tbuckley/cabot-search huggingface dataset:
Effector CD8+ T cell-derived interleukin-10 enhances acute liver immunopathology
Authors: Jessica Fioravanti, Pietro Di Lucia, Diletta Magini, Federica Moalli, Carolina Boni, Alexandre Pierre Benechet, Valeria Fumagalli, Donato Inverso, Andrea Vecchi, Amleto Fiocchi, Stefan Wieland, Robert Purcell, Carlo Ferrari, Francis V. Chisari, Luca G. Guidotti, Matteo Iannacone
Journal: Journal of Hepatology (2017)
Plasminogen Deficiency Impairs Erythropoietic Recovery Capacity In Male C57BL/6J Mice through Testosterone Defect
Authors: Yurai Okaji, Chiemi Nishida, Ismael Gritli, Yoshihiko Tashiro, Makiko Ohki, Koichi Hattori, Beate Heissig
Journal: Blood (2010)
Educational and Health Outcomes of Children Treated for Attention-Deficit/Hyperactivity Disorder
Authors: Michael Fleming, Catherine A. Fitton, Markus F. C. Steiner, James S. McLay, David Clark, Albert King, Daniel F. Mackay, Jill P. Pell
Journal: JAMA Pediatrics (2017)

Attention-deficit/hyperactivity disorder (ADHD) affects 39 million people worldwide; in isolation, it doubles annual health care costs and, when associated with comorbid mental health problems, it quadruples the costs.To compare the education and health outcomes of schoolchildren treated for ADHD with their peers.In this population-based cohort study, individual-level record linkage was performed of 8 Scotland-wide administrative databases covering dispensed prescriptions, admissions to acute and psychiatric hospitals, maternity records, annual pupil census, examinations, school absences and exclusions, and unemployment. The study cohort comprised 766 244 children attending Scottish primary, secondary, and special schools at any point between September 21, 2009, and September 18, 2013. Data analysis was performed from June 1, 2015, to December 6, 2016.Medication approved solely for ADHD treatment.Special educational needs, academic attainment, unauthorized absence, exclusion, age at leaving school, unemployment after leaving, and hospitalization. Outcomes were adjusted for potential sociodemographic, maternity, and comorbidity confounders.Of the 766 244 schoolchildren, 7413 (1.0%) were treated for ADHD; 6287 (84.8%) were male. These children had higher rates of unauthorized absence (adjusted incidence rate ratio [IRR], 1.16; 95% CI, 1.14-1.19) and exclusion (adjusted IRR, 5.79; 95% CI, 5.45-6.16), more commonly had a record of special educational need (adjusted odds ratio [OR], 8.62; 95% CI, 8.26-9.00), achieved lower academic attainment (adjusted OR, 3.35; 95% CI, 3.00-3.75), were more likely to leave school before age 16 years (1546 [64.3%] vs 61 235 [28.4%]), and were more likely to be unemployed (adjusted OR, 1.39; 95% CI, 1.25-1.53). Children with ADHD were more likely to require hospitalization overall (adjusted hazard ratio [HR], 1.25; 95% CI, 1.19-1.31) and for injury (adjusted HR, 1.52; 95% CI, 1.40-1.65).Even while receiving medication, children with ADHD fare worse than their peers across a wide range of outcomes relating not only to education but also to health.
Placental Homing Peptide-microRNA Inhibitor Conjugates for Targeted Enhancement of Intrinsic Placental Growth Signaling
Authors: Frances Beards, Lisa E Jones, Jayne Charnock, Karen Forbes, Lynda K Harris
Journal: Theranostics (2017)

Suboptimal placental growth and development are the underlying cause of many pregnancy complications. No treatments are available, primarily due to the risk of causing fetal teratogenicity. microRNAs (miRNAs) are short, non-coding RNA sequences that regulate multiple downstream genes; miR-145 and miR675 have previously been identified as negative regulators of placental growth. In this proof of principle study, we explored the feasibility of delivering miRNA inhibitors to the placentas of pregnant mice and developed novel placental homing peptide-microRNA inhibitor conjugates for targeted enhancement of intrinsic placental growth signalling. Scrambled-, miR-145- or miR-675 inhibitor sequences were synthesised from peptide nucleic acids and conjugated to the placental homing peptide CCGKRK. Intravenous administration of the miR-145- and miR-675 conjugates to pregnant C57BL/6J mice significantly increased fetal and placental weights compared to controls; the miR-675 conjugate significantly reduced placental miR-675 expression. When applied to human first trimester placental explants, the miR-145 conjugate significantly reduced placental miR-145 expression, and both conjugates induced significant enhancement of cytotrophoblast proliferation; no effect was observed in term placental explants. This study demonstrates that homing peptide-miRNA inhibitor conjugates can be exploited to promote placental growth; these novel therapeutics may represent an innovative strategy for targeted treatment of compromised placental development.
Effect of a Community Health Worker Intervention Among Latinos With Poorly Controlled Type 2 Diabetes
Authors: Olveen Carrasquillo, Cynthia Lebron, Yisel Alonzo, Hua Li, Aileen Chang, Sonjia Kenya
Journal: JAMA Internal Medicine (2017)

