tbuckley/cabot-search huggingface dataset:
Amyloid PET Positivity in Different Primary Progressive Aphasia Phenotypes
Authors: Emilie Beaufils, Johnny Vercouillie, Emilie Vierron, Jean-Philippe Cottier, Vincent Camus, Karl Mondon, Denis Guilloteau, Caroline Hommet, Maria Joao Ribeiro
Journal: Clinical Nuclear Medicine (2018)

Purpose Primary progressive aphasia (PPA) is a neurological syndrome in which language functions become progressively impaired with relative sparing of memory and other instrumental functions. The pathologic causes of PPA are heterogeneous, but studies suggest that logopenic PPA (LPA) is underpinned by Alzheimer disease (AD) pathology in a high proportion of cases. The purposes of this descriptive and retrospective study were to characterize 18 F-florbetapir PET imaging in a group of patients with a clinical syndrome of PPA, to determine the value of clinical characterization based on language phenotype in predicting the underlying pathology of PPA with 18 F-florbetapir, and to quantify amyloid load in PPA subjects classified as “positive” 18 F-florbetapir scans. Then, we compare the quantification and distribution of 18 F-florbetapir uptake with those of typical, predominantly amnestic AD patients. Methods We conducted a PET study with 18 F-florbetapir in a cohort of 12 right-handed patients diagnosed with PPA: 3 patients with semantic-variant PPA, 5 with nonfluent PPA, 1 with LPA, and 3 unclassifiable patients. We evaluated amyloid deposition between APP groups and 11 patients with typical amnestic AD. Results Among the 12 patients with PPA syndrome, 8 (66.7%) were considered as amyloid positive. One of the 3 patients with semantic-variant PPA was 18 F-florbetapir positive. In contrast, 4 of the 5 nonfluent-variant PPA, 2 of the 3 unclassifiable cases and the single patient with LPA were 18 F-florbetapir positive. A significantly higher 18 F-florbetapir uptake was observed in PPA 18 F-florbetapir–positive patients compared with typical AD patients. This difference was observed in all regions of interest, except in posterior cingulate and temporal cortex. Conclusions These results suggest that 18 F-florbetapir PET may be useful in a routine clinical procedure to improve the reliability of identifying AD pathology in patients with PPA syndrome, with different clinical subtypes of the PPA syndrome.
Morbidity and mortality of laparoscopic D2 gastrectomy with complete mesogastrium excision (D2+CME) versus conventional D2 gastrectomy for advanced gastric cancer: An interim report of a single-center, prospective, randomized trial (NCT01978444).
Authors: Daxing Xie
Journal: Journal of Clinical Oncology (2018)

TPS190 Background: In our previous research, laparoscopic D2 lymphadenectomy plus Complete Mesogastrium Excision (D2+CME) has been proven to be an optimal surgical approach for advanced gastric cancer (AGC). However, there is a lack of evidence regarding its oncologic safety. Here, we conducted a single-centre, prospective, randomized controlled trial comparing the morbidity and mortality of laparoscopic D2+CME with conventional D2 gastrectomy in AGC. Methods: Patients eligibly criteria were pathologically-proven adenocarcinoma, 18 to 75 years old, cT2-4N0-3M0 at preoperative evaluation, expected curative resection via laparoscopic distal gastrectomy, no history of other cancers, chemotherapy or radiotherapy, no history of upper abdominal operation and perioperative ASA class I, II or III. The primary end-point was 3-year disease-free survival. The morbidity and mortality were compared to evaluate the safety of this trial. We hypothesized that the morbidity of this study was not significantly different from that of previous reports on laparoscopic distal gastrectomy (5.7%-15.5%). This study is registered at ClinicalTrials.gov, ID number is NCT01978444. Clinical trial information: NCT01978444.
Evolution of respiratory function in Duchenne muscular dystrophy from childhood to adulthood
Authors: Antonella LoMauro, Marianna Romei, Sandra Gandossini, Riccardo Pascuzzo, Simone Vantini, Maria Grazia D'Angelo, Andrea Aliverti
Journal: European Respiratory Journal (2018)

