tbuckley/cabot-search huggingface dataset:
Intracellular lipid metabolism impairs β cell compensation during diet-induced obesity
Authors: Risheng Ye, Ruth Gordillo, Mengle Shao, Toshiharu Onodera, Zhe Chen, Shiuhwei Chen, Xiaoli Lin, Jeffrey A SoRelle, Xiaohong Li, Miao Tang, Mark P Keller, Regina Kuliawat, Alan D Attie, Rana K Gupta, William L Holland, Bruce Beutler, Joachim Herz, Philipp E Scherer
Journal: Journal of Clinical Investigation (2018)

The compensatory proliferation of insulin-producing β cells is critical to maintaining glucose homeostasis at the early stage of type 2 diabetes. Failure of β cells to proliferate results in hyperglycemia and insulin dependence in patients. To understand the effect of the interplay between β cell compensation and lipid metabolism upon obesity and peripheral insulin resistance, we eliminated LDL receptor-related protein 1 (LRP1), a pleiotropic mediator of cholesterol, insulin, energy metabolism, and other cellular processes, in β cells. Upon high-fat diet exposure, LRP1 ablation significantly impaired insulin secretion and proliferation of β cells. The diminished insulin signaling was partly contributed to by the hypersensitivity to glucose-induced, Ca2+-dependent activation of Erk and the mTORC1 effector p85 S6K1. Surprisingly, in LRP1-deficient islets, lipotoxic sphingolipids were mitigated by improved lipid metabolism, mediated at least in part by the master transcriptional regulator PPARγ2. Acute overexpression of PPARγ2 in β cells impaired insulin signaling and insulin secretion. Elimination of Apbb2, a functional regulator of LRP1 cytoplasmic domain, also impaired β cell function in a similar fashion. In summary, our results uncover the double-edged effects of intracellular lipid metabolism on β cell function and viability in obesity and type 2 diabetes and highlight LRP1 as an essential regulator of these processes.
Elevated tissue sodium deposition in patients with type 2 diabetes on hemodialysis detected by 23Na magnetic resonance imaging
Authors: Christoph Kopp, Peter Linz, Carolin Maier, Peter Wabel, Matthias Hammon, Armin M. Nagel, Daniela Rosenhauer, Stephan Horn, Michael Uder, Friedrich C. Luft, Jens Titze, Anke Dahlmann
Journal: Kidney International (2018)
Potency Of German Cockroach Extracts For IgE Reactivity Depends On Allergen Content And Allergen-specific IgE Titers Of The Cockroach Allergic Patient
Authors: Jill Glesner, Stephanie Filep, Véronique M. Schulten, April Frazier, Lisa D. Vailes, Sabina Wünschmann, Kyoung Y. Leong, Coby Schal, Martin D. Chapman, Alessandro Sette, Anna Pomés
Journal: Journal of Allergy and Clinical Immunology (2018)
Abstract 17469: Expanding the Donor Pool in Pediatric Heart Transplant With a Novel Three Dimensional Technique
Authors: Jonathan Plasencia, Justin Ryan, Jacob Lindquist, Susan Sajadi, Micheal VanAuker, Randy Richardson, Erik Ellsworth, Susan Park, Robyn Augustyn, Richard Southard, John Nigro, Stephen Pophal, David Frakes, Steven Zangwill
Journal: Circulation (2015)

Introduction: Heart transplant (HTx) outcomes continue to improve although organs remain limited. Donor-recipient (DR) size matching is critical in pediatrics. Usually, centers apply a subjective donor weight (wt) range based on recipient chest x-ray. DR wt ratios may vary from 0.7–4. Hypothesis: A novel 3D tool can be used to predict ideal donor size. Methods: A library of 3D reconstructed normal hearts was created from CT/MRI data. A linear fit of normal heart volume vs. body wt was determined for wts up to 22.5kgs (R 2 =0.983). The linear fit was used to predict donor heart volumes and ideal donor wt. Similarly, pre and post HTx hearts were reconstructed from 3 infant pts undergoing HTx. Results: [Table] The library was used to predict ideal donor wt targeting 1:1 DR heart volume ratio. Pt A had cardiomegaly and an ideal DR wt ratio of 3.5, which may be outside a center’s usual range. While all 3 Pts had DR wt ratios &gt; 1, Pt A had a downsized graft while Pt B and C had upsized grafts (based purely on DR heart volumes). 3D reconstructions &gt; 1 week post HTx suggest the downsized graft became larger and upsized grafts smaller. Conclusion: 3D reconstruction has tremendous potential to improve DR size matching in HTx. As the virtual library grows, the ability to accurately predict DR heart volumes will improve. Further, retrospective analysis of transplant cases, wherein 3D matching was used, will allow us to predict the limits of under and oversizing. Finally, this technique has potential to allow “virtual transplantations” wherein we can model a particular donor (green) into a patient-specific recipient (red) and assess fit along with potential for mismatch related morbidity. [Figure]
