tbuckley/cabot-search huggingface dataset:
Tumor-intrinsic PIK3CA represses tumor immunogenicity in a model of pancreatic cancer
Authors: Nithya Sivaram, Patrick A. McLaughlin, Han V. Han, Oleksi Petrenko, Ya-Ping Jiang, Lisa M. Ballou, Kien Pham, Chen Liu, Adrianus W.M. van der Velden, Richard Z. Lin
Journal: Journal of Clinical Investigation (2019)

The presence of tumor-infiltrating T cells is associated with favorable patient outcomes, yet most pancreatic cancers are immunologically silent and resistant to currently available immunotherapies. Here we show using a syngeneic orthotopic implantation model of pancreatic cancer that Pik3ca regulates tumor immunogenicity. Genetic silencing of Pik3ca in KrasG12D/Trp53R172H-driven pancreatic tumors resulted in infiltration of T cells, complete tumor regression, and 100% survival of immunocompetent host mice. By contrast, Pik3ca-null tumors implanted in T cell–deficient mice progressed and killed all of the animals. Adoptive transfer of tumor antigen–experienced T cells eliminated Pik3ca-null tumors in immunodeficient mice. Loss of PIK3CA or inhibition of its effector AKT increased the expression of MHC class I and CD80 on tumor cells. These changes contributed to the increased susceptibility of Pik3ca-null tumors to T cell surveillance. Our results indicate that tumor cell PIK3CA-AKT signaling limits T cell recognition and clearance of pancreatic cancer cells. Strategies that target this pathway may yield an effective immunotherapy for this cancer.
Tropism of influenza B viruses in human respiratory tract explants and airway organoids
Authors: Christine H.T. Bui, Renee W.Y. Chan, Mandy M.T. Ng, M-C. Cheung, Ka-chun Ng, Megan P.K. Chan, Louisa L.Y. Chan, Joanne H.M. Fong, J.M. Nicholls, J.S. Malik Peiris, Michael C.W. Chan
Journal: European Respiratory Journal (2019)

Despite causing regular seasonal epidemics with substantial morbidity, mortality and socioeconomic burden, there is still a lack of research into influenza B viruses (IBVs). In this study, we provide for the first time a systematic investigation on the tropism, replication kinetics and pathogenesis of IBVs in the human respiratory tract. Physiologically relevant ex vivo explant cultures of human bronchus and lung, human airway organoids, and in vitro cultures of differentiated primary human bronchial epithelial cells and type-I-like alveolar epithelial cells were used to study the cellular and tissue tropism, replication competence and induced innate immune response of 16 IBV strains isolated from 1940 to 2012 in comparison with human seasonal influenza A viruses (IAVs), H1N1 and H3N2. IBVs from the diverged Yamagata- and Victoria-like lineages and the earlier undiverged period were included. The majority of IBVs replicated productively in human bronchus and lung with similar competence to seasonal IAVs. IBVs infected a variety of cell types, including ciliated cells, club cells, goblet cells and basal cells, in human airway organoids. Like seasonal IAVs, IBVs are low inducers of pro-inflammatory cytokines and chemokines. Most results suggested a higher preference for the conducting airway than the lower lung and strain-specific rather than lineage-specific pathogenicity of IBVs. Our results highlighted the non-negligible virulence of IBVs which require more attention and further investigation to alleviate the disease burden, especially when treatment options are limited.
Decision-making value of nuclear dense fine speckled pattern in systemic autoimmune rheumatic disease: trick or treat?
Authors: Chuiwen Deng, Xiaohui Qu, Shaoyun Cheng, Xiaofeng Zeng, Yongzhe Li, Yunyun Fei
Journal: Annals of the Rheumatic Diseases (2019)

We read with great interest the recommendation published by Damoiseaux et al and other members of the International Consensus on Antinuclear antibody (ANA) patterns (ICAP).1 Not only the clinical relevance of human epithelial type 2 (HEp-2) indirect immunofluorescent (IIF) patterns was presented, suggestion about follow-up testing was also given in this article, which will benefit the clinical decision-making in daily practice. Nuclear dense fine speckled (DFS) pattern, a competent-level pattern evaluated by the ICAP previously (AC-02),2 is frequently discussed in the current recommendation for it being the pattern best associated with apparently healthy individuals, or negatively correlating with systemic autoimmune rheumatic disease (SARD).

