tbuckley/cabot-search huggingface dataset:
Comparison of different treatments for isoniazid-resistant tuberculosis: an individual patient data meta-analysis
Authors: Federica Fregonese, Shama D Ahuja, Onno W Akkerman, Denise Arakaki-Sanchez, Irene Ayakaka, Parvaneh Baghaei, Didi Bang, Mayara Bastos, Andrea Benedetti, Maryline Bonnet, Adithya Cattamanchi, Peter Cegielski, Jung-Yien Chien, Helen Cox, Martin Dedicoat, Connie Erkens, Patricio Escalante, Dennis Falzon, Anthony J Garcia-Prats, Medea Gegia, Stephen H Gillespie, Judith R Glynn, Stefan Goldberg, David Griffith, Karen R Jacobson, James C Johnston, Edward C Jones-López, Awal Khan, Won-Jung Koh, Afranio Kritski, Zhi Yi Lan, Jae Ho Lee, Pei Zhi Li, Ethel L Maciel, Rafael Mello Galliez, Corinne S C Merle, Melinda Munang, Gopalan Narendran, Viet Nhung Nguyen, Andrew Nunn, Akihiro Ohkado, Jong Sun Park, Patrick P J Phillips, Chinnaiyan Ponnuraja, Randall Reves, Kamila Romanowski, Kwonjune Seung, H Simon Schaaf, Alena Skrahina, Dick van Soolingen, Payam Tabarsi, Anete Trajman, Lisa Trieu, Velayutham V Banurekha, Piret Viiklepp, Jann-Yuan Wang, Takashi Yoshiyama, Dick Menzies
Journal: The Lancet Respiratory Medicine (2018)
Having “grit” helps doctors avoid burnout, researchers find
Authors: Matt Limb
Journal: BMJ (2017)

High levels of “grit” or resilience are associated with lower levels of burnout in UK doctors, researchers have found.1

The correlation was found among different groups of doctors, with consultants recording significantly higher levels of grit than trainees.

But it was not present among GPs who, as a group, had the highest levels of burnout.

The authors said that the nature of burnout in GPs could be different from that of other colleagues and that when burnout levels are very high the “protective role that grit can play could be lost.”

The UK study, …
Abstract 14217: A Significant Correlation Between Nitroglycerine-induced Vasodilation in Coronary and Brachial Arteries
Authors: Tatsuya Maruhashi, Yukihito Higashi, Masato Kajikawa, Ayumu Nakashima, Yumiko Iwamoto, Akimichi Iwamoto, Nozomu Oda, Shinji Kishimoto, Shogo Matsui, Tadanao Higaki, Takashi Shimonaga, Noriaki Watanabe, Hiroki Ikenaga, Takayuki Hidaka, Yoshiki Aibara, Kensuke Noma, Yasuki Kihara
Journal: Circulation (2016)

Introduction:  Nitroglycerine-induced vasodilation, an index of endothelium-independent vasodilation, is measured for the assessment of vascular smooth muscle cell function or alterations of vascular structure as a control for endothelial function test. Both coronary and brachial artery responses to nitroglycerine have been reported to be independent prognostic markers of cardiovascular events. The purpose of this study was to compare the nitroglycerine-induced vasodilation in the coronary and brachial arteries in the same patients.   Hypothesis:  There is a significant correlation between nitroglycerine-induced vasodilation in coronary and brachial arteries.   Methods:  We measured nitroglycerine-induced vasodilation in coronary and brachial arteries in 30 subjects who underwent coronary angiography with suspected coronary artery disease (19 men and 11 women; mean age, 69.0±8.8 years; age range, 42 to 85 years).   Results:  The mean value of nitroglycerine-induced vasodilation in the brachial artery, left anterior descending coronary artery, and left circumflex coronary artery were 12.6±5.2%, 11.6±10.3%, and 11.9±11.0%, respectively. Nitroglycerine-induced vasodilation in the brachial artery correlated significantly with that in the left anterior descending coronary artery and that in the left circumflex coronary artery (Figure), with a significant correlation between nitroglycerine-induced vasodilation in the left anterior descending coronary artery and that in the left circumflex coronary artery (r=0.72, P   Conclusions:  Vascular smooth muscle cell dysfunction may be a systemic disorder and thus impairments of endothelium-independent vasodilation in peripheral and coronary arteries are simultaneously present. Nitroglycerine-induced vasodilation in the brachial artery could be used as a surrogate for that in coronary artery and as a prognostic marker for cardiovascular events.
An ultra-endurance explorer⇓
Authors: Saheel Mukhtar
Journal: BMJ (2005)

D r Mike Stroud OBE, a consultant gastroenterologist and senior lecturer in medicine and nutrition, works at Southampton General Hospital. However, he is better known for his record breaking unsupported walks across the Arctic and Antarctic with Sir Ranulph Fiennes, as well as completing seven marathons in seven continents in seven days.

