tbuckley/cabot-search huggingface dataset:
Proposing Essential Medicines to Treat Cancer: Methodologies, Processes, and Outcomes
Authors: Lawrence N. Shulman, Claire M. Wagner, Ronald Barr, Gilberto Lopes, Giuseppe Longo, Jane Robertson, Gilles Forte, Julie Torode, Nicola Magrini
Journal: Journal of Clinical Oncology (2015)

A great proportion of the world's cancer burden resides in low- and middle-income countries where cancer care infrastructure is often weak or absent. Although treatment of cancer is multidisciplinary, involving surgery, radiation, systemic therapies, pathology, radiology, and other specialties, selection of medicines that have impact and are affordable has been particularly challenging in resource-constrained settings. In 2014, at the invitation of the WHO, the Union for International Cancer Control convened experts to develop an approach to propose essential cancer medicines to be included in the WHO Model Essential Medicines Lists (EML) for Adults and for Children, as well as a resulting new list of cancer medicines.Experts identified 29 cancer types with potential for maximal treatment impact, on the basis of incidence and benefit of systemic therapies. More than 90 oncology experts from all continents drafted and reviewed disease-based documents outlining epidemiology, diagnostic needs, treatment options, and benefits and toxicities.Briefing documents were created for each disease, along with associated standard treatment regimens, resulting in a list of 52 cancer medicines. A comprehensive application was submitted as a revision to the existing cancer medicines on the WHO Model Lists. In May 2015, the WHO announced the addition of 16 medicines to the Adult EML and nine medicines to the Children's EML.The list of medications proposed, and the ability to link each recommended medicine to specific diseases, should allow public officials to apply resources most effectively in developing and supporting nascent or growing cancer treatment programs.
Multiinstitutional home-therapy trial of recombinant human interleukin-2 and interferon alfa-2 in progressive metastatic renal cell carcinoma.
Authors: J Atzpodien, E Lopez Hänninen, H Kirchner, H Bodenstein, M Pfreundschuh, U Rebmann, B Metzner, H J Illiger, G Jakse, T Niesel
Journal: Journal of Clinical Oncology (1995)

PURPOSE In a phase II multiinstitutional outpatient trial, patients with progressive metastatic renal cell carcinoma were treated with a combination of subcutaneous (SC) recombinant interleukin-2 (rIL-2) and recombinant interferon alfa-2 (rIFN alpha 2). PATIENTS AND METHODS One hundred fifty-two patients with metastatic renal cell carcinoma were treated. Treatment courses consisted of SC rIL-2 at 20 x 10(6) IU/m2 three times per week in weeks 1 and 4, and at 5 x 10(6) IU/m2 three times per week in weeks 2, 3, 5, and 6. Additionally, patients received SC rIFN alpha 2 6 x 10(6) U/m2 once per week in weeks 1 and 4, and three times per week in weeks 2, 3, 5, and 6. RESULTS There were nine (6%) complete responses (CRs) and 29 (19%) partial responses (PRs), for an overall response rate of 25% (95% confidence interval, 19% to 32%). The median duration of responses for CRs and PRs was 16+ and 9 months, respectively. Additionally, 55 patients (36%) had stable disease (SD). Fifty-nine patients (39%) had continued disease progression (PD) despite treatment, or went off study after less than 4 weeks of therapy. The majority of patients treated experienced fever, chills, malaise, nausea, vomiting, and anorexia, side effects that were mostly limited to World Health Organization (WHO) grade 1 and 2. However, one patient developed grade 4 CNS toxicity with extended somnolence. On cessation of therapy, the neurologic symptoms in this patient were fully reversible, with no neurologic deficiency. CONCLUSION In summary, this multiinstitutional home-therapy setting of SC rIL-2 and SC rIFN alpha 2 in patients with progressive metastatic renal cell carcinoma demonstrated drastically reduced systemic toxicity, while it confirmed the therapeutic efficacy of the low-dose SC immunotherapy combination schedule.
Autoimmune diseases in Adult Life after Childhood Cancer in Scandinavia (ALiCCS)
Authors: Anna Sällfors Holmqvist, Jørgen H Olsen, Lene Mellemkjaer, Stanislaw Garwicz, Lars Hjorth, Christian Moëll, Bengt Månsson, Laufey Tryggvadottir, Henrik Hasle, Jeanette Falck Winther
Journal: Annals of the Rheumatic Diseases (2015)

