tbuckley/cabot-search huggingface dataset:
Abstract I26: Investigating the immune microenvironment in mouse models of pancreatic cancer
Authors: Karen Pickering, Laura Lapienyte, Saadia Karim, Douglas Strathdee, Owen Sansom, Jen Morton
Journal: Cancer Research (2019)

Abstract Pancreatic cancer is predicted to become the second most common cause of cancer death in the Western world by ~2025. The focus of our research has been to better understand the disease and identify more effective and targeted therapies, in particular, using genetically engineered mouse models, which develop pancreatic tumors reminiscent of the human disease including development of a complex microenvironment. The pancreatic cancer microenvironment is characterized by significant infiltration of immune cells, but a distinct lack of T cells. Thus, immunotherapies have had little efficacy in PC despite promise in other cancers. Recent data have suggested that genomic instability and increased mutation burden may predict the efficacy of immune checkpoint inhibitors. To investigate this, we have generated a model of APOBEC mutagenesis in pancreatic cancer. The APOBEC family of cytidine deaminase enzymes, whose normal function is to protect from viral infections, have been revealed as drivers of mutation in a variety of human tumors, including pancreatic cancer. We have engineered mice to express Cre-inducible APOBEC3B and crossed these with the KPC genetically engineered mouse model of pancreatic cancer. We find that overexpressing APOBEC3B results in a poorer prognosis in these animals and some changes in the immune microenvironment. We are currently performing genomic and transcriptomic analyses to determine mutational burden and tumor subtype in an effort to identify therapeutic opportunities in patients bearing this signature. In contrast with T cells, recent studies have suggested that B cells may be tumor promoting in pancreatic cancer. However, clinical trials targeting B cells have been conducted recently and the results have been very disappointing. We have now generated an autochthonous model of B-cell depletion and find that B cells are not tumor promoting in this setting. We are now investigating the mechanisms behind this and the microenvironmental differences that are observed in spontaneous versus allograft models. Citation Format: Karen Pickering, Laura Lapienyte, Saadia Karim, Douglas Strathdee, Owen Sansom, Jen Morton. Investigating the immune microenvironment in mouse models of pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr I26.
Percutaneous coronary angioplasty versus coronary artery bypass grafting in the treatment of unprotected left main stenosis: updated 5-year outcomes from the randomised, non-inferiority NOBLE trial
Authors: Niels R Holm, Timo Mäkikallio, M Mitchell Lindsay, Mark S Spence, Andrejs Erglis, Ian B A Menown, Thor Trovik, Thomas Kellerth, Gintaras Kalinauskas, Lone Juul Hune Mogensen, Per H Nielsen, Matti Niemelä, Jens F Lassen, Keith Oldroyd, Geoffrey Berg, Peteris Stradins, Simon J Walsh, Alastair N J Graham, Petter C Endresen, Ole Fröbert, Uday Trivedi, Vesa Anttila, David Hildick-Smith, Leif Thuesen, Evald H Christiansen, Niels R Holm, Timo Mäkikallio, Mitchell Lindsay, Mark S Spence, Andrejs Erglis, Ian B A Menown, Thor Trovik, Markku Eskola, Hannu Romppanen, Tholmas Kellerth, Lisette O Jensen, Gintaras Kalinauskas, Rikard B A Linder, Markku Pentikainen, Anders Hervold, Adrian Banning, Azfar Zaman, James Cotton, Erlend Eriksen, Sulev Margus, Lone J H Mogensen, Per H Nielsen, Matti Niemelä, Kari Kervinen, Jens F Lassen, Keith Oldroyd, Geoff Berg, Simon J Walsh, Colm G Hanratty, Indulis Kumsars, Peteris Stradins, Terje K Steigen, Ole Fröbert, Alastair NJ Graham, Petter C Endresen, Matthias Corbascio, Olli Kajander, Uday Trivedi, Juha Hartikainen, Ves Anttila, David Hildick-Smith, Leif Thuesen, Evald H Christiansen
Journal: The Lancet (2019)
Ultra‐Early Diagnosis of Acute Myocardial Infarction in Rats Using Ultrasound Imaging of Hollow Double‐Layer Silica Nanospheres
Authors: Mengzhe Guo, Wencheng Du, Nan Lyu, Xi Chen, Yan Du, Haibo Wang, Dongzhi Yang, Shihua Wu, Jun Liang, Yuanjiang Pan, Daoquan Tang
Journal: Advanced Healthcare Materials (2019)