In Duchenne muscular dystrophy (DMD), it is still to be determined if specific timepoints can be identified during the natural evolution of respiratory dysfunction from childhood to adulthood and if scoliosis, steroid therapy and nocturnal noninvasive mechanical ventilation (NIMV) have any effect on it. In a 7-year retrospective study performed on 115 DMD patients (6–24 years), evaluated once or twice per year, with 574 visits in total, evolution mean curves of spirometry, lung volumes, spontaneous breathing and thoraco-abdominal pattern (measured by optoelectronic plethysmography) parameters were obtained by nonlinear regression model analysis. While predicted values of forced vital capacity, forced expiratory volume in 1 s, and peak expiratory flow decline continuously since childhood, during spontaneous breathing the following parameters become significantly different than normal in sequence: abdominal contribution to tidal volume (lower after 14.8 years), tidal volume (lower after 17.2 years), minute ventilation (lower after 18.1 years) and respiratory rate (higher after 22.1 years). Restrictive lung pattern and diaphragmatic impairment are exacerbated by scoliosis severity, slowed by steroids treatment and significantly affected by NIMV. Spirometry, lung volumes, breathing pattern and thoraco-abdominal contributions show different evolution curves over time. Specific timepoints of respiratory impairment are identified during disease progression. These should be considered when defining outcome measures in clinical trials and treatment strategies in DMD.
Patients treated with oxaliplatin are at risk for thrombocytopenia caused by multiple drug-dependent antibodies
Authors: Brian R. Curtis, Yen-Michael S. Hsu, Nikolai Podoltsev, Jill Lacy, Susanna Curtis, Michael S. Samuel, Kristin Zutavern, Robert A. DeSimone, Daniel W. Bougie, Richard H. Aster
Journal: Blood (2018)
Phase Ib/II trial of durvalumab and chemoradiation (CRT) with carboplatin/paclitaxel for esophageal and gastroesophageal junction (GEJ) adenocarcinoma.
Authors: Megan Greally, Daniela Molena, Smita Sihag, Abraham Jing-Ching Wu, Pari M. Shah, Carly Fein, Marinela Capanu, David Paul Kelsen, Yelena Yuriy Janjigian, David H. Ilson, Geoffrey Yuyat Ku
Journal: Journal of Clinical Oncology (2018)

172 Background: Pre-op CRT with carboplatin (C)/paclitaxel (P) and radiation (RT) for locally advanced esophageal cancer is a standard of care, based on the CROSS trial (NEJM 2012;366:2074). However, outcomes remain poor. Early data suggest activity of durvalumab (D) in GEJ/gastric cancer [Ann Oncol 25:iv361-372; 2014]. In a pilot study, we assessed safety of D + C/P + RT as pre-op therapy. Methods: Patients (Pts) had T any N+ or T3-4N any M0 esophageal and Siewert Type I/II GEJ adenocarcinoma staged by EUS, PET/CT and CT. Pts received D 1500mg x 1 dose and 4 weeks later C AUC2 and P 50mg/m 2 weekly x 5 with RT (1.8Gy daily fractions to 50.4Gy). Pts also received D 1,500mg at first dose of C/P and RT. PET/CT was repeated 21-27 days post D and 4-6 weeks post CRT. Esophagectomy was planned 6-8 weeks after CRT. Pts who had R0 resections received adjuvant D 1,500mg 4 weekly x 6 doses. Initially, 6 patients were treated and followed for 30 days after surgery to assess for unacceptable toxicities. Results: 6 pts were enrolled: 3 Siewert I (50%), 2 Siewert II (33%), 1 esophageal (17%); 5 T3N1-2, 1 T4aN1. 5 pts (83%) underwent sx. 1 pt was retrospectively assessed to have metastases after induction D and taken off-study. Pathologic response was 60% in 2 pts, 90% in 1 pt, 80% in 1 pt and 40% in 1 pt; no complete response was seen. Significant grade 3/4 toxicity observed during D and CRT was neutropenia in 1 pt (17%). Adverse events (AEs) of any grade in ≥20%: lymphopenia (5 pts), thrombocytopenia (5 pts), leucopenia (4 pts), fatigue (3 pts), anemia (3 pts), neutropenia (3 pts) and abdominal pain (2 pts). Immune-related AEs were hypothyroidism (grade 2; 1 pt) and nephritis (grade 2; 1 pt). Surgical complications: 2 esophageal strictures, 1 pneumonia and 1 anastomotic leak with airway fistula, successfully treated with a stent. Immune correlative analyses from tumor blocks and whole blood are ongoing and will be reported in the poster. Conclusions: The addition of D to pre-op CRT in esophageal and GEJ adenocarcinoma appears feasible and safe. We observed no unacceptable toxicity. The study is being modified to incorporate use of induction chemo and PET (based on CALGB 80803 results) and expanded to a multicenter setting. Clinical trial information: NCT02962063.
Pushing forward on equality
Authors: Tom Moberly
Journal: BMJ (2014)

