tbuckley/cabot-search huggingface dataset:
Certolizumab pegol for the treatment of chronic plaque psoriasis: Results through 48 weeks from 2 phase 3, multicenter, randomized, double-blinded, placebo-controlled studies (CIMPASI-1 and CIMPASI-2)
Authors: Alice B. Gottlieb, Andrew Blauvelt, Diamant Thaçi, Craig L. Leonardi, Yves Poulin, Janice Drew, Luke Peterson, Catherine Arendt, Daniel Burge, Kristian Reich
Journal: Journal of the American Academy of Dermatology (2018)

Certolizumab pegol, the only Fc-free, PEGylated anti-tumor necrosis factor biologic, demonstrated clinically meaningful improvements suggestive of a positive risk-benefit balance in phase 2 studies in adults with moderate-to-severe chronic plaque psoriasis.Assess certolizumab efficacy and safety versus placebo in phase 3 studies.Patients with moderate-to-severe chronic plaque psoriasis were randomized 2:2:1 to certolizumab 400 mg, certolizumab 200 mg, or placebo every 2 weeks. At week 16, certolizumab-treated patients achieving a 50% reduction in Psoriasis Area and Severity Index continued treatment through week 48. Coprimary endpoints were week 16 responder rates, defined as a 75% reduction in Psoriasis Area and Severity Index and Physician's Global Assessment 0/1 (clear/almost clear) and ≥2-point improvement. Safety was assessed by treatment-emergent adverse events.Week-16 endpoints were significantly greater for both doses of certolizumab versus placebo, and the responses were maintained through week 48. For most measures, improvement was numerically greater for certolizumab 400 mg. No unexpected safety signals were identified.There was no active comparator.Treatment with either certolizumab 400 mg or 200 mg every 2 weeks was associated with significant and clinically meaningful improvements in moderate-to-severe psoriasis. The 400-mg dose could provide additional clinical benefit. The safety profile was consistent with the therapeutic class.
Time-dependent differences in management and microbiology of orthopaedic internal fixation-associated infections: an observational prospective study with 229 patients
Authors: R. Kuehl, S. Tschudin-Sutter, M. Morgenstern, M. Dangel, A. Egli, A. Nowakowski, N. Suhm, C. Theilacker, A.F. Widmer
Journal: Clinical Microbiology and Infection (2018)
Eculizumab (ECU) Inhibits Thrombotic Microangiopathy (TMA) and Improves Renal Function In Pediatric Patients (Pts) With Atypical Hemolytic Uremic Syndrome (aHUS)
Authors: Larry Greenbaum, Marc Fila, Gianluigi Ardissino, Samhar Al-Akash, Jonathan Evans, Paul Henning, Kenneth Lieberman, Silvio Maringhini, Lars Pape, Lesley Rees, Nicole Kar, Johan Vande Walle, Masayo Ogawa, Camille L. Bedrosian, Christoph Licht
Journal: Blood (2013)
Serum from Asian patients with atopic dermatitis is characterized by TH2/TH22 activation, which is highly correlated with nonlesional skin measures
Authors: Huei-Chi Wen, Tali Czarnowicki, Shinji Noda, Kunal Malik, Ana B. Pavel, Saeko Nakajima, Tetsuya Honda, Jung U. Shin, Hemin Lee, Margaret Chou, Yeriel Estrada, Xiuzhong Zheng, Hui Xu, James G. Krueger, Kwang-Hoon Lee, Kenji Kabashima, Emma Guttman-Yassky
Journal: Journal of Allergy and Clinical Immunology (2018)
New insights into the regulatory role of microRNA in tumor angiogenesis and clinical implications
Authors: Ye Wang, Liya Wang, Cheng Chen, Xiaoyuan Chu
Journal: Molecular Cancer (2018)

Angiogenesis is essential for tumor growth and metastasis. Understanding the regulation of tumor angiogenesis has become increasingly important. MicroRNAs (miRNAs) are small noncoding RNAs that function in diverse biological processes via post-transcriptional regulation. Extensive studies have revealed two important regulatory roles of miRNAs in tumor angiogenesis: miRNAs in tumor cells affect the activity of endothelial cells via non-cell-autonomous mechanisms, and miRNAs in endothelial cells regulate the cell-autonomous behavior. Recent advances have further highlighted the role of tumor-derived extracellular vesicles in the regulation of tumor angiogenesis via transferring miRNAs to endothelial cells. In this review, we summarize the regulatory role of miRNA in tumor angiogenesis, with a highlight on clinical implications of miRNAs as biomarkers for anti-angiogenic therapy response, and as therapeutic interventions against tumor angiogenesis in vivo.