Community health worker (CHW) intervention is a promising approach to address type 2 diabetes among Latinos. However, evidence from randomized clinical studies is limited.To compare a CHW intervention with enhanced usual care.This 52-week, single-blind, randomized clinical trial included 300 Latino adults aged 18 to 65 years who were treated in 2 public hospital outpatient clinics in Miami-Dade County, Florida, from July 1, 2010, through October 31, 2013. Eligible participants had a hemoglobin A1c (HbA1c) level of 8.0 or greater. Follow-up was completed January 31, 2015, and data were analyzed from March 10, 2015, to June 6, 2016.A 1-year CHW intervention consisted of home visits, telephone calls, and group-level activities.Primary outcomes included systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDLC) levels, and HbA1c levels. Secondary outcomes included body mass index, medication regimen intensification, and self-reported measures of diet, physical activity, and medication regimen adherence.Of the 300 participants randomized (135 men [45%] and 165 women [55%]; mean [SD] age, 55.2 [7.0] years), we obtained follow-up data on 215 (71.7%). Participants in the CHW group received a median of 4 home visits and 20 telephone calls. After adjusting for baseline values and covariates, participants in the CHW group had an HbA1c level that was 0.51% lower (95% CI, -0.94% to -0.08%) than that of participants in the enhanced usual care group. The reduction in SBP of 4.62 mm Hg (95% CI, -9.01 to -0.24 mm Hg) did not meet the preplanned target of 8 mm Hg and was not statistically significant in unadjusted models. No significant differences in LDLC levels (mean difference, -8.2 mg/dL; 95% CI, -18.8 to 2.3 mg/dL) or any of the preplanned secondary outcomes were observed. Post hoc analyses suggest that the intervention may be more beneficial among those with worse control of their type 2 diabetes at baseline.Among Latinos with poorly controlled type 2 diabetes, a 12-month CHW intervention lowered HbA1c levels by 0.51%. The intervention did not lead to improvements in LDLC levels, and the findings with respect to SBP were variable and half of what was targeted. Future studies should examine whether CHW interventions affect other measures, such as access to health care or social determinants of health.clinicaltrials.gov Identifier: NCT01152957.
Addressing unmet needs in understanding asthma mechanisms
Authors: Michael R. Edwards, Sejal Saglani, Jurgen Schwarze, Chrysanthi Skevaki, Jaclyn A. Smith, Ben Ainsworth, Mark Almond, Evangelos Andreakos, Maria G. Belvisi, Kian Fan Chung, William Cookson, Paul Cullinan, Catherine Hawrylowicz, Marek Lommatzsch, David Jackson, Rene Lutter, Benjamin Marsland, Miriam Moffatt, Mike Thomas, J. Christian Virchow, Georgina Xanthou, Jessica Edwards, Samantha Walker, Sebastian L. Johnston
Journal: European Respiratory Journal (2017)

Asthma is a heterogeneous, complex disease with clinical phenotypes that incorporate persistent symptoms and acute exacerbations. It affects many millions of Europeans throughout their education and working lives and puts a heavy cost on European productivity. There is a wide spectrum of disease severity and control. Therapeutic advances have been slow despite greater understanding of basic mechanisms and the lack of satisfactory preventative and disease modifying management for asthma constitutes a significant unmet clinical need. Preventing, treating and ultimately curing asthma requires co-ordinated research and innovation across Europe. The European Asthma Research and Innovation Partnership (EARIP) is an FP7-funded programme which has taken a co-ordinated and integrated approach to analysing the future of asthma research and development. This report aims to identify the mechanistic areas in which investment is required to bring about significant improvements in asthma outcomes.
Annals Story Slam - Timeline
Authors: Rachel Kelz
Journal: Annals of Internal Medicine (2017)

