tbuckley/cabot-search huggingface dataset:
Will you support a patient-centred R&amp;D agreement?—Response from David Nabarro
Authors: David Nabarro
Journal: The Lancet Global Health (2017)

I have received several letters inviting me to express my views on specific issues in global health, including the open letter published in The Lancet Global Health.1Barber MJ Gotham D Muntanyà J Balasubramaniam T on behalf of 18 other signatoriesOpen letter to the candidates for Director-General of WHO: will you support a patient-centred R&D agreement?.Lancet Glob Health. 2017; 5: e135-e136Summary Full Text Full Text PDF PubMed Scopus (6) Google Scholar My general position is that as Director-General, I will operate at all times within the context of decisions made by the WHO's Member States in the Governing Bodies. In preparing myself for serving as WHO Director-General, I anticipate my future responsibilities in a way that reflects the priorities that I have set out in the vision statement that I have submitted to the WHO. I would like to assure you that if an initiative has been advocated or endorsed in a Member State resolution I will do everything I can to ensure that it is pursued in line with that resolution. I do not intend that this be seen as a bureaucratic response on an extremely important issue. I have—throughout my career—been committed to doing all I can to ensure that all people everywhere have access to effective health services as and when they need them, including medicines, vaccines and technologies, within the context of the 2030 Agenda for Sustainable Development. To this end I have always sought to support research, development, and innovation that contribute to the health of all persons in an equitable manner. I perceive that at this time it would perhaps be unwise for me to make a commitment to advocate for and pursue a proposed intergovernmental agreement. That said, people-centred research and development has always played a vital role in supporting the WHO aim of improving global health and will certainly continue do so if I become the Director General of WHO. Open letter to the candidates for Director-General of WHO: will you support a patient-centred R&D agreement?Less than a year from now, a new Director-General will be elected to lead WHO.1 The next Director-General should commit to developing a global agreement on the research and development (R&D) of medicines, vaccines, and diagnostics of public health importance. This is critical in order to address the dual challenges posed by unaffordable medicine prices and a lack of innovation in neglected diseases, antimicrobials, and other public health priorities. Discussions at WHO on how to address failures of the current monopoly-based R&D system have been ongoing for over a decade, but R&D policy change is yet to occur and the will to address the root causes of the access and innovation crisis is still lacking. Full-Text PDF Open Access
Serum Trypsinogen Levels in Type 1 Diabetes
Authors: Xia Li, Martha Campbell-Thompson, Clive H. Wasserfall, Kieran McGrail, Amanda Posgai, Andrew R. Schultz, Todd M. Brusko, Jonathan Shuster, Faming Liang, Andrew Muir, Desmond Schatz, Michael J. Haller, Mark A. Atkinson
Journal: Diabetes Care (2017)

OBJECTIVE The pancreas in type 1 diabetes exhibits decreased size (weight/volume) and abnormal exocrine morphology. Serum trypsinogen levels are an established marker of pancreatic exocrine function. As such, we hypothesized that trypsinogen levels may be reduced in patients with pre–type 1 diabetes and type 1 diabetes compared with healthy control subjects. RESEARCH DESIGN AND METHODS Serum trypsinogen levels were determined in 100 persons with type 1 diabetes (72 new-onset, 28 established), 99 autoantibody-positive (AAb+) subjects at varying levels of risk for developing this disease, 87 AAb-negative (AAb−) control subjects, 91 AAb− relatives with type 1 diabetes, and 18 patients with type 2 diabetes. RESULTS Trypsinogen levels increased significantly with age in control subjects (r = 0.71; P &amp;lt; 0.0001) and were significantly lower in patients with new-onset (mean ± SD 14.5 ± 6.1 ng/mL; P &amp;lt; 0.0001) and established type 1 diabetes (16.7 ± 6.9 ng/mL; P &amp;lt; 0.05) versus AAb− control subjects (25.3 ± 11.2 ng/mL), AAb− relatives (29.3 ± 15.0 ng/mL), AAb+ subjects (26.5 ± 12.1 ng/mL), and patients with type 2 diabetes (31.5 ± 17.3 ng/mL). Multivariate analysis revealed reduced trypsinogen in multiple-AAb+ subjects (P &amp;lt; 0.05) and patients with type 1 diabetes (P &amp;lt; 0.0001) compared with AAb− subjects (control subjects and relatives combined) and single-AAb+ (P &amp;lt; 0.01) subjects when considering age and BMI. CONCLUSIONS These findings further support the interplay between pancreatic endocrine and exocrine dysfunction. Longitudinal studies are warranted to validate trypsinogen as a predictive biomarker of type 1 diabetes progression.
A prospective study to correlate EGFR mutations with gefitinib response
Authors: N. A. Rizvi, W. Pao, M. G. Kris, V. Rusch, M. Ladanyi, P. K. Ginex, M. F. Zakowski, L. B. Tyson, R. T. Heelan, H. Varmus
Journal: Journal of Clinical Oncology (2005)

