tbuckley/cabot-search huggingface dataset:
In vitro demonstration that pemetrexed is a good substrate for glucarpidase
Authors: Timothy Auton, James Glover, Roger Melton, Gerard Bastian, Elizabeth Lovell
Journal: Cancer Research (2007)

4773   The objective of this work was to assess the ability of glucarpidase to hydrolyse pemetrexed and to compare the kinetics of the reaction with the hydrolysis of methotrexate (MTX) by glucarpidase. Studies were performed in vitro in tris buffer. Disappearance of pemetrexed and methotrexate in the presence of glucarpidase was measured spectrophotometrically, and results were used to estimate Km and k cat  values. Pemetrexed was shown to be a good substrate for glucarpidase with comparable kinetic parameters (Km=25 µM, k cat =1808 s -1 ) to MTX (Km=10 µM, k cat =1039 s -1 ).  Glucarpidase (formerly carboxypeptidase G2, CPG2) is an enzyme that hydrolyses the glutamate subgroup from MTX. It has consistently been shown to cause a marked and rapid reduction in systemic MTX concentrations in patients whose elimination of MTX is delayed following high-dose MTX treatment 1 .  Like methotrexate, pemetrexed is a folate analogue that inhibits dihydrofolate reductase. Pemetrexed is licensed by FDA for the first-line treatment of malignant pleural mesothelioma and second-line, single-agent treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) 2 . The principal dose limiting toxicity found in Phase I was myelosuppression. In a randomized controlled comparison of pemetrexed against docetaxel, pemetrexed was as effective as docetaxel, but was associated with significantly fewer side effects 3 . Nevertheless, 5.3% of the pemetrexed treated patients had grade 3 or 4 neutropenia.  The results of this investigation show that glucarpidase is able to hydrolyse pemetrexed with similar reaction kinetics to its hydrolysis of methotrexate. Glucarpidase thus has the potential to be used to control systemic exposure of patients to pemetrexed and may allow further enhancement of its antitumor efficacy/safety profile.  1. Adamson, P. C., Balis, F. M., Boron, M., Shalabi, A., O9Brien, M., Eby, M., Jayaprakash, N., Cole, D. E., Ivy, P., Widemann, B. C. Carboxypeptidase-G2 (CPDG2) and leucovorin (LV) rescue with and without addition of thymidine (Thd) for high-dose methotrexate (HDMTX) induced renal dysfunction. ASCO Meeting Abstracts 1 Jun 2005 23: 2076  2. Rollins, K. D., Lindley, C. Pemetrexed: a multitargeted antifolate. Clin.Ther. Sep 2005 27: 1343-1382  3. Hanna, N., Shepherd, F. A., Fossella, F. V., Pereira, J. R., De Marinis, F., von Pawel, J., Gatzemeier, U., Tsao, T. C., Pless, M., Muller, T., Lim, H. L., Desch, C., Szondy, K., Gervais, R., Shaharyar, Manegold, C., Paul, S., Paoletti, P., Einhorn, L., Bunn, P. A., Jr. Randomized phase III trial of pemetrexed versus docetaxel in patients with non-small-cell lung cancer previously treated with chemotherapy. J.Clin.Oncol. 1 May 2004 22: 1589-1597
Abstract 16858: Autopsy-Defined Causes of Sudden Death in Heart Failure With Preserved vs. Reduced Ejection Fraction in the San Francisco POstmortem Systematic InvesTigation of Sudden Cardiac Death (POST SCD) Study
Authors: Satvik Ramakrishna, Annie Bedigian, Joanne Probert, Eric Vittinghoff, Jeffrey E Olgin, Philip C Ursell, Ellen Moffatt, Zian H Tseng
Journal: Circulation (2017)

