tbuckley/cabot-search huggingface dataset:
Prefrontal cortical control of a brainstem social behavior circuit
Authors: Tamara B Franklin, Bianca A Silva, Zinaida Perova, Livia Marrone, Maria E Masferrer, Yang Zhan, Angie Kaplan, Louise Greetham, Violaine Verrechia, Andreas Halman, Sara Pagella, Alexei L Vyssotski, Anna Illarionova, Valery Grinevich, Tiago Branco, Cornelius T Gross
Journal: Nature Neuroscience (2017)
Nanomechanical sensor applied to blood culture pellets: a fast approach to determine the antibiotic susceptibility against agents of bloodstream infections
Authors: P. Stupar, O. Opota, G. Longo, G. Prod'hom, G. Dietler, G. Greub, S. Kasas
Journal: Clinical Microbiology and Infection (2017)

<h2>Abstract</h2><h3>Objectives</h3> The management of bloodstream infection, a life-threatening disease, largely relies on early detection of infecting microorganisms and accurate determination of their antibiotic susceptibility to reduce both mortality and morbidity. Recently we developed a new technique based on atomic force microscopy capable of detecting movements of biologic samples at the nanoscale. Such sensor is able to monitor the response of bacteria to antibiotic's pressure, allowing a fast and versatile susceptibility test. Furthermore, rapid preparation of a bacterial pellet from a positive blood culture can improve downstream characterization of the recovered pathogen as a result of the increased bacterial concentration obtained. <h3>Methods</h3> Using artificially inoculated blood cultures, we combined these two innovative procedures and validated them in double-blind experiments to determine the susceptibility and resistance of <i>Escherichia coli</i> strains (ATCC 25933 as susceptible and a characterized clinical isolate as resistant strain) towards a selection of antibiotics commonly used in clinical settings. <h3>Results</h3> On the basis of the variance of the sensor movements, we were able to positively discriminate the resistant from the susceptible <i>E. coli</i> strains in 16 of 17 blindly investigated cases. Furthermore, we defined a variance change threshold of 60% that discriminates susceptible from resistant strains. <h3>Conclusions</h3> By combining the nanomotion sensor with the rapid preparation method of blood culture pellets, we obtained an innovative, rapid and relatively accurate method for antibiotic susceptibility test directly from positive blood culture bottles, without the need for bacterial subculture.
P3.02c-009 Anti-VEGF and Anti-EGFR Reduce Malignant Pleural Effusion and Morbidity in an Experimental Adenocarcinoma Model
Authors: Lisete Teixeira, Milena Acencio, Vanessa Alvarenga, Gabriela Silva, Zenaide Brito, Sandra Fernezlian, Juliana Puka, Vanessa Martins, Vera Capelozzi
Journal: Journal of Thoracic Oncology (2017)
Initial Results of a Randomized Phase II Study of Low Dose Decitabine (DAC) Versus Low Dose Azacitidine (AZA) in Patients with Low- or Intermediate-1-Risk Myelodysplastic Syndromes (MDS)
Authors: Elias Jabbour, Koji Sasaki, Naval Daver, Naveen Pemmaraju, Courtney D. DiNardo, Tapan Kadia, Darla Miller, Victoria Sukholutsky, Xuelin Huang, Gautam Borthakur, Zeev Estrov, Hagop M. Kantarjian, Guillermo Garcia-Manero
Journal: Blood (2014)
Prognostic Markers in Core-Binding Factor Acute Myeloid Leukaemia
Authors: Ashvind A Prabahran, Mark Tacey, Shaun Fleming, Danielle Strong, Andrew Wei, Courtney Tate, Paula Marlton, Joel Wight, Andrew Grigg, Annabel Tuckfield, Jeff Szer, David S. Ritchie, Lynette C.Y. Chee
Journal: Blood (2015)
Gemcitabine pathway genotype analysis to predict toxicity in phase II gemcitabine monotherapy in heavily pre-treated metastatic breast cancer
Authors: H. C. Chung, S. Y. Rha, H. Jeung, Y. Choi, K. Park, J. Sohn, C. Kim, G. E. Kim, J. H. Yoo, Y. S. Kim
Journal: Journal of Clinical Oncology (2004)

