tbuckley/cabot-search huggingface dataset:
Bronchial inflammation and bacterial load in stable COPD is associated with TLR4 overexpression
Authors: Antonino Di Stefano, Fabio L.M. Ricciardolo, Gaetano Caramori, Ian M. Adcock, Kian Fan Chung, Peter J. Barnes, Paola Brun, Andrea Leonardi, Filippo Andò, Davide Vallese, Isabella Gnemmi, Luisella Righi, Francesco Cappello, Bruno Balbi
Journal: European Respiratory Journal (2017)

Toll-like receptors (TLRs) and nucleotide-binding oligomerisation domain (NOD)-like receptors (NLRs) are two major forms of innate immune sensors but their role in the immunopathology of stable chronic obstructive pulmonary disease (COPD) is incompletely studied. Our objective here was to investigate TLR and NLR signalling pathways in the bronchial mucosa in stable COPD.Using immunohistochemistry, the expression levels of TLR2, TLR4, TLR9, NOD1, NOD2, CD14, myeloid differentiation primary response gene 88 (MyD88), Toll-interleukin-1 receptor domain-containing adaptor protein (TIRAP), and the interleukin-1 receptor-associated kinases phospho-IRAK1 and IRAK4 were measured in the bronchial mucosa of subjects with stable COPD of different severity (n=34), control smokers (n=12) and nonsmokers (n=12). The bronchial bacterial load of Pseudomonas aeruginosa, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae was measured by quantitative real-time PCR.TLR4 and NOD1 expression was increased in the bronchial mucosa of patients with severe/very severe stable COPD compared with control subjects. TLR4 bronchial epithelial expression correlated positively with CD4+ and CD8+ cells and airflow obstruction. NOD1 expression correlated with CD8+ cells. The bronchial load of P. aeruginosa was directly correlated, but H. influenzae inversely correlated, with the degree of airflow obstruction. Bacterial load did not correlate with inflammatory cells.Bronchial epithelial overexpression of TLR4 and NOD1 in severe/very severe stable COPD, associated with increased bronchial inflammation and P. aeruginosa bacterial load, may play a role in the pathogenesis of COPD.
Serum extracellular vesicles contain protein biomarkers for primary sclerosing cholangitis and cholangiocarcinoma
Authors: Ander Arbelaiz, Mikel Azkargorta, Marcin Krawczyk, Alvaro Santos‐Laso, Ainhoa Lapitz, Maria J. Perugorria, Oihane Erice, Esperanza Gonzalez, Raul Jimenez‐Agüero, Adelaida Lacasta, Cesar Ibarra, Alberto Sanchez‐Campos, Juan P. Jimeno, Frank Lammert, Piotr Milkiewicz, Marco Marzioni, Rocio I.R. Macias, Jose J.G. Marin, Tushar Patel, Gregory J. Gores, Ibon Martinez, Félix Elortza, Juan M. Falcon‐Perez, Luis Bujanda, Jesus M. Banales
Journal: Hepatology (2017)

Cholangiocarcinoma (CCA) includes a heterogeneous group of biliary cancers with poor prognosis. Several conditions, such as primary sclerosing cholangitis (PSC), are risk factors. Noninvasive differential diagnosis between intrahepatic CCA and hepatocellular carcinoma (HCC) is sometimes difficult. Accurate noninvasive biomarkers for PSC, CCA, and HCC are not available. In the search for novel biomarkers, serum extracellular vesicles (EV) were isolated from CCA (n = 43), PSC (n = 30), or HCC (n = 29) patients and healthy individuals (control, n = 32); and their protein content was characterized. By using nanoparticle tracking analysis, serum EV concentration was found to be higher in HCC than in all the other groups. Round morphology (by transmission electron microscopy), size (∼180 nm diameter by nanoparticle tracking analysis), and markers (clusters of differentiation 9, 63, and 81 by immunoblot) indicated that most serum EV were exosomes. Proteome profiles (by mass spectrometry) revealed multiple differentially expressed proteins among groups. Several of these proteins showed high diagnostic values with maximum area under the receiver operating characteristic curve of 0.878 for CCA versus control, 0.905 for CCA stage I‐II versus control, 0.789 for PSC versus control, 0.806 for noncirhottic PSC versus control, 0.796 for CCA versus PSC, 0.956 for CCA stage I‐II versus PSC, 0.904 for HCC versus control, and 0.894 for intrahepatic CCA versus HCC. Proteomic analysis of EV derived from CCA human cells in vitro revealed higher abundance of oncogenic proteins compared to EV released by normal human cholangiocytes. Orthotopic implant of CCA human cells in the liver of immunodeficient mice resulted in the release to serum of EV containing some similar human oncogenic proteins. Conclusion : Proteomic signatures found in serum EV of CCA, PSC, and HCC patients show potential usefulness as diagnostic tools. (H epatology 2017;66:1125‐1143).
Classifying invalid baseline scores
Authors: Martin Mrazik, Dhiren Naidu
Journal: British Journal of Sports Medicine (2017)

