tbuckley/cabot-search huggingface dataset:
Water activity does not shape the microbiota in the human colon
Authors: Doris Vandeputte, Gwen Falony, Kevin D'hoe, Sara Vieira-Silva, Jeroen Raes
Journal: Gut (2017)

We recently reported an association between stool consistency as measured by the Bristol Stool Scale (BSS) and major markers of the gut ecosystem, including microbial richness, enterotypes and bacterial growth rates in 53 healthy women.1 Meanwhile, the link between stool consistency and colon microbiota composition has been confirmed in two large-scale (n>1000) cohorts including individuals of both sexes, different age and varying health statuses.2 ,3 In our original manuscript, we hypothesised on mechanisms that would explain the associations observed. Two potential mechanisms were put forward, namely colon ecosystem differentiation through passage rate variation and reduction of water availability. While the impact of passage rate on ecosystem composition has recently been shown to partially account for BSS-associated microbiota variation,4 the potential correlation with water availability remains unexplored.

Water activity (aw) is a dimensionless variable that reflects …
MA11.02 Mutational Burden in Pulmonary Neuroendocrine Tumors (puNETs)
Authors: Ivana Sullivan, Myriam Kossai, Gwénaël Le Teuff, Marc Deloger, Nicolas Dorvault, Letizia Gianoncelli, Vincent De Montpreville, Bastien Job, Maria Bluthgen, Benjamin Besse, Jean-Charles Soria, Julien Adam, Jean-Yves Scoazec, Eric Baudin, David Planchard
Journal: Journal of Thoracic Oncology (2017)
Improving Chimeric Antigen Receptor-Modified T Cell Function by Reversing the Immunosuppressive Tumor Microenvironment of Pancreatic Cancer
Authors: Somala Mohammed, Sujita Sukumaran, Pradip Bajgain, Norihiro Watanabe, Helen E. Heslop, Cliona M. Rooney, Malcolm K. Brenner, William E. Fisher, Ann M. Leen, Juan F. Vera
Journal: Molecular Therapy (2017)

The adoptive transfer of T cells redirected to tumor-associated antigens via transgenic expression of chimeric antigen receptors (CARs) has produced tumor responses, even in patients with refractory diseases. To target pancreatic cancer, we generated CAR T cells directed against prostate stem cell antigen (PSCA) and demonstrated specific tumor lysis. However, pancreatic tumors employ immune evasion strategies such as the production of inhibitory cytokines, which limit CAR T cell persistence and function. Thus, to protect our cells from the immunosuppressive cytokine IL-4, we generated an inverted cytokine receptor in which the IL-4 receptor exodomain was fused to the IL-7 receptor endodomain (4/7 ICR). Transgenic expression of this molecule in CAR-PSCA T cells should invert the inhibitory effects of tumor-derived IL-4 and instead promote T cell proliferation. We now demonstrate the suppressed activity of CAR T cells in tumor-milieu conditions and the ability of CAR/ICR T cells to thrive in an IL-4-rich microenvironment, resulting in enhanced antitumor activity. Importantly, CAR/ICR T cells remained both antigen and cytokine dependent. These findings support the benefit of combining the 4/7 ICR with CAR-PSCA to treat pancreatic cancer, a PSCA-expressing tumor characterized by a dense immunosuppressive environment rich in IL-4.
S118 Can fractional exhaled nitric oxide help predict asthma in british foundry workers?