Prenatal Exposure to DDT and Pyrethroids for Malaria Control and Child Neurodevelopment: The VHEMBE Cohort, South Africa
Authors: Brenda Eskenazi, Sookee An, Stephen A. Rauch, Eric S. Coker, Angelina Maphula, Muvhulawa Obida, Madelein Crause, Katherine R. Kogut, Riana Bornman, Jonathan Chevrier
Journal: Environmental Health Perspectives (2018)

Background: Although indoor residual spraying (IRS) with dichlorodiphenyltrichloroethane (DDT) and pyrethroids effectively controls malaria, it potentially increases human exposure to these insecticides. Previous studies suggest that prenatal exposure to these insecticides may impact human neurodevelopment. Objectives: We aimed to estimate the effects of maternal insecticide exposure and neurodevelopment of toddlers living in a malaria-endemic region currently using IRS. Methods: The Venda Health Examination of Mothers, Babies and their Environment (VHEMBE) is a birth cohort of 752 mother–child pairs in Limpopo, South Africa. We measured maternal exposure to DDT and its breakdown product, dichlorodiphenyldichloroethylene (DDE), in maternal serum, and measured pyrethroid metabolites in maternal urine. We assessed children's neurodevelopment at 1 and 2 y of age using the Bayley Scales of Infant Development, third edition (BSID-III), and examined associations with maternal exposure. Results: DDT and DDE were not associated with significantly lower scores for any BSID-III scale. In contrast, each 10-fold increase in cis-DCCA, trans-DCCA, and 3-phenoxybenzoic acid were associated, respectively, with a −0.70 (95% CI: −1.25, −0.15), −0.49 (95% CI: −0.96, −0.02), and −0.65 (−1.23, −0.06) decrement in Social-Emotional scores at 1 y of age. In addition, each 10-fold increase in maternal cis-DBCA levels was associated with significant decrements at 2 y of age in Language Composite scores and Expressive Communication scores [β=−1.90 (95% CI: −3.67, −0.14) and β=−0.41 (95% CI: −0.81, −0.01), respectively, for a 10-fold increase]. Significant differences by sex were estimated for pyrethroid metabolites and motor function scores at 2 y of age, with higher scores for boys and lower scores for girls. Conclusions: Prenatal exposure to pyrethroids may be associated at 1 y of age with poorer social-emotional development. At 2 y of age, poorer language development was observed with higher prenatal pyrethroid levels. Considering the widespread use of pyrethroids, these findings deserve further investigation. https://doi.org/10.1289/EHP2129
Who Should Be Investigated for Haematuria? Results of a Contemporary Prospective Observational Study of 3556 Patients
Authors: Wei Shen Tan, Andrew Feber, Rachael Sarpong, Pramit Khetrapal, Simon Rodney, Rumana Jalil, Hugh Mostafid, Joanne Cresswell, James Hicks, Abhay Rane, Alastair Henderson, Dawn Watson, Jacob Cherian, Norman Williams, Chris Brew-Graves, John D. Kelly
Journal: European Urology (2018)
Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial
Authors: Annemieke Cats, Edwin P M Jansen, Nicole C T van Grieken, Karolina Sikorska, Pehr Lind, Marianne Nordsmark, Elma Meershoek-Klein Kranenbarg, Henk Boot, Anouk K Trip, H A Maurits Swellengrebel, Hanneke W M van Laarhoven, Hein Putter, Johanna W van Sandick, Mark I van Berge Henegouwen, Henk H Hartgrink, Harm van Tinteren, Cornelis J H van de Velde, Marcel Verheij, Frits Van Coevorden, Steven Vanhoutvin, Maarten CCM Hulshof, Olaf JL Loosveld, A (Bert) Jan Ten Tije, Frans LG Erdkamp, Fabienne ARM Warmerdam, Donald L Van der Peet, Henk MW Verheul, Djamila Boerma, Maartje Los, Annerie Slot, Danny Houtsma, Johanna EA Portielje, Reinoud JB Blaisse, Ernst Jan Spillenaar Bilgen, Marco B Polée, Maud M Geenen, Jeffrey PBM Braak, Karen J Neelis, Marije Slingerland, Rob LH Jansen, Jeroen Buijsen, Aart Beeker, Quirijn AJ Eijsbouts, Johanna MGH Van Riel, Tom Rozema, Dick Johan Van Spronsen, Jetske M Meerum Terwogt, Bea C Tanis, Adelheid ME Van der Torren-Conze, Richard Van Hilligersberg, Miriam Koopman, Marien O Den Boer, Geert-Jan Creemers, Maurice Van der Sangen, Marjolein EM Rentinck, H Pieter Van den Berg, Ge JPM Jonkers, Diane Grootenboers, Annelie