The pattern of autoimmune diseases in childhood cancer survivors has not been investigated previously. We estimated the risk for an autoimmune disease after childhood cancer in a large, population-based setting with outcome measures from comprehensive, nationwide health registries.From the national cancer registries of Denmark, Iceland and Sweden, we identified 20 361 1-year survivors of cancer diagnosed before the age of 20 between the start of cancer registration in the 1940s and 1950s through 2008; 125 794 comparison subjects, matched by age, gender and country, were selected from national population registers. Study subjects were linked to the national hospital registers. Standardised hospitalisation rate ratios (SHRRs) and absolute excess risks (AERs) were calculated.Childhood cancer survivors had a significantly increased SHRR of 1.4 (95% CI 1.3 to 1.5) of all autoimmune diseases combined, corresponding to an AER of 67 per 100 000 person-years. The SHRRs were significantly increased for autoimmune haemolytic anaemia (16.3), Addison's disease (13.9), polyarteritis nodosa (5.8), chronic rheumatic heart disease (4.5), localised scleroderma (3.6), idiopathic thrombocytopenic purpura (3.4), Hashimoto's thyroiditis (3.1), pernicious anaemia (2.7), sarcoidosis (2.2), Sjögren's syndrome (2.0) and insulin-dependent diabetes mellitus (1.6). The SHRRs for any autoimmune disease were significantly increased after leukaemia (SHRR 1.6), Hodgkin's lymphoma (1.6), renal tumours (1.6) and central nervous system neoplasms (1.4).Childhood cancer survivors are at increased risk for certain types of autoimmune diseases. These findings underscore the need for prolonged follow-up of these survivors.
Clinicopathologic aspects of E rosette negative T cell acute lymphocytic leukemia: a Pediatric Oncology Group study.
Authors: M J Borowitz, B L Dowell, J M Boyett, D J Pullen, W M Crist, F M Quddus, J M Falletta, R S Metzgar
Journal: Journal of Clinical Oncology (1986)

The Pediatric Oncology Group has studied 1,367 patients with non-B cell acute lymphocytic leukemia (ALL) of whom 186 (14%) had blasts that reacted with previously well-characterized heteroantisera, recognizing a T-lymphocyte specific surface membrane antigen (PT+). In 87 of these T cell cases, the leukemic cells failed to form at least 20% of sheep erythrocytic rosettes at 4 degrees C. Comparison of clinicopathologic features among PT-, E-PT+, and E+ groups of patients revealed significant differences among them. E-PT+ patients were older than PT- patients, had higher white blood cell counts (WBCs) and were more likely to have a mediastinal mass, and thus contained a higher proportion of poor-risk patients. However, the E-PT+ patients were also significantly different from the more traditionally-defined E+ patients in that they had lower WBCs and hemoglobin levels, and less frequent lymphadenopathy or mediastinal mass. In many respects, then, E-PT+ patients were intermediate in character between PT- and E+ patients. Our findings support the notion that further subclassification of ALL using antibodies recognizing lineage-specific surface determinants will permit recognition of groups of patients with distinct clinicopathologic features that may differ in prognosis or response to therapy. Such classification also focuses future biological studies on the pathogenesis of leukemias to immunologically well-defined subgroups of lymphoid neoplasms.
Keeping tobacco products out of sight in shops reduces future risk of smoking in teenagers, US study shows
Authors: Susan Mayor
Journal: BMJ (2015)

Keeping tobacco products out of sight in convenience stores significantly reduces teenagers’ susceptibility to smoking cigarettes in the future, a US study published in Tobacco Control has found.

