tbuckley/cabot-search huggingface dataset:
AB0842 Drug survival and effectiveness of the first tnf inhibitors in patient with late onset spondylarthritis: treasure real-life results
Authors: N. Alpay Kanıtez, S. Kiraz, I. Ertenli, O. Küçükşahin, E. Dalkılıç, C. Bes, T. Kaşifoğlu, H. Emmungil, S.S. Koca, M. Çınar, S. Yılmaz, V. Yazısız, B. Keleşoğlu Dinçer, S. Akar, O. Gercik, A. Ateş, S. Erten, S. Turan, B. Yağız, B. Öz, S. Yaşar Bilge, L. Kılıç, G.K. Yardımcı, B.N. Coşkun, U. Kalyoncu
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Spondylartritis (SpA) are usually observed in young patients and a clinical onset after 45 years is rare. The average life expectancy is getting longer and the proportion of late onset of SpA in rheumatology practice may became more common. SpA patients with late onset may have a distinctive clinical pattern in terms of functional impairment, extra-articular disease, co-morbidities and treatment status. <h3>Objectives</h3> The aim of this study was to compare the drug survival and effectiveness of tumour necrosis factor (TNF) inhibitors in patients with late onset SpA (LoSpA) compared with early onset SpA (EoSpA). <h3>Methods</h3> TReasure is a prospective, multicenter biological treatments registry from Turkey since 2016. It includes 15 different rheumatology centres. Patients with SpA fulfilling the ASAS criteria from TReasure database were divided into two groups as LoSpA (symptom onset &gt;45 years of age) and EoSpA (symptom onset ≤45 years of age). Drug retention rates of first TNF inhibitors were calculated using the time until drug discontinuation independent of the reason that drug interruption. Specific reasons for discontinuing drugs were also assessed. <h3>Results</h3> Of 1382 SpA patients treated with TNF inhibitors, 9.4% (n=130) were included in the LoSpA and 90.6% (n=1252) were included in the EoSpA group. LoSpA had more female, enthesitis and psoriasis The median treatment duration was 53 months in LoSpA and 61 months in EoSpA. The baseline disease activity measures were similar except from ASDAS-ESH which is higher in LoSpA (table 1). The rate of major treatment response (BASDAI50) was lower in LoSpA than EoSPA at the last visit (26.1% vs 46.2%; p=0.009). Regarding the survival rates of TNF inhibitors, there was no significant difference between the patient groups (figure 1). The major cause of discontinuation in both of groups was drug ineffectiveness (68.6% in LoSpa and 60% in EoSpA, p&gt;0.05). <h3>Conclusions</h3> LoSpA patients were almost 10% of all biological registry. LoSpA patients were predominantly female, and they had relatively higher baseline disease activity and lower biological treatment response. On the other hand the drug survival rate and discontinuation reasons of TNF inhibitors in the LoSpA group was comparable to that in the younger group. <h3>Reference</h3> [1] - Chen HA, Chen CH, Liao HT, Lin YJ, Chen PC, Chen WS, et al. Clinical, functional, and radiographic differences among juvenile-onset, adult-onset, and late-onset ankylosing spondylitis. J Rheumatol. 2012; 39:1013–8 <h3>Disclosure of Interest</h3> None declared
Aligning Programs and Policies to Support Food Security and Public Health Goals in the United States
Authors: Hilary K. Seligman, Seth A. Berkowitz
Journal: Annual Review of Public Health (2018)

Food insecurity affects 1 in 8 US households and has clear implications for population health disparities. We present a person-centered, multilevel framework for understanding how individuals living in food-insecure households cope with inadequate access to food themselves and within their households, communities, and broader food system. Many of these coping strategies can have an adverse impact on health, particularly when the coping strategies are sustained over time; others may be salutary for health. There exist multiple opportunities for aligning programs and policies so that they simultaneously support food security and improved diet quality in the interest of supporting improved health outcomes. Improved access to these programs and policies may reduce the need to rely on individual- and household-level strategies that may have negative implications for health across the life course.
Inhibition of mTOR Signaling and Clinical Activity of Rapamycin in Head and Neck Cancer in a Window of Opportunity Trial
Authors: Terry A. Day, Keisuke Shirai, Paul E. O'Brien, Maria Gisele Matheus, Kristina Godwin, Amit J. Sood, Anvesh Kompelli, Julie A. Vick, Daniel Martin, Lynn Vitale-Cross, Juan Luis Callejas-Varela, Zhiyong Wang, Xingyu Wu, Olivier Harismendy, Alfredo A. Molinolo, Scott M. Lippman, Carter Van Waes, Eva Szabo, J. Silvio Gutkind
Journal: Clinical Cancer Research (2018)