2066 Background: We evaluated the efficacy and tolerability of gemcitabine monotherapy in heavily pretreated breast cancer patients, and the polymorphism of gemcitabine-related genes to elucidate the association with toxicity. We detected the polymorphism of deoxycytidine kinase (dCK), deoxycytidine deaminase (dCDA), and ribonucleotide reductase (RNR). Methods: A weekly infusion of gemcitabine at 850mg/m2 for 3 of every 4 weeks was introduced in patients who had failed previous doxorubicin and taxane. Treatment was delayed until leukopenia was recovered with G-CSF support without dose modification. The known polymorphism site of 3 genes were evaluated by CEQ™ 8000 Genetic Analysis System (Beckman): dCK(GG->GT), dCDA(AA->AG), RNR(CC-> CT, TT->TC) with genomic DNA of peripheral lymphocytes. Results: Of 51 enrolled patients, 47 were evaluable. Total 208 cycles were administered and the relative dose intensity was 89%. The response rate was 20%. Median response duration and overall survival were 8 and 12 months, respectively. The toxicity was mild with 14% of grade III neutropenia and 6% of grade III/IV thrombocytopenia. Polymorphism was found in 13% of dCK, 11% of dCDA. 42% of the 1st RNR, 38% of the 2nd RNR and 18% of both RNR sites. By Gibbs sampling-based algorithm, AGCT was the most frequent type (0.6226) with 3 genes, and CT was the most common haplotype in RNR (0.6909). When we evaluated the association of the 4 polymorphic sites from 3 genes with maximum leukopenia, AGTC type polymorphism showed the correlation with leukopenia. Moreover, the number of polymorphism in RNR and the polymorphism of the second site in RNR showed the significant correlation with leukopenia. Subsequently, patients with more number of polymorphism in 3 genes or polymorphism in RNR gene required more numbers of G-CSF rescue without gemcitabine dose reduction. Finally, patients with AGCT type showed a less response to treatment. Conclusions: Gemcitabine monotherapy is effective as salvage treatment and dose adjustment can be done effectively by pharmacogenomic association study in heavily pretreated, breast cancer patients. No significant financial relationships to disclose.
P162 Current interstitial lung disease specialist MDT provision across the uk
Authors: TA Mikolasch, H Garthwaite, J Porter
Journal: Thorax (2016)

The advent of novel anti-fibrotic therapies and the introduction of specialist, commissioned Interstitial Lung Disease (ILD) centres, has led to an increased workload for Multidisciplinary Team (MDT) meetings. We set out to survey specialist UK centres to gain a better understanding of their organisational processes and associated challenges. <h3>Methods</h3> Between August and December 2015 we conducted an online survey of all 23 NHS England commissioned ILD centres, plus 5 specialist ILD centres in Scotland, Wales and Northern Island. The survey was sent to the clinical lead of each centre. A total of 20 questions assessed the workforce composition and frequency of meetings. Their workload was also evaluated and we asked them to identify areas that required improvement. <h3>Results</h3> 26 out of 28 centres responded. MDTs are coordinated by the ILD lead consultant (57%) or a medical secretary (26%), with only 17% directed by a MDT coordinator. Peripheral hospitals participate in MDTs in 78% of centres; in person, via video-link or paper referrals; however, the majority of discussed patients are reviewed at the specialist centre. MDTs are typically held weekly, lasting 1 to 2 hours, with 10 to 20 patients discussed. 26% of MDTs discuss all new referrals, 87% discuss all patients considered for anti-fibrotic therapy, whilst only 22% discuss all patients considered for immunosuppressive therapy (aside from oral steroids). All respondents agreed that the available MDT time was insufficient. The most common reasons were cited as; lack of dedicated MDT funding (83%), lack of sufficient respiratory radiologist consultant time (78%) and lack of dedicated administrative support (61%). In 96% of cases there is no local tariff in place to fund MDT discussion and all respondents agreed that a dedicated tariff would improve MDT provision. 92% of centres enrol MDT patients into clinical trials. <h3>Conclusion</h3> Specialist ILD MDTs are able to concentrate a high level of expertise and allow patients access to vital clinical trials. They are, however, under considerable strain due to lack of funding and administrative support. A dedicated funding stream for this specialist service would be beneficial.
P3.02b-061 A Phase II Study of Nab-Paclitaxel (Nab-P) in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) with EGFR Mutations
Authors: Christina Baik, Bernardo Goulart, Katherine Nguyen, Sylvia Lee, Keith Eaton, Laura Chow, Cristina Rodriguez, Rafael Santana-Davila, Rebecca Wood, Renato Martins
Journal: Journal of Thoracic Oncology (2017)
Documenting the complete resolution rates of venous thromboemboli (VTE) with the factor Xa inhibitor fondaparinux sodium (FS) in patients with cancer.
Authors: D. R. Budman, M. F. Barginear, R. J. Gralla, T. P. Bradley, I. Shapira, N. J. Nier-Shoulson, C. R. Greben, M. Akerman, M. Lesser
Journal: Journal of Clinical Oncology (2011)