The study, funded by the National Cancer Institute and the FDA Center for Tobacco Products, randomly allocated 241 adolescents aged 11-17 years to three different layouts in a life sized (1500 square feet) replica of a convenience store stocked with more than 650 products.1 The first displayed tobacco products in the typical position …
Tuberculosis in Germany: a declining trend coming to an end?
Authors: Lena Fiebig, Barbara Hauer, Bonita Brodhun, Doris Altmann, Walter Haas
Journal: European Respiratory Journal (2015)

In the context of the newly adopted World Health Organization (WHO) End TB strategy, an action framework towards tuberculosis (TB) elimination in low incidence countries has been launched [1, 2]. Its aim is to reach pre-elimination of TB (less than 10 cases per one million inhabitants) by 2035 and TB elimination (less than one case per one million inhabitants) by 2050. Germany belongs to the addressed countries and territories with a TB incidence lower than 10 cases per 100 000 inhabitants. To reach these targets, Germany would have to have an annual reduction in the TB incidence of about 10% [1, 2]. Coinciding with the launch of the End TB Strategy, tuberculosis case numbers are re-increasing in Germany <http://ow.ly/Tj2f0> We thank all contributors to the surveillance of tuberculosis in Germany, in particular the local public health offices and state health departments. All investigated data were anonymous and collected within the legal framework of the Protection Against Infection Act.
Assessment of estrogenic recruitment before chemotherapy in advanced breast cancer: a double-blind randomized study. European Organization for Research and Treatment of Cancer Breast Cancer Cooperative Group.
Authors: R Paridaens, J C Heuson, J P Julien, C Veyret, J Van Zyl, J G Klijn, R Sylvester, F Mignolet
Journal: Journal of Clinical Oncology (1993)

PURPOSE In the present phase III study, the specific effect of estrogenic recruitment was assessed by comparing two groups of patients with advanced breast cancer receiving either ethinylestradiol (EE2) or placebo (PL) before chemotherapy (CT). PATIENTS AND METHODS The therapeutic regimen consisted of (1) estrogen suppression by aminoglutethimide (AGL) 1 g/d plus hydrocortisone (HC) 40 mg/d, with surgical castration performed on premenopausal patients; (2) fluorouracil (5-FU) 500 mg/m2, doxorubicin 50 mg/m2, and cyclophosphamide (CPA) 500 mg/m2 (FAC) intravenously (IV) every 3 weeks; (3) following randomization, patients were double-blinded to receive either PL or EE2 50 micrograms exactly 24 hours before receiving FAC. All patients had advanced breast cancer presumably sensitive to endocrine therapy (estrogen receptor-positive [ER+] and/or progesterone receptor-positive [PgR+] status) with measurable lesions; none had received prior systemic antineoplastic therapy for metastatic disease; prior adjuvant hormonal therapy (HT) or CT (without anthracyclines) was allowed if interval since completion was longer than 1 year. RESULTS Among 154 patients treated according to the protocol, tolerance, response rates, time to progression, and median survival duration were identical in the PL and EE2 groups. Only performance status, dominant metastatic site, and menopausal status seemed to influence response (overall response, 64%), with the highest levels of partial remission (PR) and complete remission (CR) being achieved in premenopausal women (CR plus PR, 26% plus 55%) and in those with dominant soft tissue lesions (CR plus PR, 45% plus 28%). CONCLUSION We conclude that the validity of the hormonal recruitment concept has not yet been established in clinical practice so that this approach remains experimental. The results achieved by combining (near) complete estrogenic suppression and cyclical FAC chemotherapy are not significantly different from those to be expected with the more conventional use of HT followed by CT in presumably hormone-responsive (ER+) patients.
PDL1 Regulation by p53 via miR-34
Authors: Maria Angelica Cortez, Cristina Ivan, David Valdecanas, Xiaohong Wang, Heidi J. Peltier, Yuping Ye, Luiz Araujo, David P. Carbone, Konstantin Shilo, Dipak K Giri, Kevin Kelnar, Desiree Martin, Ritsuko Komaki, Daniel R. Gomez, Sunil Krishnan, George A. Calin, Andreas G. Bader, James W. Welsh
Journal: JNCI Journal of the National Cancer Institute (2015)