Timely diagnosis of acute myocardial infarction (AMI) strongly impacts the survival rate of patients. The authors report the development of a two-shell hollow silica contrast agent useful for ultrasound (US) imaging, which is able to provide ultra-early diagnosis of AMI. To target the characterization of fast blood flow and high blood pressure in the heart, two shells of hollow silica are adopted with opposite polarities, which assemble based on amino and perfluorodecyl silanes. The external amino silane facilitates the attachment of disease-targeted groups, while the internal perfluorodecyl silane provides great US imaging contrast. The material also possesses superior water dispersity, controllable morphology, low toxicity, and biodegradability both in vitro and in vivo, thus promoting its applications in the ultra-early diagnosis of AMI in rats, and is particularly useful for delineation of myocardial necrosis sites.
Abstract B52: The T-cell architecture of pancreatic ductal adenocarcinoma
Authors: Shivan Sivakumar, Enas Abu Shah, David Ahern, Nagina Mangal, Srikanth Reddy, Aniko Rendek, Zahir Soonawalla, Michael Silva, Mark Middleton, Michael Dustin
Journal: Cancer Research (2019)

Abstract Pancreatic cancer has the worst prognosis of any human malignancy. Our recent work has shown that immune infiltrate by transcriptomics and histopathology can predict prognosis after a Whipple’s operation, with lymphocyte infiltration being the most important prognostic marker. We have profiled T cells within primary pancreatic cancer to understand the T-cell architecture within the tumor. We have used a 37-marker T cell-focused panel to study the immune infiltrate. We see a diverse immunosuppressive immune microenvironment within the primary tumor. There is a complex architecture of macrophages, neutrophils, and T cells. The commonest CD4 T cells in the microenvironment are Tregs. There are potential novel therapeutic strategies for Tregs using unique checkpoint inhibitors. The CD8 T cells have PD-1 activity but are not activated or proliferating. The poor prognosis of pancreatic cancer could be explained by the immunosuppressive microenvironment, but there are opportunities to drug Tregs in this disease. Citation Format: Shivan Sivakumar, Enas Abu Shah, David Ahern, Nagina Mangal, Srikanth Reddy, Aniko Rendek, Zahir Soonawalla, Michael Silva, Mark Middleton, Michael Dustin. The T-cell architecture of pancreatic ductal adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B52.
Birth month, birth season, and overall and cardiovascular disease mortality in US women: prospective cohort study
Authors: Yin Zhang, Elizabeth E Devore, Susanne Strohmaier, Francine Grodstein, Eva S Schernhammer
Journal: BMJ (2019)

