tbuckley/cabot-search huggingface dataset:
Sun Protection and Skin Self-examination and the US Preventive Services Task Force Recommendation on Behavioral Counseling for Skin Cancer Prevention
Authors: June K. Robinson, Nina G. Jablonski
Journal: JAMA (2018)

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Ruxolitinib partially reverses functional natural killer cell deficiency in patients with signal transducer and activator of transcription 1 (STAT1) gain-of-function mutations
Authors: Alexander Vargas-Hernández, Emily M. Mace, Ofer Zimmerman, Christa S. Zerbe, Alexandra F. Freeman, Sergio Rosenzweig, Jennifer W. Leiding, Troy Torgerson, Matthew C. Altman, Edith Schussler, Charlotte Cunningham-Rundles, Ivan K. Chinn, Alexandre F. Carisey, Imelda C. Hanson, Nicholas L. Rider, Steven M. Holland, Jordan S. Orange, Lisa R. Forbes
Journal: Journal of Allergy and Clinical Immunology (2017)
Tackling situational judgment tests
Authors: Mahibur Rahman
Journal: BMJ (2007)

INTRODUCTION: Diaphragm invasion in non-small cell lung cancer (NSCLC) is a rare condition that accounts for less than 0.5%. It has been assessed as T3 according to the 7th edition of the TNM classification for lung cancer however surgical results were not clear. The aim of the study is to verify the validity of the new staging in NSCLC with diaphragm invasion.  METHODS: A retrospective review was carried out on 2195 consecutive patients with histologically proven NSCLC with anatomical lung resection between January 2010-June 2015. 14 patients with diaphragm resection for tumor invasion were analyzed.  RESULTS: Of all the 14 patients, mean age was 60 years. 12 patients had squamous cell carcinoma and 2 had adenocarcinoma. Eight patients out of the 14 were radiologically suspected to have diaphragm invasion. Diaphragm reconstruction was performed in three patients with polytetrafluoroethylene mesh. Six patients were pathologically staged as IIB (T3N0), 8 patients as stage IIIA (T3N1-N2). During the 15-month median follow-up period, all patients received adjuvant treatment, and 8 patients died. Median life expectancy was found to be 17 months. While the median life expectancy of stage IIB (T3N0) patients was 17 months, it was found as 16 months for stage IIIA (T3N1-N2) patients.  CONCLUSIONS: The results of our study are similar to the median life expectancy of T4 cases reported as being shorter. The fact that NSCLC with diaphragm invasion constitutes a very small group of patients within T3 and the results of the present study, supports that these patients would be categorized within T4 as indicated in the 8th edition of the TNM classification for lung cancer.
Effect of β-hydroxy-β-methylbutyrate (HMB) on muscle strength in older men with prostate cancer (Pca) started on androgen deprivation therapy (ADT): Preliminary results of an open-label, randomized trial.
Authors: Kathryn A. Bylow, Deepak Kilari, Matthew John Riese, John Burfeind, Melinda Stolley, Robert W Prost, Kaylinn Musto, Raquel Neilson, Aniko Szabo, James P. Thomas, Alexander V. Ng
Journal: Journal of Clinical Oncology (2018)

258 Background: ADT causes muscle weakness and wasting within 3 months (mo), causing older men on ADT to experience functional impairments and falls. HMB, a leucine metabolite which decreases muscle protein breakdown, improves strength, fat-free mass and function in older patients when given with arginine (A) and glutamine (G). Use of HMB +AG in older men with PCa starting on ADT to improve muscle loss and function has not been reported. Methods: Men age ≥ 60 with Pca starting on ADT were eligible. 42 men to date have been randomized to receive HMB + AG (Juven) twice daily for 3 mo vs no supplement. Physical performance measures using the Short Physical Performance Battery (SPPB) and hand dynamometer measurements were done at baseline and 3 mo. Both of these validated tests predict morbidity and mortality in older patients. Information on primary outcome, body composition, will be reported in the future according to study plan. Interim results are reported here to describe functional geriatric outcomes. Results: 42 men (mean age 70.2) with Pca (42.4% localized, 27.3% biochemical recurrence, 30.3% metastatic) have enrolled to date. Change in SPPB score favored HMB group: 12.6% of HMB vs 23.1% of controls had decline of ≥ 1point (pt) and 56.3% of HMB vs 15.4% of controls had increase of ≥ 1 pt (p = 0.045). The change in timed chair stand portion of SPPB (measures quadriceps strength) trended in favor of HMB group: -1.5 ± 2.9 seconds (sec) for HMB vs +0.4 ± 2.5 sec for controls, p = 0.073. 41.2% of HMB vs 15.4% of controls experienced an improvement in chair stand score. Change in hand grip strength also favored HMB group: 52.9% of HMB vs 84.6% of controls lost strength and 29.4% of HMB vs 0 controls gained strength, p = 0.047. No significant side effects were reported in HMB group. Conclusions: These are preliminary results of an ongoing trial. HMB is well tolerated in men with PCa on ADT. There is a trend in all measures of muscle function in favor of the HMB group. A much higher than expected % of men on HMB experienced improvement in measures of muscle function despite being on ADT. Further studies are ongoing to clarify the role of HMB in older men on ADT. Clinical trial information: NCT01607879.
Is there any chance for an overseas doctor to get the speciality in nuclear medicine in UK? Indeed, is there any SHO post in this field there?
Authors: John Frank
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>
MEDICAL MARRIAGES No reason to delay children
Authors: Ugo I Ekeowa
Journal: BMJ (2007)