JE Vulink, Sjoerd Hovenga, Huub CJ Van der Mijle, Arnold Baars, Annebeth W Haringhuizen, Marije IE Appels, Ron C Rietbroek, Ellen M Hendriksen, Marie-Cecile JC Legdeur, Daan Ten Bokkel Huinink, O Aart Van Dobbenburgh, Jitty M Smit, Aart Van Bochove, Gerrit-Jan Veldhuis, Erik W Muller, J (Han) J Bonenkamp, Pètra M Braam, Jaap De Boer, Henk K Van Halteren, Fransje AA Valster, Alex LT Imholz, Marjan A Van Dijk, Ate Van der Gaast, J (Hans)-Martin MB Otten, Heleen M Ceha, Bengt Glimelius, Cecillia Lagerbäck, Mats Perman, Anders Johnsson, David Borg, Niels H Nielsen, Andrzej Piwowar, Mattias Elmlund, Helene Hörberg, Per Edlund, Bengt Johansson, Petra Flygare, Marie Louise Jespersen
Journal: The Lancet Oncology (2018)
Gemcitabine loaded microbubbles for targeted chemo-sonodynamic therapy of pancreatic cancer
Authors: Heather Nesbitt, Yingjie Sheng, Sukanta Kamila, Keiran Logan, Keith Thomas, Bridgeen Callan, Mark A. Taylor, Mark Love, Declan O'Rourke, Paul Kelly, Estelle Beguin, Eleanor Stride, Anthony P. McHale, John F. Callan
Journal: Journal of Controlled Release (2018)
Mrgprs on vagal sensory neurons contribute to bronchoconstriction and airway hyper-responsiveness
Authors: Liang Han, Nathachit Limjunyawong, Fei Ru, Zhe Li, Olivia J. Hall, Haley Steele, Yuyan Zhu, Julie Wilson, Wayne Mitzner, Marian Kollarik, Bradley J. Undem, Brendan J. Canning, Xinzhong Dong
Journal: Nature Neuroscience (2018)
Phase I study with pegylated human IL-10 (AM0010) alone or in combination with anti-PD-1 or FOLFOX-immune biomarker update.
Authors: Aung Naing, Jeffrey R. Infante, J. Randolph Hecht, Kyriakos P. Papadopoulos, Deborah Jean Lee Wong, Karen A. Autio, Gerald Steven Falchook, Manish R. Patel, Patrick Alexander Ott, Amita Patnaik, Johanna C. Bendell, Peter Van Vlasselaer, David S. Hong, Nizar M. Tannir, Martin Oft
Journal: Journal of Clinical Oncology (2017)

157 Background: Persistence of activated CD8 T cells is essential for the durability of tumor immune responses. IL-10 is an anti-inflammatory cytokine, PEGylated IL-10 (AM0010) enhances tumor specific CD8 T cell expansion and cytotoxicity. We evaluated tolerability and efficacy of AM0010 alone, with chemotherapy or anti-PD-1 in a phase 1 study. AM0010 alone induces objective anti-tumor responses without auto-immune toxicities. AM0010 with anti-PD-1 was evaluated in RCC (n=8) or NSCLC (n=5) and showed improved response rates (ORR 50 and 40% respectively) compared to published ORR with anti-PD-1 monotherapy. AM0010 and FOLFOX for 2nd LOT pancreatic cancer increased the ORR compared to FOLFOX. Expansion cohorts for AM0010 and FOLFOX in pancreatic cancer (n=20) or with anti-PD-1 in RCC (n=30) or NSCLC (n=30) were evaluated. Methods: Observed tumor responses were monitored using irRC criteria. Immune responses were analysed for 96 serum cytokines. Activation of PBMC derived CD4 and CD8 T cells were analyzed by FACS. The expansion of the T cell repertoire was measured by deep sequencing of the TCR. Results: AM0010 induced systemic, sustained elevation of Th1 and Th2 type cytokines and cytotoxic products of CD8+ T cells. Th17 related cytokines were reduced. In-vitro, AM0010 inhibits activation induced cell death. Phosphorylated STAT3 (p-STAT3) was induced in activated CD8+ T cells in vitro and in tumors. In addition, PD1+ Lag-3+ KI-67+ CD8+ T cells expanded in the blood, remained Tim-3- CTLA-4-. Expansion of PD-1+ Lag-3+ CD8+ T cells correlate with objective tumor response. AM0010 treatment also resulted in the progressive systemic expansion of novel T cell clones, which were not detectable in the patient prior to treatment. This de-novo expansion coincided with tumor responses in several patients. The magnitude of this expansion correlated with the magnitude of objective tumor responses. The immune activation was similar in monotherapy and in the combination arms, suggesting a AM0010 specific and non-redundant mechanism of action. Conclusions: AM0010 has predominantly immune stimulatory activity in cancer patients, alone and in combination with other immune oncology therapies. Clinical trial information: NCT02009449.