9130 Background: Cancer patients have a significant risk of VTE. Recurrent VTE rates of 9-17% occur (Lee NEJM 2003) despite the use of therapeutic anticoagulation (AC). Low molecular weight heparins (LMWH) afford several advantages over warfarin. Nevertheless, even with LMWHs more than 20% of patients have VTE propagation. Completeresolution and partial resolution of DVTs occur in up to 38% and 54%, respectively, after 6 months of AC (Prandoni Ann Intern Med 2002, Piovella Haematologica 2002), and thrombi remaindetectable in half of non-cancer patients after a year (Kearon Circulation 2003). Recently, Factor Xa inhibitors have become available and require further study to determine if they offer therapeutic improvements in this patient population. As part of the CAT (Cancer and Thrombosis) trial, we prospectively evaluated complete resolution rates with the Factor Xa inhibitor fondaparinux sodium (FS). Methods: Inclusion criteria included an acute VTE (DVT and/or PE) in patients with cancer and creatinine clearance > 30 mL/min. Patients received FS [5mg SC for pts <50 kg or age >65, 7.5mg SC for pts 50–100 kg and 10mg SC for pts >100 kg]. Imaging studies after baseline were repeated on days 14, 30, and 56 for DVTs, and on day 56 for PEs. Results: 64 patients were entered and 63 evaluated. Cancer types included: Lung (25%); Breast (18%), Colon (14%), Pancreas (14%), Lymphoma (8%), Ovarian (6%), and 15% with other cancers. Findings included: 107 DVT sites and 43 PEs. No patient had a recurrent DVT; 2 (3%) patients had new asymptomatic PEs. Major bleeding occurred in 3 patients (5%); minor bleeding occurred in 4 patients (6%). VTE resolution results are seen in the table. Conclusions: 1) The VTE complete resolution rate documented in this prospective trial with FS is among the highest reported in patients with cancer, and occurred within 8 weeks of starting AC. 2) VTE resolution could help tailor the duration of AC. These favorable results support future randomized trials to compare resolution rates of FS with LMWHs, and to evaluate if the optimal duration of AC depends on VTE resolution. % with complete resolution day 56 (95% CI) DVTs (n=107) 51% (40.6%-60.3%) PEs (n = 43) 47% (31.2%-62.3%)
Impact of <scp>FAB</scp> classification on predicting outcome in acute myeloid leukemia, not otherwise specified, patients undergoing allogeneic stem cell transplantation in <scp>CR</scp>1: An analysis of 1690 patients from the acute leukemia working party of <scp>EBMT</scp>
Authors: Jonathan Canaani, Eric Beohou, Myriam Labopin, Gerard Socié, Anne Huynh, Liisa Volin, Jan Cornelissen, Noel Milpied, Tobias Gedde‐Dahl, Eric Deconinck, Nathalie Fegueux, Didier Blaise, Mohamad Mohty, Arnon Nagler
Journal: American Journal of Hematology (2017)

The French, American, and British (FAB) classification system for acute myeloid leukemia (AML) is extensively used and is incorporated into the AML, not otherwise specified (NOS) category in the 2016 WHO edition of myeloid neoplasm classification. While recent data proposes that FAB classification does not provide additional prognostic information for patients for whom NPM1 status is available, it is unknown whether FAB still retains a current prognostic role in predicting outcome of AML patients undergoing allogeneic stem cell transplantation. Using the European Society of Blood and Bone Marrow Transplantation registry we analyzed outcome of 1690 patients transplanted in CR1 to determine if FAB classification provides additional prognostic value. Multivariate analysis revealed that M6/M7 patients had decreased leukemia free survival (hazard ratio (HR) of 1.41, 95% confidence interval (CI), 1.01-1.99; P = .046) in addition to increased nonrelapse mortality (NRM) rates (HR, 1.79; 95% CI, 1.06-3.01; P = .028) compared with other FAB types. In the NPM1wt AML, NOS cohort, FAB M6/M7 was also associated with increased NRM (HR, 2.17; 95% CI, 1.14-4.16; P = .019). Finally, in FLT3-ITD+ patients, multivariate analyses revealed that specific FAB types were tightly associated with adverse outcome. In conclusion, FAB classification may predict outcome following transplantation in AML, NOS patients.
S57 Qualitative assessment of the experience of telemonitoring in ventilated patients with motor neurone disease
Authors: H Ashcroft, H Ando, R Halhead, B Chakrabarti, CA Young, R Cousins, RM Angus
Journal: Thorax (2016)