Although clinical studies have shown promise for targeting PD1/PDL1 signaling in non–small cell lung cancer (NSCLC), the regulation of PDL1 expression is poorly understood. Here, we show that PDL1 is regulated by p53 via miR-34. p53 wild-type and p53-deficient cell lines (p53–/– and p53+/+ HCT116, p53-inducible H1299, and p53-knockdown H460) were used to determine if p53 regulates PDL1 via miR-34. PDL1 and miR-34a expression were analyzed in samples from patients with NSCLC and mutated p53 vs wild-type p53 tumors from The Cancer Genome Atlas for Lung Adenocarcinoma (TCGA LUAD). We confirmed that PDL1 is a direct target of miR-34 with western blotting and luciferase assays and used a p53R172HΔg/+K-rasLA1/+ syngeneic mouse model (n = 12) to deliver miR-34a–loaded liposomes (MRX34) plus radiotherapy (XRT) and assessed PDL1 expression and tumor-infiltrating lymphocytes (TILs). A two-sided t test was applied to compare the mean between different treatments. We found that p53 regulates PDL1 via miR-34, which directly binds to the PDL1 3' untranslated region in models of NSCLC (fold-change luciferase activity to control group, mean for miR-34a = 0.50, SD = 0.2, P < .001; mean for miR-34b = 0.52, SD = 0.2, P = .006; and mean for miR-34c = 0.59, SD = 0.14, and P = .006). Therapeutic delivery of MRX34, currently the subject of a phase I clinical trial, promoted TILs (mean of CD8 expression percentage of control group = 22.5%, SD = 1.9%; mean of CD8 expression percentage of MRX34 = 30.1%, SD = 3.7%, P = .016, n = 4) and reduced CD8+PD1+ cells in vivo (mean of CD8/PD1 expression percentage of control group = 40.2%, SD = 6.2%; mean of CD8/PD1 expression percentage of MRX34 = 20.3%, SD = 5.1%, P = .001, n = 4). Further, MRX34 plus XRT increased CD8+ cell numbers more than either therapy alone (mean of CD8 expression percentage of MRX34 plus XRT to control group = 44.2%, SD = 8.7%, P = .004, n = 4). Finally, miR-34a delivery reduced the numbers of radiation-induced macrophages (mean of F4-80 expression percentage of control group = 52.4%, SD = 1.7%; mean of F4-80 expression percentage of MRX34 = 40.1%, SD = 3.5%, P = .008, n = 4) and T-regulatory cells. We identified a novel mechanism by which tumor immune evasion is regulated by p53/miR-34/PDL1 axis. Our results suggest that delivery of miRNAs with standard therapies, such as XRT, may represent a novel therapeutic approach for lung cancer.
Randomized Clinical Trial Comparing Basal Insulin Peglispro and Insulin Glargine in Patients With Type 2 Diabetes Previously Treated With Basal Insulin: IMAGINE 5
Authors: John B. Buse, Helena W. Rodbard, Carlos Trescoli Serrano, Junxiang Luo, Tibor Ivanyi, Juliana Bue-Valleskey, Mark L. Hartman, Michelle A. Carey, Annette M. Chang
Journal: Diabetes Care (2015)

