tbuckley/cabot-search huggingface dataset:
Efficacy and safety of BCD-021, bevacizumab biosimilar candidate, compared to Avastin: Results of international multicenter randomized double blind phase III study in patients with advanced non-squamous NSCLC.
Authors: Olga Filon, Sergey Orlov, Olga Burdaeva, Mikhail V. Kopp, Bogdan Kotiv, Sergiy Alekseev, Aleksandr Pecheniy, Daniil Stroyakovskiy, Oleg Gladkov, Andrey Khorinko, Marina Matrosova, Rinat Galiulin, Pavel Skopin, Guzel Mukhametsina, Sergey Odarchenko, Sergey Kulik, Jaroslav Kulyaba, Grigory Adamchuk, Yurii Vinnyk, Sergei Tjulandin
Journal: Journal of Clinical Oncology (2015)

8057 Background: BCD-021 demonstrated equivalence to Avastin in a comprehensive comparability exercise that included physicochemical, PK and PD studies, as well as phase I PK clinical study in patients with non-squamous NSCLC. Methods: 138 patients with advanced non-squamous NSCLC (stage IIIb/IV) were randomly assigned into 2 groups at a ratio of 1:1 to receive BCD-021 or Avastin at a dose of 15 mg/kg in combination with paclitaxel (175 mg/m2) and carboplatin (AUC 6 mg/ml×min) every 3 weeks up to 6 cycles of therapy or until progression or unbearable toxicity. Results: ORR (primary endpoint) in both groups had no statistically significant differences: 42.59 % (95% CI 30.33 – 55.83) in BCD-021 group and 39.29% (95% CI 27.58 – 52.27%) in Avastin group. The lower limit of 95% CI for ORR difference between the groups (-14.96%) did not exceed the non-inferiority margin, hence BCD-021 is non-inferior to Avastin. There were also no differences between the groups for all other efficacy parameters: CR (1.85% vs 1.79%), PR (40.74% vs 37.50%), stable disease (51.85% vs 51.79%) and progression rate (5.56% vs 8.93%) in BCD-021 and Avastin group, respectively. AEs profiles of BCD-021 and Avastin were equivalent. Rate of all observed AEs including severe AEs had no statistically significant difference between the groups. Most AEs were associated with chemotherapy : neutropenia (85.29% vs 78,7%), anemia (88.24% vs 84.85%), leukopenia (79.41% vs 75.76%), thrombocytopenia (69.12% vs 62.12%), hyperglycemia (61.76 vs 56.06), LDH increase (48.53 vs 37.88), ALP increase (35.29% vs 30.30), ALT increase (26.47% vs 28.79%), alopecia (30.88% vs 24,24%), etc. Reactions specific for bevacizumab included: arterial hypertension (26,47% vs 22,73%), weakness (17.65 vs 16.67), lung bleeding (5.88% vs 3.03%), proteinuria (2.94% vs 0%), GIT perforation (0% vs 1.52%) and VTE (0% vs 1.52%). Binding and neutralizing antibodies were transient and detected only in 1 patient in each group that indicated to low immunogenic potential of both drugs. Conclusions: BCD-021 demonstrated non-inferiority to Avastin in patients with NSCLC. Clinical trial information: NCT01763645.
Aging promotes acquisition of naive-like CD8+ memory T cell traits and enhanced functionalities
Authors: Jens Eberlein, Bennett Davenport, Tom Nguyen, Francisco Victorino, Kelsey Haist, Kevin Jhun, Anis Karimpour-Fard, Lawrence Hunter, Ross Kedl, Eric T. Clambey, Dirk Homann
Journal: Journal of Clinical Investigation (2016)