7091 Background: Retrospective analyses have correlated EGFR tyrosine kinase domain mutations with response to gefitinib. In this prospective study we test the hypothesis that specific mutations in the EGFR gene correlate with response to gefitinib. To accomplish this goal, fresh frozen tissue was procured on all patients pre-treatment for mutational analysis and the patient population was "enriched" for the presence of EGFR mutations. Methods: Eligible patients have operable and resectable Stage I/II NSCLC with clinical features that correlate with response to gefitinib and the presence of EGFR mutations (≤ 10 pack year smoking history and/or features of BAC). All patients undergo core biopsy to obtain tumor DNA followed by treatment with gefitinib for at least 21 days pre-surgery with CT scan pre- and post-gefitinib, and tumors are assessed for EGFR mutations (exons 18–24). Patients with a radiographic response (≥ 25% reduction by bidimensional measurement) to gefitinib preoperatively and /or whose tumors contain EGFR mutations continue gefitinib for 2 years post-surgery. Patients will be followed for time to recurrence and survival. Results: 8 patients have been enrolled. 5/8 had adenocarcinoma with BAC and 3/8 had adenocarcinoma. 4/8 patients had a less than 10 pack year smoking history. All 8 patients underwent core biopsy for tumor DNA sequencing. EGFR mutations were detected in 2/8 patients in preoperative specimens and were confirmed in surgical resection specimens (1 exon 21 L858R mutation, 1 exon 19 deletion). A 22% and 56% response was observed in these 2 patients. 2 patients without evidence of EGFR mutation had a 25% and 43% response. No dose limiting toxicities were observed. The 4 patients with a response are continuing post-operative gefitinib. Conclusions: Pre-treatment core biopsy for EGFR mutation studies yielded sufficient tumor DNA for EGFR mutational analysis in all 8 patients. By using clinical characteristics to enrich our patient cohort, 2/8 patients were found to have an EGFR mutation and 4/8 (50%) of patients demonstrated a radiologic response to preoperative gefitinib. Responses were observed after only 21 days of gefitinib. 50 patients are planned and accrual continues. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca
Gene Expression Profiling of CML CD34+ Cells Prior to Imatinib Therapy Reveals Differences between Patients with and without Subsequent Complete Cytogenetic Response.
Authors: L. C. Crossman, M. Loriaux, K. Vartanian, Y. Turpaz, R. Pillai, S. G. O’Brien, B. J. Druker, S. K. McWeeney, C. A. Harrington, M. W.N. Deininger
Journal: Blood (2005)
TRIM5α Variation Affects Lentiviral Transduction Efficiency for Long-Term Hematopoietic Repopulating Cells in a Rhesus Stem Cell Transplantation Model
Authors: Naoya Uchida, Matthew M. Hsieh, Aylin C. Bonifacino, Sandra D. Price, Allen E. Krouse, Mark E. Metzger, Robert E. Donahue, John F. Tisdale
Journal: Blood (2011)
Sun Protection by Beach Umbrella vs Sunscreen With a High Sun Protection Factor
Authors: Hao Ou-Yang, Lily I. Jiang, Karen Meyer, Steve Q. Wang, Aaron S. Farberg, Darrell S. Rigel
Journal: JAMA Dermatology (2017)