Web Exclusives2 May 2017Annals Story Slam - TimelineFREERachel Kelz, MDRachel Kelz, MDFrom Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W17-0041 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Timeline "Timeline," by Dr. Rachel Kelz (Duration 6:49)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: From Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.Current Author Address: Rachel Kelz, MD, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA; e-mail, Rachel.[email protected]upenn.edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 2 May 2017Volume 166, Issue 9Page: SS1 ePublished: 2 May 2017 Issue Published: 2 May 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.Loading ...
A New Computational Method to Predict Long-Term Minimal Residual Disease and Molecular Relapse after TKI-Cessation in CML
Authors: Ingmar Glauche, Hendrik Liebscher, Christoph Baldow, Matthias Kuhn, Philipp Schulze, Tom Haehnel, Astghik Voskanyan, Joelle Guilhot, Stéphanie Dulucq, Nikolas von Bubnoff, Susanne Saussele, Satu Mustjoki, Philipp J. Jost, Francois Guilhot, François-Xavier Mahon, Ingo Roeder
Journal: Blood (2016)
Blast Crisis in a Dish: Generation of a Blast Crisis Model in Chronic Myeloid Leukemia (CML) Using Patient-Specific Induced Pluripotent Stem Cells ( iPSC)
Authors: Gladys Telliam, Christophe Desterke, Olivier Féraud, Frank Griscelli, Noufissa Oudrhiri, Micheline Fontaine Arnoux, Radhia Najar, Herve Acloque, Annelise Bennaceur-Griscelli, Ali G Turhan
Journal: Blood (2016)
Doxycycline for outpatient-treated acute exacerbations of COPD: a randomised double-blind placebo-controlled trial
Authors: Patricia van Velzen, Gerben ter Riet, Paul Bresser, Jeroen J Baars, Bob T J van den Berg, Jan W K van den Berg, Paul Brinkman, Jennece W F Dagelet, Johannes M A Daniels, Dewi R G L Groeneveld-Tjiong, René E Jonkers, Coen van Kan, Frans H Krouwels, Karin Pool, Arjan Rudolphus, Peter J Sterk, Jan M Prins
Journal: The Lancet Respiratory Medicine (2017)
PIK3IP1 Inhibition of PI3K in G1 Arrest Induced By CDK4 Inhibition Reprograms MCL for Ibrutinib Therapy
Authors: Maurizio Di Liberto, Xiangao Huang, Olivier Elemento, Ken Eng, Kristie A. Blum, Nancy L. Bartlett, Steven I. Park, Jia Ruan, Kami J. Maddocks, Giorgio Inghirami, Lewis Cantley, John P. Leonard, Peter Martin, Selina Chen-Kiang
Journal: Blood (2016)
Rapid and specific detection of Asian- and African-lineage Zika viruses
Authors: Nunya Chotiwan, Connie D. Brewster, Tereza Magalhaes, James Weger-Lucarelli, Nisha K. Duggal, Claudia Rückert, Chilinh Nguyen, Selene M. Garcia Luna, Joseph R. Fauver, Barb Andre, Meg Gray, William C. Black, Rebekah C. Kading, Gregory D. Ebel, Guillermina Kuan, Angel Balmaseda, Thomas Jaenisch, Ernesto T. A. Marques, Aaron C. Brault, Eva Harris, Brian D. Foy, Sandra L. Quackenbush, Rushika Perera, Joel Rovnak
Journal: Science Translational Medicine (2017)

A rapid, specific, sensitive, and inexpensive method has been developed that detects RNA from a Zika virus strain associated with the current outbreak.
F<scp>ifty</scp> Y<scp>ears of</scp> R<scp>esearch in</scp> ARDS.Mechanical Ventilation during Extracorporeal Support for Acute Respiratory Distress Syndrome. For Now, a Necessary Evil
Authors: Eddy Fan, Daniel Brodie, Arthur S. Slutsky
Journal: American Journal of Respiratory and Critical Care Medicine (2017)
Problems to be tackled by India’s national cancer screening programme
Authors: Archana Siddaiah
Journal: BMJ (2017)

The Indian government’s plan to screen for breast, cervix, and mouth cancers is a good one.1 In India, cancers of the lung, mouth, stomach, oesophagus, breast, and cervix continue to be a public health challenge.