Objective Analysis of a proposed method for classifying invalid baseline tests in professional football players. Design Retrospective cross-sectional study. Setting Professional Canadian Football. Participants Four hundred and seventy-eight male football players from the Canadian Football League. Intervention A proposed system to classify invalid baselines used the lowest 5% of domain scores from baseline Immediate Post-concussion Assessment and Cognitive Testing (ImPACT), King Devick, and SCAT3 (balance and SAC totals) coupled with the highest 5% of total symptom report from SCAT3. Impairment on 2 or more scores was classified as invalid (INV). Main Outcome measures Descriptive statistics, correlation and stepwise regression analysis. Main Results Correlations revealed significant relationships (p&lt;0.05) between INV and all 5 domains of ImPACT and SCAT3 symptom score, but not for King Devick and SCAT3 balance and SAC totals. The forward stepwise regression yielded a significant model (R2=0.23, F(4, 473)=35.7, p&lt;0.001). Significant predictors included visual memory, reaction time, impulse control, and verbal memory from ImPACT. This system classified 3.7% of participant with invalid baseline tests. Conclusions There are few published methodologies used to classify invalid baseline tests in spite of their widespread use. Valid baseline tests are essential for proper identification and management of concussion. Our proposed method identified 4 ImPACT domains scores that predict invalid baseline scores. This system may be helpful in classifying invalid baseline tests with commonly used baseline test measures although more research is required to validate this method. Competing interests None.
Liver Metastasis Is Facilitated by the Adherence of Circulating Tumor Cells to Vascular Fibronectin Deposits
Authors: Jorge Barbazán, Lorena Alonso-Alconada, Nadia Elkhatib, Sara Geraldo, Vasily Gurchenkov, Alexandros Glentis, Guillaume van Niel, Roberta Palmulli, Beatriz Fernández, Patricia Viaño, Tomas Garcia-Caballero, Rafael López-López, Miguel Abal, Danijela Matic Vignjevic
Journal: Cancer Research (2017)

Abstract The interaction between circulating tumor cells (CTC) and endothelial cells during extravasation is a critical process during metastatic colonization, but its mechanisms remain poorly characterized. Here we report that the luminal side of liver blood vessels contains fibronectin deposits that are enriched in mice bearing primary tumors and are also present in vessels from human livers affected with metastases. Cancer cells attached to endothelial fibronectin deposits via talin1, a major component of focal adhesions. Talin1 depletion impaired cancer cell adhesion to the endothelium and transendothelial migration, resulting in reduced liver metastasis formation in vivo. Talin1 expression levels in patient CTC's correlated with prognosis and therapy response. Together, our findings uncover a new mechanism for liver metastasis formation involving an active contribution of hepatic vascular fibronectin and talin1 in cancer cells. Cancer Res; 77(13); 3431–41. ©2017 AACR.
Thermoacoustic Imaging and Therapy Guidance based on Ultra-short Pulsed Microwave Pumped Thermoelastic Effect Induced with Superparamagnetic Iron Oxide Nanoparticles
Authors: Liewei Wen, Sihua Yang, Junping Zhong, Quan Zhou, Da Xing
Journal: Theranostics (2017)

