tbuckley/cabot-search huggingface dataset:
15 Does choice of brush cytology device influence the diagnostic yield in suspected malignant biliary strictures at ERCP
Authors: JK Eccles, MT McLoughlin
Journal: Gut (2017)

Background  Suspected malignant biliary strictures lacking a confirmed tissue diagnosis pose a diagnostic dilemma, putting patients at risk of undergoing major surgery for a potentially benign disease process or repeated diagnostic procedures. Although highly specific, the disappointingly low sensitivity of biliary brush cytology has prompted development of newer equipment and techniques.  Aim  We aimed to determine if using a new, larger-bristled “Infinity” brush (US Endoscopy) led to superior detection of malignant biliary strictures at cytology than the “RX” brush (Boston Scientific).  Method  We retrospectively reviewed the case notes of 58 patients who had undergone ERCP and brushings within Mater Hospital, Belfast between May 2011–2016. Of these, 33 had been diagnosed with histopathologically-confirmed pancreaticobiliary cancers. The RX brush was used in 13 cases; the Infinity brush in 20 cases.  Results  Cytology from the 13 patients with RX brush yielded 5 with cells confirming adenocarcinoma. Of 20 patients whose strictures had been brushed with an Infinity brush, 11 had adenocarcinoma identified. Assuming atypical cells to be classified as non-malignant, the RX brush achieved a sensitivity of 38.5%, in comparison to the 55% sensitivity of the Infinity Brush.  Conclusions  The use of the Infinity cytology brush provided a higher yield in detection of malignant cells in our patients than the Boston RX cytology brush, possibly due to its size, design and bristle configuration. We acknowledge however our study numbers were small and we feel that a larger study would be required to determine if the difference in brushings yield is significant.
A case series of low-dose sorafenib plus tamoxifen in sorafenib-pretreated patients with advanced hepatocellular carcinoma.
Authors: Giovannella Palmieri, Piera Federico, Margaret Ottaviano, Carlo Buonerba, Filomena Calabrese, Pasquale Rescigno, Anapaula De Maio, Mariateresa Micillo, Giuseppe di Lorenzo, Vincenzo Damiano
Journal: Journal of Clinical Oncology (2014)

e15139 Background: No effective treatments for patients with advanced HCC who are intolerant to sorafenib or who have progressed during sorafenib are available. Several studies suggest a relationship between sex hormones receptors and hepatocellular carcinoma, but any use of anti-hormonal agents in clinical practice is not recommended f due to the lack of conclusive results. The only effective systemic therapy is sorafenib, but cancer-induced and treatment-related liver failure is a major concern in the management of these patients. We performed a retrospective review of all patients treated with sorafenib and tamoxifen at our Institution. Methods: Data from medical records of pts who were intolerant to or progressed during full dose sorafenib therapy (800 mg/daily) and were treated with sorafenib (400 mg) plus tamoxifen (40mg) were retrieved in this retrospective single center study. Eighteen patients were included in this analysis. Median age was 68 years old (range, 59 -74). All pts were male. Tumour assessment via triphasic CT scan was performed every twelve weeks, safety was assessed every 28 days. The primary end point was overall survival (OS). Secondary end points were duration of treatment and objective response rate based on RECIST criteria 1.1. Results: The median treatment duration was 11 months (range, 2-28). At the time of the analysis (31st January, 2014), eight pts are on treatment, and no pts discontinued treatment for adverse events.. We observed 2 partial responses and 11 patients with stable disease. The remaining patients had progressive disease as best response.Median OS was 16 months (range 3-28). No pt presented grade 3-4 serious adverse event. Conclusions: Our results suggest that low dose sorafenib plus tamoxifen is a promising therapeutic option in HCC patients intolerant or refractory to full dose sorafenib. A phase II study is required to assess this combination regimen.
Elsiglutide in the primary prevention of chemotherapy (CT)-induced diarrhea in patients with colorectal cancer (CRC) receiving 5-fluorouracil (5-FU)-based CT: A multinational, randomized, double-blind, placebo-controlled study.
Authors: Meinolf Karthaus, Mikhail Fedyanin, Igor Bondarenko, Salvatore Chessari, Riccardo Spezia, Ruben Giorgino
Journal: Journal of Clinical Oncology (2017)