<h3>Background</h3> The National Institute for Health and care Excellence (NICE) has recently issued recommendations on the care of people with motor neurone disease (MND), promoting tailored care for each patient, Guideline 42, 2016. Previous studies suggest remote monitoring offers a facility to regularly monitor and interact with patients, providing timely interventions so it may facilitate delivery of the recommendations. The efficacy of this approach is dependent upon acceptability of telemonitoring to patients. <h3>Aim</h3> To understand the experiences of using telemonitoring in ventilated patients with MND. <h3>Methods</h3> Semi-structured interviews were conducted with seven patients (male = 5; mean age = 63 yrs). The median illness duration was 14 m (range = 7 m–13 yrs 7 m) and the median non-invasive ventilation (NIV) usage was 12 m (range = 0 m–3 yrs). Participants used a telemonitoring device (Docobo CAREPORTAL®) for six months, completed weekly nocturnal pulse oximetry and symptom-related questions. Five caregivers were present at the interviews and provided their feedback. Interviews were audio recorded and transcribed verbatim. Thematic analysis was conducted to find overarching themes. The interpretation was reviewed and supported by a multidisciplinary team examination. <h3>Findings</h3> Five themes were identified: Technical Challenges, Increased Self-Awareness, Taking Initiative, Benefits of Timely Intervention, and Reducing the Unnecessary. Whilst participants expressed general ease of Careportal® use, technical issues included; messaging system challenges, oximetry transmission, device fault, mobile signal loss. No other negative experience of using Careportal® was reported. Overall, participants expressed how telemonitoring enabled symptom awareness and interpretation. The device also enabled the participants to raise their concerns and/or requests to the healthcare professionals via the messaging system, and this was depicted as a sharp contrast to current communication with hospitals. Timely interventions were observed as a result of regular monitoring, contributing to both physical and psychological well-being of the participants. It was also suggested that using Careportal® could reduce unnecessary cost/time and hassles created by attending hospital appointments. <h3>Conclusions</h3> Telemonitoring enabled participants to be actively involved in their care and they felt that the interventions were timely delivered to meet their needs. The findings suggest potential benefits of utilising Careportal ® in routine care as a contact point to accommodate different individual’s needs. Supported by an SBRI Grant
Dynamic near-infrared spectroscopy assessment as an important tool to explore pulmonary arterial hypertension pathophysiology
Authors: Marios Panagiotou, Ioannis Vogiatzis, Zafeiris Louvaris, Geeshath Jayasekera, Alison McKenzie, Neil Mcglinchey, Julien S. Baker, Alistair C. Church, Andrew J. Peacock, Martin K. Johnson
Journal: European Respiratory Journal (2017)

We thank S. Dimopoulos and co-workers for their particular interest in our study [1] and their contributions to this issue. The peripheral muscle hypothesis in pulmonary arterial hypertension (PAH) [2] is certainly of great and growing interest due to the potential of muscle function as a target for meaningful intervention. Accordingly, our study explored the value of quadriceps muscle oxygenation profiles in patients with PAH by means of near-infrared spectroscopy (NIRS) [1]. The satisfactory correlation between vastus lateralis muscle tissue oxygenation index ( S tO2) and mixed venous oxygen saturation ( S vO2) both at rest and during exercise support the use of NIRS in the noninvasive investigation of patients with PAH. Importantly, they suggest that skeletal muscle oxygenation profiles reflect the pathophysiology of PAH. Near-infrared spectroscopy offers a qualitative, noninvasive indication of mixed venous oxygen saturation in PAH <http://ow.ly/MctV306eEYC>
P2.01-014 miR-3941: A Novel microRNA That Controls IGBP1 Expression and is Associated with Malignant Progression of Lung Adenocarcinoma
Authors: Taiki Sato, Aya Shiba, Yun-Jung Kim, Tomoko Dai, Shingo Sakashita, Masayuki Noguchi
Journal: Journal of Thoracic Oncology (2017)
S36 Coil treatment for patients with severe emphysema and bilaterally incomplete fissures; effectiveness and complications after one-year follow-up. a single-centre experience
Authors: K Kontogianni, V Gerovasili, D Gompelmann, M Schuhmann, CP Heussel, FJF Herth, R Eberhardt
Journal: Thorax (2016)