OBJECTIVE To evaluate the efficacy and safety of basal insulin peglispro (BIL) versus insulin glargine in patients with type 2 diabetes (hemoglobin A1c [HbA1c] ≤9% [75 mmol/mol]) treated with basal insulin alone or with three or fewer oral antihyperglycemic medications. RESEARCH DESIGN AND METHODS This 52-week, open-label, treat-to-target study randomized patients (mean HbA1c 7.42% [57.6 mmol/mol]) to BIL (n = 307) or glargine (n = 159). The primary end point was change from baseline HbA1c to 26 weeks (0.4% [4.4 mmol/mol] noninferiority margin). RESULTS At 26 weeks, reduction in HbA1c was superior with BIL versus glargine (−0.82% [−8.9 mmol/mol] vs. −0.29% [−3.2 mmol/mol]; least squares mean difference −0.52%, 95% CI −0.67 to −0.38 [−5.7 mmol/mol, 95% CI −7.3 to −4.2; P &amp;lt; 0.001); greater reduction in HbA1c with BIL was maintained at 52 weeks. More BIL patients achieved HbA1c &amp;lt;7% (53 mmol/mol) at weeks 26 and 52 (P &amp;lt; 0.001). With BIL versus glargine, nocturnal hypoglycemia rate was 60% lower, more patients achieved HbA1c &amp;lt;7% (53 mmol/mol) without nocturnal hypoglycemia at 26 and 52 weeks (P &amp;lt; 0.001), and total hypoglycemia rates were lower at 52 weeks (P = 0.03). At weeks 26 and 52, glucose variability was lower (P &amp;lt; 0.01), basal insulin dose was higher (P &amp;lt; 0.001), and triglycerides and aminotransferases were higher with BIL versus glargine (P &amp;lt; 0.05). Liver fat content (LFC), assessed in a subset of patients (n = 162), increased from baseline with BIL versus glargine (P &amp;lt; 0.001), with stable levels between 26 and 52 weeks. CONCLUSIONS BIL provided superior glycemic control versus glargine, with reduced nocturnal and total hypoglycemia, lower glucose variability, and increased triglycerides, aminotransferases, and LFC.
Pulmonary Disease and Age at Immigration among Hispanics. Results from the Hispanic Community Health Study/Study of Latinos
Authors: R. Graham Barr, Larissa Avilés-Santa, Sonia M. Davis, Tom K. Aldrich, Franklyn Gonzalez, Ashley G. Henderson, Robert C. Kaplan, Lisa LaVange, Kiang Liu, Jose S. Loredo, Eliana S. Mendes, Ai Ni, Andrew Ries, Matthias Salathe, Lewis J. Smith
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Asthma has been reported to be more prevalent among Hispanics of Puerto Rican heritage than among other Hispanics and among Hispanics born in the United States or who immigrated as children than among those who came as adults; however, direct comparisons across Hispanic groups are lacking.Objectives: To test whether asthma is more prevalent among Hispanics of Puerto Rican heritage than among other Hispanic groups, whether asthma is associated with age of immigration, and whether chronic obstructive pulmonary disease varies by heritage in a large, population-based cohort of Hispanics in the United States.Methods: The Hispanic Community Health Study/Study of Latinos researchers recruited a population-based probability sample of 16,415 Hispanics/Latinos, 18–74 years of age, in New York City, Chicago, Miami, and San Diego. Participants self-reported Puerto Rican, Cuban, Dominican, Mexican, Central American, or South American heritage; birthplace; and, if relevant, age at immigration. A respiratory questionnaire and standardized spirometry were performed with post-bronchodilator measures for those with airflow limitation.Measurements and Main Results: The prevalence of physician-diagnosed asthma among Puerto Ricans (36.5%; 95% confidence interval, 33.6–39.5%) was higher than among other Hispanics (odds ratio, 3.9; 95% confidence interval, 3.3–4.6). Hispanics who were born in the mainland United States or had immigrated as children had a higher asthma prevalence than those who had immigrated as adults (19.6, 19.4, and 14.1%, respectively; P < 0.001). Current asthma, bronchodilator responsiveness, and wheeze followed similar patterns. Chronic obstructive pulmonary disease prevalence was higher among Puerto Ricans (14.1%) and Cubans (9.8%) than among other Hispanics (<6.0%), but it did not vary across Hispanic heritages after adjustment for smoking and prior asthma (P = 0.22), by country of birth, or by age at immigration.Conclusions: Asthma was more prevalent among Puerto Ricans, other Hispanics born in the United States, and those who had immigrated as children than among other Hispanics. In contrast, the higher prevalence of chronic obstructive pulmonary disease among Puerto Ricans and Cubans was largely reflective of differential smoking patterns and asthma.
Soluble and cell-associated triggering receptor expressed on myeloid cells-1 and -2 in patients with pulmonary tuberculosis
Authors: Arie J Hoogendijk, Dana C Blok, M Isabel Garcia Laorden, Liesbeth M Kager, Ivar O Lede, Wahid Rahman, Rumana Afroz, Paul Bresser, Jaring S van der Zee, Aniruddha Ghose, Caroline E Visser, Menno D de Jong, Abu Shahed Md Zahed, Md Anwar Husain, Khan Mashrequl Alam, Pravat Chandra Barua, Mahtabuddin Hassan, Ahmed Hossain, Md Abu Tayab, Rene Lutter, Nick Day, Arjen M Dondorp, Cornelis Van't Veer, Alex F de Vos, Tom van der Poll
Journal: Journal of Infection (2015)
Type 1 diabetes immunotherapy using polyclonal regulatory T cells
Authors: Jeffrey A. Bluestone, Jane H. Buckner, Mark Fitch, Stephen E. Gitelman, Shipra Gupta, Marc K. Hellerstein, Kevan C. Herold, Angela Lares, Michael R. Lee, Kelvin Li, Weihong Liu, S. Alice Long, Lisa M. Masiello, Vinh Nguyen, Amy L. Putnam, Mary Rieck, Peter H. Sayre, Qizhi Tang
Journal: Science Translational Medicine (2015)