Damoiseaux et al demonstrated that the negative relationship between DFS pattern and SARD will be valid only if both specific DFS70 and other common extractable nuclear antigen (ENA) autoantibodies were not observed.1 However, the testing strategies of DFS pattern remains controversy. Some proposed that the specific DFS70 autoantibodies should be detected after the screening DFS pattern by IIF, as suggested by Damoiseaux …
An N-/L-type calcium channel blocker, cilnidipine, suppresses autonomic, electrical, and structural remodelling associated with atrial fibrillation
Authors: Kazuko Tajiri, Jean-Baptiste Guichard, Xiaoyan Qi, Feng Xiong, Patrice Naud, Jean-Claude Tardif, Antoine Da Costa, Kazutaka Aonuma, Stanley Nattel
Journal: Cardiovascular Research (2019)

Autonomic dysfunction can promote atrial fibrillation (AF) and results from AF-related remodelling. N-type Ca2+-channels (NTCCs) at sympathetic nerve terminals mediate Ca2+-entry that triggers neurotransmitter release. AF-associated remodelling plays an important role in AF pathophysiology but the effects of NTCC inhibition on such remodelling is unknown. Here, we investigated the ability of a clinically available Ca2+-channel blocker (CCB) with NTCC-blocking activity to suppress the arrhythmogenic effects of AF-promoting remodelling in dogs.Mongrel dogs were kept in AF by right atrial tachypacing at 600 bpm. Four groups were studied under short-term AF (7 days): (i) Shams, instrumented but without tachypacing (n = 5); (ii) a placebo group, tachypaced while receiving placebo (n = 6); (iii) a control tachypacing group receiving nifedipine (10 mg orally twice-daily; n = 5), an L-type CCB; and (iv) a cilnidipine group, subjected to tachypacing and treatment with cilnidipine (10 mg orally twice-daily; n = 7), an N-/L-type CCB. With cilnidipine therapy, dogs with 1-week AF showed significantly reduced autonomic changes reflected by heart rate variability (decreases in RMSSD and pNN50) and plasma norepinephrine concentrations. In addition, cilnidipine-treated dogs had decreased extracellular matrix gene expression vs. nifedipine-dogs. As in previous work, atrial fibrosis had not yet developed after 1-week AF, so three additional groups were studied under longer-term AF (21 days): (i) Shams, instrumented without tachypacing or drug therapy (n = 8); (ii) a placebo group, tachypaced while receiving placebo (n = 8); (iii) a cilnidipine group, subjected to tachypacing during treatment with cilnidipine (10 mg twice-daily; n = 8). Cilnidipine attenuated 3-week AF effects on AF duration and atrial conduction, and suppressed AF-induced increases in fibrous-tissue content, decreases in connexin-43 expression and reductions in sodium-channel expression.Cilnidipine, a commercially available NTCC-blocking drug, prevents AF-induced autonomic, electrical and structural remodelling, along with associated AF promotion.
Dissection sous muqueuse avec traction par clip élastique: efficacité et sécurité pour la résection des lésions coliques avec fibrose
Authors: J Faller, J Jacques, R Legros, J Rivory, T Ponchon, M Pioche
Journal: Endoscopy (2019)

La résection endoscopique de lésions colorectales avec fibrose sous muqueuse par la technique de dissection sous muqueuse (DSM) est difficile. Il a été montré que la présence de fibrose est associée à une diminution de résection complète et une augmentation du nombre de complications. Plusieurs méthodes de traction ont été décrites afin de faciliter la dissection. Récemment, la technique française de contre traction par deux clips et un élastique a été étudiée et s'avère utile pour la résection des lésions coliques. Aucune de ces méthodes n'ont été évaluées pour la résection de lésions avec fibrose.
Final congenital melanocytic naevi colour is determined by normal skin colour and unaltered by superficial removal techniques: a longitudinal study
Authors: S. Polubothu, V.A. Kinsler
Journal: British Journal of Dermatology (2019)