Protective T cell memory is an acquired trait that is contingent upon the preservation of its constituents and therefore vulnerable to the potentially deleterious effects of organismal aging. Here, however, we have found that long-term T cell memory in a natural murine host-pathogen system can substantially improve over time. Comprehensive molecular, phenotypic, and functional profiling of aging antiviral CD8+ memory T cells (CD8+ TM) revealed a pervasive remodeling process that promotes the gradual acquisition of distinct molecular signatures, of increasingly homogeneous phenotypes, and of diversified functionalities that combine to confer a CD8+ TM–autonomous capacity for enhanced recall responses and immune protection. Notably, the process of CD8+ TM aging is characterized by a progressive harmonization of memory and naive T cell traits, is broadly amenable to experimental acceleration or retardation, and serves as a constitutional component for the "rebound model" of memory T cell maturation. By casting CD8+ TM populations within the temporal framework of their slowly evolving properties, this model establishes a simple ontogenetic perspective on the principal organization of CD8+ T cell memory that may directly inform the development of improved diagnostic, prophylactic, and therapeutic modalities.
Effect of Clopidogrel on Arteriovenous Fistulas for Dialysis
Authors: Costas Fourtounas
Journal: JAMA (2008)

To the Editor: The trial by Dr Dember and colleagues1 failed to show any improvement in fistula maturation for hemodialysis by using clopidrogrel, although its use decreased the frequency of early thrombosis. However, the design of the study might explain some of the results.
Prisons: health hazards, but also health opportunities
Authors: C Weilandt, D Radun
Journal: Eurosurveillance (2007)

“Prisons are among the most unhealthy places in our societies. In them, people are not only deprived of their freedom but they are also exposed to threats such as violence, addiction and infectious diseases, while at the same time their own capacity to manage these risks is severely constrained” [1].
<i>Aspergillus fumigatus</i> components distinguish IgE but not IgG4 profiles between fungal sensitization and allergic broncho-pulmonary aspergillosis
Authors: J. Vitte, T. Romain, A. Carsin, M. Gouitaa, N. Stremler-Le Bel, M. Baravalle-Einaudi, I. Cleach, M. Reynaud-Gaubert, J.-C. Dubus, J.-L. Mège
Journal: Allergy (2016)

Aspergillus fumigatus is the causative agent of allergic broncho-pulmonary aspergillosis. Prompt and accurate diagnosis may be difficult to achieve with current clinical and laboratory scores, which do not include immune responses to recombinant A. fumigatus allergens. We measured specific immunoglobulin E and G4 directed to recombinant A. fumigatus allergens in 55 cystic fibrosis patients without allergic broncho-pulmonary aspergillosis but sensitized to A. fumigatus and in nine patients with allergic broncho-pulmonary aspergillosis (two with cystic fibrosis and seven with asthma). IgG4 responses to recombinant A. fumigatus allergens were detected in all patients, but neither prevalence nor levels were different between the two patient groups. On the other hand, both prevalence and levels of IgE responses to Asp f 3, Asp f 4, and Asp f 6 helped distinguish allergic broncho-pulmonary aspergillosis from A. fumigatus sensitization with good negative and positive predictive values.
Brief Report: Association of Tumor Necrosis Factor Receptor–Associated Periodic Syndrome With Gonosomal Mosaicism of a Novel 24‐Nucleotide <i>TNFRSF1A</i> Deletion
Authors: Dorota M. Rowczenio, Hadija Trojer, Ebun Omoyinmi, Juan I. Aróstegui, Grigor Arakelov, Anna Mensa‐Vilaro, Anna Baginska, Caroline Silva Pilorz, Guosu Wang, Thirusha Lane, Paul Brogan, Philip N. Hawkins, Helen J. Lachmann
Journal: Arthritis & Rheumatology (2016)