Hypopigmented Skin Lesions After Immunotherapy
Authors: Ecaterina Ileana Dumbrava, Doina Ivan, Vivek Subbiah
Journal: JAMA Oncology (2018)

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Pretreatment Rostral Anterior Cingulate Cortex Theta Activity in Relation to Symptom Improvement in Depression
Authors: Diego A. Pizzagalli, Christian A. Webb, Daniel G. Dillon, Craig E. Tenke, Jürgen Kayser, Franziska Goer, Maurizio Fava, Patrick McGrath, Myrna Weissman, Ramin Parsey, Phil Adams, Joseph Trombello, Crystal Cooper, Patricia Deldin, Maria A. Oquendo, Melvin G. McInnis, Thomas Carmody, Gerard Bruder, Madhukar H. Trivedi
Journal: JAMA Psychiatry (2018)

Major depressive disorder (MDD) remains challenging to treat. Although several clinical and demographic variables have been found to predict poor antidepressant response, these markers have not been robustly replicated to warrant implementation in clinical care. Increased pretreatment rostral anterior cingulate cortex (rACC) theta activity has been linked to better antidepressant outcomes. However, no prior study has evaluated whether this marker has incremental predictive validity over clinical and demographic measures.To determine whether increased pretreatment rACC theta activity would predict symptom improvement regardless of randomization arm.A multicenter randomized clinical trial enrolled outpatients without psychosis and with chronic or recurrent MDD between July 29, 2011, and December 15, 2015 (Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care [EMBARC]). Patients were consecutively recruited from 4 university hospitals: 634 patients were screened, 296 were randomized to receive sertraline hydrochloride or placebo, 266 had electroencephalographic (EEG) recordings, and 248 had usable EEG data. Resting EEG data were recorded at baseline and 1 week after trial onset, and rACC theta activity was extracted using source localization. Intent-to-treat analysis was conducted. Data analysis was performed from October 7, 2016, to January 19, 2018.An 8-week course of sertraline or placebo.The 17-item Hamilton Rating Scale for Depression score (assessed at baseline and weeks 1, 2, 3, 4, 6, and 8).The 248 participants (160 [64.5%] women, 88 [35.5%] men) with usable EEG data had a mean (SD) age of 36.75 (13.15) years. Higher rACC theta activity at both baseline (b = -1.05; 95% CI, -1.77 to -0.34; P = .004) and week 1 (b = -0.83; 95% CI, -1.60 to -0.06; P < .04) predicted greater depressive symptom improvement, even when controlling for clinical and demographic variables previously linked with treatment outcome. These effects were not moderated by treatment arm. The rACC theta marker, in combination with clinical and demographic variables, accounted for an estimated 39.6% of the variance in symptom change (with 8.5% of the variance uniquely attributable to the rACC theta marker).Increased pretreatment rACC theta activity represents a nonspecific prognostic marker of treatment outcome. This is the first study to date to demonstrate that rACC theta activity has incremental predictive validity.clinicaltrials.gov Identifier: NCT01407094.
Reply to Francesco Massari and Vincenzo Di Nunno's Letter to the Editor re: Jose Luis Perez-Gracia, Yohann Loriot, Jonathan E. Rosenberg, et al. Atezolizumab in Platinum-treated Locally Advanced or Metastatic Urothelial Carcinoma: Outcomes by Prior Number of Regimens. Eur Urol 2018;73:462–8
Authors: Jose Luis Perez-Gracia
Journal: European Urology (2018)
Changes in peripheral lymphocyte subpopulations following radiation therapy.