More than a quarter of doctors registered in the United Kingdom come from black and ethnic minority groups. Yet, as Matthew Limb discusses, (http://careers.bmj.com/careers/advice/view-article.html?id=20018682&articleType=news), experiences of racism, exclusion, and discrimination contribute to low levels of wellbeing among NHS staff from these groups.

Limb looks at the findings of a report by Mala Rao and Jacqui Stevenson into wellbeing among black and ethnic minority groups. The report …
Postgraduate diploma or LLM (Master of Laws) in medical law, University of Northumbria
Authors: Kayvan Shokrollahi
Journal: BMJ (2007)

FURTHER INFORMATION 

School of Law, Sutherland Building, University of Northumbria, Newcastle NE1 8ST. (0191) 227 4433; fax: (0191) 227 4557.

The diploma or LLM is aimed at anyone interested in medical law, or anyone who wants to gain further insight into legal aspects of medicine and medicolegal aspects of the law (depending on their viewpoint or discipline). Module topics include legal principles and methodology, clinical …
Junior doctors are out of touch with healthcare reforms, finds survey
Authors: Helen Jaques
Journal: BMJ (2013)

Most foundation trainees do not understand the changes to the NHS introduced by the Health and Social Care Act, a survey of junior doctors in the south of England has found.1

Of 102 randomly selected foundation year 1 and 2 doctors responding to an online questionnaire, almost two thirds (63%) said that they did not understand the changes under way in the NHS. The online questionnaire was …
Erratum. Time Trends of Dietary and Lifestyle Factors and Their Potential Impact on Diabetes Burden in China. Diabetes Care 2017;40:1685–1694
Authors: Yanping Li, Dong D. Wang, Sylvia H. Ley, Malik Vasanti, Annie Green Howard, Yuna He, Frank B. Hu
Journal: Diabetes Care (2018)

In the article cited above, a correction was made to the last paragraph of the CONCLUSIONS section. The sentence …
Public health still has power to influence
Authors: Rod Griffiths
Journal: BMJ (2005)

Ray Lowry argues that public health has lost its way, while acknowledging that it's a good time to join the specialty.1 It is an exciting time to become a public health specialist, but I challenge his assertion that public health is in crisis. On the contrary, the specialty offers major opportunities to influence the health of the public in a positive way.

Public health works across three domains: health protection, service improvement, and health improvement. In health protection, the creation of the Health Protection Agency has provided an enormous opportunity to develop one of the best agencies of its kind. The Wanless report clearly showed the role …
I am looking for educational opportunities in a cancer research centre. I am in my second year of medical school and I want to do it in my summer vacation (two months). Can you advise me? I am an international student and don't know about UK research centres
Authors: Graham Williams
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>
Reproducible inference of transcription factor footprints in ATAC-seq and DNase-seq datasets using protocol-specific bias modeling
Authors: Aslıhan Karabacak Calviello, Antje Hirsekorn, Ricardo Wurmus, Dilmurat Yusuf, Uwe Ohler
Journal: Genome biology (2019)

