tbuckley/cabot-search huggingface dataset:
Therapeutic and prophylactic deletion of IL‐4Ra‐signaling ameliorates established ovalbumin induced allergic asthma
Authors: Jermaine Khumalo, Frank Kirstein, Martyna Scibiorek, Sabelo Hadebe, Frank Brombacher
Journal: Allergy (2019)

Abstract Background Allergic asthma is a chronic inflammatory airway disease driven predominantly by a T H 2 immune response to environmental allergens. IL‐4Rα‐signaling is essential for driving T H 2‐type immunity to allergens. Anti‐T H 2 therapies have the potential to effectively reduce airway obstruction and inflammation in allergic asthma. Objective We investigated potential therapeutic effects of selective inhibition of this pathway in mice with established allergic airway disease. We further investigated whether IL‐4Rα disruption in systemically sensitized mice can prevent the onset of the disease. Methods We used Rosa creERT2 IL‐4Rα −/lox mice, a tamoxifen (TAM)‐inducible IL‐4Rα knockdown model to investigate the role of IL‐4/IL‐13 signaling prior to the onset of the disease and during the effector phase in the ovalbumin‐induced allergic airway disease. Results Inducible deletion of IL‐4Rα demonstrated therapeutic effects, on established allergic airway disease, and prevented the development of ovalbumin‐induced airway hyperreactivity, eosinophilia, and goblet cell metaplasia in allergen‐sensitized mice. Interestingly, IL‐4Rα knockdown after allergic sensitization did not induce T H 17, a neutrophilic inflammatory response as observed in global IL‐4Rα‐deficient mice after intranasal allergen challenge. Conclusion Abrogation of IL‐4Rα signaling after allergic sensitization would have significant therapeutic benefit for T H 2‐type allergic asthma.
Efficacy of IMGN901 (huN901-DM1) in combination with bortezomib and lenalidomide against multiple myeloma cells in preclinical studies
Authors: Kathleen Whiteman, Olga Ab, Laura Bartle, Klaudia Foley, Victor Goldmacher, Robert Lutz
Journal: Cancer Research (2008)

2146  IMGN901 (huN901-DM1) is an antibody-maytansinoid conjugate which targets CD56 and is being evaluated as a single agent in patients with CD56-positive multiple myeloma (MM) in a Phase I clinical trial. Preclinical studies to assess the activity of IMGN901 in combination with drugs commonly used for the treatment of MM have previously demonstrated that combinations of IMGN901 with melphalan, thalidomide, and dexamethasone produced additive-to-synergistic cytotoxic effects (AACR 2007). However, the combination of IMGN901 with bortezomib was shown to be slightly antagonistic in vitro. Here we further examine combinations of IMGN901 with bortezomib and with the recently approved anti-myeloma agent, lenalidomide, using human CD56-positive MM cell lines in culture and as xenografts in mice.  To understand the nature of the in vitro interaction of IMGN901 with bortezomib, we evaluated whether bortezomib affected the rate of IMGN901 internalization, the release of the maytansinoid agent (MAY) from the conjugate within MM cells, or the ability of the MAY to kill cancer cells. While bortezomib had no effect on conjugate internalization or processing, we found that bortezomib did antagonize the cytotoxic activity of MAY similarly to its effect on conjugate. Interestingly, combinations of IMGN901 with bortezomib were found to be additive-to-synergistic against human MM xenografts in mice, suggesting that the interaction of these agents in vivo is different than observed in vitro. The difference may be related to the potential impact of bortezomib on the tumor microenvironment in vivo.  As lenalidomide is now used to treat MM, we also examined the cytotoxic activity of IMGN901 in combination with lenalidomide and found them to be synergistic in vitro against MOLP8 and NCI H929 cells. The combination of IMGN901 and lenalidomide also demonstrated additive-to-synergistic efficacy when used to treat SCID mice bearing established subcutaneous human MM xenograft tumors.  Our preclinical results provide strong rationale for the clinical evaluation of IMGN901 in combination with the commonly used anti-neoplastic agents melphalan, thalidomide, dexamethasone, bortezomib or lenalidomide for the treatment of patients with CD56-positive multiple myeloma.
Transactions of the American Pediatric Society.
Journal: JAMA (1898)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Maternal exposure to fine particulate matter during pregnancy induces progressive senescence of hematopoietic stem cells under preferential impairment of the bone marrow microenvironment and aids development of myeloproliferative disease
Authors: Govinda Bhattarai, Jae Bong Lee, Min-Hye Kim, Suhan Ham, Han-Sol So, Sangmin Oh, Hyun-Jaung Sim, Jeong-Chae Lee, Mijung Song, Sung-Ho Kook
Journal: Leukemia (2019)
Standalone smartphone apps for mental health—a systematic review and meta-analysis
Authors: Kiona K. Weisel, Lukas M. Fuhrmann, Matthias Berking, Harald Baumeister, Pim Cuijpers, David D. Ebert
Journal: npj Digital Medicine (2019)