Authors: RE Wiggans, E Robinson, J Sumner, A Codling, L Lewis, CM Barber
Journal: Thorax (2016)

<h3>Background</h3> Foundry work may involve exposure to respiratory sensitisers and irritants. There is limited evidence for the use of FE<sub>NO</sub> in occupational settings, and particularly in foundries. <h3>Aim</h3> To examine the usefulness of FE<sub>NO</sub> in identifying foundry workers at risk of asthma. <h3>Methods</h3> Foundry workers undertook a respiratory questionnaire. Spirometry (­­Ndd Easy on-PC Spirometer, Zurich) and FE<sub>NO</sub> (NOBreath, Bedfont Scientific, Kent) were measured to ATS/ERS standards. The ATS upper limit of normal (ULN) of 50 parts per billion (ppb), or 45.9ppb for current smokers, determined the high FE<sub>NO</sub> category (FE<sub>NO</sub> &gt;ULN). Workers with FE<sub>NO</sub> &gt;ULN were compared with those with at least one work-related respiratory symptom (WRRS) and those with obstructive lung function (FEV<sub>1</sub>/FVC &lt;0.7) using Chi Square and Fisher’s Exact Tests. <h3>Results</h3> 351 workers (350 men, 99%) participated. 350 workers had a valid FE<sub>NO</sub> performed. Arithmetic mean FE<sub>NO</sub> was 30.2ppb (95% CI: 27.3–33.2); geometric mean (GM) FE<sub>NO</sub>20.8 (18.9–22.9) ppb. FE<sub>NO</sub> exceeded the ULN in 61 (17%) workers. Average age for the FE<sub>NO</sub> &gt;ULN group was 41.5 (95% CI: 38.3–44.7), with a mean of 15.8 (12.4 – 19.2) years working in the foundry industry. Workers in the FE<sub>NO</sub> &gt;ULN group were significantly more likely to have a current diagnosis of asthma (12% vs 5%, p &lt; 0.05), have ever suffered allergies (55% vs 31%, p &lt; 0.01), or report work-related shortness of breath (3% vs 0%, p &lt; 0.05). Fourteen workers (4%) had a FE<sub>NO</sub> &gt;ULN and WRRS (Figure1). Of these 14, only 2 (14%) had a current diagnosis of asthma (Fisher’s p = 0.20). Eight (2%) workers had a FE<sub>NO</sub> &gt; ULN and FEV<sub>1</sub>/FVC &lt;0.7, though only 2 (25%) had a current asthma diagnosis (Fisher’s p = 0.08). <h3>Conclusion</h3> A significant proportion of foundry workers have FE<sub>NO</sub> levels that exceed the ATS cut point for likely eosinophilic airway inflammation. Of these workers, most had a raised FE<sub>NO</sub> but no WRRS or obstructive lung disease. Only a minority of workers with FE<sub>NO</sub> &gt;ULN and either WRRS or obstruction had a current diagnosis of asthma. FE<sub>NO</sub> may be useful in identifying foundry workers at risk of asthma and warrants further study.
P2.03b-092 Predictive and Prognostic Effect of Circulating Tumor Cells in Non-Small Cell Lung Cancer Treated with Targeted Therapy
Authors: Chunxia Su, Xuefei Li, Tao Jiang, Jing Zhao, Chao Zhao, Wenchen Zhao, Jiqiao Shen, Shengxiang Ren, Caicun Zhou
Journal: Journal of Thoracic Oncology (2017)
A pilot trial of chronic low-dosegranulocyte-macrophage colony-stimulating factor therapy in patients with intensively pretreated breast or female genital tract cancer
Authors: C. M. Kurbacher, E.-M. Cramer, K. Rhiem, P. K. Mallmann, I. A. Cree
Journal: Journal of Clinical Oncology (2004)