Compliance With Guideline-Directed Medical Therapy in Contemporary Coronary Revascularization Trials
Authors: Ana-Catarina Pinho-Gomes, Luis Azevedo, Jung-Min Ahn, Seung-Jung Park, Taye H. Hamza, Michael E. Farkouh, Patrick W. Serruys, Milan Milojevic, Arie Pieter Kappetein, Gregg W. Stone, Andre Lamy, Valentin Fuster, David P. Taggart
Journal: Journal of the American College of Cardiology (2018)
Prise en charge endoscopique des fistules post-opératoires compliquant une chirurgie bariatrique
Authors: G Claudé, B Vedrenne, T Degand, P Claudé, JB Chevaux, L Vuitton, S Koch
Journal: Endoscopy (2018)

Le nombre de chirurgies bariatriques a augmenté au cours des dernières décennies, avec comme principale complications l'apparition de fistules post-opératoires. Les stratégies de prise en charge endoscopiques ont prouvé leur efficacité, initialement via le placement de stents métalliques couverts pour couvrir l'orifice fistuleux, associés à un drainage radiologique ou chirurgical. Le drainage endoscopique interne, utilisant une prothèse en double queue de cochon semble être aussi efficace et mieux toléré. L'objectif principal de notre étude était de déterminer l'efficacité de la prise en charge endoscopique d'une fistule post-opératoire après une chirurgie bariatrique. Les objectifs secondaires étaient d'évaluer l'efficacité d'un drainage endoscopique interne, de déterminer les facteurs associés à une guérison.
Brachytherapy-Based Radiotherapy and Radical Prostatectomy Are Associated With Similar Survival in High-Risk Localized Prostate Cancer
Authors: Ronald D. Ennis, Liangyuan Hu, Shannon N. Ryemon, Joyce Lin, Madhu Mazumdar
Journal: Journal of Clinical Oncology (2018)

Purpose There are no randomized trials to guide treatment decisions between radiotherapeutic and surgical options for patients with high-risk localized prostate cancer. Comparative studies have been limited by their ability to match patients on the basis of pretreatment prognostic variables and to adjust for the cancer-related, medical, and socioeconomic differences between patients who choose radiotherapeutic or surgical approaches. Methods We analyzed the outcome of all patients in the National Cancer Database with high-risk, clinically localized prostate cancer with complete prognostic data who were treated with either radical prostatectomy (RP), external beam radiotherapy (EBRT) combined with androgen deprivation (AD), or EBRT plus brachytherapy with or without AD. Inverse probability of treatment weighting was used to adjust for covariable imbalance among treatment groups. The weighted time-dependent Cox proportional hazards model was then used to estimate the effects of treatment groups on survival, accounting for differential treatment initiation times. A predictive model of pathologic nodal (pLN) status was built using prostate-specific antigen level, Gleason score, and clinical T stage; predicted pLN status was used to repeat the inverse probability of treatment weighting and time-dependent Cox proportional hazards model. Results A total of 42,765 patients were analyzed. There was no statistically significant difference in survival between RP and EBRT plus brachytherapy with or without AD (hazard ratio [HR], 1.17; 95% CI, 0.88 to 1.55). However, EBRT plus AD was associated with higher mortality than RP (HR, 1.53; 95% CI, 1.22 to 1.92). Adjustment for predicted pLN status did not yield statistically different results. A sensitivity analysis showed that EBRT plus AD ≥ 7920 cGy narrowed the difference, but a significantly higher mortality remained (HR, 1.33; 95% CI, 1.05 to 1.68). Conclusion After comprehensively adjusting for imbalances in prostate cancer prognostic factors, other medical conditions, and socioeconomic factors, this analysis showed no statistical difference in survival between patients treated with RP versus EBRT plus brachytherapy with or without AD. EBRT plus AD was associated with lower survival.