Abstract While smartphone usage is ubiquitous, and the app market for smartphone apps targeted at mental health is growing rapidly, the evidence of standalone apps for treating mental health symptoms is still unclear. This meta-analysis investigated the efficacy of standalone smartphone apps for mental health. A comprehensive literature search was conducted in February 2018 on randomized controlled trials investigating the effects of standalone apps for mental health in adults with heightened symptom severity, compared to a control group. A random-effects model was employed. When insufficient comparisons were available, data was presented in a narrative synthesis. Outcomes included assessments of mental health disorder symptom severity specifically targeted at by the app. In total, 5945 records were identified and 165 full-text articles were screened for inclusion by two independent researchers. Nineteen trials with 3681 participants were included in the analysis: depression ( k = 6), anxiety ( k = 4), substance use ( k = 5), self-injurious thoughts and behaviors ( k = 4), PTSD ( k = 2), and sleep problems ( k = 2). Effects on depression (Hedges’ g = 0.33, 95%CI 0.10–0.57, P = 0.005, NNT = 5.43, I 2 = 59%) and on smoking behavior ( g = 0.39, 95%CI 0.21–0.57, NNT = 4.59, P ≤ 0.001, I 2 = 0%) were significant. No significant pooled effects were found for anxiety, suicidal ideation, self-injury, or alcohol use ( g = −0.14 to 0.18). Effect sizes for single trials ranged from g = −0.05 to 0.14 for PTSD and g = 0.72 to 0.84 for insomnia. Although some trials showed potential of apps targeting mental health symptoms, using smartphone apps as standalone psychological interventions cannot be recommended based on the current level of evidence.
Primary Plasma Cell Leukemia Outcomes Remain Dismal Despite Novel Agents and Hematopoietic Cell Transplantation
Authors: Sagar Patel, Saulius K. Girnius, Binod Dhakal, Lohith Gowda, Raphael Fraser, Omar Davila, Nina D. Shah, Muzaffar H. Qazilbash, Shaji K. Kumar, Anita D'Souza, Parameswaran Hari
Journal: Blood (2019)
Incidence of Serious Adverse Events, Pneumonitis, Infection and Sepsis in Patients with Relapsed and Refractory Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma Treated with Phosphatidylinositol 3-Kinase (PI3K) Inhibitors
Authors: Sriman Swarup, Donald P. Quick, Anita Sultan, Myint Aung Win, Ei Moe Phyu, Thura Win Htut, Sariya Wongsaengsak, Myet Mon Zin, Myat Min Han, Yin Mon Myat, Sanjay Awasthi, Lukman Tijani, Kyaw Zin Thein
Journal: Blood (2019)
PD1Hi CD8+ T cells correlate with exhausted signature and poor clinical outcome in hepatocellular carcinoma
Authors: Jiaqiang Ma, Bohao Zheng, Shyamal Goswami, Lu Meng, Dandan Zhang, Chunmei Cao, Teng Li, Fangming Zhu, Lijie Ma, Zhao Zhang, Shuhao Zhang, Meng Duan, Qin Chen, Qiang Gao, Xiaoming Zhang