After finishing my A levels I planned to become a geologist. But during my gap year I changed my mind. I first became interested in medicine while working as a hospital porter, when I was given a book entitled The Mind of Man . My enthusiasm for “all things medical” grew after my sister was hospitalised. Later, while playing rugby, I was knocked unconscious and cared for by an attractive nurse—by the time I left hospital that day I had decided to become a doctor. I also had a taste for adventure and I realised I would be able to pursue my interest in exploration far more easily as a doctor.

During my gap …
I am a chartered physiotherapist who regrets not pursuing my original career choice to become a doctor. Do I have to attend the full five years of medical school in order to qualify as a GP, or can I just do the clinical years? Also, I have a first degree in human biology obtained at King's College, London where some subjects were taken with the medical school
Authors: Ruth Chambers
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>
No difference in ultraviolet B-induced changes in antigen-presenting cells and cytokines between patients with and without loss-of-function mutations in <i>FLG</i>
Authors: S. Simonsen, C.M. Bonefeld, J.P. Thyssen, A.T. Christiansen, C. Geisler, L. Skov
Journal: British Journal of Dermatology (2018)
Abstract 15396: Maintenance of Endothelial NO Release after Inhibition of NADPH Oxidase 4
Authors: Claudia Eickholt, Coy Brunssen, Heike Langbein, Melanie Brux, Anja Hofmann, Claudia Goettsch, Winfried Goettsch, Henning Morawietz
Journal: Circulation (2014)

The NADPH oxidase isoform NOX4 mainly produces H 2 O 2 . Previously we could show, that NOX4 is the major endothelial NOX isoform and constitutively active. Regulation of NOX4 and formation of reactive oxygen species are involved in NO release. The transcription factor NRF2 is a key mediator of cellular adaptation to redox stress. Therefore, regulation of NOX4 on the transcriptional level by NRF2 might be directly linked to NO release and endothelial function. Besides endothelial nitric oxide synthase (eNOS), a role of neuronal nitric oxide synthase (nNOS) in endothelial NO and H 2 O 2 release has been proposed. In this study, endothelial cells (HUVEC) were constantly exposed to high laminar shear stress (24 h, 30 dyn/cm 2 ). Application of shear stress stimulated NO formation and induced elongation of endothelial cells in the direction of flow. Lentiviral overexpression of NOX4 strongly increased endothelial H 2 O 2 release, while downregulation using shNOX4 decreased H 2 O 2 release. Furthermore, application of shear stress caused downregulation of NOX4 as well as upregulation of eNOS and antioxidative response via NRF2 and its target genes NQO-1 and HMOX-1. H 2 O 2 can affect NO release by eNOS. We could show that downregulation of NOX4 leads to upregulation of eNOS mRNA and protein expression accompanied by attenuation of NRF2 pathway under flow conditions. Determination of NO release confirmed these results. This supports a compensatory mechanism maintaining a stable NO release after NOX4 inhibition in response to flow. Attenuation of NRF2 by shNRF2 inhibited shear stress-dependent induction of NRF2 mRNA and protein expression and its target genes. In addition, shNRF2 enhanced the shear stress-dependent downregulation of NOX4. Finally, we detected a stable mRNA and protein expression of nNOS in endothelial cells, which was unaffected by flow. Interestingly, downregulation of NOX4 resulted in induction of nNOS expression. In conclusion, our data suggest an important role of H 2 O 2 production by NADPH oxidase 4 in maintaining NO release and endothelial function in response to flow. Inactivation of NADPH oxidase 4 attenuates NRF2 pathway and increases neuronal nitric oxide synthase as compensatory mechanisms.
Predict: Evaluation of baseline characteristics predictive of distant metastases in patients with castration-resistant prostate cancer—Updated data.
Authors: Stephen J. Freedland, Matthew R. Smith, Raoul S. Concepcion, Christopher Michael Pieczonka, Benjamin Adam Gartrell, Zvi Schiffman, Tim Van Mouwerik, Robert C. Tyler, Nancy N. Chang, Neal D. Shore
Journal: Journal of Clinical Oncology (2018)