Sun-protective behavior affects skin cancer prevention. Shade works by physically shielding skin from direct harmful UV rays; however, skin may still remain exposed to reflected and indirect UV rays. There is no current standard metric to evaluate shade for its effectiveness in sun protection, and there is insufficient clinical evidence that a beach umbrella alone can provide adequate sun protection.To directly measure sunburn protection offered by a standard beach umbrella compared with that provided by sunscreen with a high sun protection factor under actual use conditions.A single-center, evaluator-blinded, randomized clinical study was conducted from August 13 to 15, 2014, in Lake Lewisville, Texas (elevation, 159 m above sea level), among 81 participants with Fitzpatrick skin types I (n = 1), II (n = 42), and III (n = 38). Participants were randomly assigned to 2 groups: 1 using only a beach umbrella, and the other using only sunscreen with a sun protection factor of 100. All participants remained at a sunny beach for 3½ hours at midday. Clinical sunburn evaluation of each individual for all exposed body sites was conducted 22 to 24 hours after sun exposure.The shade provided by a beach umbrella or protection provided by sunscreen with a sun protection factor of 100.Sunburn on all exposed body sites 22 to 24 hours after sun exposure.Among the 81 participants (25 male and 56 female; mean [SD] age, 41 [16] years) for all body sites evaluated (face, back of neck, upper chest, arms, and legs), the umbrella group showed a statistically significant increase in clinical sunburn scores compared with baseline and had higher postexposure global scores than the sunscreen group (0.75 vs 0.05; P < .001). There was a total of 142 sunburn incidences in the umbrella group vs 17 in the sunscreen group. Thirty-two of the 41 participants (78%) in the umbrella group showed erythema in 1 or more sites vs 10 of the 40 participants (25%) in the sunscreen group (P < .001). Neither umbrella nor sunscreen alone completely prevented sunburn.A beach umbrella alone may not provide sufficient protection for extended UV exposure. It is important to educate the public that combining multiple sun protection measures may be needed to achieve optimal protection.isrctn.org Identifier: ISRCTN19177299.
Low‐Dose Prostate Cancer Brachytherapy with Radioactive Palladium–Gold Nanoparticles
Authors: Myriam Laprise‐Pelletier, Jean Lagueux, Marie‐France Côté, Thomas LaGrange, Marc‐André Fortin
Journal: Advanced Healthcare Materials (2017)

Prostate cancer (PCa) is one of the leading causes of death among men. Low‐dose brachytherapy is an increasingly used treatment for PCa, which requires the implantation of tens of radioactive seeds. This treatment causes discomfort; these implants cannot be removed, and they generate image artifacts. In this study, the authors report on intratumoral injections of radioactive gold nanoparticles (Au NPs) as an alternative to seeds. The particles ( 103 Pd:Pd@Au‐PEG and 103 Pd:Pd@ 198 Au:Au‐PEG; 10–14 nm Pd@Au core, 36–48 nm hydrodynamic diameter) are synthesized by a one‐pot process and characterized by electron microscopy. Administrated as low volume (2–4 µL) single doses (1.6–1.7 mCi), the particles are strongly retained in PCa xenograft tumors, impacting on their growth rate. After 4 weeks, a tumor volume inhibition of 56% and of 75%, compared to the controls, is observed for 103 Pd:Pd@Au‐PEG NPs and 103 Pd:Pd@ 198 Au:Au‐PEG NPs, respectively. Skin necrosis is observed with 198 Au; therefore, Au NPs labeled with 103 Pd only are a more advisable choice. Overall, this is the first study confirming the impact of 103 Pd@Au NPs on tumor growth. This new brachytherapy procedure could allow tunable doses of radioactivity, administered with smaller needles than with the current technologies, and leading to fewer image artifacts.
Gold Compound Auranofin (RIDAURA®) Induces Apoptosis of Human Myeloma Cells by Targeting STAT3 and NF-κB Pathways, with Clinical Potential.
Authors: Morihiko Sagawa, Aya Nakaya, Tatsuki Tomikawa, Yuichiro Haba, Tomoe Nemoto, Kyoko Hanzawa, Reiko Watanabe, Michihide Tokuhira, Shigehisa Mori, Hideo Uchida, Akihiro Muto, Masahiro Kizaki
Journal: Blood (2009)
Clinicopathological Differences Between Asian and Western Patients with De Novo Diffuse Large B Cell Lymphoma Treated with R-CHOP
Authors: Natalie Sinclair, Brady E Beltran, Moo-Kon Song, Ivana Ilic, Sirpa Leppa, Heidy Nyman, Silvia Uccella, Ritsuko Seki, Jun-ming Li, Diana O Treaba, James N Butera, Jorge J Castillo
Journal: Blood (2011)
P14.08 Neurological complications of emerging targeted therapies
Authors: E. Jaramillo-Jiménez, M. Simó, M. J. Gil-Gil, C. Majós, E. Nadal, J. M. Piulats, J. Bruna
Journal: Neuro-Oncology (2016)