Spontaneous lightening of congenital melanocytic naevi (CMN) has not been studied systematically. Final colour is considered an important outcome after superficial removal techniques such as curettage, dermabrasion or laser ablation, and is often compared with colour at birth.To quantify the natural history of CMN lightening over time, and explore phenotypic and genotypic predictors of colour change.A longitudinal cohort study was undertaken of 110 patients with CMN (mean follow-up 5·3 years). Accurate colour-space measurements were taken from professional serial photographs of CMN and normal skin. Changes in colour over time were modelled using multiple logistic regression, against phenotypic and genotypic variables.Lightening of CMN was significantly associated with lighter normal skin colour (P < 0·001) and with MC1R variant alleles (red/blonde hair gene) (P < 0·001), but not with CMN colour in the first 3 months of life, NRAS genotype or projected adult size of CMN. Importantly, the final colours of adjacent treated and untreated areas of CMN were indistinguishable.Final CMN colour in childhood is related to the genetically determined skin colour of the individual, is unrelated to the colour of CMN at birth, and is unaffected by superficial removal. What's already known about this topic? Final colour of congenital melanocytic naevi (CMN) is considered an important outcome after superficial removal techniques such as curettage, dermabrasion or laser ablation, and is often compared with colour at birth. The phenomenon of spontaneous lightening in CMN, in which naevi lighten gradually and sometimes dramatically during childhood, has been described but not systematically studied. What does this study add? Final CMN colour in childhood is significantly associated with the individual's normal skin colour, and with MC1R genotype, and is therefore genetically determined. Final CMN colour is not predictable from CMN colour in the first 3 months of life. Superficial removal techniques do not alter the final colour of CMN.
Robot-assisted Level III-IV Inferior Vena Cava Thrombectomy: Initial Series with Step-by-step Procedures and 1-yr Outcomes
Authors: Baojun Wang, Qingbo Huang, Kan Liu, Yang Fan, Cheng Peng, Liangyou Gu, Taoping Shi, Peng Zhang, Wenzheng Chen, Songliang Du, Shaoxi Niu, Rong Liu, Guodong Zhao, Qiuyang Li, Cangsong Xiao, Rong Wang, Shuanglei Li, Maoqiang Wang, Fengyong Liu, Haiyi Wang, Hongzhao Li, Xin Ma, Xu Zhang
Journal: European Urology (2019)
Protein tyrosine phosphatase non-receptor type 22 modulates colitis in a microbiota-dependent manner
Authors: Marianne R. Spalinger, Thomas S.B. Schmidt, Marlene Schwarzfischer, Larissa Hering, Kirstin Atrott, Silvia Lang, Claudia Gottier, Annelies Geirnaert, Christophe Lacroix, Xuezhi Dai, David J. Rawlings, Andrew C. Chan, Christian von Mering, Gerhard Rogler, Michael Scharl
Journal: Journal of Clinical Investigation (2019)

The gut microbiota is crucial for our health, and well-balanced interactions between the host's immune system and the microbiota are essential to prevent chronic intestinal inflammation, as observed in inflammatory bowel diseases (IBD). A variant in protein tyrosine phosphatase non-receptor type 22 (PTPN22) is associated with reduced risk of developing IBD, but promotes the onset of autoimmune disorders. While the role of PTPN22 in modulating molecular pathways involved in IBD pathogenesis is well studied, its impact on shaping the intestinal microbiota has not been addressed in depth. Here, we demonstrate that mice carrying the PTPN22 variant (619W mice) were protected from acute dextran sulfate sodium (DSS) colitis, but suffered from pronounced inflammation upon chronic DSS treatment. The basal microbiota composition was distinct between genotypes, and DSS-induced dysbiosis was milder in 619W mice than in WT littermates. Transfer of microbiota from 619W mice after the first DSS cycle into treatment-naive 619W mice promoted colitis, indicating that changes in microbial composition enhanced chronic colitis in those animals. This indicates that presence of the PTPN22 variant affects intestinal inflammation by modulating the host's response to the intestinal microbiota.
Air Pollution Exposure and Asthma Incidence in Children
Authors: George D. Thurston, Mary B. Rice
Journal: JAMA (2019)

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IS DIFFICULT CHOLEDOCHOLITHIASIS RELATED TO EARLY RECURRENCE?
Authors: C Konstantakis, P Patrikakos, I Aggeletopoulou, C Triantos, K Thomopoulos
Journal: Endoscopy (2019)

To investigate if presence of difficult common bile duct (CBD) stones (CBDS) is associated with an early recurrence of CBDS following endoscopic extraction.
Comparison of Prasugel With Clopidogrel on Platelet Function in Coronary Artery Disease Patients With Type 2 Diabetes Mellitus - Third Optimizing Anti-Platelet Therapy in Diabetes MellitUS (OPTIMUS-3)
Authors: Dominick J. Angiolillo, Juan Badimon, Jorge F. Saucedo, Andrew L. Frelinger, Alan D. Michelson, Joseph A. Jakubowski, Baojin Zhu, Clement K. Ojeh, Brian Baker, Mark B. Effron
Journal: Circulation (2009)
APPLICATION OF DEEP LEARNING NEURAL NETWORK FOR HISTOLOGICAL PREDICTION OF COLON POLYP IMAGES WITH BLI ZOOM TECHNOLOGY
Authors: M Szalai, K Zsobrak, B Dorottya Lovasz, L Oczella, Z Dubravcsik, L Madacsy
Journal: Endoscopy (2019)