Data from population based cancer registries show that the incidence of cancers varies geographically. For example, in …
Narrow-band imaging in the diagnosis of deep submucosal colorectal cancers: a systematic review and meta-analysis
Authors: Qing-Wei Zhang, La-Mei Teng, Xin-Tian Zhang, Jing-Jing Zhang, Ying Zhou, Zhi-Rui Zhou, Yi-Chao Hou, Zhi-Zheng Ge, Xiao-Bo Li
Journal: Endoscopy (2017)

Abstract Background and aims Magnifying endoscopy with narrow-band imaging (M-NBI) has been widely used in the differential diagnosis of deep submucosal colorectal cancers (dSMCs) from superficial submucosal cancers (sSMCs) and intramucosal neoplasms. We aimed to pool the diagnostic efficacy of M-NBI and compare it with that of magnifying chromoendoscopy (M-CE) in diagnosing colorectal dSMC. Methods PubMed, EMBASE, and the Cochrane Library were searched to identify eligible studies. Meeting abstracts were also searched. A bivariate mixed-effects binary regression model was used in the meta-analysis to calculate the pooled diagnostic efficacy of M-NBI and compare it with that of M-CE in the diagnosis of dSMC. Subgroup analyses and meta-regression were conducted to explore sources of heterogeneity. Results We included 17 studies: 14 full texts and 3 meeting abstracts. The pooled sensitivity, specificity, and area under the summary receiver operating characteristic curve (AUC) with 95 % confidence intervals (CIs) in diagnosing dSMC were 74 % (66 % – 81 %; I2 = 84.6 %), 98 % (94 % – 99 %; I2 = 94.4 %), and 0.91 (0.88 – 0.93), respectively, for M-NBI. The pooled sensitivity, specificity and AUC (95 %CI) were 84 % (76 % – 89 %; I2 = 76.9 %), 97 % (94 % – 99 %; I2 = 90.2 %), and 0.97 (0.95 – 0.98), respectively, for M-CE. M-NBI had lower sensitivity (P &lt; 0.01) than M-CE with similar specificity (P = 0.32). Subgroup analyses and meta-regression indicated that endoscopic diagnostic criteria, study type, endoscope type, risk of index test bias, and histopathological diagnostic criteria might be the sources of heterogeneity. Conclusions M-NBI and M-CE had comparable specificities in diagnosing dSMC, but the sensitivity of M-NBI was slightly lower than that of M-CE.
A Novel Diagnostic Strategy Using 16α-[18F]-Fluoro-17-β-Estradiol (18F-FES) PET/MRI to Achieve Complete Resection of Intravenous Leiomyomatosis in Reproductive-Age Women
Authors: Yoko Chino, Hideaki Tsuyoshi, Tetsuya Tsujikawa, Hidehiko Okazawa, Yoshio Yoshida
Journal: Clinical Nuclear Medicine (2017)

Intravenous leiomyomatosis is a life-threatening leiomyoma that grows into the extrauterine venous system. A high recurrence rate has been reported in reproductive-age women who undergo only tumor excision to preserve fertility. Precise diagnosis of tumor extension is essential to achieve complete resection. A 24-year-old woman presented with hypermenorrhea. Contrast-enhanced MRI showed an intramural myoma with worm-like extension into the right parametrium. F-FES PET/MRI accurately depicted the extension with strong FES activity into the right uterine vein, whereas F-FDG PET/MRI excluded the possibility of malignancy. These modalities can be a novel strategy to manage such cases of intractable intravenous leiomyomatosis.
Sorafenib as bridging therapy in patients with intermediate hepatocellular carcinoma.
Authors: Alessandro Vitale, Giuseppe Lombardi, Rafael Ramirez Morales, Sara Lonardi, Giacomo Zanus, Vittorina Zagonel, Umberto Cillo
Journal: Journal of Clinical Oncology (2012)