<b>Aim:</b> To establish long term outcomes and incidence of complications following refractive lens exchange (RLE) for the correction of high myopia. <b>Methods:</b> Operative and postoperative records of 62 cases of small incision phacoemulsification RLE performed in 37 patients over an 11 year period, by a single surgeon, were reviewed. In addition, patients were recalled for a follow up examination, which included dilated retinal examination with scleral indentation. <b>Results:</b> Two cases (3.2%) of retinal detachment occurred at intervals of 2 months and 5 months following uncomplicated RLE procedures. A posterior chamber intraocular lens was inserted in 46 eyes (74%). YAG laser posterior capsulotomy was performed in 38 of 62 eyes (61%) and did not represent a risk for retinal detachment. <b>Conclusion:</b> Refractive lens exchange results in rapid and predictable improvement in unaided vision in patients with high myopia. However, the risks of sight threatening complications inherent in any intraocular procedure underlie the need for appropriate patient selection.
Differential Association of Microvascular Attributions With Cardiovascular Disease in Patients With Long Duration of Type 1 Diabetes
Authors: Daniel Gordin, Valma Harjutsalo, Liane Tinsley, Ward Fickweiler, Jennifer K. Sun, Carol Forsblom, Peter S. Amenta, David Pober, Stephanie D’Eon, Maya Khatri, Isaac E. Stillman, Per-Henrik Groop, Hillary A. Keenan, George L. King
Journal: Diabetes Care (2018)

OBJECTIVE Independent association of chronic kidney disease (CKD) and proliferative diabetic retinopathy (PDR) with cardiovascular disease (CVD) has not been established. In the Joslin 50-Year Medalist study, characterizing individuals with type 1 diabetes for 50 years or more, we examined the associations of CKD and PDR with CVD, which was validated by another cohort with type 1 diabetes from Finland. RESEARCH DESIGN AND METHODS This cross-sectional study characterized U.S. residents (n = 762) with type 1 diabetes of 50 years or longer (Medalists) at a single site by questionnaire, clinical, ophthalmic, and laboratory studies. A replication cohort (n = 675) from the longitudinal Finnish Diabetic Nephropathy Study (FinnDiane) was used. CKD and PDR were defined as estimated glomerular filtration rate &amp;lt;45 mL/min/1.73 m2 (CKD stage 3b) and according to the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol, respectively. CVD was based on questionnaires and/or hospital discharge registers. Associations of CVD status with CKD and PDR were analyzed by multivariable logistic regression. RESULTS CVD prevalence in the Medalists with CKD and without PDR (+CKD/−PDR) (n = 30) and CVD prevalence in the −CKD/+PDR group (n = 339) were half the prevalence in the +CKD/+PDR group (n = 66) (34.5% and 42.8% vs. 68.2%, P = 0.002). PDR status was independently associated with CVD (odds ratio 0.21 [95% CI 0.08–0.58], P = 0.003) in patients with CKD. Among the Finnish cohort, a trend toward a lower prevalence of CVD in the +CKD/−PDR group (n = 21) compared with the +CKD/+PDR group (n = 170) (19.1% vs. 37.1%, P = 0.10) was also observed. CONCLUSIONS Absence of PDR in people with type 1 diabetes and CKD was associated with a decreased prevalence of CVD, suggesting that common protective factors for PDR and CVD may exist.
DUAL ANTIPLATELET THERAPY OR ORAL ANTICOAGULATION REDUCES THE INCIDENCE OF ACUTE CORONARY SYNDROMES IN PATIENTS WITH CORONARY ARTERY ECTASIA
Authors: Prasad C. Gunasekaran, Taylor Drees, John Fritzlen, Megan Haghnegahdar, Matthew Earnest, Ashwani Mehta, Eric Hockstad, Mark Wiley, Peter Tadros, Buddhadeb Dawn, Kamal Gupta
Journal: Journal of the American College of Cardiology (2018)
Abstract PD2-12: Molecular imaging for early identification of patients who benefit from palbociclib in addition to letrozole
Authors: CM Venema, EFJ de Vries, AWJM Glaudemans, GAP Hospers, CP Schröder
Journal: Cancer Research (2018)