10101 Background: Diarrhea is a burdensome toxicity of 5-FU-based regimens and may lead to CT dose intensity reduction. We investigated the efficacy of 3 subcutaneous (s.c.) doses of elsiglutide (a GLP-2 analog) vs. placebo and vs. each other, in the primary prevention of CT induced diarrhea in patients (pts) with CRC receiving FOLFOX or FOLFIRI. Methods: Pts were randomized equally to receive placebo or elsiglutide 10, 20, or 40 mg s.c. on days (d)1–4 of the first 2 CT cycles and were followed up in cycle 3 for safety only. Stratification factors were CT regimen and country. Primary endpoint was the proportion of pts with diarrhea of CTC grade ≥2 in cycle 1. Changes in plasma levels of citrulline, a marker of intestinal mass, from baseline to d5 and d14 of each cycle were analyzed. With 480 pts randomized, the study had 85% power to detect a 15% difference vs. placebo for each dose at an alpha level of 0.1, assuming a 20% frequency of diarrhea CTC grade ≥2 in the placebo arm. Results: Treatment groups were comparable for the 484 pts (142 receiving FOLFIRI) who were randomized to receive placebo (n = 123), elsiglutide 10 mg (n = 120), 20 mg (n = 121), or 40 mg (n = 120), respectively. The proportion of pts with diarrhea CTC grade ≥2 was higher with placebo (10%) than with elsiglutide 10 mg (3%), 20 mg (5%) and 40 mg (6%); differences were not statistically significant. A similar pattern was observed in cycle 2. Differences in diarrhea frequency between placebo and elsiglutide groups were pronounced in the FOLFIRI subgroup (cycle 1: 18% with placebo, 6% with 10 mg and 20 mg; 3% with 40 mg elsiglutide). Reduction of citrulline levels was smaller with elsiglutide compared with placebo. The safety profile of all elsiglutide doses was acceptable with few related injection site reactions, mostly at the highest dose. Conclusions: Although a lower frequency of diarrhea CTC grade ≥2 was observed with elsiglutide, this difference was not statistically significant in pts receiving FOLFOX or FOLFIRI for CRC. Interpretation must consider the unexpectedly low reported frequency of diarrhea of grade ≥2, particularly with FOLFOX regimens. Clinical trial information: 2014-000998-39.
Next-generation sequencing of thymic malignancies.
Authors: Milan Radovich, Ryan Frederick Porter, Madison Conces, Yaman Suleiman, Sunil S. Badve, Kenneth Kesler, Bryan P. Schneider, Patrick J. Loehrer
Journal: Journal of Clinical Oncology (2012)