2537 Background: Prolonged low-dose (PLD) granulocyte-macrophage colony-stimulating factor (GM-CSF) treatment which stimulates dendritic cell differentiation has been successfully used in patients (pts) with stage III-IV melanoma. However, data of PLD GM-CSF therapy in other tumors are still lacking. This pilot trial was thus initiated in order to evaluate both the efficacy and tolerabilty of PLD GM-CSF in pts with various heavily pretreated solid malignancies. Methods: 16 pts failing 2–7 prior (median, 4) chemotherapies were included with: metastatic breast cancer (MBC), n=6; recurrent ovarian carcinoma (ROC), n=8; metastatic endometrial carcinoma (MEC), n=1; recurrent cervical cancer (RCC, n=1). PLD GM-CSF (Leukine®) was delivered subcutaneously at a daily starting dose of 125 μg. The treatment was monitored by weekly whole blood cell counts (WBC). GM-CSF was increased at 25 μg increments until a maximum of 200 μg or when mild leukocytosis (i. e. 10–20 G/l) was achieved. Therapy was continued until progression or refusal by the pts. Response was assessed using either the common ECOG score (in 13 pts with measurable disease) or the Rustin criteria for CA 125-positive ROC (n=3). Results: All pts are evaluable for toxicity which was generally mild. In 2 pts, temporary dose-reduction was necessary due to mild skin reactions, which recovered spontaneously. Mild to moderate leucytosis was obvious in 7 pts. Hypersensitivity-like reactions did not occur nor did any pt require hospitalization to other life-threatening side effects. The objective response rate was 38% with 1 CR, 5 PR, 3 SD, and 7 PD. Response-duration ranged between 2 and 13 months, respectively. Until today, 8 pts are still alive. Notably, 5 of 6 responders but only 1 of 7 pts with PD developed leukocytosis during therapy. Conclusion: PLD GM-CSF exhibits substantial activity in heavily pretreated patients with either MBC or female genital tract cancer with mild leukocytosis being a potential predictor of response. Large-scaled clinical trials are now warranted to define the exact clinical value of this promising new strategy. No significant financial relationships to disclose.
Treating Depression in the Myeloproliferative Neoplasms: The Role and Implications of Poorly Controlled Symptoms and Psychosocial Factors
Authors: Robyn M. Scherber, Zhenya Senyak, Heidi E. Kosiorek, Amylou C. Dueck, Matthew M Clark, Michael Boxer, Michael A. Goldstein, Mary Cotter, Archie McCallister, Barbara VanHusen, Claire N. Harrison, Ruben A. Mesa
Journal: Blood (2016)
P2.02-010 Prognosis Impact of Oligoprogression Following Definitive Chemo-Radiotherapy in Stage III Non-Small Cell Lung Cancer
Authors: Maria Saigi, Aj Rullan, Milana Bergamino Sirvén, Arturo Navarro-Martin, Ma Dolores Arnaiz, Ramon Palmero, Maria Plana, Jose Carlos Ruffinelli, Carles Mesia, Susana Padrones, Samantha Aso, Isabel Brao, Monica Arellano, Joana Saldaña, Valentin Navarro, Felipe Cardenal, Ernest Nadal
Journal: Journal of Thoracic Oncology (2017)
Innovative Approaches to Improve Anti-Infective Vaccine Efficacy
Authors: Michael R. Yeaman, John P. Hennessey
Journal: The Annual Review of Pharmacology and Toxicology (2017)

Safe and efficacious vaccines are arguably the most successful medical interventions of all time. Yet the ongoing discovery of new pathogens, along with emergence of antibiotic-resistant pathogens and a burgeoning population at risk of such infections, imposes unprecedented public health challenges. To meet these challenges, innovative strategies to discover and develop new or improved anti-infective vaccines are necessary. These approaches must intersect the most meaningful insights into protective immunity and advanced technologies with capabilities to deliver immunogens for optimal immune protection. This goal is considered through several recent advances in host-pathogen relationships, conceptual strides in vaccinology, and emerging technologies. Given a clear and growing risk of pandemic disease should the threat of infection go unmet, developing vaccines that optimize protective immunity against high-priority and antibiotic-resistant pathogens represents an urgent and unifying imperative.