Abstract Palbociclib plus letrozole has improved both progression free survival and overall response rate in metastatic breast cancer (MBC) patients. For response to palbociclib, the best biomarker is ER expression. 16α-[18F]Fluoro-17β-estradiol (FES) -PET allows whole body ER level assessment, and provides insight in the heterogeneity of ER expression throughout the body. We hypothesized that lesions with low uptake on FES-PET are unlikely to respond to letrozole plus palbociclib. METHODS: Post-menopausal women with ER positive MBC were eligible for this pilot study. All patients were staged with fludeoxyglucose (FDG)-PET and CT scan, and in addition a FES-PET was performed at baseline. After 8 weeks treatment an FDG-PET/CT was used for response evaluation. The primary endpoint was the relation between standard uptake value (SUV) per lesion on FES-PET to response, as measured by RECIST 1.1 criteria in case of measurable disease. In case of non-measurable bone lesions, progression was defined as an increase in SUV on FDG-PET of more than 30% per lesion compared to baseline (based on PERCIST). RESULTS: 15 patients were included of which 14 were evaluable for primary endpoint. Mean age was 50 years (range 35-76). Median number of prior therapies was 1. A total of 280 lesions were detected on conventional imaging of which 50 showed low uptake (SUV&amp;lt;1.5) on FES-PET. 29/50 low uptake lesions showed progression based on diagnostic CT (n=9) or FDG PET (n=20). In contrast, 28/230 FES positive lesions showed progression. ResponseStable diseaseProgression FES uptake &amp;gt;1.51089428230FES uptake &amp;lt;1.57142950 11510857280 DISCUSSION: this pilot trial indicates negative predictive value of low FES uptake for response to letrozol plus palbociclib in ER positive MBC. The FES-PET may therefore be a biomarker for response for this combination treatment. This will have to be explored further in future clinical trials. Citation Format: Venema CM, de Vries EFJ, Glaudemans AWJM, Hospers GAP, Schröder CP. Molecular imaging for early identification of patients who benefit from palbociclib in addition to letrozole [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr PD2-12.
Capturing the complexity of the immune microenvironment of acute myeloid leukemia with 3D biology technology.
Authors: Sergio Rutella, Jayakumar Vadakekolathu, Heidi Altmann, Tasleema Patel, Stephen Reeder, Yan Liang, Marc Schmitz, Tressa Hood, Patrick Danaher, Sarah Warren, Alessandra Cesano, Joseph M Beechem, A. Graham Pockley, Sarah K. Tasian, Martin Bornhäuser
Journal: Journal of Clinical Oncology (2018)