To investigate the molecular cause of persistent fevers in a patient returning from working overseas, in whom investigations for tropical diseases yielded negative results.DNA was extracted from the patient's whole blood, leukocyte subpopulations, saliva, hair root, and sperm. The TNFRSF1A gene was analyzed by polymerase chain reaction (PCR), allele-specific PCR, Sanger sequencing, and next-generation sequencing. In silico molecular modeling was performed to predict the structural and functional consequences of the tumor necrosis factor receptor (TNFR) type I protein mutation in the extracellular domain.Sanger sequencing corroborated by allele-specific PCR detected a novel in-frame deletion of 24 nucleotides (c.255_278del) in the TNFRSF1A gene, and this was subsequently confirmed using next-generation sequencing methods (targeted sequencing and amplicon-based deep sequencing). Results of amplicon-based deep sequencing revealed variable frequency of the mutant allele among different cell lines, including sperm, thus supporting the presence of gonosomal TNFRSF1A mosaicism. The patient had a complete response to treatment with interleukin-1 (IL-1) blockade, with resolution of symptoms and normalization of acute-phase protein levels.We describe the first case of gonosomal TNFRSF1A mosaicism in a patient with TNFR-associated periodic syndrome (TRAPS), which was attributable to a novel, somatic 24-nucleotide in-frame deletion. The clinical picture in this patient, including the complete response to IL-1 blockade, was typical of that found in TRAPS. This case adds TRAPS to the list of dominantly inherited autoinflammatory diseases reported to be caused by somatic (or postzygotic) mutation.
Surgical outcomes of total thyroidectomy using the LigaSure™ Small Jaw versus LigaSure Precise™: A retrospective study of 2000 consecutive patients
Authors: Oscar Vidal, David Saavedra-Perez, Mauro Valentini, Emiliano Astudillo, Laureano Fernández-Cruz, Juan C. García-Valdecasas
Journal: International Journal of Surgery (2016)
The United States needs a health system like other countries
Authors: B. Schlafly
Journal: JAMA (1994)

To the Editor.  —Dr Glaser 1 tells us in his article that he has grown weary of the debate about health care reform. It's time for action now. The task is to organize the entire country, and Glaser is more than willing to be the organizer.  Glaser informs us that America needs  comprehensive health system. He describes Social Security in glowing terms and his solution for financing his system is a payroll tax modeled after the Social Security tax. Of course, this is how Medicare Part A is financed. He rightly observes that the Medicare program is embroiled in complexities and endless political disputes, yet he implies that his new national health system will somehow avoid the same problems. I don't believe it.  I am afraid that the Social Security model for health care acclaimed by Glaser is not so reassuring. Workers I know who are younger than 40
Cytidine Deaminase Deficiency Reveals New Therapeutic Opportunities against Cancer
Authors: Hamza Mameri, Ivan Bièche, Didier Meseure, Elisabetta Marangoni, Géraldine Buhagiar-Labarchède, André Nicolas, Sophie Vacher, Rosine Onclercq-Delic, Vinodh Rajapakse, Sudhir Varma, William C. Reinhold, Yves Pommier, Mounira Amor-Guéret
Journal: Clinical Cancer Research (2016)

Purpose: One of the main challenges in cancer therapy is the identification of molecular mechanisms mediating resistance or sensitivity to treatment. Cytidine deaminase (CDA) was reported to be downregulated in cells derived from patients with Bloom syndrome, a genetic disease associated with a strong predisposition to a wide range of cancers. The purpose of this study was to determine whether CDA deficiency could be associated with tumors from the general population and could constitute a predictive marker of susceptibility to antitumor drugs.Experimental Design: We analyzed CDA expression in silico, in large datasets for cancer cell lines and tumors and in various cancer cell lines and primary tumor tissues using IHC, PDXs, qRT-PCR, and Western blotting. We also studied the mechanism underlying CDA silencing and searched for molecules that might target specifically CDA-deficient tumor cells using in silico analysis coupled to classical cellular experimental approaches.Results: We found that CDA expression is downregulated in about 60% of cancer cells and tissues. We demonstrate that DNA methylation is a prevalent mechanism of CDA silencing in tumors. Finally, we show that CDA-deficient tumor cells can be specifically targeted with epigenetic treatments and with the anticancer drug aminoflavone.Conclusions: CDA expression status identifies new subgroups of cancers, and CDA deficiency appears to be a novel and relevant predictive marker of susceptibility to antitumor drugs, opening up new possibilities for treating cancer. Clin Cancer Res; 23(8); 2116-26. ©2016 AACR.
Developing EZH2-Targeted Therapy for Lung Cancer
Authors: Arthur E. Frankel, Xin Liu, John D. Minna
Journal: Cancer Discovery (2016)