AbstractIntroduction:The development of new biological and immunotherapeutic agents to treat cancer associates unknown neurological toxicities. Crizotinib (Cri), an anaplastic lymphoma kinase and c-ros oncogene 1 hepatocyte growth factor receptor tyrosine-kinase inhibitor, has been approved for the treatment of advanced ALK-positive non-small cell lung cancer. Ipilimumab (Ipi), an anticytotoxic T-lymphocyte antigen-4 antibody, was the first agent to demonstrate improved survival in patients with metastatic melanoma. This report describes a patient treated with Ipi showing a not previously reported neurological adverse event; and a patient treated with Cri showing atypical brain metastases.Patients and methods:Patient 1(P1): 66-year-old male with a history of irresectable nasal melanoma, started on Ipi plus concomitant radiotherapy on September/2015, obtaining a radiological partial response. Two months later he developed progressive cognitive impairment, urinary incontinence and gait difficulties. A neuroaxis MRI revealed multiple acute and subacute subcentimeter ischemic lesions with contrast enhancement and restricted diffusion with diffuse FLAIR signal changes. CSF reported protein elevation, normal glucose and mild lymphocytic pleocytosis without neoplastic cells. Microbiological cultures and PCRs were negative. Echocardiography was normal. Patient 2(P2): 54-year-old non-smoker female with lung adenocarcinoma (EGFR wild-type and ALK translocation) and spinal metastatic disease at diagnosis, started on Cri after failure of first-line treatment with cisplatin plus pemetrexed. After 16 cycles, an increase in carcinoembryonic antigen was noted without progression of ganglio-pulmonary disease. Although asymptomatic, CNS progression was suspected and follow-up brain MRI reported multiple bilateral supra and infratentorial large cystic lesions with perilesional edema and no contrast enhancement.Results:P1: primary angiitis of the CNS was suspected, although arteriography was unremarkable. He received high-dose metilprednisolone followed by cyclophosphamide bolus. The inflammatory component of CSF and neurological symptoms presented partial improvement but brain MRI showed a dissociate response. P2: PET scan revealed irregular distribution of the radiotracer and hypometabolic lesions. Follow-up brain MRI revealed stabilization with a perfusion-weighted sequence reporting an increase in the relative cerebral blood volume of the bigger cystic lesion. These features led us to the diagnostic of indolent brain metastases.Conclusions:Early recognition of new neurological patterns of toxicity may lead to drug discontinuation or dose adjustment preventing further neurological deterioration. A better knowledge of these toxicities will help differentiate treatment-related complications from metastatic progression.
A Somatic HIF2α Mutation-Induced Multiple and Recurrent Pheochromocytoma/Paraganglioma with Polycythemia: Clinical Study with Literature Review
Authors: Qiuli Liu, Yan Wang, Dali Tong, Gaolei Liu, Wenqiang Yuan, Jun Zhang, Jin Ye, Yao Zhang, Gang Yuan, Qingxing Feng, Dianzheng Zhang, Jun Jiang
Journal: Endocrine Pathology (2017)
High Body Mass Index (BMI) as a Predictor of Differentiation Syndrome (DS) In Acute Promyelocytic Leukemia (APL).
Authors: Ramzi Jeddi, Béchir Achour, Agnès Guerci-Bresler, Héla Ghédira, Hervé Dombret, Françoise Huguet, Patrice Chevallier, Norbert Vey, Stephane de Botton, Dominique Bordessoule, Beatrice U. Muller, Virginie Eclache, Claude Gardin, Balkis Meddeb, Lionel Adès, Pierre Fenaux
Journal: Blood (2010)
Renal Function Impairment (creatinine&gt;=2mg/dL) Limits Progress Noted with the Transition From Total Therapies TT1 to TT2 to TT3 Across Age Groups
Authors: Sarah Waheed, Monica Grazziutti, Alejandro Restrepo, Saad Z Usmani, Frits van Rhee, Jameel Muzaffar, Al-Ola Abdallah, Bijay Nair, Antje Hoering, Bart Barlogie
Journal: Blood (2012)
A Retrospective Analysis of Treatment Patterns in Elderly Patients with Chronic Myeloid Leukemia Receiving Dasatinib or Nilotinib As Second-Line Therapy after Imatinib
Authors: B. Douglas Smith, Jun Liu, Dominick Latremouille-Viau, Zhou Zhou, Annie Guerin, Daniel Fernandez, Dingdong Yi, Xufei Wang, Eric Q Wu, Shivani K Mhatre, Christopher H Keir, Lei Chen
Journal: Blood (2014)
The transcription factor musculin promotes the unidirectional development of peripheral Treg cells by suppressing the TH2 transcriptional program
Authors: Chuan Wu, Zuojia Chen, Valerie Dardalhon, Sheng Xiao, Theresa Thalhamer, Mengyang Liao, Asaf Madi, Rafael F Franca, Timothy Han, Mohammed Oukka, Vijay Kuchroo
Journal: Nature Immunology (2017)
Hydroxyurea Reduces the Hypercoagulable State In Sickle Cell Anemia
Authors: Marina P Colella, Joao Machado-Neto, Susan K.P. Quaino, Nicola Conran, Joyce M Annichino-Bizzacchi, Fernando Ferreira Costa, Sara Olalla Saad, Erich V de Paula, Fabiola Traina
Journal: Blood (2011)
Air trapping on computed tomography: regional <i>versus</i> diffuse
Authors: Firdaus A. Mohamed Hoesein, Pim A. de Jong
Journal: European Respiratory Journal (2017)