Abstract Purpose: We studied the impact of mTOR signaling inhibition with rapamycin in head and neck squamous cell carcinoma (HNSCC) in the neoadjuvant setting. The goals were to evaluate the mTOR pathway as a therapeutic target for patients with advanced HNSCC, and the clinical safety, antitumor, and molecular activity of rapamycin administration on HNSCC. Patients and Methods: Patients with untreated stage II–IVA HNSCC received rapamycin for 21 days (day 1, 15 mg; days 2–12, 5 mg) prior to definitive treatment with surgery or chemoradiation. Treatment responses were assessed clinically and radiographically with CT and FDG-PET. Pre- and posttreatment biopsies and blood were obtained for toxicity, immune monitoring, and IHC assessment of mTOR signaling, as well as exome sequencing. Results: Sixteen patients (eight oral cavity, eight oropharyngeal) completed rapamycin and definitive treatment. Half of patients were p16 positive. One patient had a pathologic complete response and four (25%) patients met RECIST criteria for response (1 CR, 3 PR, 12 SD). Treatment was well tolerated with no grade 4 or unexpected toxicities. No significant immune suppression was observed. Downstream mTOR signaling was downregulated in tumor tissues as measured by phosphorylation of S6 (P &amp;lt; 0.0001), AKT (P &amp;lt; 0.0001), and 4EBP (P = 0.0361), with a significant compensatory increase in phosphorylated ERK in most patients (P &amp;lt; 0.001). Ki67 was reduced in tumor biopsies in all patients (P = 0.013). Conclusions: Rapamycin treatment was well tolerated, reduced mTOR signaling and tumor growth, and resulted in significant clinical responses despite the brief treatment duration, thus supporting the potential role of mTOR inhibitors in treatment regimens for HNSCC.
Therapy-Related Myeloid Neoplasms (T-MN) and Primary MDS (PMDS) Patients with Very Low (VL) or Low (L) IPSS-R Score Share Clinical and Biological Characteristics and Have Similar Outcome
Authors: Deepak Singhal, Amilia Wee, Monika M Kutyna, Milena Babic, Rakchha Chhetri, Wendy Parker, Sarah Moore, Jinghua Feng, Andreas Schreiber, Joel Goeghegan, Peer Arts, Suzanne Edwards, Peter G Bardy, Nimit Singhal, Raghvendra Gowda, Richard D'Andrea, Anna L. Brown, Ian D Lewis, Christopher N. Hahn, Hamish S. Scott, Devendra K Hiwase
Journal: Blood (2018)
Abstract 14057: Cardiovascular Outcomes Associated With Masked Hypertension by Home BP Monitoring in a Japanese Nationwide General Practice Population: The J-HOP Study
Authors: Takeshi Fujiwara, Yuichiro Yano, Satoshi Hoshide, Hiroshi Kanegae, Kazuomi Kario
Journal: Circulation (2017)

We assessed cardiovascular disease (CVD) outcomes associated with masked hypertension (MH) by home blood pressure (BP) monitoring, and investigated whether the association between MH and incident C...
Associations of Intimate Partner Violence, Sexual Assault, and Posttraumatic Stress Disorder With Menopause Symptoms Among Midlife and Older Women
Authors: Carolyn J. Gibson, Alison J. Huang, Brigid McCaw, Leslee L. Subak, David H. Thom, Stephen K. Van Den Eeden
Journal: JAMA Internal Medicine (2018)