Introduction:  Sudden cardiac death (SCD) rates are higher in heart failure patients with reduced ejection fraction (HFrEF) than those with preserved EF (HFpEF), but prior studies have inferred causes of SCD from EMS records or death certificates. As ICDs only rescue from sudden arrhythmic death (SAD), it is critical to exclude non-arrhythmic causes in HF patients. We sought to determine autopsy-defined SADs in subjects with HF in a prospective comprehensive postmortem study of SCD in San Francisco (SF) County.   Methods:  From 2/2011 to 3/2014, all incident World Health Organization (WHO)-defined SCDs ages 18-90 were autopsied via active surveillance of consecutive out of hospital deaths in the SF POstmortem Systematic InvesTigation of Sudden Cardiac Death (POST SCD) Study. Subjects were identified to have HFpEF or HFrEF by premortem cardiac imaging and/or clinical report as part of usual care. SADs were adjudicated by a multidisciplinary committee and had no extra-cardiac cause of death or acute HF. We defined occult HF as cardiomyopathy and pulmonary edema on autopsy but no known HF premortem.   Results:  We autopsied 525 WHO-defined SCDs in SF over 37 months. Complete medical records were collected in 94%: 83 subjects (16%) had known HF (25 HFpEF, 58 HFrEF) and 16 (3%) had occult HF. For 61 patients (73%) with echo, mean EF for HFpEF v. HFrEF was 64% v. 36% (p   Conclusions:  In a comprehensive postmortem study of all incident SCDs in a metro area, 1 in 5 had clinical or occult HF. Autopsy-defined SAD accounted for three-quarters of HFrEF SCDs but less than half of HFpEF SCDs. Only HFrEF was independently associated with SAD.
Safety and Effectiveness of Oral Food Challenge in Children with Cow's Milk Allergy: Clinical Experience from a Brazilian Reference Center
Authors: Ana Laura Mendes Becker Andrade, Príscila da Silva Pereira, Carla de Oliveira Parra Duarte, Atila Lima da Silva, Maria Marluce Dos Santos Vilela, Marcos Tadeu Nolasco da Silva, Maria Angela Bellomo Brandão, Adriana Gut Lopes Riccetto
Journal: Journal of Allergy and Clinical Immunology (2018)
Response to: ’Standard dose of ustekinumab for childhood-onset deficiency of interleukin-36 receptor antagonist’ by Cherqaoui <i>et al</i>
Authors: Nadia Bonekamp, Roberta Caorsi, Joost Frenkel, Marco Gattorno
Journal: Annals of the Rheumatic Diseases (2018)

Response to: 'Standard dose of ustekinumab for childhood-onset deficiency of interleukin-36 receptor antagonist' by Cherqaoui et alThe case reported by Cherqaoui et al 1 on ustekinumab in the treatment of deficiency of interleukin-36 receptor antagonist (DITRA) is interesting in several aspects.The authors describe intrathecal elevation of proinflammatory cytokines, which is a novel and intriguing finding.The mutation in their case is identical to that of the Dutch/Moroccan patient we described.The total absence of any clinical disease activity in a genetically affected younger sister of the patient further supports the variable expression of identical IL36RN mutations as reported by Cherqaoui et al.As observed in our cases, the patient was treated with several drugs with an absent or only transient improvement. 2 At variance with our previous experience, the use of ustekinumab at standard dose in monotherapy was able to completely control the clinical picture, without the need for any topical steroids.These observations underline the clinical spectrum of disease severity associated with DITRA.In our previous experience, both patients displayed an initial response at standard doses but displayed a tendency to mild/ moderate relapses in proximity to the scheduled doses.According to the few cases so far described, it is therefore conceivable that ustekinumab should be considered among the first-line treatments for this severe condition.As suggested by Cherqaoui et al, a standard dose of 0.75 mg/ kg every 12 weeks could be sufficient to completely control disease flares and should therefore be used as an initial approach.However, higher doses at more frequent intervals could be necessary to achieve a complete remission in patients with a partial clinical response, with a good safety profile.
Casein kinase 1 is a therapeutic target in chronic lymphocytic leukemia
Authors: Pavlina Janovska, Jan Verner, Jiri Kohoutek, Lenka Bryjova, Michaela Gregorova, Marta Dzimkova, Hana Skabrahova, Tomasz Radaszkiewicz, Petra Ovesna, Olga Vondalova Blanarova, Tereza Nemcova, Zuzana Hoferova, Katerina Vasickova, Lucie Smyckova, Alexander Egle, Sarka Pavlova, Lucie Poppova, Karla Plevova, Sarka Pospisilova, Vitezslav Bryja
Journal: Blood (2018)
Pustular psoriasis and related pustular skin diseases
Authors: H. Bachelez
Journal: British Journal of Dermatology (2018)

Patients with pustular psoriasis or related pustular diseases may have genetic abnormalities impairing the function of key players of the innate skin immune system. Recently, identification of these abnormalities has changed the paradigm of several of these diseases. These include generalized pustular psoriasis, palmoplantar pustular psoriasis and acrodermatitis continua of Hallopeau, and also drug‐induced acute exanthematous generalized pustular eruption. Identified mutations in IL36RN, CARD14 and AP1S3 in different groups of patients lead to enhanced inflammatory cascade in several cellular subtypes including keratinocytes, and to the recruitment and activation of neutrophils and macrophages. These insights have unveiled pathophysiological features that shift the existing paradigms and emphasize the autoinflammatory nature of skin pustular disorders. They also highlight the crucial role of the innate immune system across entities belonging to the psoriasis disease spectrum, allowing identification of new appealing therapeutic targets.
Building Evidence for Health: Green Buildings, Current Science, and Future Challenges
Authors: J.G. Cedeño-Laurent, A. Williams, P. MacNaughton, X. Cao, E. Eitland, J. Spengler, J. Allen
Journal: Annual Review of Public Health (2018)