Abstract Summary: Epigenetic targets are exciting new avenues for cancer drug discovery. Zhang and colleagues have designed the open-source EZH2 inhibitor JQEZ5 and shown antitumor efficacy in vitro and in vivo in preclinical studies in murine and human lung adenocarcinoma models expressing high levels of EZH2. Cancer Discov; 6(9); 949–52. ©2016 AACR. See related article by Zhang and colleagues, p. 1006.
Maharishi Ayur-Veda
Authors: Marcia R. Rudin
Journal: JAMA (1991)

<h3>To the Editor.</h3> —The medical techniques promoted by TM<sup>1</sup>are not scientifically based and are, in fact, harmful. I have been working in the field of destructive cults for 20 years and have concluded that the TM movement is a dangerous cult, damaging both physically and, especially, psychologically to its followers. By publishing this article in your journal, you have given TM the legitimacy it seeks and you have damaged the journal's intellectual integrity.
Runkeeper: a complete app for monitoring outdoor sports
Authors: A Martinez-Nicolas, A Muntaner-Mas, F B Ortega
Journal: British Journal of Sports Medicine (2016)

Runkeeper.

Android: health and wellness; iOS: health and fitness.

Android, iOS.

Free/premium (€29.01/year, US$39.99/year).

Runkeeper is an app designed to log several outdoor sports by Global Positioning System (GPS), such as running, walking, skiing or skating (figure 1A). The track of the training obtained from GPS is plotted on a map from Google Maps (figure 1B). This app is able to record all the basic data: duration, distance, speed (eg, km/hour, total and by splits), pace (min/1 km) and elevation. Pace and elevation are continuously monitored and plotted to know the exact value at any moment of …
Cytopenia levels for aiding establishment of the diagnosis of myelodysplastic syndromes
Authors: Peter L. Greenberg, Heinz Tuechler, Julie Schanz, Guillermo Sanz, Guillermo Garcia-Manero, Francesc Solé, John M. Bennett, David Bowen, Pierre Fenaux, Francois Dreyfus, Hagop Kantarjian, Andrea Kuendgen, Alessandro Levis, Luca Malcovati, Mario Cazzola, Jaroslav Cermak, Christa Fonatsch, Michelle M. Le Beau, Marilyn L. Slovak, Otto Krieger, Michael Luebbert, Jaroslaw Maciejewski, Silvia M. M. Magalhaes, Yasushi Miyazaki, Michael Pfeilstöcker, Mikkael Sekeres, Wolfgang R. Sperr, Reinhard Stauder, Sudhir Tauro, Peter Valent, Teresa Vallespi, Arjan A. van de Loosdrecht, Ulrich Germing, Detlef Haase
Journal: Blood (2016)
Fludarabine, Low Dose Busulfan and Antithymocyte Globulin for Reduced-Intensity Conditioning (RIC) Prior to Allogeneic Stem Cell Transplantation (allo-SCT).
Authors: F. Malard, Eolia Brissot, Patrice Chevallier, Thierry Guillaume, Jacques Delaunay, Sameh Ayari, Viviane Dubruille, Steven Le Gouill, Beatrice Mahe, Thomas Gastinne, Nicolas Blin, Beatrice Saulquin, Jean-Luc Harousseau, Philippe Moreau, Noel-Jean Milpied, Mohamad Mohty
Journal: Blood (2009)
Stem Cell Substrates: Pulsed‐Electromagnetic‐Field‐Assisted Reduced Graphene Oxide Substrates for Multidifferentiation of Human Mesenchymal Stem Cells (Adv. Healthcare Mater. 16/2016)
Authors: Ki‐Taek Lim, Hoon Seonwoo, Kyung Soon Choi, Hexiu Jin, Kyung‐Je Jang, Jangho Kim, Jin‐Woo Kim, Soo Young Kim, Pill‐Hoon Choung, Jong Hoon Chung
Journal: Advanced Healthcare Materials (2016)