50 Background: Tumor phenotypes are dictated not only by the neoplastic cell component, but also by the tumor microenvironment (TME), which includes immune and inflammatory cells. We characterized the immune ecosystem of the bone marrow (BM) TME in patients with acute myeloid leukemia (AML) to correlate transcriptomic and proteomic profiles with patient outcome. Methods: We used the nCounter system (NanoString Technologies) to characterize BM specimens from 42 children and 28 adults with AML. Ninety BM samples (63 from de novo AML, 18 from AML in complete remission [CR] and 9 from relapsed AML) were analyzed using the RNA Pan-Cancer Immune Profiling Panel. In situ leukemia-immune system interactions were visualized using Digital Spatial Profiling (DSP). Results: Hierarchical clustering identified subgroups with heightened expression of lymphocyte-associated genes, including NK cell and cytotoxicity genes (“immune-enriched” samples). They also expressed CD8A, IFNG, FOXP3, the cell chemoattractants CXCL9, CXCL10, and inhibitory molecules including IDO1 and the immune checkpoints LAG3, CTLA4 and PD-L1. Conversely, ‘immune-depleted’ samples over-expressed genes associated with mast cell functions and CD8 T-cell exhaustion and showed low expression of T-cell and B-cell genes. Importantly, relapse-free survival (RFS) and overall survival (OS) were significantly shorter in patients with “immune-enriched” compared with “immune-depleted” AMLs (2.2 vs. 18.3 months, p = 0.0064, and 6.3 vs. 22.4 months, p = 0.017, respectively). DSP of the BM TME showed the co-localization of CD8 T cells with FoxP3 Treg cells and PD-L1- and VISTA-expressing cell types, an immune landscape which is consistent with the establishment of adaptive immune resistance mechanisms of immune escape. Conclusions: Our study has identified heterogeneous immune profiles in children and adults with AML. From a clinical standpoint, ‘immune enriched’ AMLs might be amenable to immunotherapy approaches tailored to the BM microenvironment, including blockade of co-inhibitory molecules and/or small-molecule IDO1 inhibitors. Grant support: Roger Counter Foundation, UK; Qatar National Research Fund (#NPRP8-2297-3-494).
RISK FACTORS OF STROKE DO NOT COINCIDE WITH THOSE OF THE LEFT ATRIAL THROMBUS/SPONTANEOUS ECHO CONTRAST IN PATIENTS WITH ATRIAL FIBRILLATION
Authors: Satoshi Takahashi, Takanao Mine, Kenki Ashida, Hideyuki Kishima, Masaharu Ishihara, Tohru Masuyama
Journal: Journal of the American College of Cardiology (2018)
Reducing CXCR4-mediated nociceptor hyperexcitability reverses painful diabetic neuropathy
Authors: Nirupa D. Jayaraj, Bula J. Bhattacharyya, Abdelhak A. Belmadani, Dongjun Ren, Craig A. Rathwell, Sandra Hackelberg, Brittany E. Hopkins, Herschel R. Gupta, Richard J. Miller, Daniela M. Menichella
Journal: Journal of Clinical Investigation (2018)

Painful diabetic neuropathy (PDN) is an intractable complication of diabetes that affects 25% of patients. PDN is characterized by neuropathic pain and small-fiber degeneration, accompanied by dorsal root ganglion (DRG) nociceptor hyperexcitability and loss of their axons within the skin. The molecular mechanisms underlying DRG nociceptor hyperexcitability and small-fiber degeneration in PDN are unknown. We hypothesize that chemokine CXCL12/CXCR4 signaling is central to this mechanism, as we have shown that CXCL12/CXCR4 signaling is necessary for the development of mechanical allodynia, a pain hypersensitivity behavior common in PDN. Focusing on DRG neurons expressing the sodium channel Nav1.8, we applied transgenic, electrophysiological, imaging, and chemogenetic techniques to test this hypothesis. In the high-fat diet mouse model of PDN, we were able to prevent and reverse mechanical allodynia and small-fiber degeneration by limiting CXCR4 signaling or neuronal excitability. This study reveals that excitatory CXCR4/CXCL12 signaling in Nav1.8-positive DRG neurons plays a critical role in the pathogenesis of mechanical allodynia and small-fiber degeneration in a mouse model of PDN. Hence, we propose that targeting CXCR4-mediated DRG nociceptor hyperexcitability is a promising therapeutic approach for disease-modifying treatments for this currently intractable and widespread affliction.
Systematic Functional Annotation of Somatic Mutations in Cancer
Authors: Patrick Kwok-Shing Ng, Jun Li, Kang Jin Jeong, Shan Shao, Hu Chen, Yiu Huen Tsang, Sohini Sengupta, Zixing Wang, Venkata Hemanjani Bhavana, Richard Tran, Stephanie Soewito, Darlan Conterno Minussi, Daniela Moreno, Kathleen Kong, Turgut Dogruluk, Hengyu Lu, Jianjiong Gao, Collin Tokheim, Daniel Cui Zhou, Amber M. Johnson, Jia Zeng, Carman Ka Man Ip, Zhenlin Ju, Matthew Wester, Shuangxing Yu, Yongsheng Li, Christopher P. Vellano, Nikolaus Schultz, Rachel Karchin, Li Ding, Yiling Lu, Lydia Wai Ting Cheung, Ken Chen, Kenna R. Shaw, Funda Meric-Bernstam, Kenneth L. Scott, Song Yi, Nidhi Sahni, Han Liang, Gordon B. Mills
Journal: Cancer Cell (2018)
I studied law and worked in the city before starting medicine. I am now almost two years postgraduate, but know that I don't want to practise clinical medicine or work in the NHS. I don't want to leave medicine entirely, but I don't know where to go to find out what my career options are. Can you help?
Authors: Carl Gray
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>
Proprioceptive Opsin Functions in Drosophila Larval Locomotion
Authors: Damiano Zanini, Diego Giraldo, Ben Warren, Radoslaw Katana, Marta Andrés, Suneel Reddy, Stephanie Pauls, Nicola Schwedhelm-Domeyer, Bart R.H. Geurten, Martin C. Göpfert
Journal: Neuron (2018)
Psychiatry and rehabilitation medicine are added to list of occupations in shortage
Authors: Helen Jaques
Journal: BMJ (2013)

Psychiatry and rehabilitation medicine posts in non-consultant, non-training medical staff roles should be added to the United Kingdom’s shortage occupation list, the Migration Advisory Committee has said.