Delta-tocotrienol is the most bioactive natural tocotrienol in the prevention of pancreatic cancer transformation
Authors: Kazim Husain, Rony Francois, Teruo Yamauchi, Said Sebti, Mokenge Malafa
Journal: Cancer Research (2008)

3826    Background:  Pancreatic cancer is one of the most lethal cancers in need of novel interventions. A role for dietary bioactive compounds in pancreatic cancer prevention is plausible because epidemiological studies indicate that consumption of fruits, vegetables, and cereal foods is associated with a lower risk of developing pancreatic cancer. Tocotrienols are bioactive components of cereal foods such as oats, barley, rice bran, and palm. These compounds have been demonstrated to have anticancer and chemopreventive activity in a wide variety of cancer types; however their activity in pancreatic cancer is unknown. In this study we investigated the comparative effects of the four natural tocotrienol compounds in order to determine the most bioactive tocotrienol against pancreatic cancer   Methods:  We first determined the anti-proliferative (MTT assay) and pro-apoptotic activity of α, β, γ and δ-tocotrienol in immortalized normal human pancreatic ductal epithelial cells (HPDE C7), HPDE cells transformed with oncogenic Kras (C7-Kras), as well as human pancreatic cancer cell lines MiaPaCa-2 and AsPc-1. We then determined the effect of the tocotrienol compounds on malignant transformation (colony formation) in MiaPaca-2 cells and NF-κB/p65 activity in these cells. The activity of the tocotrienol was also compared to gemcitabine, α-tocopherol, and δ-tocopherol.   Results:  Tocotrienols significantly inhibited the cell growth of transformed C7-Kras, and pancreatic cancer cells in a concentration and time-dependent manner but had no effect on ‘normal’ HPDE cells. The IC 50  of growth inhibition were 40, 45 and 60 μ M for δ, γ and β tocotrienol compounds, respectively. The IC 50  of growth inhibition for gemcitabine was 20 μ M. In contrast α-tocotrienol, α-tocopherol and δ-tocopherol had no growth inhibitory activity. Malignant transformation was inhibited by 70, 30, 19 and 6% with δ, γ, β and α tocotrienol compounds, respectively in MiaPaca-2 cells. Malignant transformation inhibition for gemcitabine was 89%.The apoptosis inducing activity of δ tocotrienol was far greater than γ and β-tocotrienols and gemcitabine. Furthermore nuclear DNA binding of NF-κB/p65 activity was inhibited by 36, 30, 15 and 5% with δ, γ, β and α tocotrienols, respectively.   Conclusion:  (1) δ-tocotrienol is the most bioactive tocotrienol compound against pancreatic cancer; (2) δ-tocotrienol is not toxic to non-transformed pancreatic epithelial cells; (3) δ-tocotrienol has more apoptotic activity against pancreatic cancer cells compared to gemcitabine; (4) δ and γ-tocotrienols significantly inhibit nuclear DNA binding activity of NF-κB/p65. These data support further studies to determine the role of δ-tocotrienol in the prevention of pancreatic cancer progression.