Civilizational challenges have questioned the status quo of energy and material consumption by humans. From the built environment perspective, a response to these challenges was the creation of green buildings. Although the revolutionary capacity of the green building movement has elevated the expectations of new commercial construction, its rate of implementation has secluded the majority of the population from its benefits. Beyond reductions in energy usage and increases in market value, the main strength of green buildings may be the procurement of healthier building environments. Further pursuing the right to healthy indoor environments could help the green building movement to attain its full potential as a transformational public health tool. On the basis of 40 years of research on indoor environmental quality, we present a summary of nine environment elements that are foundational to human health. We posit the role of green buildings as a critical research platform within a novel sustainability framework based on social-environmental capital assets.
PD-1 blockade in HIV-infected patients with lung cancer: a new challenge or already a strategy?
Authors: A. Lavolé, A. Guihot, M. Veyri, O. Lambotte, B. Autran, N. Cloarec, G. Le Garff, T. Flament, J. Cadranel, J.-P. Spano
Journal: Annals of Oncology (2018)
Reframing Fantasy: Toward a Common Language of Hope, Dying, and Death in Long-Shot Pediatrics
Authors: Courtney Addison, Courtney Hempton
Journal: The American Journal of Bioethics (2018)

This response piece engages the target article's suggestion for a communication rubric around long-shot pediatric medicine (Weiss and Fiester 2018). We offer constructive criticism of the authors’ ...
MiR-25-3p promotes the proliferation of triple negative breast cancer by targeting BTG2
Authors: Hua Chen, Hong Pan, Yi Qian, Wenbin Zhou, Xiaoan Liu
Journal: Molecular Cancer (2018)

Triple-negative breast cancer (TNBC) is highly invasive and aggressive and lacks specific molecular targets to improve the prognosis. MiR-25-3p promotes proliferation of many tumors and its role and underlying mechanisms in TNBC remain to be well elucidated.Differential expression of miR-25-3p in TNBC was measured with quantitative real-time PCR (qRT-PCR) in both TNBC tissues and cell lines and was validated in the Cancer Genome Atlas (TCGA) database. The effects of miR-25-3p on proliferation, apoptosis capacity of TNBC were evaluated using Cell counting kit-8 (CCK-8), colony formation assay and Annexin V-FITC/PI analyses. The tumor growth in vivo was observed in xenograft model. Luciferase reporter assay, qPCR and western blot were performed to validate a potential target of miR-25-3p in TNBC. Involvement of the AKT and MAPK pathways was investigated by western blot.MiR-25-3p was found to be upregulated in TNBC in tissues and cell lines. MiR-25-3p promoted TNBC cell proliferation in vitro and tumor growth in xenograft model, while suppression of miR-25-3p induced cell apoptosis. The luciferase reporter assay confirmed that B-cell translocation gene 2 (BTG2) might be a direct target of miR-25-3p, and its expression was negatively regulated by miR-25-3p. Moreover, inhibition of BTG2 expression accounted for the role of miR-25-3p in TNBC. Furthermore, BTG2 suppression might indirectly activate the AKT and ERK-MAPK signaling pathways to mediate the downstream effects of miR-25-3p.This study demonstrates that miR-25-3p promotes proliferation by targeting tumor suppressor BTG2 and may identify new diagnostic and therapeutic targets in TNBC.
Nonuniversity-Based Surgeons Coming Up Anything but Short in Solutions to the Future Surgeon Shortage
Authors: Kathryn J. Balinger, Lillian S. Kao
Journal: JAMA Surgery (2018)

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 Surgery 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 Surgery journal
Clinical Outcomes of Patients with 3rd or Higher Relapsed Classical Hodgkin Lymphoma: Results from the German Hodgkin Study Group
Authors: Paul Broeckelmann, Horst Mueller, Esra Kücüksarioglan, Peter Kaskel, Veronika Metterlein, Hilde Giezek, Arun Balakumaran, Monika Raut, Andreas Engert, Bastian von Tresckow
Journal: Blood (2017)
Tuberculosis elimination: a dream or a reality? The case of Oman
Authors: Fatma Al Yaquobi, Seif Al-Abri, Bader Al-Abri, Idris Al-Abaidani, Amina Al-Jardani, Lia D'Ambrosio, Rosella Centis, Alberto Matteelli, Davide Manissero, Giovanni Battista Migliori
Journal: European Respiratory Journal (2018)