Surveying opinions of 149 registrants to the Research Registry: Awareness of and attitudes towards research registration
Authors: Riaz A. Agha, Daniyal J. Jafree, Martinique Vella-Baldacchino, Christopher Limb, Ter-Er Kusu-Orkar, Mirabel C. Millip, Alexander J. Fowler
Journal: International Journal of Surgery (2017)
P1.07-009 Outcomes of Patients with Relapsed Small-Cell Lung Cancer Treated with Paclitaxel plus Gemcitabine. 10 Year-Analysis
Authors: Ana Laura Ortega Granados, Natalia Luque Caro, Juan Francisco Marín Pozo, Nuria Cárdenas Quesada, Francisco José García Verdejo, David Fernández Garay, Capilla De La Torre Cabrera, María Ruiz Sanjuan, Mónica Fernández Navarro, Carmen Rosa Garrido, Miguel Ángel Moreno Jiménez, Pedro Sánchez Rovira
Journal: Journal of Thoracic Oncology (2017)
P2.05-029 Microwave Thermal Therapy Enhances Radiosensitivity of Highly Invasive Human Non-Small Cell Lung Cancer H460 Cells via Inhibiting DNA Repair
Authors: Yanyan Zhao, Shirong Zhang, Zhibing Wu, Jingjing Zhang, Lucheng Zhu, Yasi Xu, Shenglin Ma
Journal: Journal of Thoracic Oncology (2017)
P4 A prospective assessment of the clinical utility of intercostal artery identification in pleural intervention
Authors: A Talwar, JP Corcoran, RJ Hallifax, J Wrightson, I Psallidas, NM Rahman
Journal: Thorax (2016)

<h3>Background</h3> Respiratory Specialists perform an increasing number of complex pleural procedures. With this comes a greater focus on patient safety and risk reduction. There is strong evidence that ultrasound guidance in procedure site selection for pleural effusion reduces organ puncture and pneumothorax, but it remains important to choose intervention sites to avoid the intercostal arteries (ICA). Previous data suggest that the ICA can follow a tortuous course especially in the elderly. The use of colour Doppler to identify intercostal and collateral arteries has been shown to be accurate in research studies and may assist in selecting a safe intervention site. This study aimed to prospectively assess identification of the ICA in routine practice and the effect on procedure site selection. <h3>Methods</h3> Data on identification of the ICA was prospectively collected as part of routine clinical care and documented in the pleural procedure records in a tertiary centre between July 2015 and July 2016. Successful identification of the ICA and its influence in choosing the procedure site was recorded. <h3>Results</h3> 404 procedures were carried out over the study period. The mean age of the patients was 69.3 years (sd 14.2). Identification of the ICA was attempted in 386 (95.5%) procedures and the ICA was identified within the intercostal space in 192 (49.7%) of cases. The site of the procedure was altered after ICA detection in 56/192 (29.2%) of procedures and in 16/32 (50.0%) of image guided pleural biopsies. In 7/192 (3.6%) procedures the ICA was identified in all rib spaces at potential intervention sites, leading to the procedure not being attempted. No complications related to post procedure haemorrhage were reported. A more detailed analysis of the identification of the ICA and its influence on practice by procedure type is shown in Table 1. <h3>Conclusion</h3> Screening for the ICA in routine clinical practice influences procedural site selection. In some cases identification can result in abandoning a procedure, which may have led to intercostal bleeding. Patient position and potential rib crowding may explain differences in the rates of successful identification between procedures. If these findings are replicated in larger prospective studies, identification of the ICA may become routine practice to maximise safety.
Sustained Control of Hemolysis and Symptoms and Reduced Transfusion Requirements over a Period of 2 Years in Paroxysmal Nocturnal Hemoglobinuria (PNH) with Eculizumab Therapy.
Authors: Anita Hill, Dupe Elebute, Judith C. Marsh, Stephen J. Richards, Bruce McNutt, Beth E. Petro, Russell P. Rother, Peter Hillmen
Journal: Blood (2004)
Effects of the Factor Xa Inhibitor Apixaban on Venous Thrombosis and Hemostasis in Rabbits.