253 Background: Metrics predicting a positive imaging test for men presumed M0 castration-resistant prostate cancer (CRPC) are not universally accepted/implemented. PREDICT (NCT01981109) evaluates characteristics predictive of a baseline (BL) imaging study positive for distant mets (M1) in men with presumed M0 CRPC, and follows those with confirmed M0 disease to M1 development. Methods: Men with no imaging in the previous 3 months (mos) were enrolled in the registry. Imaging modality to detect mets was at investigator’s discretion. Based on BL imaging, patients were classified as M0 or M1. Results: PREDICT enrolled 224 men, of whom 208 had BL scan/image data; 55 (25%) men presented with undetected M1. Visceral disease was noted in 11% of men presenting with M1 disease; 60% had bone only disease, 18% had nodal only disease and 11% had bone + nodal disease. Bone mets were found in 16% (25/160) of Tc99 scans vs 40% (19/48) of NaF PET (p = 0.0004). Of men with M0 at BL, 37/153 (24%) became M1 at a mean time from study entry of 11.9 mos. Mean follow-up was 28 mos. In these men, the only notable change in laboratory values from BL was PSA (mean: 16 vs 69 ng/mL; p = 0.020) and PSADT (7.7 vs 6.3 mos; p &lt; 0.001). Baseline PSADT was 10.9 (M0) and 5.7 (M1) mos. BL mean laboratory values were significantly higher (p &lt; 0.01) in the M1 vs M0 group for PSA (47 vs 10 ng/mL), alkaline phosphatase (111 vs 77 U/L), and prostatic acid phosphatase (8.2 vs 2.5 ng/mL). Conclusions: A high proportion (25%) of men presented with asymptomatic, occult mets, and 11% of the occult mets involved visceral disease. In men with documented M0 CRPC, approximately a quarter will develop mets in the next 12 mos. Early detection of occult mets will allow patients to initiate therapies shown to improve overall survival. Clinical trial information: NCT01981109.
Flare on Serial Prostate-Specific Membrane Antigen–Targeted 18F-DCFPyL PET/CT Examinations in Castration-Resistant Prostate Cancer
Authors: Katherine A. Zukotynski, John Valliant, François Bénard, Steven P. Rowe, Chun K. Kim, Martin G. Pomper, Steve Y. Cho
Journal: Clinical Nuclear Medicine (2018)

Abstract A 71-year-old man with castration-resistant prostate cancer demonstrated a flare phenomenon on 99m Tc-MDP and CT after 10 weeks of enzalutamide. Prostate-specific membrane antigen–targeted 18 F-DCFPyL PET/CT demonstrated minimal uptake at sites of baseline bone and lymph node disease with increasing uptake at sites of osseous disease following therapy. Although this is likely related in part to decreased androgen receptor activity and a consequent increase in prostate-specific membrane antigen expression, other mechanisms (neovascularization, cell infiltration from the bone repair process, osteoblastic turnover, or minimal radiotracer impurity) may also be involved in causing the increased 18 F-DCFPyL uptake at sites of osseous flare.
Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet
Authors: Tiziano Barbui, Ayalew Tefferi, Alessandro M. Vannucchi, Francesco Passamonti, Richard T. Silver, Ronald Hoffman, Srdan Verstovsek, Ruben Mesa, Jean-Jacques Kiladjian, Rȕdiger Hehlmann, Andreas Reiter, Francisco Cervantes, Claire Harrison, Mary Frances Mc Mullin, Hans Carl Hasselbalch, Steffen Koschmieder, Monia Marchetti, Andrea Bacigalupo, Guido Finazzi, Nicolaus Kroeger, Martin Griesshammer, Gunnar Birgegard, Giovanni Barosi
Journal: Leukemia (2018)
Clinical excellence awards for 2012 are to go ahead
Authors: Helen Jaques
Journal: BMJ (2012)

The 2012 national and local award rounds for clinical excellence awards are to open this month, the Department of Health has announced.

On Friday the health minister Simon Burns wrote to the Advisory Committee on Clinical Excellence Awards (ACCEA) to ask it to launch the 2012 award rounds.

“In building a modern NHS we want to continue to reward and recognise those who make outstanding achievements …
An epigenetically controlled PML/Slit axis at the root of cell migration in both normal and neoplastic cells in the CNS
Authors: A Deli, Valeria Amodeo, Joanne Betts, Stefano Bartesaghi, Mikaella Vouri, Rozita Roshani, Sara Galavotti, Ying Zhang, Matthew Ellis, Joanne Lau, Sarah Oberndorfer, Ana Leite, David Dinsdale, Chris Jones, Pierluigi Nicotera, David Michod, Sebastian Brandner, Paolo Salomoni
Journal: Neuro-Oncology (2018)