Multifunctional nanoparticle-mediated imaging and therapeutic techniques are promising modalities for accurate localization and targeted treatment of cancer in clinical settings. Thermoacoustic (TA) imaging is highly sensitive to detect the distribution of water, ions or specific nanoprobes and provides excellent resolution, good contrast and superior tissue penetrability. TA therapy is a potential non-invasive approach for the treatment of deep-seated tumors. In this study, human serum albumin (HSA)-functionalized superparamagnetic iron oxide nanoparticle (HSA-SPIO) is used as a multifunctional nanoprobe with clinical application potential for MRI, TA imaging and treatment of tumor. In addition to be a MRI contrast agent for tumor localization, HSA-SPIO can absorb pulsed microwave energy and transform it into shockwave via the thermoelastic effect. Thereby, the reconstructed TA image by detecting TA signal is expected to be a sensitive and accurate representation of the HSA-SPIO accumulation in tumor. More importantly, owing to the selective retention of HSA-SPIO in tumor tissues and strong TA shockwave at the cellular level, HSA-SPIO induced TA effect under microwave-pulse radiation can be used to highly-efficiently kill cancer cells and inhibit tumor growth. Furthermore, ultra-short pulsed microwave with high excitation efficiency and deep penetrability in biological tissues makes TA therapy a highly-efficient anti-tumor modality on the versatile platform. Overall, HSA-SPIO mediated MRI and TA imaging would offer more comprehensive diagnostic information and enable dynamic visualization of nanoagents in the tumorous tissue thereby tumor-targeted therapy.
Erratum: Individual and combined effects of age, breast density, and hormone replacement therapy use on the accuracy of screening mammography (Annals of Internal Medicine (2003) 138 (168-175))
Authors: P. A. Carney, Diana L Miglioretti, B. C. Yankaskas, K. Kerlikowske, R. Rosenberg, C. M. Rutter
Journal: Annals of Internal Medicine (2003)
Infection-Related Mortality (IRM) after Allogeneic Hematopoietic Stem Cell Transplantation: Age, CMV Status, Pre-Transplant IgA and IgM Levels Predict IRM and Survival in a New Clinico-Biological Scoring System Developed in 492 Consecutive Patients
Authors: Alessandra Forcina, Paola Maria Vittoria Rancoita, Vincenzo Marasco, Raffaella Greco, Maria Teresa Lupo-Stanghellini, Matteo Giovanni Carrabba, Marcatti Magda, Clelia Di Serio, Massimo Bernardi, Jacopo Peccatori, Consuelo Corti, Attilio Bondanza, Fabio Ciceri
Journal: Blood (2016)
Quantifying Overdiagnosis in Cancer Screening: A Systematic Review to Evaluate the Methodology
Authors: Theodora M Ripping, Kevin ten Haaf, André L M Verbeek, Nicolien T van Ravesteyn, Mireille J M Broeders
Journal: JNCI Journal of the National Cancer Institute (2017)

Overdiagnosis is the main harm of cancer screening programs but is difficult to quantify. This review aims to evaluate existing approaches to estimate the magnitude of overdiagnosis in cancer screening in order to gain insight into the strengths and limitations of these approaches and to provide researchers with guidance to obtain reliable estimates of overdiagnosis in cancer screening. A systematic review was done of primary research studies in PubMed that were published before January 1, 2016, and quantified overdiagnosis in breast cancer screening. The studies meeting inclusion criteria were then categorized by their methods to adjust for lead time and to obtain an unscreened reference population. For each approach, we provide an overview of the data required, assumptions made, limitations, and strengths. A total of 442 studies were identified in the initial search. Forty studies met the inclusion criteria for the qualitative review. We grouped the approaches to adjust for lead time in two main categories: the lead time approach and the excess incidence approach. The lead time approach was further subdivided into the mean lead time approach, lead time distribution approach, and natural history modeling. The excess incidence approach was subdivided into the cumulative incidence approach and early vs late-stage cancer approach. The approaches used to obtain an unscreened reference population were grouped into the following categories: control group of a randomized controlled trial, nonattenders, control region, extrapolation of a prescreening trend, uninvited groups, adjustment for the effect of screening, and natural history modeling. Each approach to adjust for lead time and obtain an unscreened reference population has its own strengths and limitations, which should be taken into consideration when estimating overdiagnosis.
Gender differences in clinical presentation and recovery of sports related concussion
Authors: Shannon Bauman, Mira Ray, Paul P Joseph
Journal: British Journal of Sports Medicine (2017)