In our present study we aimed to develop an Artificial Intelligence-based Decision Support System (AI-DSS) that can be used to analyze the polyp images in differentiation between neoplastic and non-neoplastic subcentrimetric polyps.
Renal Pelvis Involvement of Immunoglobulin G4–Related Disease Mimicking Malignancy on 18F-FDG PET/CT
Authors: Yuanyuan Jiang, Guozhu Hou, Wuying Cheng
Journal: Clinical Nuclear Medicine (2019)

A 70-year-old woman with bilateral submandibular gland enlargement was referred to our hospital. Submandibular gland biopsy indicated immunoglobulin G4 (IgG4)-related disease (IgG4-RD) involvement. Contrast-enhanced CT was undergone for evaluation of IgG4-RD and revealed a mass located at the left renal pelvis. F-FDG PET/CT showed bilateral FDG-avid submandibular gland and a hypermetabolic mass in the left renal pelvis. The lesions were decreased in both size and metabolism on follow-up PET/CT 2 months after treatment with prednisone. This case illustrated a rare site for IgG4-RD, and the renal pelvis involvement should be considered into differential diagnosis in patients with IgG4-RD history.
RISK FACTOR OF LYMPH NODE METASTASIS IN ENDOSCOPICALLY RESECTED T1 COLORECTAL CANCER
Authors: GA Song, DH Baek, EY Park, JW Park, SH Lee
Journal: Endoscopy (2019)

Early colorectal cancer is defined as a carcinoma confined to the submucosa, regardless of lymph node (LN) status. The risk of LN metastasis in early colon cancer is ranging from 6.3% to 17%, and submucosal invasion more than 1000um, lymphovascular invasion (LVI), poor differentiation and tumor budding are well-known risk factor. We aimed to clarify the risk factors for LN metastasisin early colorectal cancer.
Diversity: Boards of NHS national bodies fail to reflect BME workforce
Authors: Gareth Iacobucci
Journal: BMJ (2019)

The boards of England’s national NHS organisations continue to be dominated by white people, show the findings of the 2018 annual report of the Workforce Race Equality Standard for the NHS.1 None of the eight organisations that submitted data had a proportion of black and minority ethnic (BME) staff on their boards that matched the 19.1% of such staff in NHS trusts, though one board exceeded this level when expressed as a …
Sonic Hedgehog Effectively Improves Oct4-Mediated Reprogramming of Astrocytes into Neural Stem Cells
Authors: Hao Yang, Cuicui Liu, Hong Fan, Bo Chen, Dageng Huang, Lingling Zhang, Qian Zhang, Jing An, Jingjing Zhao, Yi Wang, Dingjun Hao
Journal: Molecular Therapy (2019)
Biological features of estrogen receptor-positive breast cancer with elevated RANK (TNFRSF11A) expression
Authors: S. Casimiro, I. Gomes, B. Almeida, P. Alves, P. Félix, G. Vilhais, A.B. Mansinho, M.R. Dionísio, N. Barbosa-Morais, L. Costa
Journal: Annals of Oncology (2019)

Background: The receptor activator of NFkB (RANK)-RANK ligand (RANKL) pathway, pivotal regulator of bone remodeling, has emerged as a major mediator of progesterone-driven breast cancer (BC) carcinogenesis. RANK expression is particularly elevated in triple negative BC and has been associated with aggressiveness and poor prognosis. This study addressed the impact of elevated RANK expression in estrogen receptor (ER)-positive BC. Methods: In silico analysis of RANK (TNFRSF11A) expression was performed in the TCGA BC cohort. ER+HER2- cell lines overexpressing RANK were obtained by lentiviral transduction and standard assays were used for gene expression and phenotype evaluation. In vivo tumor growth was measured in orthotopic xenografts or after tail vein inoculation. Comparisons between two groups were performed using unpaired t-test. Survival analyzes used the Kaplan–Meier method and log-rank test. Results: RANK expression was higher in ER- breast tumors (p < 0.001); and associated with decreased 5-year overall survival (HR = 2.12 (1.16-3.87), p = 0.012). However, 5% of ER+ tumors were found to express RANK within the ER- 75%Q range. ER+ cell lines overexpressing RANK (MCF-7OE and T47DOE) were characterized by hyper activation of downstream pathways; upregulation of mesenchymal and stem cell phenotype. In silico, elevated RANK expression in ER+ tumors was significantly correlated with mesenchymal and stemness-related genes. In vivo, MCF-7OE xenografts were consistently smaller in comparison with parental ones. However, tail vein inoculation showed that MCF-7 and MCF-7OE cells where identically metastatic in the lungs and skeleton, and animals harboring MCF-7OE cells had more circulating tumor cells. Conclusions: Our data shows for the first time that RANK expression in ER+ BC is not unneglectable, and may impact on the tumor progression, particularly in the metastatic setting. Legal entity responsible for the study: Instituto de Medicina Molecular. Funding: This project was funded by National Funds (FCT-MEC), under the research project PTDC/MED-ONC/28636/2017. IG is supported by FCT grant SFRH/BD/139178/2018. Disclosure: S. Casimiro: Research support: Amgen. L. Costa: Research support, advisory board: Amgen. All other authors have declared no conflicts of interest.
High multiplicity of infection following transplantation of hepatitis C virus–positive organs
Authors: Muhammad N. Zahid, Shuyi Wang, Gerald H. Learn, Peter L. Abt, Emily A. Blumberg, Peter P. Reese, David S. Goldberg, George M. Shaw, Katharine J. Bar
Journal: Journal of Clinical Investigation (2019)

