tbuckley/cabot-search huggingface dataset:
Clinicopathologic characteristics of patients with TP63 mutations in Chinese non-small cell lung cancer
Authors: Q. Zhang, C. Xu, W. Wang, W. Zhuang, Z. Huang, G. Chen, M. Fang, T. Lv, Y. Song
Journal: Annals of Oncology (2019)

Background: Variation at TP63 has recently been shown to be associated with non-small cell lung cancer patients (NSCLC) in the Chinese population. There is some clinical evidence for the use of TP63 mutations as prognostic and predictive biomarker. The aim of this study is to investigate mutations and prognosis of NSCLC harboring TP63 mutations. Methods: A total of 1236 patients with non-small-cell lung cancer were recruited between July 2012 and December 2016. The status of TP63 mutations and other genes were detected by next generation sequencing. Results: TP63 gene mutation rate was 2.02% (25/1236) in non-small cell lung cancer, including R643* (1 patient), H247N (1 patient), A139V (1 patient), V626F (1 patient), Q70* (1 patient), Q274E (1 patient), H615D (1 patient), R350T (1 patient), Y202Kfs*29 (1 patient), P229H (1 patient), M40V (1 patient), E409Q (1 patient), V179M (1 patient), W658* (1 patient), S365* (1 patient), T193M (1 patient), L50F (1 patient), A554E (1 patient), R226H (1 patient), Q99* (1 patient), S310N (1 patient), T169N (1 patient), R266Q (1 patient), D372H (1 patient), and P492T (1 patient), and median overall survival (OS) for these patients was 15.0 months. Among them, all patients were TP63 gene with co-occurring mutations. Briefly, patients with (n = 5) or without (n = 20) co-occurring EGFR mutations had a median OS of 22.5 months and 14.0 months respectively (p = 0.23); patients with (n = 21) or without (n = 4) co-occurring TP53 mutations had a median OS of 15.0 months and 13.0 months respectively (p = 0.33); patients with (n = 5) or without (n = 20) co-occurring BRAF mutations had a median OS of 14.0 months and 15.0 months respectively (p = 0.72); patients with (n = 5) or without (n = 20) co-occurring KRAS mutations had a median OS of 6.0 months and not up to now respectively (P < 0.01). Conclusions: TP63 is structurally and functionally similar to TP53 and their activity as transcription factors is regulated by a wide repertoire of shared and unique post-translational modifications and interactions with regulatory cofactors. EGFR, TP53 and BRAF gene accompanied may have less correlation with TP63 mutation in NSCLC patients. KRAS accompanied mutations might play a worse prognosis in TP63 gene mutation NSCLC. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
DIAGNOSTIC ABILITY OF BLUE LIGHT IMAGING FOR PREDICTING DEEP SUBMUCOSAL INVASION IN COLORECTAL LESIONS
Authors: H Neumann, P Grimminger, KF Rahman, F Thieringer, PR Galle, T Zimmermann, K Mönkemüller, A Kreft, GE Tontini
Journal: Endoscopy (2019)

Blue Light Imaging (BLI) was recently introduced as a novel imaging technology allowing for enhanced visualization of the mucosal surface and vascular pattern morphology. Data regarding the applicability of BLI for prediction of deep submucosal invasion of colorectal lesions is missing.
Government commits £10m to doctors’ rest facilities
Authors: Abi Rimmer
Journal: BMJ (2019)

All hospital trusts in England will receive £30 000 from the government to expand and improve their rest spaces for doctors, and hospitals in the greatest need will receive extra support, the BMA has said.

Patient care was being placed at risk, the association said, if doctors providing care around the clock did not have somewhere to rest.

The Department of Health and Social Care has now confirmed that 92 trusts in England will receive £30 000 in 2019-20 to help improve facilities, and 122 trusts defined as having a greater need will each …
Prévention des sténoses oesophagiennes après dissection sous-muqueuse étendue par application de gel Pluronic F127 associé ou non à des vésicules extracellulaires de cellules souches mésenchymateuses dans le modèle porcin
Authors: E Coffin, A Brun, G Perrod, M Piffoux, I Boucenna, M Bruzzi, L M'harzi, J Assouline, T Lecomte, O Clément, C Cellier, G Rahmi
Journal: Endoscopy (2019)