Abstract Objectives To evaluate the associations between birth month, birth season, and overall and cardiovascular disease mortality, and to examine the role of familial and socioeconomic factors in these associations. Design Prospective cohort study. Setting Nurses’ Health Study, established in 1976, an ongoing prospective cohort study in the United States. Participants Female registered nurses who reported information on date of birth at study enrolment (n=116 911, 1976-2014, followed for 38 years). Exposure Birth month and astronomical birth season (based on solstices and equinoxes as boundaries of the season categories). Main outcome measures Age and various multivariable adjusted hazard ratios and 95% confidence intervals for the association between birth months (using November as the reference), astronomical birth season (using autumn as the reference), and overall and cardiovascular disease specific mortality were assessed using Cox proportional hazards models. Results Among study participants, 43 248 overall deaths were documented during 4 136 364 person years of follow-up since enrolment, including 8360 cardiovascular disease related deaths. In fully adjusted multivariable analyses, no significant association was observed between birth month, birth season, and overall mortality. Compared with women born in November, increased cardiovascular disease mortality was observed among those born from March to July (hazard ratio for March, 1.09, 95% confidence interval 0.98 to 1.21; April, 1.12, 1.00 to 1.24; May, 1.08, 0.98 to 1.20; June, 1.07, 0.96 to 1.19; and July 1.08, 0.98 to 1.20). Those born in April had the highest cardiovascular disease mortality, and those born in December had the lowest (December, 0.95, 0.85 to 1.06). The relative difference between the lowest and highest risk month was 17.89%. Women born in spring (1.10, 1.04 to 1.17) and summer (1.09, 1.03 to 1.16) had a higher cardiovascular disease mortality than women born in the autumn. Adjustment for familial and socioeconomic factors did not change these results. The relative difference between the lowest and highest risk season was 10.00%. Conclusion Participants born in the spring and summer (especially those born in March-July) had a slight but significant increase in cardiovascular disease specific mortality. However, no seasonal birth month effect was observed among women for overall mortality. Familial and socioeconomic factors did not appear to alter these associations. Further studies are required to confirm these findings and reveal mechanisms of these seasonal birth month effects in cardiovascular disease mortality.
Behavioral Conceptualization and Treatment of Chronic Pain
Authors: Johan W.S. Vlaeyen, Geert Crombez
Journal: Annual Review of Clinical Psychology (2019)

Pain is considered a hardwired signal of bodily disturbance belonging to a basic motivational system that urges the individual to act and to restore the body's integrity, rather than just a sensory and emotional experience. Given its eminent survival value, pain is a strong motivator for learning. Response to repeated pain increases when harm risks are high (sensitization) and decreases in the absence of such risks (habituation). Discovering relations between pain and other events provides the possibility to predict (Pavlovian conditioning) and control (operant conditioning) harmful events. Avoidance is adaptive in the short term but paradoxically may have detrimental long-term effects. Pain and pain-related responses compete with other demands in the environment. Exposure-based treatments share the aim of facilitating or restoring the pursuit of individual valued life goals in the face of persistent pain, and further improvements in pain treatment may require a paradigm shift toward more personalized approaches.
Safety and efficacy of allogeneic stem cell transplantation after nivolumab therapy for patients with relapsed/refractory classical Hodgkin lymphoma
Authors: A. Beynarovich, K. Lepik, N. Mikhailova, E. Kondakova, Y. Zalyalov, I. Moiseev, B. Afanasyev
Journal: Annals of Oncology (2019)
A personalised approach for anti-GITR-based immunotherapy in pre-clinical models of pancreatic ductal adenocarcinoma
Authors: K. Desai, C. Ragulan, P.V. Lawrence, S. Wullschleger, M.L. Tichet, G. Box, E. Fontana, K. Young, J.M.J. Larkin, D. Hanahan, D. Cunningham, N. Starling, A. Sadanandam
Journal: Annals of Oncology (2019)
Challenges abound for women’s sexual and reproductive rights
Authors: Rojita Adhikari
Journal: BMJ (2019)

Health leaders gathered at the second International Conference on Population and Development in Nairobi last month to discuss how to improve women’s sexual and reproductive health. At the meeting <b>Rojita Adhikari</b> talked to Herminia Palacio, newly appointed president of the Guttmacher Institute, about the challenges and possibilities
Lymphatic remodelling in response to lymphatic injury in the hind limbs of sheep
Authors: Tyler S. Nelson, Zhanna Nepiyushchikh, Joshua S. T. Hooks, Mohammad S. Razavi, Tristan Lewis, Cristina C. Clement, Merrilee Thoresen, Matthew T. Cribb, Mindy K. Ross, Rudolph L. Gleason, Laura Santambrogio, John F. Peroni, J. Brandon Dixon
Journal: Nature Biomedical Engineering (2019)
Alginate microencapsulated human hepatocytes for the treatment of acute liver failure in children
Authors: Anil Dhawan, Nataruks Chaijitraruch, Emer Fitzpatrick, Sanjay Bansal, Celine Filippi, Sharon C. Lehec, Nigel D. Heaton, Pauline Kane, Anita Verma, Robin D. Hughes, Ragai R. Mitry
Journal: Journal of Hepatology (2019)
BELA trial update: Bosutinib (BOS) versus imatinib (IM) in patients (pts) with newly diagnosed chronic phase chronic myeloid leukemia (CP CML) after 30 months of follow-up.
Authors: Carlo Gambacorti-Passerini, Jeffrey Howard Lipton, Goh Yeow Tee, Luis Felipe Casado, Andrey Zaritskey, Philipp D. le Coutre, Ladan Duvillie, Dmitri Pavlov, Athena Maria Countouriotis, Jennifer Byrne
Journal: Journal of Clinical Oncology (2012)