P059 Ex vivo comparison of baricitinib, upadacitinib, filgotinib and tofacitinib for cytokine signalling in human leukocyte subpopulations
Authors: IB McInnes, R Higgs, J Lee, WL Macias, S Na, RA Ortmann, G Rocha, T Wehrman, X Zhang, SH Zuckerman, PC Taylor, C Perrier
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Baricitinib (BARI), an oral selective Janus kinase (JAK) 1/2 inhibitor, approved in the EU for moderate to severe active RA. <h3>Objectives</h3> To compare <i>in vitro</i> cellular pharmacology of BARI to upadacitinib (ABT), filgotinib (FILGO), and tofacitinib (TOFA), three JAK inhibitors (JAKis) currently approved or in clinical development. <h3>Methods</h3> Peripheral blood mononuclear cells from healthy donors (n=6–12) were incubated with different JAKis. After cytokine stimulation, phosphorylated signal transducer and activator of transcription (pSTAT) levels were measured and IC<sub>50</sub> calculated in phenotypically gated leukocyte subpopulations. Therapeutic dose relevance of <i>in vitro</i> analysis was assessed using calculated mean concentration-time (CT) profiles over 24 hour JAKi-treated subjects (BARI 4 mg QD; ABT 15 and 30 mg QD; FILGO 100 and 200 mg QD; TOFA 5 and 10 mg BID). Time above IC<sub>50</sub> (T&gt;IC; h/day) and average daily% inhibition of pSTAT formation (%SI) were calculated for each JAKi, cytokine, and cell type. <h3>Results</h3> Tested cytokines did not signal in all cell types. When signalling was detected, IC<sub>50</sub>,%SI, and T&gt;IC for a particular JAKi exhibited similar dose dependent inhibition across cell types. For JAK1/3 dependent signalling across 4 cytokines (IL-2, 4, 15, 21), IC<sub>50</sub> for ABT and TOFA were more potent than BARI; FILGO was the least potent. Overlaid on CT profiles, this indicated generally higher%SI and longer T&gt;IC for ABT and TOFA compared to BARI and FILGO. For IL-6 (JAK1/2),%SI and T&gt;IC was TOFA&gt;BARI/ABT&gt;FILGO and for IL-10 (JAK1/TYK2),%SI was TOFA&gt;BARI/ABT&gt;FILGO. IFN-γ (JAK1/2) was modulated only by BARI, ABT, and TOFA. IFN-α (JAK1/TYK2) signalling was most potently inhibited by BARI and ABT. FILGO did not appear to modulate GM-CSF signalling (JAK2/2), while%SI and T&gt;IC were similar between BARI and ABT. <h3>Conclusions</h3> JAKis modulate distinct cytokine pathways to differing degrees and durations over 24 hour. BARI and FILGO inhibited JAK1/3 signalling less than ABT and TOFA. No JAKis agent potently or continuously inhibited an individual cytokine signalling pathway throughout dosing interval, implying the varying efficacy and safety profiles of JAKis across disease states. <h3>Acknowledgements</h3> <h3>Study support</h3> Eli Lilly and Company and Incyte Corporation. Encore of ACR/ARHP-2017 Annual Scientific Meeting, Nov 4–8, 2016; San Diego, CA, USA. <h3>Disclosure of interest</h3> None declared
Résection endoscopique trans-pariétale au niveau du colon et du rectum: Résultats d'une série multicentrique rétrospective
Authors: S Chaussade, MA Guillaumot, J Jacques, M Pioche, G Rahmi, V Lepilliez, E Chabrun, R Legros, J Rivory, S Leblanc, T Ponchon
Journal: Endoscopy (2018)

La dissection endoscopique (ESD) est une technique permettant l'exérèse de lésions bénignes ou de carcinomes intra muqueux voir sous muqueux superficiels (sm1). Elle permet une exérèse en monobloc et facilite ainsi l'analyse anatomopathologique. Dans certaines situations (présence d'une fibrose sous muqueuse, tentative d'une résection antérieure, cancer avec atteinte de la sous muqueuse) la dissection sous muqueuse est insuffisante et présente de résection incomplète en rasion d'un envahissement en profondeur. La résection endoscopique trans-parietale apparaît comme la technique de choix lorsqu'il existe un risque d'envahissement en profondeur à l'instar de ce que les chirurgiens proposent dans le rectum («Trans anal Endoscopic Microsurgery ou TEM»). L'intérêt de la résection endoscopique «full-thickness» est de permettre une exérèse en totalité de la lésion, en monobloc et trans-murale avec des marges latérales et profondes saines.