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> CD8<sup>+</sup> T cells differentiate into exhausted status within tumors, including hepatocellular carcinoma (HCC), which constitutes a solid barrier to effective anti-tumor immunity. A detailed characterization of exhausted T cells and their prognostic value in HCC is lacking. <h3>Methods</h3> We collected fresh tumor tissues with adjacent non-tumor liver tissues and blood specimens of 56 HCC patients, as well as archived samples from two independent cohorts of HCC patients (<i>n</i> = 358 and <i>n</i> = 254), who underwent surgical resection. Flow cytometry and multiplex immunostaining were used to characterize CD8<sup>+</sup> T cells. Patient prognosis was evaluated by Kaplan-Meier analysis and Cox regression analysis. <h3>Results</h3> CD8<sup>+</sup> T cells were classified into three distinct subpopulations: PD1<sup>Hi</sup>, PD1<sup>Int</sup> and PD1<sup>−</sup>. PD1<sup>Hi</sup> CD8<sup>+</sup> T cells were significantly enriched in tumor compared to adjacent non-tumor liver tissues. PD1<sup>Hi</sup> CD8<sup>+</sup> T cells highly expressed exhaustion-related inhibitory receptors (TIM3, CTLA-4, etc.) and transcription factors (Eomes, BATF, etc.). In addition, PD1<sup>Hi</sup> CD8<sup>+</sup> T cells expressed low levels of cytotoxic molecules and displayed a compromised capacity to produce pro-inflammatory cytokines while the expression of anti-inflammatory IL-10 was up-regulated following mitotic stimulation. Furthermore, PD1<sup>Hi</sup> CD8<sup>+</sup> T cells shared features with tissue resident memory T cells and were also characterized in an aberrantly activated status with an apoptosis-prone potential. In two independent cohorts of HCC patients (<i>n</i> = 358 and <i>n</i> = 254), we demonstrated that PD1<sup>Hi</sup> or TIM3<sup>+</sup>PD1<sup>Hi</sup> CD8<sup>+</sup> T cells were significantly correlated with poor prognosis, and the latter was positioned in close proximity to PD-L1<sup>+</sup> tumor associated macrophages. <h3>Conclusion</h3> The current study unveils the unique features of PD1<sup>Hi</sup> CD8<sup>+</sup> exhausted T cells in HCC, and also suggests that exhausted T cells could act as a biomarker to select the most care-demanding patients for tailored therapies.
Clinical characteristics of portal hypertension complicated by gastroesophageal varices in patients with myeloproliferative neoplasms
Authors: Jaejun Lee, Pil Soo Sung, Ki-Seong Eom, Hyun Yang, Soon Kyu Lee, Aung Hlaing Bwa, Angelo Lozada, Jeong Won Jang, Si Hyun Bae, Jong Young Choi, Seung Kew Yoon
Journal: Clinical and Molecular Hepatology (2019)
Retinal vasculometric characteristics and their associations with polymyalgia rheumatica and giant cell arteritis in a prospective cohort: EPIC-Norfolk Eye Study
Authors: Max Yates, Roshan Welikala, Alicja Rudnicka, Tunde Peto, Alexander J MacGregor, Anthony Khawaja, Richard Watts, David Broadway, Shabina Hayat, Robert Luben, Sarah Barman, Christopher Owen, Kay-Tee Khaw, Paul Foster
Journal: Annals of the Rheumatic Diseases (2019)