7032 Background: Thymic malignancies are rare with ~500 cases in the US per year. Apart from standard chemotherapy, treatment options are limited. Further, the challenge of histologic subtyping of these tumors along with an inadequate understanding of the transcriptional biology is a hindrance to the development of targeted therapies. Methods: Thymic malignancies and normal tissues were obtained from the Indiana University Simon Cancer Center. The WHO subtypes of our samples include: (4) type A, (2) A/B, (1) B2, (5) B3, (1) C, and (3) normal tissues. RNA was sequenced on a Life Technologies SOLiD sequencer. For gene expression, reads were mapped to the genome using BioScope and outputs imported into Partek GS. In Partek, statistical comparison of gene expression as well as PCA &amp; clustering analyses were performed. Results: Unsupervised hierarchical clustering of gene expression values revealed 100% concordance between gene expression clusters and WHO subtype. A subsequent unsupervised clustering of 705 pre-miRNAs also showed substantial concordance between clusters and subtype. By analyzing the dendrograms, A &amp; A/B tumors were significantly different from B type tumors, as well as C and normal. A substantial differentiator was a large cluster of overexpression in A&amp;A/B tumors that was nearly absent in the others on chr19q13.42 corresponding to the miR-515 cluster (43 miRNAs). When comparing A &amp; A/B tumors vs. B type tumors, 1334 genes are differentially expressed (258 downregulated) (FDR&lt;5%). 95/258 genes are predicted to be downregulated by the miR-515 cluster including several transcription factors and tumor suppressors. When looking at mutations, we detected no recurrent gene fusions, though we are detecting several point mutations and small insertion deletions. These are being followed up by exome sequencing. Conclusions: Analyses reveal that RNA-seq can be used to accurately subtype Thymic Malignancies and the development of an expression based diagnostic is feasible. Further, these data support that the main differentiator of thymomas may lie in the expression of a single miRNA cluster. In addition, several mutations in key pathways are implicated. Ongoing analyses include: alternative splicing, noncoding RNAs, viral analysis and exome sequencing.
内因性TGaseにより仲介される注射用マイクロ足場カプセルによる病理標的細胞送達【Powered by NICT】
Authors: Qi Chunxiao, Li Yaqian, Badger Patrick, Yu Hongsheng, You Zhifeng, Yan Xiaojun, Liu Wei, Shi Yan, Xia Tie, Dong Jiahong, Huang Chenyu, Du Yanan
Journal: Biomaterials (2017)
Moving point of GMC registration is “out of remit” of training review body
Authors: Abi Rimmer
Journal: BMJ (2017)

The body tasked with interpreting proposed changes to doctors’ training will not work on moving the point of GMC registration.

In 2013 the UK-wide Shape of Training review, led by David Greenaway, recommended that full registration with the General Medical Council should be moved from the end of the first year of foundation training to the point of graduation from medical school.1

The BMA has previously warned that the plans would put patients and junior doctors at risk.2

However, …
THU0312 Performance characteristics and predictors of temporal artery ultrasound and biopsy for the diagnosis of giant cell arteritis in a real world population; a prospective cohort study
Authors: R Conway, S Di Bello, L O'Neill, GM McCarthy, CC Murphy, DJ Veale, U Fearon, RP Killeen, EJ Heffernan, ES Molloy
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> The diagnosis of giant cell arteritis (GCA) remains a clinical one. Temporal artery (TA) ultrasound (US) has been proposed as a new diagnostic tool in GCA. <h3>Objectives</h3> To assess the performance characteristics of TA US and biopsy in routine clinical practice. <h3>Methods</h3> All patients presenting with suspected GCA to our institutions are recruited to a prospective registry. Patients who had both a TA US and biopsy performed at the time of presentation were included in the current study. US was performed by 2 radiologists. The performance characteristics of both tests were compared to physician diagnosis at six months following presentation. Predictive factors for positive US and biopsy were explored in univariate and multivariable logistic regression analyses. <h3>Results</h3> 162 patients were included, 123 (76%) with GCA. Mean (SD) duration of glucocorticoids was 6.6 days (19.4) at the time of TA US and 6.2 days (8.4) at the time of TA biopsy. US had a sensitivity of 52.8% (95% CI 43.7, 61.9) and specificity of 71.8% (95% CI 54.9, 84.5). There were 11 false positive US results; 5 with migraine, 2 other vasculitides, 2 local infections, 2 malignancies. Biopsy had a sensitivity of 48.8% (95% CI 39.7, 57.9) and specificity of 97.4% (95% CI 84.9, 99.9). A hypothetical sequential strategy of US followed by biopsy in the case of negative US had a sensitivity of 78.9% (95% CI 70.1, 85.5) and specificity of 71.8% (95% CI 54.9, 84.5), equivalent to a simultaneous testing strategy. Time on glucocorticoids did not significantly impact the results of US or biopsy. The only factor independently predictive of a positive US was male sex (OR 5.53, 95% CI 2.72 to 11.22, p&lt;0.001). The only factor independently predictive of a positive biopsy was jaw claudication (OR 2.40, 95% CI 1.11, 5.21, p=0.027). <h3>Conclusions</h3> TA US is a useful tool in the diagnosis of GCA; however false positive tests occur in 7% and thorough clinical assessment remains crucial. Prior glucocorticoid treatment has no clear impact on results. <h3>Disclosure of Interest</h3> None declared
It's time to move beyond the “Great Chain of Being”
Authors: Robert J. Sternberg
Journal: Behavioral and Brain Sciences (2017)