Little is known about the prevalence of traumatic exposures among midlife and older women and the association of these traumatic exposures with health issues.
Targeting B-cell maturation antigen with GSK2857916 antibody–drug conjugate in relapsed or refractory multiple myeloma (BMA117159): a dose escalation and expansion phase 1 trial
Authors: Suzanne Trudel, Nikoletta Lendvai, Rakesh Popat, Peter M Voorhees, Brandi Reeves, Edward N Libby, Paul G Richardson, Larry D Anderson, Heather J Sutherland, Kwee Yong, Axel Hoos, Michele M Gorczyca, Soumi Lahiri, Zangdong He, Daren J Austin, Joanna B Opalinska, Adam D Cohen
Journal: The Lancet Oncology (2018)
Decreased mortality strongly correlated with the upregulation of BCR in breast cancer metastasis to bone
Authors: S.N.T. Mai, H.N. Vu, X.T. Hoang, V.T. Than, T.V. Nguyen, M.T. Le, P.-L. Luu, H.Q. Tran, M.N. Nguyen
Journal: Annals of Oncology (2018)
Assessment of tumor response, alpha-fetoprotein (AFP) response, and time to progression (TTP) in the phase III CELESTIAL trial of cabozantinib (C) versus placebo (P) in advanced hepatocellular carcinoma (HCC)
Authors: T. Yau, P. Merle, L. Rimassa, B.-Y. Ryoo, I. Cicin, W.P. Harris, E. Banu, D. Sarker, B. Tan, H. van Vlierberghe, S. Sen, C. Love, A.-L. Cheng, T. Meyer, R.K. Kelley, G.K. Abou-Alfa
Journal: Annals of Oncology (2018)
Long Term Socioeconomic Outcomes of Childhood Acute Lymphoblastic Leukemia (ALL) Survivors Enrolled in EORTC Children Leukemia Group Trials 58741, 58831/2 and 58881
Authors: Mélissa Barbati, Michal Kicinski, Stefan Suciu, Yves Benoit, Françoise Mazingue, Teresa De Rojas, Els Vandecruys, Geneviève Plat, Anne Uyttebroeck, Patrick Lutz, Marie-Françoise Dresse, Pauline Simon, Claire Pluchart, Odile Minckes, Alice Ferster, Claire Freycon, Frédéric Millot, Jutte Van Der Werff, Christophe Chantrain, Robert Paulus, Pierre Rohrlich, Caroline Piette
Journal: Blood (2017)
<i> <scp>POT</scp> 1 </i> germline mutations but not <i> <scp>TERT</scp> </i> promoter mutations are implicated in melanoma susceptibility in a large cohort of Spanish melanoma families
Authors: M. Potrony, J.A. Puig‐Butille, M. Ribera‐Sola, V. Iyer, C.D. Robles‐Espinoza, P. Aguilera, C. Carrera, J. Malvehy, C. Badenas, M.T. Landi, D.J. Adams, S. Puig
Journal: British Journal of Dermatology (2018)

Germline mutations in telomere-related genes such as POT1 and TERT predispose individuals to familial melanoma.To evaluate the prevalence of germline mutations in POT1 and TERT in a large cohort of Spanish melanoma-prone families (at least two affected first- or second-degree relatives).Overall, 228 CDKN2A wild-type melanoma-prone families were included in the study. Screening of POT1 was performed in one affected person from each family and TERT was sequenced in one affected patient from 202 families (26 families were excluded owing to DNA exhaustion/degradation). TERT promoter sequencing was extended to an additional 30 families with CDKN2A mutation and 70 patients with sporadic multiple primary melanoma (MPM) with a family history of other cancers.We identified four families with potentially pathogenic POT1 germline mutations: a missense variant c.233T>C (p.Ile78Thr); a nonsense variant c.1030G>T (p.Glu344*); and two other variants, c.255G>A (r.125_255del) and c.1792G>A (r.1791_1792insAGTA, p.Asp598Serfs*22), which we confirmed disrupted POT1 mRNA splicing. A TERT promoter variant of unknown significance (c.-125C>A) was detected in a patient with MPM, but no germline mutations were detected in TERT promoter in cases of familial melanoma.Overall, 1·7% of our CDKN2A/CDK4-wild type Spanish melanoma-prone families carry probably damaging mutations in POT1. The frequency of TERT promoter germline mutations in families with melanoma in our population is extremely rare.
A cabazitaxel liposome for increased solubility, enhanced antitumor effect and reduced systemic toxicity
Authors: Xiaoyi Yin, Lihua Luo, Wei Li, Jie Yang, Chunqi Zhu, Mengshi Jiang, Bing qin, Xiaoling Yuan, Hang Yin, Yichao Lu, Yongzhong Du, Dawei Chen, Jian You
Journal: Asian Journal of Pharmaceutical Sciences (2018)