Chronic obstructive pulmonary disease (COPD) is diagnosed and classified by spirometry, assessing the presence of airflow obstruction and extent of forced expiratory flow deterioration. Spirometry, however, is unsuitable for characterising and quantifying the underlying pulmonary pathology of COPD, including alveolar destruction (emphysema) and airway remodelling (large- and small-airway disease). Accurate diagnosis of the pulmonary pathologies underlying COPD is seen as an important step towards better understanding its biology and "personalised" treatment. Computed tomography (CT) of the lungs provides an excellent opportunity to assess COPD in vivo and quantify its macroscopic pathology [1–3]. Emphysema and airway remodelling can be visually assessed and automatically quantified, and several studies have shown associations with morbidity and mortality [4–7]. In addition, CT can provide information on the spatial distribution of disease. Future studies on the distribution of air trapping in the lungs of COPD patients are needed <http://ow.ly/86hc304JiIK>
CPX-351: A randomized phase IIb study first-relapse patients younger than age 65.
Authors: J. E. Kolitz, J. E. Cortes, K. Paulsen, A. C. Louie
Journal: Journal of Clinical Oncology (2010)

TPS275 Background: CPX-351 is a liposomal formulation that co-encapsulates cytarabine and daunorubicin enabling in vivo delivery of both drugs at a 5:1 molar ratio shown to be synergistic in preclinical studies. A phase I study in advanced leukemia patients demonstrated markedly prolonged cytarabine and daunorubicin half-life and substantial efficacy in advanced AML patients with CRs at doses as low as 1/3 the MTD with acceptable safety. Of 48 patients treated, 18 had 1st relapse, 6 of whom achieved CR with 4 CRs among 8 patients <65 yo. A randomized phase IIb design was chosen to assess the relative safety and efficacy of CPX-351 when compared to conventional salvage regimens in the 1st relapse setting for patients ≤65 yo. Methods: This open-label study will treat 80 patients with CPX-351 (100 u/m2; D 1, 3, 5; 90 min infusion) and 40 patients with intensive salvage treatment (investigators choice). A unit of CPX-351 is 1 mg of cytarabine and 0.44 mg of daunorubicin. Up to 2 inductions and 2 consolidation courses are allowed and responders are permitted stem cell transplantation at the investigator's discretion. Patients must have AML in 1st relapse, ECOG PS= 0-2, SCr < 2.0 mg/dL, total bilirubin < 2.0 mg/dL, ALT/AST < 3 × ULN, and LVEF > 50%. The primary efficacy endpoint is % survival at 1 year and 2° efficacy endpoints include CR rate, CR duration, EFS, aplasia rate, and % transferred for stem cell transplantation. Safety endpoints include deaths at Day 30, 60, 90, >90; Grade 3 and 4 AEs; and SAE frequency. EKG and LVEF are centrally monitored. By Jan 2010, 44 of the planned 120 patients had been accrued at 31 centers located in