In the central nervous system (CNS), regulation of nuclear function has been implicated in the control of cell cycle and migratory processes during neurogenesis. Alterations of these processes can lead to neoplastic transformation of neural stem cells (NSCs) and glioblastoma multiforme (GBM). The ability of GBM cells to migrate through the brain parenchyma represents a key factor underlying GBM aggressiveness and resistance to treatment. Notably, brain cancer cells use the same routes utilized by neuroblasts/immature neurons and NSCs, suggesting a neurobiological root of brain cancer migration. However, our understanding of potentially common mechanisms regulating cell migration/invasion during neurogenesis and brain tumourigenesis remains limited. Our previous work has implicated the Promyelocytic Leukaemia protein (PML), the essential component of the PML nuclear body (PML-NB), in regulation of embryonic neurogenesis via its ability to control proliferation in NSCs. We set out to investigate the role of PML in adult neurogenesis and GBM. Loss of PML leads to impaired NSC and neuroblast migration and to a smaller olfactory bulb in the adult mouse brain. A similar migration defect is observed in primary GBM cells where PML expression has been knocked down. Mechanistically, PML controls cell migration in both mouse NSCs and primary GBM cells via down-regulation of Slit genes, which are key regulators of axon guidance during development. Changes in Slits transcription upon PML kd are caused by global reduction of the repressive H3K27me3 epigenetic mark. This is associated with its redistribution to nuclear lamina-associated domains (LADs). Finally, PML controls tumor invasion and survival in an orthotopic animal model and inversely correlates with patient prognosis in GBM. Taken together, these findings support a model whereby PML-mediated modifications of chromatin structure and function regulate cell migration during normal neurogenesis and brain tumorigenesis, suggesting a neurobiological root of brain cancer invasion.
Comment on Russell-Jones et al. Diabetes Care 2017;40:943–950. Comment on Bowering et al. Diabetes Care 2017;40:951–957
Authors: Tongzhi Wu, Chinmay S. Marathe, Michael Horowitz, Karen L. Jones, Christopher K. Rayner
Journal: Diabetes Care (2018)

We read with interest the recent papers relating to the onset 1 and onset 2 trials (1,2), which compared the clinical efficacy and safety profiles of fast-acting insulin aspart (faster aspart) with insulin aspart (IAsp) in patients with type 1 and type 2 diabetes who concurrently received basal insulin. The authors recognize the importance of lowering postprandial glycemia to achieve HbA1c goals, particularly when fasting glucose is adequately controlled or only modestly elevated.

The central hypothesis underlying the trials is that mealtime insulin with a faster action will provide better control of postprandial glycemia and, potentially, HbA1c when used with basal insulin. However, postprandial blood glucose concentrations are determined by glucose disposal and both exogenous and endogenous glucose production, i.e., interrelated …
Anti-NaPi2b antibody–drug conjugate lifastuzumab vedotin (DNIB0600A) compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer in a randomized, open-label, phase II study
Authors: S. Banerjee, A.M. Oza, M.J. Birrer, E.P. Hamilton, J. Hasan, A. Leary, K.N. Moore, B. Mackowiak-Matejczyk, J. Pikiel, I. Ray-Coquard, P. Trask, K. Lin, E. Schuth, A. Vaze, Y. Choi, J.C. Marsters, D.J. Maslyar, V. Lemahieu, Y. Wang, E.W. Humke, J.F. Liu
Journal: Annals of Oncology (2018)
No Difference in Effectiveness of 8 vs 12 Weeks of Ledipasvir and Sofosbuvir for Treatment of Hepatitis C in Black Patients
Authors: Julia L. Marcus, Leo B. Hurley, Scott Chamberland, Jamila H. Champsi, Laura C. Gittleman, Daniel G. Korn, Jennifer B. Lai, Jennifer O. Lam, Mary Patricia Pauly, Charles P. Quesenberry, Joanna Ready, Varun Saxena, Suk I. Seo, David J. Witt, Michael J. Silverberg
Journal: Clinical Gastroenterology and Hepatology (2018)
Sequential BMP7/TGF-β1 signaling and microbiota instruct mucosal Langerhans cell differentiation
Authors: Tal Capucha, Noam Koren, Maria Nassar, Oded Heyman, Tsipora Nir, Maayan Levy, Gili Zilberman-Schapira, Katya Zelentova, Luba Eli-Berchoer, Martin Zenke, Thomas Hieronymus, Asaf Wilensky, Herve Bercovier, Eran Elinav, Björn E. Clausen, Avi-Hai Hovav
Journal: The Journal of Experimental Medicine (2018)

