birth. As women mature into adulthood, lack of education and empowerment increases health inequities, acting as a barrier to seeking medical care and to making medical choices. Although the process of women's empowerment is complex to measure, one indicator is confidence in ability. We sought to increase the confidence of rural Indian women in their abilities by training them as health-care providers for their community.MethodsOur partner organisation selected women through an application process requiring (1) 1 year experience as community health facilitators and (2) availability to travel and participate in a lay provider programme. Women educated to primary school level were trained by adapting an application-based curriculum previously successful in training secondary-school graduates in Haiti. We adapted the curriculum to suit the gendered context and cultivate the following skills: (1) public speaking (each woman had to teach her small group a portion of the curriculum); (2) leadership (each woman led a large group discussion on the topic); and (3) autonomy and decision making (each woman had to care for several simulated patients, making decisions about diagnosis, treatment, and transportation, and simulating a phone call to an urban doctor laying out her plan for the patient). An 11-question survey assessing confidence as care providers was administered before and after the course. Answer choices varied from "not confident" to "completely confident".Findings55 women from villages in Uttar Pradesh and Bihar underwent training between August and December 2016. 54 participants completed both the pre-training and post-training surveys. Changes in mean number of responses corresponding to each confidence level are as follows: "not confident" 39·6 (SD 14·4) pre-training to 0 post-training (p<0·0001); "a little confident" 12·9 (11·8) pre-training to 0 post-training (p<0·0001); "confident" 1·5 (3·1) pre-training to 3·5 (3·9) post-training (p=0·26); "very confident" 0 pre-training to 11·5 (8·2) post-training (p<0·0001); and "completely confident" 0 pre-training to 39·2 (10·9) post-training (p<0·0001).InterpretationRural Indian women's confidence in their abilities as a care provider can be significantly improved by practising roles as leaders, decision-makers, and public speakers.FundingNone.