Highly effective direct-acting antivirals against Hepatitis C virus (HCV) have created an opportunity to transplant organs from HCV-positive individuals into HCV-negative recipients, since de novo infection can be routinely cured. As this procedure is performed more widely, it becomes increasingly important to understand the biological underpinnings of virus transmission, especially the multiplicity of infection. Here, we used single genome sequencing of plasma virus in four genotype 1a HCV-positive organ donors and their seven organ recipients to assess the genetic bottleneck associated with HCV transmission following renal and cardiac transplantation. In all recipients, de novo infection was established by multiple genetically distinct viruses that reflect the full phylogenetic spectrum of replication-competent virus circulating in donor plasma. This was true in renal and cardiac transplantation and in recipients with peak viral loads ranging between 2.9 and 6.6 log10 IU/mL. The permissive transmission process characterized here contrasts sharply with sexual or injection-related transmission, which occurs less frequently per exposure and is generally associated with a stringent genetic bottleneck. These findings highlight the effectiveness of current anti-HCV regimens, while raising caution regarding the substantially higher multiplicity of infection seen in organ transplantation-associated HCV acquisition.
A TROUBLESOME ENTEROSCOPIC ATTEMPT TO REMOVE MIGRATED BILIARY STENTS IN THE SMALL BOWEL IN A PATIENT WITH ALTERED ANATOMY
Authors: P Cortegoso Valdivia, L Venezia, M Pennazio
Journal: Endoscopy (2019)

The management of migrated stents is variable and is generally dictated by the site, type of stent, and anticipated likelihood of complications. Enteroscopy can be useful for stents migrated deeply in the small bowel, although very challenging especially in patients with altered anatomy.
Pravastatin combination with sorafenib does not improve survival in advanced hepatocellular carcinoma
Authors: Jean-Louis Jouve, Thierry Lecomte, Olivier Bouché, Emilie Barbier, Faiza Khemissa Akouz, Ghassan Riachi, Eric Nguyen Khac, Isabelle Ollivier-Hourmand, Maryline Debette-Gratien, Roger Faroux, Anne-Laure Villing, Julien Vergniol, Jean-François Ramee, Jean-Pierre Bronowicki, Jean-François Seitz, Jean-Louis Legoux, Jacques Denis, Sylvain Manfredi, Jean-Marc Phelip
Journal: Journal of Hepatology (2019)
Oral submucous fibrosis: A global challenge. Rising incidence, risk factors, management, and research priorities
Authors: Jay Gopal Ray, Raghunath Chatterjee, Keya Chaudhuri
Journal: Periodontology 2000 (2019)

Abstract Oral submucous fibrosis is a potentially malignant disorder of the oral cavity, with a high rate of malignant transformation. It is very common among habitual areca nut chewers. The pathogenesis of oral submucous fibrosis is not well established, but it is believed to be a disease of multifactorial origin, including areca nut chewing, ingestion of chilies, genetic factors, immunologic processes and nutritional deficiencies. Genetically susceptible individuals when exposed to areca nut chewing develop this disease over a variable period of time. Oral submucous fibrosis is considered to be a disease of collagen metabolism. Several genetic factors are reported but there is no consensus about the exact mechanism of disease initiation. Variations in histopathological presentation are noted among oral submucous fibrosis patients with habitual areca nut chewing in different forms and other additive agents, eg betel quid, pan masala and gutkha, together with a variety of tobacco habits. The role of epigenetic modifications, such as mi RNA regulation, and DNA methylation is also being reported as part of the pathogenesis of oral submucous fibrosis. A combined approach, including analysis of genetic and epigenetic regulations with different habits, might be helpful to better understand the contributory factors and pathogenesis of this serious disorder.