Objective To determine if gender plays a role in clinical presentation and recovery in concussion. Design Retrospective Setting one clinic Participants 207 athletes (115 females, 92 males) presenting to clinic from September 2014 – January 2016. 79 athletes achieved clearance. Inclusion: sports or exercise, age 10–60 yrs. Exclusion non-sports Outcome measures Athletes completed computerised neurocognitive testing and physical assessments. A physician-led interdisciplinary team treated each athlete until resolution of signs and symptoms. Athletes were grouped by gender into recovery time groups (0–2 mo.; 3–5 mo.;≥ 6 mo.). An analysis by gender, age, symptoms, neurocognitive data, and concussion features was performed. Main results Females report higher post-concussion symptom scores than males (p&lt;0.0002).Females had a higher total number of features 4.5 to 3.6(p&lt;0.00003). With respect to recovery, 34% of all males in our study were discharged within 0–2 mo. of injury date, compared to 12% of females. Females continued to experience symptoms at ≥ 6 months. Overall, females had a longer recovery period than males (p&lt;0.002). Among discharged females, those requiring longer treatment (≥3 mo) were of a more mature age (23.8±13.2), presented later to clinic (t=3.3±3.6 mo.)and reported moresymptoms (PCSS=40.83±19.53). Conclusions Female athletes present with higher post- concussion symptom scores and clinical features than their male counterparts. Mature females who later for treatment have a protracted recovery. Athletes of both genders who seek care earlier in the injury process have a shorter recovery. Competing interests None.
A multidisciplinary treatment comprising standard chemotherapy with vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide for Ewing sarcoma family of tumor (ESFT) in Japan: Results of the first Japan Ewing Sarcoma Study (JESS) 04.
Authors: Atsushi Makimoto, Motoaki Chin, Minako Sumi, Ryohei Yokoyama, Tsuyoshi Ishida, Hajime Okita, Akinobu Matsuzaki, Atsushi Kikuta, Hiroyoshi Watanabe, Toshifumi Ozaki, Kazuo Isu, Michihiro Yano, Masahito Hatori, Masahito Tsurusawa, Hideaki Ohta, Yoshifumi Kawano, Takeshi Ishii, Hiroshi Kawamoto, Satoshi Morita, Hideo Mugishima
Journal: Journal of Clinical Oncology (2012)

9574 Background: Survival rate of ESFT in Japan was reportedly less than 50% in 1990s. The JESS started in order to improve this condition by conducting clinical trials for ESFT in Japan. Methods: This is a phase II, non-randomized trial to test safety and efficacy of multidisciplinary treatment for non-metastatic ESFT. Age under 30 is eligible. Chemotherapy regimens are alternating vincristine 1.5 mg/m 2 on day 1, doxorubicin 37.5 mg/m 2 on days 1 and 2, cyclophosphamide 1200 mg/m 2 on day 1 (VDC) and ifosfamide 1800 mg/m 2 on days 1 through 5 and etoposide 100 mg/m 2 on days 1 through 5 (IE) repeating every 21 days for 52 weeks. Local treatment includes surgical resection and/or radiation therapy, of which dosage varies from 0 to 55.8 Gy based on margin of the resection and pathological response. Primary endpoint is 3 year progression free survival (PFS). Statistical design was made to test whether the lower limit of 90% confidence interval (CI) of PFS will exceed the threshold of 60%. Planned sample size is 53 patients including 10% ineligible patients. Results: Fifty-three patients were registered from December 2004 to May 2008. Among the 53 patients, 7 patients were judged ineligible after the registration (metastatic disease 1, changed diagnoses 6). Forty six patients were considered as per protocol set and used for efficacy analyses. Three year PFS is 71.7% (90% CI: 0.59 – 0.81). Estimated 5 year PFS and OS are both 69.6%. Radiographic response rate (RR) in evaluable 38 patients is 71.1% and pathological RR in 25 is 52.0%. In safety data, hematological toxicities are significant such as grade 4 neutropenia observed in 98%. Although there is no previously unknown adverse event reported, there are three patients who experienced secondary malignancies (ALL 1, MDS 1, osteosarcoma 1). Conclusions: A multi-disciplinary treatment comprising standard multi-agent chemotherapy with vincristine, doxorubicin, cyclophosphamide, ifosfamide and etoposide improved outcome of Ewing sarcoma family of tumor in Japan although statistical confirmation of absolute efficacy was not successful.
Multiple white flat lesions in the gastric corpus are not intestinal metaplasia
Authors: Noriya Uedo, Rino Yamaoka, Kenshi Yao
Journal: Endoscopy (2017)

See also: A multicenter prospective study of the real-time use of narrow-band imaging in the diagnosis of premalignant gastric conditions and lesionsEndoscopy 2016; 48(08): 723-730DOI: 10.1055/s-0042-108435 See also: White flat lesions in the gastric corpus may be intestinal metaplasiaEndoscopy 2017; 49(06): 617-618DOI: 10.1055/s-0043-108549
MM-014: A phase 2 trial evaluating efficacy, safety, and biomarkers of pomalidomide plus low-dose dexamethasone (POM + LoDEX) in relapsed/refractory multiple myeloma (RRMM) following second-line lenalidomide plus dexamethasone (LEN + DEX).
Authors: David Samuel DiCapua Siegel, Richy Agajanian, Rakesh Gaur, Kasra Karamlou, Hakan Kaya, Michael Sturniolo, Rosanna J. Ricafort, Gail Larkins, Shankar Srinivasan, Rajesh Chopra, Anjan Thakurta, Yasir M. Nagarwala, Flavio Kruter
Journal: Journal of Clinical Oncology (2014)