Abstract The target article provides an anthropocentric model of understanding intelligence in nonhuman animals. Such an idea dates back to Plato and, more recently, Lovejoy: On Earth, humans are at the top and other animals at successively lower levels. We then evaluate these other animals by our anthropocentric folk theories of their intelligence rather than by their own adaptive requirements.
An unusual cause of chest pain
Authors: Kevin Conroy, Abdul Aziz
Journal: BMJ (2017)

A 65 year old man with a 40 pack year smoking history described a one month history of worsening breathlessness and chest discomfort on walking. He presented to hospital following a collapse after self-administering sublingual glyceryl trinitrate to relieve his symptoms. He reported no history of cough or coryza and had neither lost weight nor experienced any haemoptysis. A chest radiograph was taken (fig 1⇓). What is the most likely diagnosis?



Fig 1  Chest radiograph on admission



Lymphangitis carcinomatosa and underlying malignancy would account for this radiograph appearance and history.

### Discussion

Lymphangitis carcinomatosa describes …
THEMISはTCRシグナリングを増強し,ホスファターゼSHP‐1の選択的阻害により正の選択を可能にする
Authors: Choi Seeyoung, Warzecha Claude, Zvezdova Ekaterina, Lee Jan, Argenty Jeremy, Lesourne Renaud, Aravind L, Love Paul E
Journal: Nature Immunology (2017)
血中単球サブセットはin vitroで生体材料へのマクロファージの肥満関連応答と相関する【Powered by NICT】
Authors: Boersema G.S.A., L Utomo, Y Bayon, N Kops, E van der Harst, J F Lange, Y M Bastiaansen-Jenniskens
Journal: Biomaterials (2016)
Accessing off-field brains in sport; an applied research model to develop practice
Authors: Ben Jones, Kevin Till, Stacey Emmonds, Sharief Hendricks, Peter Mackreth, Joshua Darrall-Jones, Gregory Roe, Sir Ian McGeechan, Richard Mayhew, Richard Hunwicks, Neill Potts, Michael Clarkson, Andy Rock
Journal: British Journal of Sports Medicine (2017)

Applied researchers (eg, academic researchers, PhD students) strive to undertake research that can inform practice in sport, and evidence ‘ impact.’ Conversely, practitioners (eg, coaches, physiotherapists, clinicians, sports scientists) strive to apply relevant up-to-date research findings to develop or optimise practice, adopting ‘ evidence based practice. ’ Despite the researcher and practitioner within a discipline having similar overall aims (eg, improve athletic performance, reduce injury risk, optimise return to play practices), their primary roles appear different due to various contextual factors.1 2 Researchers are able to work slowly, dedicating time to solving complex problems, whereas practitioners working in the field are required to work fast, to provide day-to-day support to coaches and athletes.1 The differences in how the researcher and practitioner work can be problematic and challenge the alignment of their respective priorities within their roles (eg, timescales required to deliver outcomes, specific expertise and experience, resources). Here we share a model demonstrating how the ‘working fast1 on-field brain3’, ‘working slow1 off-field brain3’ and ‘research-practitioner2’ can work together to undertake and integrate research into practice and solve the above problems.