e14563 Background: Patients with intermediate stage hepatocellular carcinoma (HCC) obtaining an unsatisfactory response after loco regional (LR) therapies are at high risk of drop-out from a new chance of LR treatment or progression to advanced-terminal stages of disease. We prospectively used Sorafenib in this particular category of patients as a bridge therapy. The aim was to decrease the risk of tumour progression and to make them again eligible for loco regional therapies. Methods: Primary endpoint: disease control (DC) with Sorafenib, defined as complete/partial response or stable disease as by the modified RECIST criteria, maintained for ≥ 28 days from the first indications of response. Secondary endpoints: proportion of patients progression free at 2 months; median overall and progression free survivals. Patients obtaining DC with Sorafenib were again considered eligible for LR therapy. Inclusion criteria: a) intermediate stage; b) Child Pugh class A; c) performance status 0; d) unsatisfactory response to LR therapies (resection, ablation, chemoembolization), defined as incomplete response after at least 2 LR therapies. Study period: 01/04/2008–31/10/2011. End of follow-up: 31/01/2012. Results: Forty one patients were enrolled according to the study design. Thirty seven patients (90%) were progression free at the 2 months evaluation. A persistent DC was obtained in 29 patients (71%). According to the study hypothesis these patients were considered again eligible for loco regional therapies: 19 patients (65%) had ablation ± chemoembolization; 6 had liver transplantation (22%); 3 had liver resection (13%); 1 had radioembolization. Median duration of therapy with Sorafenib was 5 months (1–22). Sixteen patients (55%) had Sorafenib therapy both before and after LR therapy. Fourteen patients (48%) had more than one LR procedure. Median survival was 21 months (range, 1–39) in the whole group, while it was 25 months (range, 2–39) in the DC subgroup (median time to progression = 21 months, range 2–39). Conclusions: Sorafenib achieves high DC rates in BCLC B HCC patients with unsatisfactory response to LR therapies making them again eligible for LR therapies.
Abstract 30: Endurance Exercise Induces Cardiac Hypertrophy in Aged Nrf2-/- Mice
Authors: Rajasekaran Namakkal Soorappan, Dinesh Devdoss, Snkaranarayanan Kannan, Curtis Olsen, Sellamuthu Subbanna Gounder, Christopher J Davidson, Kevin Whitehead, E. Dale Abel
Journal: Circulation Research (2012)

Background: Radical forms of oxygen and nitrogen species (ROS/RNS) are highly reactive with nucleic acids, proteins and lipids and promote their oxidation. Normally, cellular ROS/RNS concentrations are tightly controlled by the inducible antioxidant system, which is predominantly regulated by the transcription factor Nrf2 (nuclear erythroid-2 like factor-2) and its cytosolic repressor protein, Keap1. We hypothesized that a decrease or an abrogation of Nrf2 impairs cardiac function and induce hypertrophy upon endurance stress in aging heart. Methods: Age-matched wild-type (WT) and Nrf2-/- (KO) mice (n=12/gp) at 2 and &gt;20 months were subjected to endurance exercise stress (EES; 20 meter/min, 12% grade) and assessed the activation of Nrf2/ARE-dependent transcriptional mechanisms in the heart. Cardiac hypertrophy was determined by echocardiography, heart/body weight ratio and biochemical/molecular marker analyses. Results: Interestingly, both old-WT and Nrf2-/- mice exhibited oxidative stress on EES due to significant decrease or abrogation of Nrf2 nuclear levels, respectively, suggesting that aged-WT is equally susceptible to stress as Nrf2-/- mice. Age-dependent loss of Nrf2 decreased the transcription of Nrf2-dependent antioxidants and thereby elevated ROS levels to cause a more oxidized intracellular environment. Importantly, the loss of Nrf2 induced cardiac hypertrophy upon endurance stress in the aged (&gt;20 mon) mice. At the end of 2-weeks of endurance stress, both the old-WT and Nrf2-/- mice had developed cardiac hypertrophy. Also, qPCR analysis showed significant (p&lt;0.05) upregulation of hypertrophy markers (ANF and BNF) in the old-WT or Nrf2-/- when compared to sedentary WT mice confirmed cardiac hypertrophy due to loss of Nrf2. These results indicate that either a decrease or an abrogation of Nrf2 can increase susceptibility to stress induced hypertrophy in an aging heart. Conclusions: We conclude that enhancing protein levels and stability of nuclear Nrf2 could activate the transcription of major antioxidant enzymes and biosynthesis of key antioxidants. Enhancing protective mechanisms against oxidative stress in the elderly is expected to prevent or delay the onset of age-associated cardiac hypertrophy and cardiomyopathy.
Clinical Outcome and Immune Recovery after Adoptive Infusion of BPX-501 Cells (donor T cells transduced with iC9 suicide gene) in Children with Hemoglobinopathies and Diamond-Blackfan Anemia Given α/β T-Cell Depleted HLA-Haploidentical Stem Cell Transplantation (HSCT)
Authors: Alice Bertaina, Pietro Merli, Daria Pagliara, Giuseppina Li Pira, Biagio De Angelis, Letizia Pomponia Brescia, Luisa Strocchio, Francesca Del Bufalo, Mauro Montanari, Barbarella Lucarelli, Mattia Algeri, Martha French, Annemarie Moseley, Franco Locatelli
Journal: Blood (2016)