La dissection sous-muqueuse (DSM) est un des traitements de référence des cancers superficiels de l'oesophage. Lorsque la résection est étendue, elle est responsable d'une sténose oesophagienne. L'objectif de cette étude est d'évaluer la faisabilité et l'efficacité de la greffe de vésicules extracellulaires (VE) de cellules souches mésenchymateuses (CSM) allogéniques dérivées du tissu adipeux associées à un gel thermosensible, le Pluronic F127, dans la prévention des sténoses oesophagiennes après DSM dans un modèle porcin.
Utility of Plasma Concentration of Trimethylamine N-Oxide in Predicting Cardiovascular and Renal Complications in Individuals With Type 1 Diabetes
Authors: Signe A. Winther, Jens C. Øllgaard, Nete Tofte, Lise Tarnow, Zeneng Wang, Tarunveer S. Ahluwalia, Anders Jorsal, Simone Theilade, Hans-Henrik Parving, Tine W. Hansen, Stanley L. Hazen, Oluf Pedersen, Peter Rossing
Journal: Diabetes Care (2019)

Trimethylamine N-oxide (TMAO) is suggested as an independent gut microbiota-derived risk factor for cardiovascular and renal disease. We investigated associations between plasma TMAO concentrations and cardio-renal outcomes in a prospective study of individuals with type 1 diabetes.Plasma TMAO was measured at baseline in 1,159 individuals with type 1 diabetes (58% male, mean ± SD age 46 ± 13 years). End points were all-cause and cardiovascular mortality, cardiovascular disease (CVD), and renal events tracked from national registries. Associations between TMAO and end points were tested using Cox regression models.After 15.0 (6.7-19.3) (median [interquartile range]) years of follow-up, we recorded all-cause and cardiovascular mortality (n = 363 and 120, respectively), combined CVD (n = 406), coronary outcome (myocardial infarction and coronary intervention) (n = 163), stroke (n = 115), hospitalization for heart failure (n = 81), and end-stage renal disease (n = 144). In univariate analyses, higher TMAO concentrations were associated with all end points (P ≤ 0.005). Except for stroke and heart failure, all end points remained significantly associated with higher TMAO concentrations after adjustment for conventional cardiovascular risk factors (P ≤ 0.003). After further adjustment for baseline estimated glomerular filtration rate (eGFR), results became insignificant for all end points. TMAO was inversely associated with baseline eGFR (R2 = 0.29; P < 0.001).In individuals with type 1 diabetes, higher concentrations of plasma TMAO were associated with mortality, CVD events, and poor renal outcome, independent of conventional risk factors. However, the association became insignificant after further adjustment for baseline eGFR. This could reflect TMAO as a renal function marker or a risk factor for micro- and macrovascular complications mediated through impaired renal function.
FACTORS INFLUENCING THE LONG TERM OUTCOME OF CAUSTIC ESOPHAGEAL STRICTURE DILATATION USING SAVARY DILATORS
Authors: M Manzoor Haque, Z Majid, N Hassan Luck, N Mehmood, G Bux Soomro
Journal: Endoscopy (2019)

Less is known in the literature about the management and long-term outcome of Caustic esophageal stricture (CES). It is reported from developing countries particularly in pediatric and adolescent age group. The study is aimed to assess the long-term outcome of CES dilatation using Savary Gilliard dilator and also the factors associated with better outcome.
COLORECTAL CANCERS DETECTED FOLLOWING SURGERY AT ANASTOMOSES OR OTHER COLORECTAL LOCATIONS DURING COLONOSCOPY SURVEILLANCE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: L Fuccio, D Rex, T Ponchon, L Frazzoni, M Dinis-Ribeiro, P Bhandari, E Dekker, M Pellisé, L Correale, J van Hooft, R Jover, D Libanio, F Radaelli, S Alfieri, F Bazzoli, C Senore, J Regula, T Seufferlein, T Rösch, P Sharma, A Repici, C Hassan
Journal: Endoscopy (2019)

Outcomes of endoscopic surveillance following surgery for colorectal cancer (CRC) vary with the incidence and timing of CRC detection, at anastomosis or elsewhere in the colorectum. We performed systematic review and meta-analysis to evaluate the incidence of CRCs identified during surveillance colonoscopies of patients with previous CRC surgery.
WE CAN JUDGE THE PRESENT OR PAST H.PYLORI INFECTION WITH ONLY ONE ENDOSCOPIC CARDIAC IMAGE (WHALE SHARK SIGN: WSS)
Authors: T Yamasaki, M Chibai, T Sakurai, J Mitobe, Y Maruyama, H Miyashita, Y Akita, R Miyazaki, M Mitsunaga, M Saruta
Journal: Endoscopy (2019)