Until recently, the fight against tuberculosis (TB) was designed to pursue control of the disease, e.g. ensuring that infectious cases are rapidly diagnosed and effectively treated, thus breaking the chain of transmission [1–5]. Tuberculosis pre-elimination approached in native population in Oman <http://ow.ly/mwQs30h4z4L>
Effectiveness of interventions for reducing non-occupational sedentary behaviour in adults and older adults: a systematic review and meta-analysis
Authors: Nipun Shrestha, Jozo Grgic, Glen Wiesner, Alexandra Parker, Hrvoje Podnar, Jason A Bennie, Stuart J H Biddle, Zeljko Pedisic
Journal: British Journal of Sports Medicine (2018)

Background No systematic reviews of the effectiveness of interventions for reducing non-occupational sedentary behaviour are available. Therefore, the aim of this systematic review was to assess the effectiveness of interventions for reducing non-occupational sedentary behaviour in adults and older adults. Methods An electronic search of nine databases was performed. Randomised controlled trials (RCT) and cluster RCTs among adults testing the effectiveness of interventions aimed to reduce non-occupational sedentary behaviour were considered for inclusion. Two review authors independently screened studies for eligibility, completed data extraction and assessed the risk of bias. Results Nineteen studies that evaluated multicomponent lifestyle interventions, counselling or education, television (TV) control devices and workplace interventions were included. Evidence from the meta-analyses suggested that interventions can reduce leisure sitting time in adults in the medium term (−30 min/day; 95% CI −58 to –2), and TV viewing in the short term (−61 min/day; 95% CI −79 to –43) and medium term (−11 min/day; 95% CI −20 to –2). No significant pooled effects were found for transport sitting time, leisure-time computer use and longer term outcomes. No evidence was available on the effectiveness of interventions for reducing non-occupational sedentary time in older adults. Conclusions The findings of this systematic review suggest the interventions may be effective in reducing non-occupational sedentary behaviour in the short to medium term in adults. However, no significant effect was found on longer term outcomes. The quality of evidence was, however, low to very low. No evidence was available on the effectiveness of non-occupational interventions on reducing sedentary time in older adults. Further high-quality research with larger samples is warranted.
Changes in Quality of Life in Indolent Non-Hodgkin Lymphoma 3 Years after Diagnosis
Authors: Carrie A Thompson, Kathleen Yost, Melissa C. Larson, Cristine Allmer, Matthew J Maurer, Amylou C. Dueck, Tait D. Shanafelt, Thomas M Habermann, Allison C. Rosenthal, Umar Farooq, Brian K Link, James R Cerhan
Journal: Blood (2017)
LAL test and RPT for endotoxin detection of CPT-11/DSPE-mPEG 2000 nanoformulation: What if traditional methods are not applicable?
Authors: Yanan Jin, Juanjuan Jia, Chan Li, Jianqi Xue, Jiabei Sun, Kaiyuan Wang, Yaling Gan, Jing Xu, Yaqin Shi, Xingjie Liang
Journal: Asian Journal of Pharmaceutical Sciences (2018)

Endotoxin detection is an important step in drug characterization. Herein we found that a chemotherapeutic drug nanoformulation composed of irinotecan hydrochloride (CPT-11) and an amphiphilic molecule DSPE-mPEG
An Exaggerated Type I Interferon Antiviral Response is Associated with Exacerbations in Pediatric Asthma
Authors: Cristina L. Swanson, Denise Babineau, Elizabeth Whalen, Michelle A. Gill, Baomei Shao, Andrew H. Liu, Brett Jepson, Rebecca S. Gruchalla, George T. O'Connor, Jacqueline A. Pongracic, Carolyn M. Kercsmar, Gurjit K. Khurana Hershey, Edward M. Zoratti, Christine Cole Johnson, Stephen J. Teach, Meyer Kattan, Leonard B. Bacharier, Avraham Beigelman, Steve M. Sigelman, Peter J. Gergen, Lisa M. Wheatley, Scott Presnell, Alkis Togias, William W. Busse, Daniel J. Jackson, Matthew C. Altman
Journal: Journal of Allergy and Clinical Immunology (2018)
Mitoferrin Deficiency Provokes An Ecdysone Synthesis Impairment And An Immune System Overreaction
Authors: Jose Llorens, Christoph Metzendorf, Fanis Missirlis, Maria Lind
Journal: American Journal of Hematology (2016)