6512 Background: The BELA study compared the efficacy and safety of BOS (dual Src/Abl kinase inhibitor) with IM in newly diagnosed CP CML. Methods: 502 pts with newly diagnosed CP CML were randomized to BOS 500 mg/d (n = 250) or IM 400 mg/d (n = 252) and stratified by Sokal risk group and geographic region. Efficacy analyses included all randomized pts (ITT); safety analyses included all treated pts (BOS, n = 248; IM, n = 251). Data described below are for ≥24 mo of follow-up; updated data for ≥30 mo of follow-up will be presented. Results: Median treatment duration was 27.5 mo in both cohorts; 63% of BOS pts and 71% of IM pts were still receiving treatment. The primary reason for BOS discontinuation was a treatment-emergent adverse event (TEAE; 24% vs 7% with IM); the primary reason for IM discontinuation was disease progression (13% vs 4% with BOS). Cumulative complete cytogenetic response (CCyR) rates by 24 mo were 79% for BOS and 80% for IM. Cumulative major molecular response (MMR) rates by 24 mo were 59% for BOS and 49% for IM (P = 0.019), including 16% and 12% of pts with complete molecular response (4.0-log sensitivity). On-treatment transformation to accelerated/blast phase occurred in 4 (2%) BOS pts and 13 (5%) IM pts. Deaths were reported for 7 BOS pts (6 due to CML progression) and 13 IM pts (10 due to CML progression); 24-mo Kaplan-Meier overall survival estimates were 97% (BOS) and 95% (IM). BOS was associated with higher incidences of gastrointestinal events than IM (diarrhea [70% vs 25%], vomiting [32% vs 16%]; primarily transient), but lower incidences of edema (13% vs 40%) and musculoskeletal events (cramps [4% vs 22%], bone pain [4% vs 10%]). Grade ≥3 TEAEs in ≥2% of BOS or IM pts were diarrhea (12% vs 1%), vomiting (3% vs 0%), and rash (2% vs 1%). Grade ≥3 lab abnormalities (≥15% of pts) with BOS and IM were neutropenia (10% vs 24%), thrombocytopenia (14% vs 15%), elevated alanine aminotransferase (23% vs 4%), and hypophosphatemia (6% vs 20%). Conclusions: BOS was effective for newly diagnosed CP CML and had a distinct toxicity profile. With continued follow-up both on-treatment transformation to accelerated/blast phase and overall survival continue to favor BOS versus IM.
Mutation-Specific Dominant Negative Effects Determine the Phenotype in SRP54 Deficiency
Authors: Christoph Schuerch, Thorsten Schaefer, Joelle S. Müller, Pauline Hanns, Jonas Schärer, Julia Skokowa, Karl Welte, Raphael Carapito, Seiamak Bahram, Martina Konantz, Claudia Lengerke
Journal: Blood (2019)
Sport and exercise genomics: the FIMS 2019 consensus statement update
Authors: Kumpei Tanisawa, Guan Wang, Jane Seto, Ioanna Verdouka, Richard Twycross-Lewis, Antonia Karanikolou, Masashi Tanaka, Mats Borjesson, Luigi Di Luigi, Michiko Dohi, Bernd Wolfarth, Jeroen Swart, James Lee John Bilzon, Victoriya Badtieva, Theodora Papadopoulou, Maurizio Casasco, Michael Geistlinger, Norbert Bachl, Fabio Pigozzi, Yannis Pitsiladis
Journal: British Journal of Sports Medicine (2020)