Authors: Franco Campostrini, M Zorzi, G Capodaglio, E Guizzardi, E Nicolis, P Battaglia
Journal: Journal of Clinical Oncology (2017)

128 Background: Since ionizing radiation can affect the immune system, in this research we sought to analyze the changes of peripheral blood lymphocyte subpopulations (LS) in patients undergoing Radiation Therapy (RT). Methods: In 2015 we enrolled 58 patients, 97% with no systemic cancer (breast 47%, prostate 23%,head and neck 16%, abdomen-pelvis 11%, metastases 3%). The percentages of patients with lowered LS were determined prior to RT, and at different intervals in the patients’ history.The average dose of RT was 50Gy (+/-10 ) with 2 Gy/day fractions. Results: As baseline, total T lymphocytes, T helper, T suppressor, B lymphocytes and Natural Killer cells, were reduced vs. normal range in 24%, 33%, 24%, 59% and null of patients, respectively.A second blood sample was withdrawn after 14-58 days (mean 36) from starting RT, in which we found significantly increased the patients damaged up to 66%, 65%, 62%, 88% and 7% (p=&lt; 0,0001 for each LS ). Compared with the nadir of LS depletion, at 44 (5-180) and 153 (43-130) days from the completion of RT, all the LS raised significantly, except for a weak value of T Helper category (p=0,0145 and 0,0226 respectively). Conclusions: After common RT regimens for solid tumors, all LS can be substantially impaired, and for the T Helper the recovery is particularly slow in the following months.
Genetic and mechanistic diversity in pediatric hemophagocytic lymphohistiocytosis
Authors: Ivan K. Chinn, Olive S. Eckstein, Erin C. Peckham-Gregory, Baruch R. Goldberg, Lisa R. Forbes, Sarah K. Nicholas, Emily M. Mace, Tiphanie P. Vogel, Harshal A. Abhyankar, Maria I. Diaz, Helen E. Heslop, Robert A. Krance, Caridad A. Martinez, Trung C. Nguyen, Dalia A. Bashir, Jordana R. Goldman, Asbjørg Stray-Pedersen, Luis A. Pedroza, M. Cecilia Poli, Juan C. Aldave-Becerra, Sean A. McGhee, Waleed Al-Herz, Aghiad Chamdin, Zeynep H. Coban-Akdemir, Shalini N. Jhangiani, Donna M. Muzny, Tram N. Cao, Diana N. Hong, Richard A. Gibbs, James R. Lupski, Jordan S. Orange, Kenneth L. McClain, Carl E. Allen
Journal: Blood (2018)
Potential role of hypovitaminosis D in renal cell carcinoma patients treated with immune-checkpoint inhibitors.
Authors: Melissa Bersanelli, Augusto Vaglio, Nicola Sverzellati, Maricla Galetti, Monia Incerti, Raffaele Parziale, Michele Corrado, Agnese Cosenza, Leonarda Ferri, Francesco Leonardi, Sebastiano Buti
Journal: Journal of Clinical Oncology (2017)

50 Background: hypovitaminosis D is frequent in renal diseases but it was never reported in metastatic renal cell carcinoma (mRCC). The interaction between vitamin D and its receptor (VDR) has a key role for T-cell activation. Naïve T-cells do not express VDR and had very low expression of phospholipase C-γ1 (PLC-γ1), with low responsiveness to T-cell receptor (TCR). Initial TCR signaling induces VDR expression and upregulates PLC-γ1 via the kinase p38 pathway. VDR interaction with high concentrations of vitamin D and PLC-γ1 increase are required to trigger classical TCR signaling, increasing T-cell responsiveness. On these basis, we hypothesized that hypovitaminosis D could contribute to lower responsiveness to immune-checkpoint inhibitors (CKI). Methods: we assessed vitamin D levels of mRCC patients undergoing therapy with CKI, with the aim to reveal hypovitaminosis D, evaluate its prevalence and hypothesize its potential role in the outcome of treatment with CKI. Results: of 10 mRCC patients pretreated with tyrosine-kinase inhibitors, vitamin D levels assessed before the first treatment with nivolumab (anti-PD1 CKI) revealed deficiency in 80% of cases (8 patients). Hypovitaminosis D was severe ( &lt; 20 ng/ml) in 7 cases and moderate ( &lt; 30 ng/ml) in one. The 2 patients without deficiency (20%), had vitamin D values near to the lower limit of normality. Oral supplementation with cholecalciferol was given when necessary, likely confounding the possible influence of vitamin D deficiency on the outcome of CKI treatment. Vitamin D normal values after two months of therapy were recovered in the great majority of cases. Interestingly, the only patient who achieved a good objective response to treatment had normal values of vitamin D before therapy. Conclusions: hypovitaminosis D could have a relevant prevalence in mRCC patients. Considering the role of vitamin D in T-cell activation, assessment of its levels and initiation of a supplementation before immunotherapy should be considered to enhance responsiveness. On the basis of these observations, we are planning a perspective multicenter study to investigate the role of hypovitaminosis D in mRCC patients treated with CKI (PRoviDenCe study).