DNase-seq and ATAC-seq are broadly used methods to assay open chromatin regions genome-wide. The single nucleotide resolution of DNase-seq has been further exploited to infer transcription factor binding sites (TFBSs) in regulatory regions through footprinting. Recent studies have demonstrated the sequence bias of DNase I and its adverse effects on footprinting efficiency. However, footprinting and the impact of sequence bias have not been extensively studied for ATAC-seq.Here, we undertake a systematic comparison of the two methods and show that a modification to the ATAC-seq protocol increases its yield and its agreement with DNase-seq data from the same cell line. We demonstrate that the two methods have distinct sequence biases and correct for these protocol-specific biases when performing footprinting. Despite the differences in footprint shapes, the locations of the inferred footprints in ATAC-seq and DNase-seq are largely concordant. However, the protocol-specific sequence biases in conjunction with the sequence content of TFBSs impact the discrimination of footprint from the background, which leads to one method outperforming the other for some TFs. Finally, we address the depth required for reproducible identification of open chromatin regions and TF footprints.We demonstrate that the impact of bias correction on footprinting performance is greater for DNase-seq than for ATAC-seq and that DNase-seq footprinting leads to better performance. It is possible to infer concordant footprints by using replicates, highlighting the importance of reproducibility assessment. The results presented here provide an overview of the advantages and limitations of footprinting analyses using ATAC-seq and DNase-seq.
RORα-expressing T regulatory cells restrain allergic skin inflammation
Authors: Nidhi Malhotra, Juan Manuel Leyva-Castillo, Unmesh Jadhav, Olga Barreiro, Christy Kam, Nicholas K. O’Neill, Francoise Meylan, Pierre Chambon, Ulrich H. von Andrian, Richard M. Siegel, Eddie C. Wang, Ramesh Shivdasani, Raif S. Geha
Journal: Science Immunology (2018)

Atopic dermatitis is an allergic inflammatory skin disease characterized by the production of the type 2 cytokines in the skin by type 2 innate lymphoid cells (ILC2s) and T helper 2 (T
Image Gallery: Lenalidomide for the treatment of pseudotumoral herpes simplex virus type 2 infection in human immunodeficiency virus infection
Authors: J. Gottlieb, M. Janier, M. Battistella, H. Bachelez
Journal: British Journal of Dermatology (2018)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, A 62‐year‐old man, who was known to be human immunodeficiency virus type 1‐infected, presented with recurrent anogenital herpes simplex virus type 2‐related pseudotumours (a) since 1993, while showing undetectable plasma viral load with CD4 absolute count of 619 mm−3 on antiretroviral therapy. Histopathological examination confirmed diagnosis by showing a fibrous chorion with dense lymphocytic and plasma cell infiltrate. Due to lack of efficacy of antiherpetic drugs1 and neurotoxicity of thalidomide, which was partly effective,2 lenalidomide was further introduced, and led to complete clinical remission within 6 months, without adverse effects (b, c).
Stimulation of TNF receptor type 2 expands regulatory T cells and ameliorates established collagen-induced arthritis in mice
Authors: Vanessa Lamontain, Tobias Schmid, Dorothea Weber-Steffens, David Zeller, Zsuzsa Jenei-Lanzl, Harald Wajant, Rainer H Straub, Daniela N Männel
Journal: Cellular and Molecular Immunology (2018)
CARDIOVASCULAR MAGNETIC RESONANCE OR COMPUTED TOMOGRAPHY ANGIOGRAPHY FIRST VERSUS A ROUTINE INVASIVE STRATEGY IN HIGH-SENSITIVE TROPONIN-POSITIVE SUSPECTED NON-ST-ELEVATION MYOCARDIAL INFARCTION: RANDOMIZED CONTROLLED TRIAL
Authors: Martijn Smulders, Bas Kietselaer, Joachim Wildberger, Pieter Dagnelie, Hans-Peter Brunner-La Rocca, Alma Mingels, Yvonne van Cauteren, Ralph Theunissen, Mark Post, Simon Schalla, Sander van Kuijk, Marco Das, Raymond Kim, Harry Crijns, Sebastiaan Bekkers
Journal: Journal of the American College of Cardiology (2018)
miR-34c-5p promotes eradication of acute myeloid leukemia stem cells by inducing senescence through selective RAB27B targeting to inhibit exosome shedding
Authors: Danyue Peng, Huifang Wang, Lei Li, Xiao Ma, Ying Chen, Hao Zhou, Yi Luo, Yin Xiao, Lingbo Liu
Journal: Leukemia (2018)
<i>In Vivo</i> E2F Reporting Reveals Efficacious Schedules of MEK1/2–CDK4/6 Targeting and mTOR–S6 Resistance Mechanisms
Authors: Jessica L.F. Teh, Phil F. Cheng, Timothy J. Purwin, Neda Nikbakht, Prem Patel, Inna Chervoneva, Adam Ertel, Paolo M. Fortina, Ines Kleiber, Kim HooKim, Michael A. Davies, Lawrence N. Kwong, Mitch P. Levesque, Reinhard Dummer, Andrew E. Aplin
Journal: Cancer Discovery (2018)