TPS8627 Background: Challenging relapsed disease with drugs of the same class remains an area of investigation. Subanalyses of MM-002 and MM-003 in advanced RRMM demonstrated comparable efficacy for POM + LoDEX in patients (pts) refractory to LEN as last prior treatment (Tx) vs. all pts (Richardson, 2014; San Miguel, 2013). To confirm this, MM-014, a multicenter, single-arm, open-label phase 2 trial in the US and Canada evaluating POM + LoDEX immediately following second-line LEN + DEX, was designed (NCT01946477). Methods: Pts (N = 85 planned) must have received 2 prior lines of myeloma Tx, with LEN + DEX as second line. Pts must have relapsed from or become refractory to LEN + DEX as last prior Tx (≥ 2 cycles). Prior Tx may include all predetermined components of induction followed by ASCT and maintenance. Key exclusion criteria are creatinine clearance < 30 mL/min requiring dialysis, ECOG PS > 2, neutrophils < 1000/μL, platelets < 75,000 or < 30,000/μL (for pts with < 50% or ≥ 50% of bone marrow [BM] nucleated cells as plasma cells, respectively), Hb < 8 g/dL, and prior (< 5 y) non-MM malignancies. Pts must provide a BM sample at screening to establish presence or absence of myelodysplastic changes. Tx is POM 4 mg D1-21 of a 28-day cycle and LoDEX 40 mg/day (20 mg for pts aged > 75 y) on D1, 8, 15, and 22 until progression or unacceptable toxicity. Thromboprophylaxis with low-dose aspirin or equivalent is mandated. Upon discontinuation, follow-up will continue for OS, second primary malignancies, and subsequent anti-MM Tx for up to 5 y from enrollment. The primary endpoint is ORR by modified IMWG criteria (with minimal response). Secondary endpoints include PFS, OS, duration of response, TTP, and safety. To elucidate POM mechanism of action in LEN-exposed disease, MM-014 includes exploratory endpoints to identify molecular, immune, and cellular biomarkers and evaluate clonality. Specifically, markers that may predict POM response or resistance, underlie POM + LoDEX synergy, indicate dysregulated pathways or key MM targets, and chromosomal aberrations will be evaluated. Sites are open for enrollment. Clinical trial information: NCT01946477.
Comparaison prospective randomisée multicentrique de la coloscopie à l'eau bleue et à l'air: étude Grand Bleu
Authors: A Lesne, O Rouquette, F Petit-Laurent, G Tourlonias, A Pasquion, J Rivory, G Aguero garcete, J Scanzi, S Chalumeau, C Chambon-Augoyard, D Moussata, F Leger-Nguyen, S Degeorges, M Chauvenet, T Fontanges, S Baubet, D Pere-verge, JC Souquet, JM Phelip, L Poincloux, S Poupon-Bourdy, S Touzet, L Magaud, T Ponchon, M Pioche
Journal: Endoscopy (2016)

La coloscopie standard avec insufflation d'air est actuellement la technique de référence pour la détection des lésions colorectales. Le taux d'adénomes manques reste néanmoins, d'après les études menées sur le sujet, de 16 à 24%. De nouvelles techniques sont testées afin d'améliorer le taux de détection d'adénomes (TDA), et l'instillation d'eau au cours de la coloscopie, teintée ou non de bleu, a apporté des résultats prometteurs. Cette étude avait pour objectif de comparer la coloscopie avec instillation d'eau tiède teintée de bleu à la technique de référence en terme de TDA, à la recherche d'une amélioration.
Myth of medicine’s “golden age” is burden to young doctors, says Gerada
Authors: Abi Rimmer
Journal: BMJ (2017)

Older doctors who present the past as a “golden age” of medicine are contributing to the deteriorating mental health of younger doctors, one of the founders of a national mental health service for doctors has said.

Clare Gerada, a partner at the group of general practices that run the NHS GP Health Service and the Practitioner Health Programme, said that a mythologised age of medicine places a burden on younger doctors. She made her comments while giving the William Pickles lecture at the Royal College of General Practitioners’ spring general meeting in London on 12 May.

“I believe that the rise in mental illness among doctors has been made worse by the older generation, my generation, clinging …