We have confused with various newly endoscopic findings (patchy redness and map-like redness etc.) after H.pylori (HP) eradication. On this time, we have found out a new other ultimate useful finding showing HP related gastritis at gastric cardia including present and post HP infection. Our aim of this study is to elucidate the possibility of judgement with only this cardiac endoscopic view about presence or absence with HP infection.
Effect of prenatal and postnatal exposure to urban air pollution on the myocardial lipid peroxidation levels of adult mice
Authors: Nilsa Regina Damaceno-Rodrigues, Mariana Matera Veras, Elnara Marcia Negri, Ana Claudia Tedesco Zanchi, Claudia Rodhen, Paulo Hilario Nascimento Saldiva, Marisa Dolhnikoff, Elia Garcia Caldini
Journal: European Respiratory Journal (2008)
ADVANCED CHOLANGIOSCOPY GUIDED LITHOTRIPSY IN 2 PATIENTS WITH COMPLEX BILIARY STONES
Authors: J Fernandes, F Lucas, M Moreira, H Ribeiro, S Giestas, T Araújo, J Ramada, M Certo, J Canena, L Lopes
Journal: Endoscopy (2019)

ERCP is the first-line technique for the treatment of biliary stones. Most stones are successfully removed using extraction balloons and/or Dormia baskets, and in more complex cases, using mechanical lithotripsy and/or balloon dilation of the ampulla after sphincterotomy. There are, however, a small group of patients with complicated stones, in which these techniques are not effective.
Recreational and ergogenic substance use and substance use disorders in elite athletes: a narrative review
Authors: David McDuff, Todd Stull, João Mauricio Castaldelli-Maia, Mary E Hitchcock, Brian Hainline, Claudia L Reardon
Journal: British Journal of Sports Medicine (2019)

Substances from various classes may be used for recreational purposes, self-treatment or to boost performance. When substance use shifts from occasional to regular, heavy or hazardous use, positive and negative effects can develop that vary by substance class and athlete. Regular use of recreational or performance enhancing substances can lead to misuse, sanctions or use disorders.To review the prevalence, patterns of use, risk factors, performance effects and types of intervention for all classes of recreational and performance enhancing substances in elite athletes by sport, ethnicity, country and gender.A comprehensive search was conducted to identify studies that compared the prevalence and patterns of substance use, misuse and use disorders in elite athletes with those of non-athletes and provided detailed demographic and sport variations in reasons for use, risk factors and performance effects for each main substance class.Alcohol, cannabis, tobacco (nicotine) and prescribed opioids and stimulants are the most commonly used substances in elite athletes, but generally used at lower rates than in non-athletes. In contrast, use/misuse rates for binge alcohol, oral tobacco, non-prescription opioids and anabolic-androgenic steroids are higher among athletes than non-athletes, especially in power and collision sports. Cannabis/cannabinoids seem to have replaced nicotine as the second most commonly used substance.Substance use in elite athletes varies by country, ethnicity, gender, sport and competitive level. There are no studies on substance use disorder prevalence in elite male and female athletes and few studies with direct comparison groups.
THU0342 SYSTEMIC SCLEROSIS IS A DISEASE OF A PREMATURELY SENESCENT, INFLAMMATORY AND ACTIVATED IMMUNOME
Authors: Bhairav Paleja, Andrea Low, Pavanish Kumar, Suzan Saidin, Ahmad Lajam, Sharifah Nur Hazirah, Camillus Chua, Liyun Lai, Salvatore Albani
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Systemic sclerosis (SSc) is an autoimmune disease characterised by excessive fibrosis of skin and internal organs, and vascular dysfunction (1). Association of T and B cell subsets have been reported in SSc, however there is lack of systematic studies of functional relations between immune cell subsets in this disease (2,3,4). This lack of mechanistic knowledge hampers targeted intervention. <h3>Objectives:</h3> In the current study we ought to determine differential immune cell composition and their interactions in peripheral blood of SSc patients and its impact on disease severity and progression. <h3>Methods:</h3> Mononuclear cells from blood of SSc patients (n=20) and healthy controls (n=10) were analysed by mass cytometry using a 36 marker (cell-surface and intracellular) panel to aid in identification of major PBMC lineages including T cells, B cells, monocytes and NK cells and their subsets. Transcriptome analysis (m-RNA sequencing) was performed on sorted T and B cell subsets. Unsupervised clustering of mass cytometry data was performed using in-house developed analysis software MARVIS. This software combines dimension reduction and clustering steps to identify all possible cellular subsets. Further, custom R scripts helped in identifying nodes that were differentially expressed between the study groups and also phenotype of these nodes. <h3>Results:</h3> Unsupervised clustering analysis revealed significant differences in the frequencies of T and B cell subsets in patients. Correlation network analysis highlighted an overall dysregulated immune architecture coupled with domination of inflammatory senescent T cell modules in SSc patients. Transcriptome analysis of sorted immune cells revealed an activated phenotype of CD4 and MAIT cells in patients, accompanied with increased expression of inhibitory molecules, reminiscent of phenotype exhibited by functionally adapted, exhausted T cells in response to chronic stimulation. <h3>Conclusion:</h3> Overall this study provides an in depth analysis of systemic immunome in SSc, highlighting role of inflammation and chronic stimulation mediated "premature senescence" of immune cells, with implications to delineate mechanism of pathogenesis and identify diagnostic/therapeutic targets. <h3>References:</h3> [1] Denton, C. P. and D. Khanna (2017). "Systemic sclerosis." Lancet 390(10103): 1685-1699. [2] Fuschiotti, P. (2017). "Current perspectives on the role of CD8+ T cells in systemic sclerosis." Immunol Lett. In Press [3] Liu, M., et al. (2016). "New insights into CD4(+) T cell abnormalities in systemic sclerosis." Cytokine Growth Factor Rev 28: 31-36. [4] Sanges, S., et al. (2017). "Role of B cells in the pathogenesis of systemic sclerosis." Rev Med Interne 38(2): 113-124. <h3>Disclosure of Interests:</h3> None declared
Response to: ‘TARA Study: a new perspective on tapering drugs in RA’ by Mishra <i>et al</i>
Authors: Elise van Mulligen, Johanna M W Hazes, Angelique E A M Weel, Pascal H P de Jong
Journal: Annals of the Rheumatic Diseases (2019)