The potential side effects of cabazitaxel (CBZ) in the field of cancer treatment have become a great limitation to its further clinical application. Liposomal delivery is a well-established approach to increase the therapeutic index of hydrophobic drugs. In this study, a PEG-modified liposome was developed for efficiently encapsulating CBZ, thus enhancing its specific tumor inhibition effect and reducing the systemic toxicity. It was found that the loading efficiency of CBZ into the liposome could be improved with the increase of lipophilic materials, as it could be over 80% under the weight ratio of 20:1 (total lipid: CBZ). The diameter of CBZ loaded liposome ([email protected]) was ∼100 nm. And the liposome suspending in aqueous medium was stable at 4 °C for at least one month, according to the change of its size distribution. The killing ability of [email protected] to cancer cells was significantly lower comparing to that of CBZ solution, which could be attributed to the slow release of CBZ from the liposomes. However, [email protected] could induce an obvious apoptosis of the cancer cells at low concentration. Furthermore, [email protected] exhibited an expressively enhanced tumor growth inhibition effect comparing to CBZ solution. More importantly, [email protected] showed an obviously higher biosafety proved by lower hemolysis probability, stable body weight of mice during the whole experiment and no obvious lesion in histology analysis. Our work provided a useful reference of the formulation of CBZ, which had potential for greater clinical application.
Efficacy and safety of regorafenib after progression on sorafenib in Korean patients with advanced hepatocellular carcinoma (HCC)
Authors: C. Yoo, J.-W. Park, Y.J. Kim, D.Y. Kim, S.J. Yu, T.S. Lim, B.-Y. Ryoo, S.J. Lee, H.-Y. Lim
Journal: Annals of Oncology (2018)
Investigating tumour evolution in a single patient with disseminated cancer
Authors: T. Robb, C. Blenkiron, P. Tsai, K. Parker, A. Drummond, M. Black, A. Gavryushkin, B. Woodhouse, P. Houseman, E. Coats, P. Shields, S. Fitzgerald, D. Wright, R. Tse, N. Kramer, C. Barker, Y. Triggs, S. Stables, B. Lawrence, C. Print
Journal: Annals of Oncology (2018)
Mapping Yellow Fever Virus in Brazil
Authors: M.J. Friedrich
Journal: JAMA (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 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
Treatment Patterns and Healthcare Resource Utilization (HRU) in Patients with Relapsed/Refractory (R/R) FLT3-Mutated (FLT3mut) and FLT3-Wild Type (FLT3wt) Acute Myeloid Leukemia (AML): A Multi-Country Medical Chart Study
Authors: James D. Griffin, Manasee V Shah, Yan Song, Hongbo Yang
Journal: Blood (2018)
Eligibility for Car-T Trials: An Analysis of Selection Criteria and Survival Outcomes in Chemorefractory DLBCL
Authors: Prathima Reddy, Alexandra Sokolova, Victor A. Chow, Ryan C. Lynch, Mazyar Shadman, Brian G. Till, Andrei R Shustov, Edus H. Warren, Manoj P. Menon, Sandra Kanan, Yolanda D. Tseng, Ajay K. Gopal, Stephen D. Smith
Journal: Blood (2018)
Tolerance of Chromosomal Instability in Cancer: Mechanisms and Therapeutic Opportunities
Authors: Eva Gronroos, Carlos López-García
Journal: Cancer Research (2018)

Abstract Chromosomal instability (CIN) is the result of ongoing changes in the number (aneuploidy) and structure of chromosomes. CIN is induced by chromosome missegregation in mitosis and leads to karyotypic diversity within the cancer cell population, thereby adding to intratumor heterogeneity. Regardless of the overall pro-oncogenic function of CIN, its onset is typically detrimental for cell fitness and thus tumors must develop CIN-tolerance mechanisms in order to propagate. There is overwhelming genetic and functional evidence linking mutations in the tumor suppressor TP53 with CIN-tolerance. However, the pathways leading to p53 activation following chromosome missegregation remain controversial. Recently, additional mechanisms have been identified in CIN-surveillance, resulting in a more complex network of pathways acting independently or in cooperation with p53. Tolerance might also be achieved by modifying aspects of the cancer cell physiology in order to attenuate CIN or by adaptation to the consequences of aneuploid karyotypes. In this review, we summarize the current knowledge about p53-dependent and -independent mechanisms of CIN-tolerance in cancer, the adaptations observed in CIN cells buffering CIN levels, its consequences for cellular homeostasis, and the potential of exploiting these adaptations in order to design new cancer therapies.
Yemen: Number of children under 5 who have died from malnutrition may be as high as 85 000, says Save the Children
Authors: Owen Dyer
Journal: BMJ (2018)

An estimated 85 000 children aged under five may have starved or died from hunger related disease since Saudi Arabia and its allies began fighting in Yemen in March 2015, according to the charity Save the Children.1

“For every child killed by bombs and bullets, dozens are starving to death and it’s entirely preventable,” said Tamer Kirolos, Save the Children’s country director in Yemen.