Mitoferrin Deficiency Provokes An Ecdysone Synthesis Impairment And An Immune System Overreaction
Clofarabine-Based Consolidation Improves Relapse-Free Survival of Patients with Acute Myeloid Leukemia with Complex or Micro-Complex Karyotype: Results from the Randomized ALFA-0702 Study
Authors: Laurène Fenwarth, Nicolas Duployez, Xavier Thomas, Nicolas Boissel, Sandrine Geffroy, Alice Marceau-Renaut, Denis Caillot, Emmanuel Raffoux, Emilie Lemasle, Jean-Pierre Marolleau, Céline Berthon, Meyling H. Cheok, Pauline Peyrouze, Arnaud Pigneux, Norbert Vey, Karine Celli-Lebras, Christine Terré, Claude Preudhomme, Herve Dombret
Journal: Blood (2017)
Isolation of a high‐affinity Bet v 1‐specific IgG‐derived ScFv from a subject vaccinated with hypoallergenic Bet v 1 fragments
Authors: E. Gadermaier, K. Marth, C. Lupinek, R. Campana, G. Hofer, K. Blatt, D. Smiljkovic, U. Roder, M. Focke‐Tejkl, S. Vrtala, W. Keller, P. Valent, R. Valenta, S. Flicker
Journal: Allergy (2018)

Recombinant hypoallergenic allergen derivatives have been used in clinical immunotherapy studies, and clinical efficacy seems to be related to the induction of blocking IgG antibodies recognizing the wild-type allergens. However, so far no treatment-induced IgG antibodies have been characterized.To clone, express, and characterize IgG antibodies induced by vaccination with two hypoallergenic recombinant fragments of the major birch pollen allergen, Bet v 1 in a nonallergic subject.A phage-displayed combinatorial single-chain fragment (ScFv) library was constructed from blood of the immunized subject and screened for Bet v 1-reactive antibody fragments. ScFvs were tested for specificity and cross-reactivity to native Bet v 1 and related pollen and food allergens, and epitope mapping was performed. Germline ancestor genes of the antibody were analyzed with the ImMunoGeneTics (IMGT) database. The affinity to Bet v 1 and cross-reactive allergens was determined by surface plasmon resonance measurements. The ability to inhibit patients' IgE binding to ELISA plate-bound allergens and allergen-induced basophil activation was assessed.A combinatorial ScFv library was obtained from the vaccinated donor after three injections with the Bet v 1 fragments. Despite being almost in germline configuration, ScFv (clone H3-1) reacted with high affinity to native Bet v 1 and homologous allergens, inhibited allergic patients' polyclonal IgE binding to Bet v 1, and partially suppressed allergen-induced basophil activation.Immunization with unfolded hypoallergenic allergen derivatives induces high-affinity antibodies even in nonallergic subjects which recognize the folded wild-type allergens and inhibit polyclonal IgE binding of allergic patients.
Immune Response to Dengue and Zika
Authors: Annie Elong Ngono, Sujan Shresta
Journal: Annual Review of Immunology (2018)

Flaviviruses such as dengue (DENV), yellow fever (YFV), West Nile (WNV), and Zika (ZIKV) are human pathogens of global significance. In particular, DENV causes the most prevalent mosquito-borne viral diseases in humans, and ZIKV emerged from obscurity into the spotlight in 2016 as the etiologic agent of congenital Zika syndrome. Owing to the recent emergence of ZIKV as a global pandemic threat, the roles of the immune system during ZIKV infections are as yet unclear. In contrast, decades of DENV research implicate a dual role for the immune system in protection against and pathogenesis of DENV infection. As DENV and ZIKV are closely related, knowledge based on DENV studies has been used to prioritize investigation of ZIKV immunity and pathogenesis, and to accelerate ZIKV diagnostic, therapeutic, and vaccine design. This review discusses the following topics related to innate and adaptive immune responses to DENV and ZIKV: the interferon system as the key mechanism of host defense and viral target for immune evasion, antibody-mediated protection versus antibody-dependent enhancement, and T cell–mediated protection versus original T cell antigenic sin. Understanding the mechanisms that regulate the balance between immune-mediated protection and pathogenesis during DENV and ZIKV infections is critical toward development of safe and effective DENV and ZIKV therapeutics and vaccines.
Managing Expectations: Delivering the Worst News in the Best Way?
Authors: Alyssa M. Burgart, David Magnus
Journal: The American Journal of Bioethics (2018)

In this issue, Weiss and Fiester's (2018) “From ‘Longshot’ to ‘Fantasy’: Obligations to Patients and Families When Last-Ditch Medical Efforts Fail” calls attention to the weight of clinician word c...