A further nine medical consultant and staff grade posts should remain on the list for as long as necessary, the committee has said, but 12 consultant and trainee …
Postgraduate diploma in medical toxicology
Authors: Venkateswara Rao S Kotamraju
Journal: BMJ (2011)

The postgraduate diploma in medical toxicology is a distance e-learning course delivered online by the Department of Pharmacology, Therapeutics and Toxicology at Cardiff School of Medicine.

The course is suitable for professionals from a wide range of specialties: emergency medicine and acute medicine trainees, pharmacists, life science graduates, and those working in close association with the National Poisons Information Service.

The aims of the course are to offer knowledge and expertise in the practical management of toxicological problems.

It provides an in-depth understanding of the mechanisms by which drugs produce toxic effects and how the effects can be predicted, treated …
Tumor suppressor aberrations and outcomes in localized and metastatic hormone sensitive prostate cancer (PrCa).
Authors: Anis Hamid, Kathryn P. Gray, Grace Shaw, Laura E MacConaill, Carolyn Evan, Brandon David Bernard, Atish Dipankar Choudhury, Christopher Sweeney
Journal: Journal of Clinical Oncology (2018)

184 Background: Aberrations of tumor suppressors (TS) TP53, PTEN and RB1 are recurrent genomic events in PrCa and associated with adverse clinical outcomes. Preclinical data suggest that cooperative functional loss of these genes drives development of even more aggressive disease phenotypes. Methods: We identified a retrospective cohort of men with PrCa who underwent DFCI Oncopanel targeted sequencing (NGS) on prostate gland (n = 230) or metastatic tissue (n = 7) for TP53, PTEN and RB1. Biomarker(BM)-positive was defined as copy number loss or likely deleterious mutation of ≥1 TS. For pts presenting with localized disease, Kaplan-Meier method estimated time from biopsy preceding local therapy to PSA relapse/metastasis/death (EFS), castration resistance (CRPC) and death (OS). Cox model assessed association of BM status and outcomes, adjusted for age, clinical stage and Gleason score in multivariate analyses (MVA). For M1 disease, time from ADT start to CRPC and death was estimated. We explored the association of cumulative BM-positive gene hits (0 vs 1 vs 2/3) with EFS (local disease) and OS (M1 disease). Results: Of pts presenting with localized disease (n = 205), 39% were BM-positive and 73 (36%) relapsed after median follow-up of 3.1 years. BM positivity was associated with significantly shorter EFS (driven by PSA relapse) (median 2.6 years, HR 1.95, 95% CI 1.22-3.13) and time to CRPC (HR 3.36, 95% CI 1.01-11.16). MVA confirmed the association with EFS (HR 1.84, p = 0.029). More gene hits lead to incremental risk of relapse (1 gene: HR 1.8, 95% CI 1.09-2.99; 2/3 genes: HR 2.68, 95% CI 1.27-5.63; both vs 0 hits) and this remained significant in MVA (1 gene: HR 1.75, p = 0.05; 2/3 genes: HR 2.74, p = 0.04). 43 patients had relapsed or de novo M1 disease. BM positivity (enriched at 63% of M1) was associated with poorer OS (10 deaths [of 27 BM-pos] vs 0 deaths [of 16 BM-neg] at median follow-up 3.3 years, HR not eval). A trend to incremental worse survival with cumulative gene hits was again observed. Conclusions: Deleterious TP53, PTEN and RB1 variants are associated with a short time to PSA relapse in localized disease, occur at a higher frequency in M1 disease and confer poorer OS. Worse outcomes are seen with cumulative gene hits.
A pay rise next year could risk jobs, warns health department
Authors: Caroline White
Journal: BMJ (2012)

The recommended 1% pay rise for NHS staff would increase pressure on staffing levels, and cuts in clinical posts could not be ruled out, the Department of Health has warned in its submission to the Review Body on Doctors’ and Dentists’ Remuneration.

Its evidence, which included a detailed breakdown of the continuing fiscal pressures facing the UK economy while it tackles its deficit, will be used to inform next year’s pay awards for NHS staff.

The department argued that the case for pay restraint in the public sector “remains strong” as a result of increased “baseline non-discretionary costs” affecting the NHS, including rising demand …