Abstract Targeting cyclin-dependent kinases 4/6 (CDK4/6) represents a therapeutic option in combination with BRAF inhibitor and/or MEK inhibitor (MEKi) in melanoma; however, continuous dosing elicits toxicities in patients. Using quantitative and temporal in vivo reporting, we show that continuous MEKi with intermittent CDK4/6 inhibitor (CDK4/6i) led to more complete tumor responses versus other combination schedules. Nevertheless, some tumors acquired resistance that was associated with enhanced phosphorylation of ribosomal S6 protein. These data were supported by phospho-S6 staining of melanoma biopsies from patients treated with CDK4/6i plus targeted inhibitors. Enhanced phospho-S6 in resistant tumors provided a therapeutic window for the mTORC1/2 inhibitor AZD2014. Mechanistically, upregulation or mutation of NRAS was associated with resistance in in vivo models and patient samples, respectively, and mutant NRAS was sufficient to enhance resistance. This study utilizes an in vivo reporter model to optimize schedules and supports targeting mTORC1/2 to overcome MEKi plus CDK4/6i resistance. Significance: Mutant BRAF and NRAS melanomas acquire resistance to combined MEK and CDK4/6 inhibition via upregulation of mTOR pathway signaling. This resistance mechanism provides the preclinical basis to utilize mTORC1/2 inhibitors to improve MEKi plus CDK4/6i drug regimens. Cancer Discov; 8(5); 568–81. ©2018 AACR. See related commentary by Sullivan, p. 532. See related article by Romano et al., p. 556. This article is highlighted in the In This Issue feature, p. 517
Decipher test’s impact on the postoperative management of prostate cancer.
Authors: Brian P. Calio, Matt Murphy, Anne Calvaresi, James Ryan Mark, Mark Mann, Robert Benjamin Den, Leonard G. Gomella, Edouard John Trabulsi, Costas D. Lallas
Journal: Journal of Clinical Oncology (2018)