Autologous regulatory T cells can be expanded and are well tolerated in patients with recent-onset type 1 diabetes.
Welcoming conservatives to the field
Authors: Richard Nisbett
Journal: Behavioral and Brain Sciences (2015)

Abstract More conservatives would provide advantages, and social psychologists may not be as opposed to increasing the number of conservatives as Duarte et al. think. Recruitment problems concern primarily self-selection and biases in undergraduate instruction. Social psychologists should welcome having conservatives in the field to serve as a conduit for our theories and methods to conservative intellectuals and policy makers.
Crimean–Congo haemorrhagic fever and secondary bacteraemia in Turkey
Authors: Mustafa Sunbul, Hakan Leblebicioglu, Tom E. Fletcher, Nazif Elaldi, Zulal Ozkurt, Aliye Bastug, Gurdal Yilmaz, Rahmet Guner, Fazilet Duygu, Nick J. Beeching
Journal: Journal of Infection (2015)
Microtubule-Associated Proteins: Their Potential Role in Determining Neuronal Morphology
Authors: A Matus
Journal: Annual Review of Neuroscience (1988)

The brain's default mode network consists of discrete, bilateral and symmetrical cortical areas, in the medial and lateral parietal, medial prefrontal, and medial and lateral temporal cortices of the human, nonhuman primate, cat, and rodent brains. Its ...Read More
Incidence of invasive meticillin-resistant Staphylococcus aureus infections in Germany, 2010 to 2014
Authors: Jan Walter, Sebastian Haller, Hans-Peter Blank, Tim Eckmanns, Muna Abu Sin, Julia Hermes
Journal: Eurosurveillance (2015)

Voluntary surveillance systems in Germany suggest a recent decline in the incidence of infections (subsequent to at least 2010) with meticillin-resistant Staphylococcus aureus (MRSA) from various types of specimens and settings. We asked whether this decline is reflected by data from the mandatory national surveillance system for invasive MRSA infections. Our analysis is based on the population in Germany in 2010 to 2014. Cases were identified from passive reporting by microbiological laboratories of the diagnosis of MRSA from blood culture or cerebrospinal fluid. Respective clinical data were subsequently added to the notification. We calculated risk ratios (RR) between consecutive years, stratifying cases by sex, age and federal state of residence. The national incidence increased from 4.6 episodes per 100,000 persons in 2010 to 5.6 in 2012 (2011 vs 2010: RR: 1.13, 95% confidence interval (CI): 1.08–1.18; 2012 vs 2011: RR: 1.08, 95% CI: 1.04–1.13). It stagnated at 5.4 per 100,000 in 2013 (RR: 0.97, 95% CI: 0.93–1.01) before declining to 4.8 in 2014 (RR: 0.88, 95% CI: 0.84–0.91). This trend was observed in most, but not all federal states and strata of sex and age groups. Only 204 of 20,679 (1%) episodes of infection were notified as belonging to an outbreak. Our analysis corroborates previous findings that the incidence of invasive MRSA infections in Germany may be declining.
Classification of treatment-related mortality in children with cancer: a systematic assessment
Authors: Sarah Alexander, Jason D Pole, Paul Gibson, Michelle Lee, Tanya Hesser, Susan N Chi, Christopher C Dvorak, Brian Fisher, Henrik Hasle, Jukka Kanerva, Anja Möricke, Bob Phillips, Elizabeth Raetz, Carlos Rodriguez-Galindo, Sujith Samarasinghe, Kjeld Schmiegelow, Wim Tissing, Thomas Lehrnbecher, Lillian Sung
Journal: The Lancet Oncology (2015)