In the study of Soo Young Kim, Pill-Hoon Choung, and Jong Hoon Chung, and co-workers, the combinational use of reduced graphene oxide and pulsed electromagnetic fields is reported to enhance multidifferentiation of human stem cells, e.g., osteogenesis, neurogenesis and adipogenesis on page 2069. In particular, these days electromagnetic-field-based therapy is preferred in clinical application due to its noninvasiveness. Therefore, the method will not only be easily applied in clinical study, but also eventually change clinical methods.
The Yersinia Virulence Factor YopM Hijacks Host Kinases to Inhibit Type III Effector-Triggered Activation of the Pyrin Inflammasome
Authors: Lawton K. Chung, Yong Hwan Park, Yueting Zheng, Igor E. Brodsky, Patrick Hearing, Daniel L. Kastner, Jae Jin Chae, James B. Bliska
Journal: Cell Host & Microbe (2016)
Paclitaxel and cisplatin combination chemotherapy for advanced gastric cancer failed to 5-fluorouracil-based chemotherapy.
Authors: Y. Kim, M. Kim, S.H. Lee
Journal: Journal of Clinical Oncology (2010)

e14608 Background: There is no standard treatment in patients with metastatic gastric cancer failed to first- line treatment. Taxane is one of novel agents recognized as having significant activity in gastric cancer. We performed a trial to estimate the effectiveness and toxicity of paclitaxel plus cisplatin combination regimen as a salvage chemotherapy for metastatic gastric cancer failed to 5-fluorouracil (5-FU)-based chemotherapy. Methods: Metastatic or recurrent gastric cancer patients failed to 5- FU based treatment (FAM,FL,FP) with an Eastern Cooperative Oncology Group (ECOG) performance score ≤ 2 were qualified in this trial. Paclitaxel 175mg/m2 was infused over 3 hour, before cisplatin 70 mg/m2 infused over 2 hours on day 1, once every 3 weeks until disease progression or intolerable toxicity was detected. Response to treatment was assessd every three cycles. Results: From October 2004 to December 2008, 31 patients were enrolled in this study. 31 patients were assessable for response. Partial response was observed in seven patients and stable disease in four patients. The response rate was 22.5% (95% confidence interval: 17.4-27.6%). The median survival of all enrolled patients was 26 weeks (range: 8-67 weeks). For a total of 125 cycles of chemotherapy, grade 3 and 4 toxicity was 12.8% for neutropenia, 3.2% for nausea/ vomiting and 1.6% for mucositis. Conclusions: Salvage chemotherapy with paclitaxel plus cisplatin regimen in gastric cancer was effective with acceptable toxicities. No significant financial relationships to disclose.
A protocol for blood conservation in breast cancer care in a resource-poor setting
Authors: N. I. Usoro, M. A. Inyama, G. A. Ebughe, I. U. Ilori
Journal: Journal of Clinical Oncology (2008)