We are pleased about the interest in our article by Mishra et al and we would like to respond to their questions so that there can be no ambiguity.1 2 

First of all, there is some clarification needed on the conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) that were used in combination with the TNF-inhibitors at baseline in the TApering strategies in Rheumatoid Arthritis (TARA) study. In table 1, we elaborate on the different combinations of csDMARDs that were used for each intervention arm separately. In the csDMARD tapering group, the methotrexate (MTX) was tapered, except for the three patients who did not use MTX. These patients gradually tapered leflunomide (n=1) and sulfasalazine (n=2).

View this table:

Table 1 
Use of csDMARDs at baseline in the TARA study …
Unexpected link between mitochondrial DNA and T cell help in systemic lupus erythematosus
Authors: David S Pisetsky
Journal: Annals of the Rheumatic Diseases (2019)

Since the discovery of anti-DNA antibodies, DNA has been the subject of fascination as a target of autoimmunity in systemic lupus erythematosus (SLE).1 As the material of heredity, DNA is usually hidden from the immune system in the safe confines of the cell nucleus. How then can DNA become an autoantigen? The answer lies in DNA’s capacity for geographic translocation. Like many molecules, DNA can move around the cell and even escape outside, especially during cell death.2 Depending on the mechanism, cell death can induce inflammation, providing adjuvant activity to induce anti-DNA production. Another mechanism for antibody induction is cross-reactivity with another foreign or even self-antigen during infection, a setting for intense immune activation. The genetic background of the individual may influence these responses.3 

Once outside the cell, DNA can display immunological properties by forming immune complexes with anti-DNA antibodies. These complexes have two key roles in disease: deposition in the kidney to incite nephritis and stimulation of cytokine production via interaction with both Toll-like receptor (TLR) and non-TLR internal nucleic acid sensors that operate in various subcellular compartments.4 The location of these sensors contrasts with that of TLR receptors such as TLR4, which are found on the cell membrane. While the response to infection is usually conceptualised as beginning in the extracellular space in the blood or tissue, the intracellular space is also an important site of host defence, with internal nucleic acid sensors key to activation of innate immunity