North America and Europe. Phase II studies are intended to generate hypotheses and reduce the risk of failure in future trials. Randomized phase II designs are often criticized for their reduced statistical power. By providing relative efficacy and safety data in settings where accrual depends on the benefit of the study drug and choice of control, such designs effectively detect and reduce the risks of insufficient accrual, selection of unpopular controls, and overestimation of sample size for future trials. The value of such information from this randomized phase IIb study for effectively designing subsequent phase III trials will be discussed. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celator Pharmaceuticals, Inc. Celator Pharmaceuticals, Inc. Celator Pharmaceuticals, Inc.
Personalised “stop smoking” tasters double sign-up and increase quit rate
Authors: Susan Mayor
Journal: BMJ (2017)

Giving smokers personalised information on their risk and inviting them to a “stop smoking” taster session more than doubled the likelihood that they would go on to attend NHS stop smoking services and increased their quit rate compared with giving standard information, a randomised trial has shown.1

Government funded smoking cessation services were established in England in 2000 to help smokers quit. But under 5% of smokers attend these services each year, and numbers have been decreasing since 2012. Previous research suggests that proactive, personalised invitations can increase attendance.

Researchers randomly allocated 4384 smokers to personalised information on quitting smoking or …
Survival Based on Metaphase Versus Interphase Cells for 154 Patients with Newly Diagnosed Multiple Myeloma.
Authors: You Kyoung Lee, Fink Stephanie, Therneau Terry, Smoley Stephanie, Paternoster Sarah, Adeyinka Adewale, Larson Dirk, Fonseca Raphael, Kyle Robert, Dewald Gordon
Journal: Blood (2004)
Epidemiology and Clinical Features of Adults Myelodysplastic Syndromes in Algeria: A Population-Based Study. Review of the Algerian Myelodysplastic Syndromes Study Group
Authors: MA Bekadja, R Ahmed Nacer, RM Hamladji, N Boudjerra, M Belhani, Fz Ardjoun, MT Abad, H Touhami, H Ait Ali, Z Zouaoui, N Sidi Mansour, S Hamdi, F Grifi, N Mesli, M Saidi, N Lakhdari, N Mehalhal, A Bachiri, B Bendjabellah, S Nekkal, S Osmani, Z Kaci, S Taoussi, S Zouani, A Graine, M Benlazhar, S Bouabellah, B Benzineb, Fz Belkhodja, S Bougherira, M Aiche, M Aberkane, L Touati, M Benakli
Journal: Blood (2015)
A Phase 1 Dose Escalation Study of a Fully Human, Antagonist Anti-CD40 Antibody, HCD122 (Formerly CHIR-12.12) in Patients with Relapsed and Refractory Multiple Myeloma.
Authors: William Bensinger, Sundar Jagannath, Pamela S. Becker, Kenneth C. Anderson, Edward A. Stadtmauer, Lea Aukerman, Judith Fox, Sandhya Girish, Sanela Bilic, Serge Guzy, Alan Solinger, Sherri Dort, Yongyu Wang, Deborah Hurst
Journal: Blood (2006)