11565 Background: Breast cancer is the commonest cancer among women in Nigeria, and the incidence seems to be increasing. Most cases present late and receive palliative care utilizing traditional chemotherapy regimens, with bone marrow depression as a major side effect. Repeated blood transfusion has been the norm here, but it is hazardous, expensive, and of questionable benefit. We devised a protocol for managing breast cancer patients without allogeneic blood transfusion in a resource-poor setting. Methods: Female breast cancer patients were placed on prophylactic oral iron on diagnosis, along with Vitamin B12, and Vitamin C. Parenteral iron was given to patients with PCV <27%. During surgery, acute normovolemic hemodilution, appropriate positioning, normothermia, and meticulous hemostasis were applied. Parenteral iron was given prophylactically with each course of chemotherapy. Phlebotomies were restricted. Full blood count, liver function test, serum urea, electrolytes and creatinine were assayed before each cycle and 4 weeks after the last course. Results: Out of 10 female patients in this study ranging from 35 to 73 years in age, only 2 were postmenopausal. Two patients were diagnosed clinically as early disease, but only 1 turned out to be so. All patients tolerated oral iron therapy, and 1 reacted to parenteral iron, but subsequently tolerated it when preceded by 100mg Hydrocortisone IV. Two of the 10 patients underwent modified radical mastectomy without blood before chemotherapy. Two have successfully completed 6 cycles of chemotherapy without allogeneic blood transfusion, while 4 are currently at various stages in their regimen with satisfactory remission. Four patients died from non-anemia related disease complications; all were Stage IV, and 3 of these had defaulted repeatedly. Conclusions: Bloodless breast cancer care is possible and desirable in a resource-poor environment as in any other environment. Further studies are needed to assess the long-term effects of this intervention and compare with patients who receive blood transfusion. No significant financial relationships to disclose.
Estimating true hospital morbidity of complications associated with mumps outbreak, England, 2004/05
Authors: CF Yung, M Ramsay
Journal: Eurosurveillance (2016)

Mumps outbreaks in highly vaccinated populations continue to be reported globally. Therefore, quantifying the burden of mumps morbidity accurately will be necessary to better assess the impact of mumps vaccination programmes. We aim to estimate the true morbidity resulting from mumps complications in terms of hospitalised orchitis, meningitis, oophoritis and pancreatitis in England during the outbreak in 2004/05. This outbreak in England led to a clear increase in hospitalisations coded to mumps for complications of orchitis in those born in the 1970s and 1980s and possibly for meningitis in those born in the 1980s. A simple statistical model, based on analysing time trends for diagnosed complications in hospital databases with routine laboratory surveillance data, found that the actual morbidity was much higher. There were 2.5 times (166 cases) more mumps orchitis cases in the 1970s cohort and 2.0 times (708 cases) more mumps orchitis cases in the 1980s cohort than complications coded to mumps in hospital databases. Our study demonstrated that the mumps outbreak in England 2004/05 resulted in a substantial increase in hospitalised mumps complications, and the model we used can improve the ascertainment of morbidity from a mumps outbreak.
A Global Theme Issue on Emerging and Reemerging Global Microbial Threats-Reply
Authors: Annette Flanagin
Journal: JAMA (1996)

<h3>In Reply.</h3> —Dr Plaut suggests that the declining rates of some infectious diseases in the United States over the last 2 years mitigates the need to address emerging and reemerging microbial threats and quotes the AMA Council on Scientific Affairs report<sup>1</sup>as further evidence. For many of the infectious diseases he presents in the selected list, a significant trend in either direction is unlikely to be established over a 3-year period. Furthermore, the content of the Council report challenges his assumption. The victories cited by the Council—smallpox, poliomyelitis, diphtheria, measles, and<i>Haemophilus influenzae</i>type B—have all been won through the use of nationwide vaccination campaigns. The victory of vaccination is cause for celebration, but not complacency. Diphtheria in the former Soviet Union and measles in the United States resurged as vaccination programs became less comprehensive, pointing to the need for continued vigilance against even those diseases we have "conquered." The Council
Acute Kidney Injury With Buffered Crystalloids vs Saline Among ICU Patients—Reply
Authors: Paul Young, Michael Bailey, Rinaldo Bellomo
Journal: JAMA (2016)

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