The figure is an estimate, since there is no accurate death reporting system. Only about half of Yemen’s health facilities are still operating—several have been bombed by the Saudi led coalition and most staff have not been paid since August 2016.

Instead, Save the Children analysed UNICEF data on malnutrition …
Macrophage de novo NAD+ synthesis specifies immune function in aging and inflammation
Authors: Paras S. Minhas, Ling Liu, Peter K. Moon, Amit U. Joshi, Christopher Dove, Siddhita Mhatre, Kevin Contrepois, Qian Wang, Brittany A. Lee, Michael Coronado, Daniel Bernstein, Michael P. Snyder, Marie Migaud, Ravindra Majeti, Daria Mochly-Rosen, Joshua D. Rabinowitz, Katrin I. Andreasson
Journal: Nature Immunology (2018)
Lnk inhibits myeloproliferative disorder-associated JAK2V617F and JAK2K539L mutations
Authors: Sigal Gery, Qi Cao, Saskia Gueller, H. Phillip Koeffler
Journal: Cancer Research (2008)

3465  The JAK2 mutation, JAK2V617F is frequently found in myeloproliferative disorder (MPD) patients and transforms hematopoietic cells to cytokine-independent proliferation, when expressed with specific cytokine receptors. JAK2K539L is a MPD-associated JAK2 exon 12 mutation, with similar effects as JAK2V617F. The SH2 and PH domain-containing adapter protein, Lnk, negatively regulates hematopoietic cytokine receptors through its SH2 domain. Here, we show that Lnk inhibits the constitutive activation of JAK2V617F and JAK2K539L. Lnk overexpression blocked JAK2V617F-meditated transformation of hematopoietic Ba/F3-EpoR cells, while suppression of Lnk by shRNA enhanced proliferation of JAK2V617F-postive leukemic HEL cells. Lnk was phosphorylated by JAK2V617F and interacted with endogenous wild type JAK2 and JAK2V617F. Experiments with a series of Lnk deletion constructs showed that Lnk SH2 domain binds to phosphorylated JAK2, while its PH domain interacts with non-phosphorylated JAK2, and this latter interaction is critical for inhibition of JAK2V617F/K539L constitutive activation. Our results suggest a model wherein Lnk downregulation of JAK2 mutants involves two mechanisms: indirect inhibition of the cytokine receptor utilizing JAK2, and direct suppression of JAK2 kinase activity. These data demonstrate that JAK2V617F is susceptible to negative feedback mechanisms, providing new insights into the molecular pathogenesis of MPD.
Characteristics of Hospitals Exiting the Newly Voluntary Comprehensive Care for Joint Replacement Program
Authors: Hyunjee Kim, Thomas H. A. Meath, Jenny I. Grunditz, Ana R. Quiñones, Said A. Ibrahim, K. John McConnell
Journal: JAMA Internal Medicine (2018)

In 2018, Medicare made participation in the Comprehensive Care for Joint Replacement (CJR) program, which had been mandatory for all hospitals in 67 metropolitan statistical areas (MSAs), voluntary in the 33 of 67 MSAs with the lowest historical costs. CJR was designed to hold hospitals accountable for the cost and quality of care during hip or knee replacement episodes, defined as hospitalization and 90 days of post-discharge care. We compared hospitals that stayed with the CJR program against those that withdrew. This information is important for understanding the effects of voluntary payment models.
Viagra for fetal growth restriction: STRIDER Consortium replies to letter by Symonds and Budge
Authors: Louise C Kenny, Zarko Alfirevic, Philip N Baker, Wessel Ganzevoort, Christian Gluud, Katie M Groom, Janus C Jakobsen, K Lim, Laura A Magee, Aris T Papageorghiou, Peter von Dadelszen
Journal: BMJ (2018)

Symonds and Budge’s comments on a news article in The BMJ about the Dutch STRIDER trial are erroneous.12 They state that the “intervention resulted in 11 infant deaths due to lung related problems.” In fact, the study was stopped after an interim analysis that showed possible (but unproven) harm and to allow detailed review of the findings—specifically, an increased incidence …