Rapid advances in technologies in the field of genomics such as high throughput DNA sequencing, big data processing by machine learning algorithms and gene-editing techniques are expected to make precision medicine and gene-therapy a greater reality. However, this development will raise many important new issues, including ethical, moral, social and privacy issues. The field of exercise genomics has also advanced by incorporating these innovative technologies. There is therefore an urgent need for guiding references for sport and exercise genomics to allow the necessary advancements in this field of sport and exercise medicine, while protecting athletes from any invasion of privacy and misuse of their genomic information. Here, we update a previous consensus and develop a guiding reference for sport and exercise genomics based on a SWOT (Strengths, Weaknesses, Opportunities and Threats) analysis. This SWOT analysis and the developed guiding reference highlight the need for scientists/clinicians to be well-versed in ethics and data protection policy to advance sport and exercise genomics without compromising the privacy of athletes and the efforts of international sports federations. Conducting research based on the present guiding reference will mitigate to a great extent the risks brought about by inappropriate use of genomic information and allow further development of sport and exercise genomics in accordance with best ethical standards and international data protection principles and policies. This guiding reference should regularly be updated on the basis of new information emerging from the area of sport and exercise medicine as well as from the developments and challenges in genomics of health and disease in general in order to best protect the athletes, patients and all other relevant stakeholders.
Wash your hands, Brother John!
Authors: Nisha Thampi, Lekha N Villeneuve, Yves Longtin
Journal: BMJ (2019)

Use of a six step hand hygiene technique as recommended by the World Health Organization is important to ensure thorough cleansing of hands, but learning and memorising the steps is a major barrier to its adoption. We hereby describe a musical mnemonic based on the popular nursery rhyme “Brother John” (also known as “Frère Jacques”) that can help learning and remembering of the proper technique.
Systematic meta-analyses, field synopsis and global assessment of the evidence of genetic association studies in colorectal cancer
Authors: Zahra Montazeri, Xue Li, Christine Nyiraneza, Xiangyu Ma, Maria Timofeeva, Victoria Svinti, Xiangrui Meng, Yazhou He, Yacong Bo, Samuel Morgan, Sergi Castellví-Bel, Clara Ruiz-Ponte, Ceres Fernández-Rozadilla, Ángel Carracedo, Antoni Castells, Timothy Bishop, Daniel Buchanan, Mark A Jenkins, Temitope O Keku, Annika Lindblom, Fränzel J B van Duijnhoven, Anna Wu, Susan M Farrington, Malcolm G Dunlop, Harry Campbell, Evropi Theodoratou, Wei Zheng, Julian Little
Journal: Gut (2019)

To provide an understanding of the role of common genetic variations in colorectal cancer (CRC) risk, we report an updated field synopsis and comprehensive assessment of evidence to catalogue all genetic markers for CRC (CRCgene2).
Abstract 122: The Role of Plasma Lysophosphatidylcholine in Patients With Out-of-Hospital Cardiac Arrest
Authors: Tsukasa Yagi, Tai Yin, Koichiro Shinozaki, Lance B Becker, Junhwan Kim
Journal: Circulation (2018)