Authors: Pancras C. Wong, Carol A. Watson, Earl J. Crain, Joseph M. Luettgen, Martin L. Ogletree, Ruth R. Wexler, Patrick Y.S. Lam, Donald J. Pinto, Robert M. Knabb
Journal: Blood (2006)
The effect of VISHRAM, a grass-roots community-based mental health programme, on the treatment gap for depression in rural communities in India: a population-based study
Authors: Rahul Shidhaye, Vaibhav Murhar, Siddharth Gangale, Luke Aldridge, Rahul Shastri, Rachana Parikh, Ritu Shrivastava, Suvarna Damle, Tasneem Raja, Abhijit Nadkarni, Vikram Patel
Journal: The Lancet Psychiatry (2017)
Protective role of endogenous plasmalogens against hepatic steatosis and steatohepatitis in mice
Authors: Jung Eun Jang, Han‐Sol Park, Hyun Ju Yoo, In‐Jeoung Baek, Ji Eun Yoon, Myoung Seok Ko, Ah‐Ram Kim, Hyoun Sik Kim, Hye‐Sun Park, Seung Eun Lee, Seung‐Whan Kim, Su Jung Kim, Jaechan Leem, Yu Mi Kang, Min Kyo Jung, Chan‐Gi Pack, Chong Jai Kim, Chang Ohk Sung, In‐Kyu Lee, Joong‐Yeol Park, José C. Fernández‐Checa, Eun Hee Koh, Ki‐Up Lee
Journal: Hepatology (2017)

Free cholesterol (FC) accumulation in the liver is an important pathogenic mechanism of nonalcoholic steatohepatitis (NASH). Plasmalogens, key structural components of the cell membrane, act as endogenous antioxidants and are primarily synthesized in the liver. However, the role of hepatic plasmalogens in metabolic liver disease is unclear. In this study, we found that hepatic levels of docosahexaenoic acid (DHA)‐containing plasmalogens, expression of glyceronephosphate O‐acyltransferase ( Gnpat ; the rate‐limiting enzyme in plasmalogen biosynthesis), and expression of Pparα were lower in mice with NASH caused by accumulation of FC in the liver. Cyclodextrin‐induced depletion of FC transactivated Δ‐6 desaturase by increasing sterol regulatory element‐binding protein 2 expression in cultured hepatocytes. DHA, the major product of Δ‐6 desaturase activation, activated GNPAT, thereby explaining the association between high hepatic FC and decreased Gnpat expression. Gnpat small interfering RNA treatment significantly decreased peroxisome proliferator‐activated receptor α ( Pparα ) expression in cultured hepatocytes. In addition to GNPAT, DHA activated PPARα and increased expression of Pparα and its target genes, suggesting that DHA in the DHA‐containing plasmalogens contributed to activation of PPARα. Accordingly, administration of the plasmalogen precursor, alkyl glycerol (AG), prevented hepatic steatosis and NASH through a PPARα‐dependent increase in fatty acid oxidation. Gnpat +/– mice were more susceptible to hepatic lipid accumulation and less responsive to the preventive effect of fluvastatin on NASH development, suggesting that endogenous plasmalogens prevent hepatic steatosis and NASH. Conclusion : Increased hepatic FC in animals with NASH decreased plasmalogens, thereby sensitizing animals to hepatocyte injury and NASH. Our findings uncover a novel link between hepatic FC and plasmalogen homeostasis through GNPAT regulation. Further study of AG or other agents that increase hepatic plasmalogen levels may identify novel therapeutic strategies against NASH. (H epatology 2017;66:416–431).
Ganglioside-Storage Diseases
Authors: John S. O'Brien
Journal: New England Journal of Medicine (1971)

FIVE ganglioside-storage diseases are now recognized (Table 1). All involve progressive mental and motor deterioration, with onset in childhood and ultimate fatal outcome, autosomal recessive inheritance, neuronal lipidosis secondary to storage of a specific ganglioside, storage of structurally related glycolipids, polysaccharides or glycoproteins, and absence or severe deficiency of specific lysosomal hydrolase enzymes. No treatment is available for these diseases other than palliative therapy. The most effective approach to their control is the detection of heterozygous carriers followed by family planning and the prenatal diagnosis of affected fetuses followed by selective abortion. Major features of each ganglioside-storage disease are listed . . .