146 Background: The Decipher Prostate Cancer Test provides risk stratification for prostate cancer aggressiveness and predicts the probability of metastasis after surgery. We aim to determine the impact on clinical decision-making Decipher risk designation has had at our institution since its implementation. Methods: A prospectively maintained single institution database was analyzed for patients who underwent prostate biopsy and prostatectomy between 2006-2017. Patients with pathologic T3 cancer, Gleason ≥3+4, or positive surgical margins were considered for the study. In cohort 1, patients’ Decipher scores were available prior to postoperative decision-making, in cohort 2 patients’ scores were not available. Postoperative management was then compared between cohorts to determine if presence of Decipher score influenced the rate of adjuvant and salvage radiation administered. The EMR was queried for the words “adjuvant”, “RT”, “salvage”, “SRT”, to record rates of radiation given to each patient. Chi Square and Mann Whitney test was used to compare rates between cohorts and Decipher risk categories. Results: 454 patients were included in the study with median (IQR) age of 62.0 (7.0) years. Mean time of follow-up was 2.0 years and 8.2 years in cohorts 1 and 2, respectively. In the cohort that received Decipher scores, rate of adjuvant radiation administered was significantly higher than in patients who did not receive a Decipher score (27.0% vs. 6.8%, p&lt;0.001), and higher Decipher risk was associated with higher rate of adjuvant administration (9% vs 27.8% vs 35.4% for low, average and high risk, respectively; p&lt;0.001). Rate of salvage radiation given was not significantly different between the cohorts (5.2% vs 4.0%; p=0.228). Conclusions: The Decipher Prostate Cancer Test provides valuable data regarding risk stratification of disease. As demonstrated here, the availability of Decipher scores has lead to a demonstrable effect in the postoperative management of prostate cancer.
Clinical Utility of Combined Optical Coherence Tomography and Near-Infrared Spectroscopy for Assessing the Mechanism of Very Late Stent Thrombosis
Authors: Yasushi Ino, Takashi Kubo, Takeyoshi Kameyama, Kunihiro Shimamura, Kosei Terada, Yoshiki Matsuo, Hironori Kitabata, Yasutsugu Shiono, Manabu Kashiwagi, Akio Kuroi, Naoki Maniwa, Shingo Ota, Yuichi Ozaki, Atsushi Tanaka, Takeshi Hozumi, Takashi Akasaka
Journal: JACC. Cardiovascular imaging (2018)
Abstract 19787: Cardiovascular Risk Assessment in the South Texas HIV+ Cohort: Is Risk Estimation or Risk Categorization More Appropriate for Patient Counseling?
Authors: Yuanyuan Liang, Norma S Ketchum, Barbara J Turner, John M Flores, Delia Bullock, Roberto Villarreal, Polly H Noel, Michael T Yin, Barbara S Taylor
Journal: Circulation (2015)

Introduction: Existing cardiovascular disease (CVD) risk calculators underestimate the risk of CVD among people with human immunodeficiency virus (HIV+). This is the first study to compare CVD risk estimations and categories in an HIV+ cohort using AHA, Framingham (FRC), and D:A:D (Data collection on Adverse Effects of Anti-HIV Drugs Study) calculators. Methods: Of patients seen in a public HIV clinic in South Texas ≥2 times in 2013, 668 HIV+ adults &gt;40 years old without prevalent CVD had sufficient data for CVD risk calculations. Patients’ continuous 10 year CVD risks were estimated by three calculators and compared pairwisely using Wilcoxon signed-rank test. Patients were classified into risk categories per guidelines for each risk calculation, which differ: AHA: 10y risk&lt;7.5% Low, ≥7.5% High; FRC: 10y risk &lt;10% Low, 10-20% Moderate, &gt;20% High; D:A:D: 5y risk &lt;1% Low, 1-5% Moderate, ≥5% High. The proportion of patients at high risk was compared with McNemar’s test. Results: Mean patient age was 49.8y (SD=6.2), 79.9% were men, 63.3% Hispanic, 19.6% white non-Hispanic, 14.7% African American, mean BMI was 27.9 kg/m 2 (SD=5.6), 41.6% were treated for hypertension, and 17.2% had diabetes. HIV disease was relatively controlled, with 85.2% on antiretroviral therapy and 69% virologically suppressed. Median estimated 10y CVD risk was highest with FRC (all p&lt;0.001, Table). The percentage of patients classified at high risk ranged from 20.4% to 44.2%, with D:A:D placing the highest proportion of patients into a high risk group (all p&lt;0.001). Conclusions: Risk calculators behaved differently based on whether continuous risk estimates or categorical risk classifications were used. Median 10-year risk was highest with FRC, yet D:A:D classified the highest proportion of patients at elevated risk. Since CVD risk calculators underestimate risk for HIV+ adults, clinicians may find the risk categorization with AHA or D:A:D calculators more appropriate for patient counseling.