Mucosal Langerhans cells (LCs) originate from pre–dendritic cells and monocytes. However, the mechanisms involved in their in situ development remain unclear. Here, we demonstrate that the differentiation of murine mucosal LCs is a two-step process. In the lamina propria, signaling via BMP7-ALK3 promotes translocation of LC precursors to the epithelium. Within the epithelium, TGF-β1 finalizes LC differentiation, and ALK5 is crucial to this process. Moreover, the local microbiota has a major impact on the development of mucosal LCs, whereas LCs in turn maintain mucosal homeostasis and prevent tissue destruction. These results reveal the differential and sequential role of TGF-β1 and BMP7 in LC differentiation and highlight the intimate interplay of LCs with the microbiota.
Abstract P1-07-27: Prognostic value of programmed death 1/Programmed death ligand 1/ mammalian target of rapamycin/Rictor/Tuberin in human breast cancer
Authors: M Uhercik, AJ Sanders, S Owen, EL Davies, AK Sharma, WG Jiang, K Mokbel
Journal: Cancer Research (2018)

Abstract Background:The Mammalian Target of Rapamycin (mTOR) regulates a multitude of cellular processes including metabolism, proliferation and growth. It is known to form two multi-protein complexes - complex 1 (mTORC1) and complex 2 (mTORC2) with Raptor and Rictor being their core proteins vital for their integrity. Tuberin, the product of the Tuberous Sclerosis Complex gene 2, TSC2, has been characterized as a tumour suppressor and negatively regulates the mTOR pathway. Programmed Death 1 (PD-1), a transmembrane protein particularly expressed on the surface of tumour cells, acts as an immune checkpoint receptor. Together with its ligand Programmed Death Ligand 1 (PDL-1) they form a pathway which when activated influences anti-tumour immunity and supresses anti-tumour adaptive responses. The expression of PD1/PDL-1 is lightly regulated by the mTOR pathway. We investigated the value of expression patterns of all these molecules in breast cancer as potential prognostic factors. Materials and Methods: Quantitative PCR (qPCR) analysis was used to determine the transcript expression profile of the five genes of interest (PD-1, PDL-1, mTOR, Rictor and Tuberin) in 128 breast cancer specimens.The correlation between PD-1 or PDL-1 with mTOR, Rictor and Tuberin was assessed using the Spearman Rank Order Correlation. Subsequently, a combined analysis was performed, where the influence of favourable expression in relation to patient overall (OS) and disease free survival (DFS) using the Kaplan Meier survival curves and multivariate analysis. Results: The mRNA expression of the molecules showed a varying degree of association with the clinicopathological parameters. PD-1 transcript expression showed a significant correlation with mTOR expression (p &amp;lt; 0.001). PDL-1 transcript expression was seen to correlate with mTOR (p &amp;lt; 0.001), Rictor (p &amp;lt; 0.001) and Tuberin (p &amp;lt; 0.01) transcript expression. However, when the expression profile was analysed using an integrated expression score, the combined predictive value for the clinical outcome of the five genes was highly significant in terms of OS (p &amp;lt; 0.001) and DFS (p = 0.001), and was found to be an independent prognostic factor (p&amp;lt;0.001) for breast cancer related death using a multivariate analysis. Conclusions: Our study identifies a molecular signature of 5 genes as a powerful prognostic predictor of OS and DFS in patients with breast cancer. Citation Format: Uhercik M, Sanders AJ, Owen S, Davies EL, Sharma AK, Jiang WG, Mokbel K. Prognostic value of programmed death 1/Programmed death ligand 1/ mammalian target of rapamycin/Rictor/Tuberin in human breast cancer [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 P1-07-27.
Hepatic Epithelioid Angiomyolipoma and 18F-FDG PET/CT
Authors: Yiqiu Zhang, Beilei Li, Jun Hou, Haojun Yu, Hongcheng Shi
Journal: Clinical Nuclear Medicine (2018)

Hepatic epithelioid angiomyolipoma (AML) is rare. Although generally epithelioid AML shows benign biological behavior, it can occasionally have malignant potential. In this study, we report a case of 2 hepatic epithelioid AMLs with different F-FDG uptake; one is intensely FDG avid, and the other is non-FDG avid.
Lovelorn patients are increasingly using digital media to pursue relationships with doctors
Authors: Caroline White
Journal: BMJ (2012)

Doctors should take swift action to fend off romantic advances from patients who are increasingly taking to digital media to express their feelings, a medical defence body has warned.

Withholding mobile phone numbers when telephoning patients and adjusting privacy settings on social networking sites such as Facebook and Twitter may all be needed to block approaches from such patients, said the Medical Defence Union (MDU).

Its advice comes after a review of more than 100 cases over the past …