Both polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) have been associated with an increased future risk of cardiovascular disease (CVD).1 However, it remains uncertain whether this is a consequence of inflammatory disease or relates to a common underlying mechanism. Retinal vascular images are a sensitive measures of vascular health, which are emerging as important biomarkers of future cardiovascular risk with changes affecting arterioles and venules.2 In this study, we assess whether vasculometric features associated with CVD are detectable prior to the onset of PMR and GCA.

We analysed data from initially healthy subjects enrolled in the EPIC-Norfolk Study, a prospective population-based cohort which enrolled participants between the years 1993 and 1997.3 4 Digital photographs of the retinal fundus were taken of 8112 participants between 2004 and 2011 using a TRC-NW6S non-mydriatic retinal camera and IMAGEnet Telemedicine System (Topcon Corporation, Tokyo, Japan) with a 10 MP Nikon D80 camera (Nikon Corporation, Tokyo, Japan). Retinal vessel widths were measured using the QUARTZ (QUantitative Analysis of Retinal vessel Topology and siZe) programme.5 The fully automated algorithm uses an ensemble classifier of bagged decision trees to allocate vessels into arterioles and venules at 80% probability and calculates summary measures for each participant with an averaged measure between right and left eyes.

Cases of PMR …
Gain-of-function mutations in <i>interleukin-7 receptor</i>-α (<i>IL7R</i>) in childhood acute lymphoblastic leukemias
Authors: Chen Shochat, Noa Tal, Obul R. Bandapalli, Chiara Palmi, Ithamar Ganmore, Geertruy te Kronnie, Gunnar Cario, Giovanni Cazzaniga, Andreas E. Kulozik, Martin Stanulla, Martin Schrappe, Andrea Biondi, Giuseppe Basso, Dani Bercovich, Martina U. Muckenthaler, Shai Izraeli
Journal: The Journal of Experimental Medicine (2011)
Clinical outcomes of ibrutinib in patients with relapsed or refractory mantle cell lymphoma: Korean multicenter, retrospective analysis
Authors: J.H. Yi, W.S. Kim, S.J. Kim, D.H. Yoon, C. Suh, M.H. Chang, D.H. Yang, J.-C. Jo, S.Y. Hyun, H.-S. Eom, J.-O. Lee, J.H. Kwon, S.H. Han, S.-S. Lee, J.-Y. Kwak, S.H. Kim
Journal: Annals of Oncology (2019)
Prevalence of heart failure and left ventricular dysfunction in China: the China Hypertension Survey, 2012–2015
Authors: Guang Hao, Xin Wang, Zuo Chen, Linfeng Zhang, Yuhui Zhang, Bingqi Wei, Congyi Zheng, Yuting Kang, Linlin Jiang, Zhenhui Zhu, Jian Zhang, Zengwu Wang, Runlin Gao
Journal: European Journal of Heart Failure (2019)
OP0054 Cost-effectiveness of combined spa-exercise therapy in ankylosing spondylitis: a randomised controlled trial
Authors: A Van Tubergen, A Boonen, R Landewé, M Rutten-van Mölken, D Van der Heijde, A Hidding, SJ Van der Linden
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To evaluate the incremental cost-effectiveness and cost-utility of a 3 weeks course of combined spa-exercise therapy followed by weekly group physical therapy, compared to weekly group physical therapy alone in ankylosing spondylitis (AS) patients. <h3>Methods</h3> 120 Dutch AS outpatients were randomly allocated into three groups of 40 patients each. Group 1 was treated at a spa resort in Bad Hofgastein, Austria; group 2 at a spa resort in Arcen, The Netherlands. A control group stayed at home and continued weekly group physical therapy. Spa-exercise therapy consisted of physical exercises, walking, postural correction therapy, hydrotherapy, sports and either visits to the so-called Gasteiner Heilstollen (Austria) or the sauna (The Netherlands). After spa-exercise therapy all patients followed weekly group physical therapy for another 37 weeks. Effectiveness of the intervention was assessed by functional ability (BASFI) (range 0–10). Utilities were measured with the EuroQoL (EQ-5D<sub>utility</sub>) (range 0–1). A time-integrated summary score defined the clinical effects (BASFI-AUC) and utilities (EQ-5D<sub>utility</sub>-AUC) over time. Both direct (health care and non-health care) and indirect costs were included. Resource utilisation and absence from paid work were registered weekly by the patients in a diary. All costs were calculated from a societal perspective. <h3>Results</h3> 111 patients completed the diary (group 1 n = 38; group 2 n = 36; control group n = 37). The between-group difference (95% CI) for the BASFI-AUC was 1.0 (0.4 to 1.6; p = 0.001) for group 1 versus controls, and 0.6 (0.1 to 1.1; p = 0.020) for group 2 versus controls. The between-group difference for the EQ-5D<sub>utility</sub>-AUC was 0.17 (0.09 to 0.25; p &lt; 0.001) for group 1 versus controls, and 0.08 (0.00 to 0.15; p = 0.04) for group 2 versus controls. The mean total costs per patient (including costs for spa therapy) during the study period were ?3023 for group 1, ?3240 for group 2, and ?1754 for the control group. The incremental cost-effectiveness ratio was ?1269 per unit effect gained in functional ability for group 1, and ?2477 for group 2. The costs per QALY gained were ?7465 for group 1 and ?18575 for group 2. <h3>Conclusion</h3> Combined spa-exercise therapy is more effective and shows favourable cost-effectiveness and cost-utility ratios compared to weekly group physical therapy alone in patients with ankylosing spondylitis.
Involvement of industry in review articles published in Annals of the Rheumatic Diseases
Authors: Martin Rudwaleit
Journal: Annals of the Rheumatic Diseases (2019)

Specifically, I refer to the Review Article on IL-17A by McGonagle et al .1 The article is excellent and reads very well, and the authors are highly acknowledged scientists and clinicians, some of them I know personally—nice colleagues and friends. Yet, I was puzzled to find out that the article was written by a professional medical writer sponsored by a company. Although all this information on funding and involvement of medical writers is transparantly provided in the article in the sections on acknowledgements, contributors and funding, the value of such a Review Article may change once the reader becomes aware of the involvement of pharmaceutical industry.