<h3>Background</h3> The aim of this retrospective analysis, was to evaluate the safety and efficacy of Lung Volume Reduction with coils (LVR-Coil) treatment in a single-centre setting in patients with severe heterogeneous emphysema and bilaterally incomplete fissures <h3>Methods</h3> In this retrospective analysis 86 patients with severe COPD (&amp;male;/&amp;female;:40/46, age: 64 ± 7 years) and bilateral incomplete fissures were included. A total of 10 coils were unilaterally implanted in a single lobe. 28 patients received additional treatment of a contralateral lobe. At 90, 180 and 365 days’ follow-up changes in pulmonary function tests, 6-Minute-Walk-Test (6MWT) and modified Medical Research Council (mMRC) dyspnea scale, as well as possible complications were recorded. <h3>Results</h3> FEV<sub>1</sub> improved significantly at the 90-day follow up (p:0.001) but the improvement was not sustained at 180 and 365 days (0.71 ± 0.21 L vs 0.76 ± 0.23 L vs 0.73 ± 0.22 L vs 0.69 ± 0.18 L). FEV<sub>1 </sub>improved more than 12% (minimal clinically significant change, MCID) in 30 patients (38%). Vital Capacity improved significantly at the 90- (p &lt; 0.001) and 180-day (p:0:13) follow up but improvement was lost after 365 days. RV improved significantly at 90 days (6.1 ± 1.4 L vs 5.5 ± 1.3 L, p &lt; 0.0001) and at 180 days (6.1 ± 1.4 L vs 5.7 ± 1.2 L, p:0.008), but the improvement was not sustained at 365 days. 6MWT improved at 90 days (247 ± 90 m vs 278 ± 81 m, p &lt; 0.0001) and 180 days (247 ± 90 m vs 267 ± 90 m, p:0.02) but the improvement was lost at the 365-day follow up. Forty-two from 71 (59%) patients improved by more than 26 m (MCID) at 90 days while 21 patients (30%) improved more than 54 m. mMRC improved significantly at 90 and 180 days. In a total of 114 procedures no periprocedural deaths occurred. Four patients died within the first 3 months after the treatment (mortality rate 3.5%). Complications observed within the first 90 days included pneumonia requiring hospital admission (28%), pneumothorax with chest tube insertion (6%), significant, persistent hemoptysis was documented in 4 cases (3.5%) and hypercapnia and hypoxemia in 4.4% and 1.75% respectively. <h3>Conclusions</h3> LVR-coil improved PFT, 6MWT and mMRC initially but improvement was lost after 365 days. However, this improvement came at a cost of significant complications and with a 3.5% mortality rate.
Identification of Novel Fusion Genes and Differentially Expressed Genes in Acute Leukemia through Transcriptome Analysis
Authors: Dong-Hyun Lee, Young-Uk Cho, Seongsoo Jang, Chan-Jeoung Park, Mi Hyun Bae, Dae-Young Kim, Jung-Hee Lee, Je-Hwan Lee, Kyoo-Hyung Lee, Jong Jin Seo, Eul-Ju Seo
Journal: Blood (2015)
Peritoneal macrophage heterogeneity is associated with different peritoneal dialysis outcomes
Authors: Chia-Te Liao, Robert Andrews, Leah E. Wallace, Mohd Wajid A. Khan, Ann Kift-Morgan, Nicholas Topley, Donald J. Fraser, Philip R. Taylor
Journal: Kidney International (2017)

Peritonitis remains the major obstacle for the maintenance of long-term peritoneal dialysis and dysregulated host peritoneal immune responses may compromise local anti-infectious defense, leading to treatment failure. Whilst, tissue mononuclear phagocytes, comprising macrophages and dendritic cells, are central to a host response to pathogens and the development of adaptive immune responses, they are poorly characterized in the human peritoneum. Combining flow cytometry with global transcriptome analysis, the phenotypic features and lineage identity of the major CD14+ macrophage and CD1c+ dendritic cell subsets in dialysis effluent were defined. Their functional specialization was reflected in cytokine generation, phagocytosis, and antigen processing/presentation. By analyzing acute bacterial peritonitis, stable (infection-free) and new-starter patients receiving peritoneal dialysis, we identified a skewed distribution of macrophage to dendritic cell subsets (increasing ratio) that associated with adverse peritonitis outcomes, history of multiple peritonitis episodes, and early catheter failure, respectively. Intriguingly, we also noted significant alterations of macrophage heterogeneity, indicative of different maturation and activation states that were associated with different peritoneal dialysis outcomes. Thus, our studies delineate peritoneal dendritic cells from macrophages within dialysate, and define cellular characteristics associated with peritoneal dialysis treatment failure. These are the first steps to unravelling the detrimental adaptive immune responses occurring as a consequence of peritonitis.