The Impact of Diabetes on Breast Cancer Treatments and Outcomes: A Population-Based Study
Authors: Iliana C. Lega, Peter C. Austin, Hadas D. Fischer, Kinwah Fung, Monika K. Krzyzanowska, Eitan Amir, Lorraine L. Lipscombe
Journal: Diabetes Care (2018)

Women with breast cancer and diabetes face worse outcomes than those with breast cancer without diabetes; however, the contribution of comorbidity to these disparities remains unclear. We evaluated the impact of diabetes on receipt of cancer treatments as well as mortality while accounting for other comorbidities.Ontario administrative databases were used to compare the rate of receipt of breast cancer treatments between women with and without diabetes. We also performed adjusted cause-specific hazard models to account for comorbidities when evaluating differences in treatments received and mortality outcomes between the two groups.Women with diabetes and stage III breast cancer were slightly less likely to receive chemotherapy (relative risk [RR] 0.93 [95% CI 0.89-0.97]), although this difference was not significant when we adjusted for comorbidities (adjusted hazard ratio [aHR] 1.03 [95% CI 0.93-1.13]). We saw similar trends for receipt of guideline-adherent radiotherapy (RR 0.97 [0.95-0.99], aHR 0.98 [0.94-1.02]). All-cause mortality was increased in women with diabetes after adjusting for comorbidities (aHR 1.16 [1.06-1.27]), but breast cancer-specific mortality was not increased overall. Women with a longer duration of diabetes and those with preexisting cardiovascular disease had increased all-cause and cancer-specific mortality.Although cancer treatments received were similar between women with and without diabetes, breast cancer-specific mortality remains higher among women with diabetes who have longer diabetes duration or preexisting cardiovascular disease. This study uncovers new information about key risk factors for poorer prognosis in women with diabetes and breast cancer.
Abstract 13059: Diagnostic Performance of Left Ventricular Contractile Entropy in Patients With Heart Failure: Analysis by Quantitative Gated Semiconductor-SPECT
Authors: Masahiko Setoguchi, Masato Shimizu, Yuta Taomoto, Miki Amemiya, Yosuke Yamakami, Yoshikazu Sato, Munehiro Iiya, Rena Nakamura, Kuniaki Nakano, Hiroshi Shimada, Hiroyuki Fujii, Noriyoshi Yamawake, Mitsuhiro Nishizaki
Journal: Circulation (2016)

Background: Left ventricular (LV) dyssynchrony is considered as an important cause of congestive heart failure (CHF) admission. However, among the parameters of dyssynchrony, the prognostic value of LV contractile entropy is not elucidated. Hypothesis: Left ventricular contractile entropy can predict early re-hospitalization of heart failure patients. Method: Ninety-eight consecutive patients with first onset CHF who underwent quantitative gated demiconductor SPECT (QGS) before discharge were investigated retrospectively. Patients with re-hospitalization after discharge within 30-days were assigned to Group A, and patients without re-hospitalization were assigned to Group B. Data regarding electrocardiogram, and parameters of QGS including LV remodeling, systolic function, diastolic function and phase analysis (Phase SD, bandwidth, entropy) were collected automatically, and compared between Group A and B. Kaplan-Meier survival curves were used to compare variables between the patients, as appropriate. Multivariate analysis was performed on variables with a value of P &lt; 0.05 using the stepwise regression approach. Result (See figure and table): Of 98 patients, 92 patients did not readmit and other 6 patients readmitted within 30-days. ROC analysis showed that the cut-off value 0.785 predicted Group A (95% CI: 0.563-0.894) with 0.652 specificity and 0.833 sensitivity. Multivariate analysis showed that ‘entropy &gt; 0.785’ was a significant and independent predictor with a high odds ratio (OR:9.375, 95%CI :1.050-83.724). The Kaplan-Meier survival curve revealed a significant difference between the patients of ‘entropy ≧ 0.785’ and ‘entropy &lt; 0.785’ in 30-days re-hospitalization rate (Log-rank test, p=0.016). Conclusion: The LV contractile entropy was a powerful indicator of early phase re-hospitalization in patients with CHF, rather than ejection fraction or other parameters of LV dyssynchrony.