The alignment of (applied) research questions, expectations and usability of outcomes into practice …
Neurostimulation for abdominal pain-related functional gastrointestinal disorders in adolescents: a randomised, double-blind, sham-controlled trial
Authors: Katja Kovacic, Keri Hainsworth, Manu Sood, Gisela Chelimsky, Rachel Unteutsch, Melodee Nugent, Pippa Simpson, Adrian Miranda
Journal: The Lancet. Gastroenterology & hepatology (2017)
An Oxidative Central Metabolism Enables Salmonella to Utilize Microbiota-Derived Succinate
Authors: Luisella Spiga, Maria G. Winter, Tatiane Furtado de Carvalho, Wenhan Zhu, Elizabeth R. Hughes, Caroline C. Gillis, Cassie L. Behrendt, Jiwoong Kim, Daniela Chessa, Helene L. Andrews-Polymenis, Daniel P. Beiting, Renato L. Santos, Lora V. Hooper, Sebastian E. Winter
Journal: Cell Host & Microbe (2017)
βバレル型膜貫通ナノ細孔からのPNIPAAmグラフト化【Powered by NICT】
Authors: Charan Himanshu, Kinzel Julia, Glebe Ulrich, Anand Deepak, Garakani Tayebeh Mirzaei, Zhu Leilei, Bocola Marco, Schwaneberg Ulrich, Boker Alexander
Journal: Biomaterials (2016)
Role of Thrombocytopenia in Hemorrhage Produced in Sarcoma 37
Authors: Michael B. Shimkin, Leo Zon
Journal: JNCI Journal of the National Cancer Institute (1943)

Journal Article Role of Thrombocytopenia in Hemorrhage Produced in Sarcoma 37 Get access Michael B. Shimkin, Michael B. Shimkin passed assistant surgeon Search for other works by this author on: Oxford Academic PubMed Google Scholar Leo Zon Leo Zon passed assistant surgeon (R) Research Laboratory, Tumor Clinic, Marine Hospital, Baltimore Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 3, Issue 4, February 1943, Pages 379–382, https://doi.org/10.1093/jnci/3.4.379 Published: 01 February 1943
Patience pays in spinal repair
Authors: Steven A. Goldman
Journal: Journal of Clinical Investigation (2017)

Transplantation of human neural stem cells has long been proposed as a potential strategy for treating CNS injury and disease; however, application of this approach has had limited therapeutic benefit. Yet compared with rodents and other experimental mammals, humans have a relatively long time window for development of the brain and spinal cord. In this issue of the JCI, Lu and colleagues asked whether the results of neural stem cell transplantation might be improved by accommodating the protracted development of human neural cells. They used a rodent model of spinal cord injury, in which human neural progenitor cells were transplanted at the site of damage. While there was no observable benefit at early time points after transplantation, both anatomic and functional improvements in the injured animals emerged over the course of a year. In particular, the human progenitor cell population differentiated, matured, and integrated into the rodent spinal cords over a time frame that aligned with the normal development of these cells in humans. This study demonstrates that neural stem cells may offer significant therapeutic benefit after CNS injury; however, this process may take time and demands patience on the part of investigators, patients, and clinicians alike.
Effect of Losartan on Mitral Valve Changes After Myocardial Infarction
Authors: Philipp E. Bartko, Jacob P. Dal-Bianco, J. Luis Guerrero, Jonathan Beaudoin, Catherine Szymanski, Dae-Hee Kim, Margo M. Seybolt, Mark D. Handschumacher, Suzanne Sullivan, Michael L. Garcia, James S. Titus, Jill Wylie-Sears, Whitney S. Irvin, Emmanuel Messas, Albert A. Hagège, Alain Carpentier, Elena Aikawa, Joyce Bischoff, Robert A. Levine
Journal: Journal of the American College of Cardiology (2017)
生体直交型ラベリングとイメージングのためのイリジウム(III)をベースにしたphosphorogenic生体材料の設計における付加的な発光消光経路を設置【Powered by NICT】
Authors: Li Steve Po-Yam, Yip Alex Man-Hei, Liu Hua-Wei, Lo Kenneth Kam-Wing
Journal: Biomaterials (2016)
KEYNOTE-059 cohort 1: Efficacy and safety of pembrolizumab (pembro) monotherapy in patients with previously treated advanced gastric cancer.
Authors: Charles S. Fuchs, Toshihiko Doi, Raymond Woo-Jun Jang, Kei Muro, Taroh Satoh, Manuela Machado, Weijing Sun, Shadia Ibrahim Jalal, Manish A. Shah, Jean-Philippe Metges, Marcelo Garrido, Talia Golan, Mario Mandala, Zev A. Wainberg, Daniel V.T. Catenacci, Yung-Jue Bang, Jiangdian Wang, Minori Koshiji, Rita P. Dalal, Harry H. Yoon
Journal: Journal of Clinical Oncology (2017)