During infection, these internal sensors can bind DNA (as well as RNA) from intracellular bacterial or viral infection and trigger the same systems as those activated by extracellular pathogen associated molecular patterns.5–7 Mitochondrial DNA (mtDNA) can also trigger these sensors during cell stress since mitochondria can leak or release their DNA.8 9 Genetically …
Cysteine depletion targets leukemia stem cells through inhibition of electron transport complex II
Authors: Courtney L. Jones, Brett M. Stevens, Angelo D’Alessandro, Rachel Culp-Hill, Julie A. Reisz, Shanshan Pei, Annika Gustafson, Nabilah Khan, James DeGregori, Daniel A. Pollyea, Craig T. Jordan
Journal: Blood (2019)
Identification and transcriptome analysis of erythroblastic island macrophages
Authors: Wei Li, Yaomei Wang, Huizhi Zhao, Huan Zhang, Yuanlin Xu, Shihui Wang, Xinhua Guo, Yumin Huang, Shijie Zhang, Yongshuai Han, Xianfang Wu, Charles M. Rice, Gang Huang, Patrick G. Gallagher, Avital Mendelson, Karina Yazdanbakhsh, Jing Liu, Lixiang Chen, Xiuli An
Journal: Blood (2019)
Downregulation of CD73 associates with T cell exhaustion in AML patients
Authors: Yaxian Kong, Bei Jia, Chenchen Zhao, David F. Claxton, Arati Sharma, Charyguly Annageldiyev, Joseph S. Fotos, Hui Zeng, Robert F. Paulson, K. Sandeep Prabhu, Hong Zheng
Journal: Journal of Hematology & Oncology (2019)

Successful treatment for acute myeloid leukemia (AML) remains challenging. Inhibiting immune checkpoint to enhance anti-tumor response is an attractive strategy for effective leukemia therapeutics. CD73 is a recently recognized immune checkpoint mediator that is highly expressed on tumor cells and stromal cells in tumor microenvironment. The ectonucleotidase activity of CD73 catalyzes AMP to adenosine, which subsequently inhibits anti-tumor immune responses. In this study, we aim to explore the effect of CD73 in AML. Peripheral blood samples collected from patients with newly diagnosed AML (n = 27) were used in this study. CD73 expression on each immune cell component was examined by flow cytometry. Phenotypic study of CD73-expressing T cells and analysis of the correlation between CD73 and other immune checkpoints were performed using flow cytometry-based assays. Functional status of CD73+ vs. CD73− T cells was assessed in an in vitro cytokine release assay upon CD3/CD28 antibody stimulation. In contrast to the long recognized immune suppressive effect of CD73-adenosine signaling in tumor tissue, we made a striking observation that in AML, CD73 expression on CD8 T cells associates with an increased immune response. CD73+ CD8 T cells are more functional, whereas CD73− CD8 T cells exhibit features of exhaustion manifested by high expression of inhibitory receptors such as PD-1 and TIGIT, increased intracellular expression of Eomes, reduced capacity of cytokine production, and high susceptibility to apoptosis. Our data highlight the potential of CD73 as a double-edged sword in anti-leukemia immunity and argue strongly for the combinational treatment by adding immune checkpoint inhibitors to the CD73-targeting approaches.
Prognostic Value of Interim Positron Emission Tomography Among Children with Advanced Hodgkin Lymphoma in Developing Countries: Children Cancer Hospital Egypt Experience
Authors: Reham Khedr, Asmaa Hamouda, Sawsan Naguib, Mohamed Khalaf, Sally Fikry, Amr Elsayed, Hala Taha, Mohamed Zaghloul, Iman Attia
Journal: Blood (2016)
PET-BASED PLANNING IN LA-NSCLC: SHOULD WE RE-CONSIDER ELECTIVE NODAL IRRADIATION IN THE IMRT ERA?
Authors: A Nulens, A G Mousa, G Defraene, S Stroobants, W De Wever, F Van den Heuvel, Y Lievens, Grp Lllc.
Journal: Journal of Thoracic Oncology (2011)
Abstract 15963: Is an Extracardiac Pacing/ICD Lead an Option for Patients With Lung Disease?
Authors: Martin C Burke, Alan Marcovecchio, Rick Sanghera, Anne Floor Quast, Richard Wasley
Journal: Circulation (2018)

Introduction: Efforts to deliver completely extracardiac pacing/defibrillation into the anterior mediastinum over the cardiac notch, have been previously described. These efforts aim to eliminate c...
Abstract 13766: Ongoing Local Inflammation of Thoracic Aortic in Patients With a History of Kawasaki Disease
Authors: Kenji Suda, Nobuhiro Tahara, Tomohisa Nakamura, Munehisa Bekki, Yoshiyuki Kagiyama, Shintaro Kishimoto, Motofumi Iemura, Yoshihiro Fukumoto
Journal: Circulation (2017)

Introduction: Though Kawasaki disease (KD) is known as small - medium sized vasculitis in children, accumulating data have shown that aortic vascular property is altered after KD. These changes of ...