In Review Articles in highly accredited journals like Annals of the Rheumatic Diseases , authors express their views and interpretation of recent findings in the field, usually in a scientifically adequate and, importantly, pharmaceutical industry-independent way! Readers of such Review …
Verification of metabolic regulatory mechanisms in androgen receptor-positive triple negative breast cancer
Authors: Y. Asano, S. Kashiwagi, R. Kouhashi, S. Ishihara, Y. Tauchi, T. Morisaki, S. Noda, T. Takashima, N. Onoda, K. Hirakawa, M. Ohira
Journal: Annals of Oncology (2019)
RNA Sequencing in Childhood B-Lymphoblastic Leukemia Improves Molecular and Risk Assignment
Authors: Allen Eng Juh Yeoh, Zhenhua Li, Shawn Lee, Winnie Hui Ni Chin, Nan Jiang, Yi Lu, Shirley Kow Yin Kham, Ah Moy Tan, Hai_peng Lin, Thuan Chong Quah, Hany Ariffin, Jun J. Yang
Journal: Blood (2019)
Trends in Inpatient and Intensive Care Resource Utilization after Chimeric Antigen Receptor T Cell Therapy for Pediatric Acute Lymphoblastic Leukemia from 2012-2019
Authors: Regina M. Myers, Julie C Fitzgerald, Amanda M. DiNofia, Lisa Wray, Allison Barz Leahy, Yimei Li, Laura Smith, Evanette Burrows, Mark Ramos, Laura S Motley, Raabia N Khan, Kelly D Getz, Richard Aplenc, Stephan Grupp, Shannon L. Maude
Journal: Blood (2019)
High incidence and mortality of transitional cell carcinoma in Thai kidney transplant patients
Authors: S. Laowalert, N. Prasongsook, T. Ativitasvas, W. Liwlompaisan, P. Thanak, N. Techawathanawanna, R. Khunprakant, V. Mavichak
Journal: Annals of Oncology (2019)
FER and FES tyrosine kinase fusions in follicular T-cell lymphoma
Authors: Koen Debackere, Jo-Anne van der Krogt, Thomas Tousseyn, Julio Antonio Finalet Ferreiro, Katrien Van Roosbroeck, Lukas Marcelis, Carlos Graux, Daan Dierickx, Geneviève Ameye, Peter Vandenberghe, Lucienne Michaux, Jan Cools, Iwona Wlodarska
Journal: Blood (2019)
The Hazard of Negative (Not Neutral) Trials on Treatment of Acute Stroke
Authors: Philip M. Bath, Jason P. Appleton, Timothy England
Journal: JAMA Neurology (2019)

While there are a limited number of beneficial treatments for acute stroke (eg, stroke units, reperfusion, aspirin, hemicraniectomy), there are more negative (as opposed to neutral) interventions spanning multiple different mechanisms of action. To reduce the risk of future negative studies, it is vital to understand why previous interventions appeared to cause harm.The limited number of beneficial treatments for acute ischemic stroke are far outnumbered by negative (not neutral) interventions that worsened outcomes in randomized clinical trials (RCTs), including those with putative neuroprotectant, anticoagulant, anti-inflammatory, free radical-scavenging, hemorrhagic, or vasoactive activity. Other agents reduced thrombolytic efficiency or exhibited neuropsychiatric or cardiac toxicity. In intracerebral hemorrhage, platelet transfusion was hazardous. Although reperfusion treatments should be given as soon as possible, very early intervention with other strategies may instead be hazardous, as has been seen with physical therapy and vasodepressors.The lessons learned from negative stroke RCTs are vital for designing future studies. Multicenter preclinical studies are necessary, and animals that die must be included in analyses. Randomized clinical trials must assess multiple neurological, vascular, cardiac, and general safety effects, whether these are on target or off target. All preclinical trials and RCTs must be published in full. Learning from the past will help to reduce the number of negative stroke RCTs in the future.
Translating Allergic Contact Dermatitis Data to the Patients and Populations We Serve
Authors: Susan T. Nedorost
Journal: JAMA Dermatology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Genetic T-cell receptor diversity at 1 year following allogeneic hematopoietic stem cell transplantation
Authors: Stéphane Buhler, Florence Bettens, Carole Dantin, Sylvie Ferrari-Lacraz, Marc Ansari, Anne-Claire Mamez, Stavroula Masouridi-Levrat, Yves Chalandon, Jean Villard
Journal: Leukemia (2019)
Mutations associated with age-related clonal hematopoiesis in PMF patients with rapid progression to myelofibrosis
Authors: Stephan Bartels, Muhammad Faisal, Guntram Büsche, Jerome Schlue, Britta Hasemeier, Elisa Schipper, Julia Vogtmann, Lina Westphal, Ulrich Lehmann, Hans Kreipe
Journal: Leukemia (2019)