Background: Phosphatidylcholine (PC) is the most abundant class of phospholipid found in plasma. Lysophosphatidylcholine (LPC), PC missing one acyl chain, is believed to be the main carrier of polyunsaturated fatty acids (PUFAs) to the brain. The continuous supply of PUFAs, such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and arachidonic acid (AA), are important to maintain proper function of the brain. Therefore, alterations in the plasma levels of LPC containing these fatty acids, LPC-EPA, LPC-DHA, and LPC-AA, indicate impaired delivery of fatty acids, which in turn may indicate abnormal brain function. Numerous animal studies have found altered LPC compositions in Alzheimer’s disease, cognitive impairment, brain ischemia, and aging. Moreover, administration of LPC has been shown to improve brain function in these pathological conditions. Since brain damage is the main cause of death in cardiac arrest, altered LPC profiles may be indicative of brain damage and also play a role in the recovery of brain function. The aim of this study was to measure the content of plasma LPC species in out-of-hospital cardiac arrest (OHCA) patients compared to healthy controls. Methods: Blood samples were obtained from 11 OHCA patients, who were admitted to Northshore University Hospital and achieved return of spontaneous circulation. Within 4 h of drawing, plasma was separated from the whole blood using centrifugation and stored at -80°C. Control samples were obtained from 19 healthy volunteers. The contents of LPC species were measured using LC-mass spectrometry. Results: We found the overall content of LPC is significantly lower in OHCA patients. The decrease is found in all species of LPC, including LPC-EPA (patients vs Controls = 0.17 vs 0.55 μmol/L, p=0.003), LPC-DHA (patients vs Controls = 0.47 vs 1.72 μmol/L, p=0.003), and LPC-AA (patients vs Controls = 1.98 vs 5.39 μmol/L, p&lt;0.001). We also found decreased in LPC species containing saturated fatty acids, showing the decrease was not specific to PUFAs. Conclusion: We found OHCA patients have a significantly lower plasma LPC content. Understanding the detailed mechanism for this decrease and the role that LPC plays in the recovery of patients after OHCA requires more investigation.
The VLA-4 Integrin Is Constitutively Activated in a Fraction of CD49d-Expressing Chronic Lymphocytic Leukemia Via Autonomous BCR-Mediated Signaling
Authors: Erika Tissino, Tamara Bittolo, Dania Benedetti, Riccardo Bomben, Andrea Härzschel, Palash Maity, Gabriela Forestieri, Antonella Nicolò, Moumita Datta, Enrico Santinelli, Francesca Maria Rossi, Alexandre Chigaev, Larry A. Sklar, Francesco Zaja, Gabriele Pozzato, Pietro Bulian, Giovanni Francesco D'Arena, Annalisa Chiarenza, Francesco Di Raimondo, Hassan Jumaa, Davide Rossi, Giovanni Del Poeta, Tanja Nicole Hartmann, Antonella Zucchetto, Valter Gattei
Journal: Blood (2019)
LRBA deficiency: a new genetic cause of monogenic lupus
Authors: Bernadete L Liphaus, Iris Caramalho, Andreia Rangel-Santos, Clóvis A Silva, Jocelyne Demengeot, Magda Maria Salles Carneiro-Sampaio
Journal: Annals of the Rheumatic Diseases (2019)

Juvenile systemic lupus erythematosus (JSLE) is considered a polygenic disease, although identified causes of monogenic SLE and lupus-like syndrome are enlarging.1 2 The genetic basis of polyautoimmune syndromes is also being elucidated, now including lipopolysaccharide-responsive beige-like anchor (LRBA) deficiencies.3 We report a patient carrying a new deleterious LRBA mutation that associates with JSLE .

The patient, a girl born from healthy consanguineous parents, presented recurrent respiratory infections since 1 year of age, and since 7 years of age, chronic non-bloody diarrhoea diagnosed as non-specific colitis, IgA deficiency (<1.0 mg/dL) and arthralgia. At 10 years of age, laboratory tests revealed normal C1q, C2, C3, C4, CH50 and lymphocyte counts, homogeneous antinuclear antibody (ANA; HEp-2 1/640) and negative anti-dsDNA. Six months later, she presented respiratory distress, acute diarrhoea, pericardial effusion, serum glucose of 724 mg/dL, positive anti-IAA (42 IU/mL), and type 1 diabetes (T1D) was diagnosed. When 11 years of age, she clearly fulfilled the American College of Rheumatology 1997 SLE classification criteria by presenting polyarthritis, pericarditis, autoimmune haemolytic anaemia, alopecia, persistent malar rash, homogeneous ANA (1/1280), positive anti-dsDNA (119 IU/mL, ELISA, confirmed by Crithidia luciliae ), anticardiolipin IgG, anti-thyroglobulin and anti-thyroid peroxidase. Prednisone and …