Synergistic immunoreaction of acupuncture-like dissolving microneedles containing thymopentin at acupoints in immune-suppressed rats
Authors: Qian Zhang, Chuncao Xu, Shiqi Lin, Huanbin Zhou, Gangtao Yao, Hu Liu, Lili Wang, Xin Pan, Guilan Quan, Chuanbin Wu
Journal: Acta Pharmaceutica Sinica B (2018)

Dissolving microneedles carried drug molecules can effectively penetrate the stratum corneum of skin to improve the transdermal drug delivery. The traditional Chinese medicine acupuncture is based on the needle stimulation at a specific location (acupoint) to generate and transmit biochemical and physiological signals which alter the pathophysiological state of patients. However, the pain associated with conventional acupuncture needles and the requirement of highly trained professionals limit the development of acupuncture in non-Asian countries. The purpose of this study is to investigate whether the dissolving microneedles can be utilized as a self-administered painless replacement for acupuncture and locally released drug molecules can achieve expected therapeutic outcomes. Immunosuppressive rats were treated with acupuncture at Zusanli (ST36) acupoint using microneedles containing thymopentin. The immune functions and psychological mood of the immunosuppressed animals were examined. The proliferation of splenocytes was examined by CCK-8 assay. CD4 and CD8 expression patterns in spleen cells were detected by flow cytometry. The current study showed that use of either microneedles containing thymopentin or conventional acupuncture both resulted in immune cell proliferation, which was confirmed by flow cytometry. Furthermore, either conventional acupuncture or microneedles were able to effectively mitigate the anxiety caused by immune-suppression when applied on the ST36.
The Lancet Psychiatry Commission on psychological treatments research in tomorrow's science
Authors: Emily A Holmes, Ata Ghaderi, Catherine J Harmer, Paul G Ramchandani, Pim Cuijpers, Anthony P Morrison, Jonathan P Roiser, Claudi L H Bockting, Rory C O'Connor, Roz Shafran, Michelle L Moulds, Michelle G Craske
Journal: The Lancet Psychiatry (2018)
British Thoracic Society Guideline for the investigation and management of malignant pleural mesothelioma
Authors: Ian Woolhouse, Lesley Bishop, Liz Darlison, Duneesha De Fonseka, Anthony Edey, John Edwards, Corinne Faivre-Finn, Dean A Fennell, Steve Holmes, Keith M Kerr, Apostolos Nakas, Tim Peel, Najib M Rahman, Mark Slade, Jeremy Steele, Selina Tsim, Nick A Maskell
Journal: Thorax (2018)

Section 3: Clinical features which predict the presence of mesothelioma Recommendations Section 4: Staging systems Recommendation Section 5: Imaging modalities for diagnosing and staging Recommendations Section 6: Pathological diagnosis Recommendations