4003 Background: Pembro has shown promising antitumor activity and manageable safety in a phase 1 study of pts with previously treated advanced gastric cancer. We conducted a global, multicohort, phase 2 study of pembro in pts with advanced gastric or gastroesophageal junction (G/GEJ) cancer (KEYNOTE-059;NCT02335411). Methods: Cohort 1 enrolled 259 pts, aged ≥18 y with measurable recurrent or metastatic G/GEJ adenocarcinoma who had progressed on ≥2 prior chemotherapy regimens and had ECOG PS 0-1. Pts received pembro 200 mg Q3W up to 2 y or up to disease progression, investigator/pt decision to withdrawal, or unacceptable toxicity. PD-L1 + pts had expression in ≥1% tumor or stromal cells using IHC (22C3 antibody). Primary end points: ORR (RECIST 1.1, by central review), safety, and tolerability. Results: Of 259 pts in cohort 1, 76.4% were men; median age was 62.0 y. 51.7% and 48.3% received pembro as 3rd-line (3L) and 4L+ therapy, respectively. 57.1% had PD-L1 + tumors. At data cutoff (Oct 19, 2016), median duration of follow-up was 5.4 mo (range, 0.5 to 18.7). Overall ORR (CR + PR) was 11.2% (95% CI, 7.6-15.7); 1.9% of pts (95% CI, 0.6-4.4) had CR, 9.3% had PR (95% CI, 6.0-13.5), 17% (95% CI, 12.6-22.1) had SD, and 55.6% (95% CI, 49.3-61.7) had PD. Median DOR was 8.1 mo (range, 1.4+ to 15.1+). ORR was 14.9% (95% CI, 9.4-22.1) in 3L pts and 7.2% (95% CI, 3.3-13.2) in 4L+. In PD-L1 + pts, ORR was 15.5% (95% CI, 10.1-22.4) with 2.0% (95% CI, 0.4-5.8) CR and 13.5% (95% CI, 8.5-20.1) PR; in PD-L1 – pts, ORR was 5.5% (95% CI, 2.0-11.6), with 1.8% (95% CI, 0.2-6.5) CR and 3.7% (95% CI, 1.0-9.1) PR. In 3L pts with PD-L1 + tumors, ORR was 21.3% (95% CI, 12.7-32.3), with 4.0% (95% CI, 0.8-11.2) CR; in 3L pts with PD-L1 – tumors, ORR was 6.9% (95% CI, 1.9-16.7), with 3.4% (95% CI, 0.4-11.9) CR. Grade 3-5 treatment-related AEs (TRAEs) occurred in 43 pts (16.6%). TRAEs led to discontinuation in 2 pts (abnormal LFT, bile duct stenosis) and were fatal in 2 pts (acute kidney injury, pleural effusion). Conclusions: Pembro showed encouraging efficacy and manageable safety after ≥2 prior lines of therapy in pts with advanced G/GEJ cancer in this large phase 2 trial. Survival and additional biomarker data, including MSI status, will be presented. Clinical trial information: NCT02335411.