Blocking Adhesion of Sickle Erythrocytes to Endothelial αVβ3 Using RNA Aptamer.
Authors: Jun-ichi Nishimura, Angela D. Burnette, Milena Batchvarova, Shahid M. Nimjee, Rahima Zennadi, Bruce A. Sullenger, Marilyn J. Telen
Journal: Blood (2006)
Treatment of Stage I-II A Non-Bulky Hodgkin's Lymphoma (HL): An Individual Patient-Data Comparison of German Hodgkin Study Group (GHSG) HD10 and HD11 Combined-Modality Therapy (CMT) and NCIC Clinical Trials Group (NCIC CTG) HD.6 ABVD Alone
Authors: Annette E. Hay, Beate Klimm, Bingshu E. Chen, Helen Goergen, Lois E. Shepherd, Michael Fuchs, Mary Gospodarowicz, Peter Borchmann, Joseph M. Connors, Jana Markova, Michael Crump, Andreas Lohri, Jane N. Winter, Bernd Dörken, Robert G. Pearcey, Volker Diehl, Sandra J. Horning, Hans Theodor Eich, Andreas Engert, Ralph M. Meyer
Journal: Blood (2012)
P1.05-074 Factors Predicting Discordance between Clinical and Surgical-Pathologic Staging in Operable Non-Small Cell Lung Cancer
Authors: Ioannis Koukis, Dimitra Grapsa, Periklis Tomos, Athanasia Papazafiropoulou, Anna Karakatsani, Ilias Kotteas, Andriani Charpidou, Kostas Syrigos
Journal: Journal of Thoracic Oncology (2017)
P96 Physiotherapy management of adult patients with cystic fibrosis on Intensive Care Units (ICU) – a survey of uk physiotherapists
Authors: F Cathcart, H Parrott, A Jones, N Simmonds
Journal: Thorax (2016)

<h3>Introduction and objectives</h3> Currently no guidelines or data exist on the physiotherapy management of adults with CF on the ICU. The aim was to explore the views and experiences of the specialist physiotherapists (SPs) managing adults with CF admitted to an ICU. <h3>Methods</h3> An online survey was designed which included questions (open and closed) on staff confidence, communication, learning needs, extracorporeal membrane oxygenation (ECMO) and end of life care. The survey was sent to CF, ICU and transplant SPs across the UK. <h3>Results</h3> 42 SPs responded (74% response rate), 52% (n = 22) adult CF, 40% (n = 17) ICU and 7% (n = 3) transplant specialists. 73% (n = 30) had been specialists in their area for &gt;5 years. 27% (n = 11) reported no CF admissions to their ICU in the last year, only 24% (n = 10) had &gt;3 in the last year. Physiotherapy care was shared between the ICU and CF SPs teams in 43% (n = 18) of respondents. 90% (n = 37) felt this joint working was essential to optimise patient care. On a confidence scale of 1 – 10 (1 = low, 10 = high) the median (IQR) confidence score of SPs to manage patients with CF on ICU was 7 (7–9). 43% (n = 17) had experienced pre transplant patients with CF being invasively ventilated and reported that the challenges included airway clearance, weaning, inhalation therapy and nursing staff education. Of the 17 respondents who worked in ECMO centres, 57% (n = 12) had never had a patient with CF on ECMO and 90% had no physiotherapy ECMO protocol. Reported challenges were mobilisation, chest clearance, inhalation therapy and palliative care. Of respondents 50% (n = 21) had managed a patient with CF who died on ICU. 79% (n = 33) of respondents wanted more education on managing patients with CF on ICU with comments around, joint training, national guidelines being developed and the importance of collaborative care. <h3>Conclusions</h3> The number of adults with CF admitted to ICU remains low nationally however SPs need to maintain competence and confidence in managing these complex patients. National, expert consensus guideline development, including a physiotherapy ECMO protocol would assist in ensuring equitable quality care in this setting.