tbuckley/cabot-search huggingface dataset:
Framing Financial Incentives to Increase Physical Activity Among Overweight and Obese Adults
Authors: Mitesh S. Patel, David A. Asch, Roy Rosin, Dylan S. Small, Scarlett L. Bellamy, Jack Heuer, Susan Sproat, Chris Hyson, Nancy Haff, Samantha M. Lee, Lisa Wesby, Karen Hoffer, David Shuttleworth, Devon H. Taylor, Victoria Hilbert, Jingsan Zhu, Lin Yang, Xingmei Wang, Kevin G. Volpp
Journal: Annals of Internal Medicine (2016)

Background: Financial incentive designs to increase physical activity have not been well-examined. Objective: To test the effectiveness of 3 methods to frame financial incentives to increase physical activity among overweight and obese adults. Design: Randomized, controlled trial. (ClinicalTrials.gov: NCT 02030119) Setting: University of Pennsylvania. Participants: 281 adult employees (body mass index ≥27 kg/m2). Intervention: 13-week intervention. Participants had a goal of 7000 steps per day and were randomly assigned to a control group with daily feedback or 1 of 3 financial incentive programs with daily feedback: a gain incentive ($1.40 given each day the goal was achieved), lottery incentive (daily eligibility [expected value approximately $1.40] if goal was achieved), or loss incentive ($42 allocated monthly upfront and $1.40 removed each day the goal was not achieved). Participants were followed for another 13 weeks with daily performance feedback but no incentives. Measurements: Primary outcome was the mean proportion of participant-days that the 7000-step goal was achieved during the intervention. Secondary outcomes included the mean proportion of participant-days achieving the goal during follow-up and the mean daily steps during intervention and follow-up. Results: The mean proportion of participant-days achieving the goal was 0.30 (95% CI, 0.22 to 0.37) in the control group, 0.35 (CI, 0.28 to 0.42) in the gain-incentive group, 0.36 (CI, 0.29 to 0.43) in the lottery-incentive group, and 0.45 (CI, 0.38 to 0.52) in the loss-incentive group. In adjusted analyses, only the loss-incentive group had a significantly greater mean proportion of participant-days achieving the goal than control (adjusted difference, 0.16 [CI, 0.06 to 0.26]; P = 0.001), but the adjusted difference in mean daily steps was not significant (861 [CI, 24 to 1746]; P = 0.056). During follow-up, daily steps decreased for all incentive groups and were not different from control. Limitation: Single employer. Conclusion: Financial incentives framed as a loss were most effective for achieving physical activity goals. Primary Funding Source: National Institute on Aging.
Emergence of triple-subtype reassortants of fatal human H5N6 avian influenza virus in Yunnan, China
Authors: Yue Feng, Wenda Guan, Bing Yuan, Yajuan Wang, Zhengtu Li, Yindi Song, Siming Li, Zifeng Yang, Nanshan Zhong, Yunhui Zhang, Xueshan Xia
Journal: Journal of Infection (2016)
Differences between culture &amp; non-culture confirmed invasive meningococci with a focus on factor H-binding protein distribution
Authors: Stephen A. Clark, Aiswarya Lekshmi, Jay Lucidarme, Li Hao, How Tsao, Lisa Lee-Jones, Kathrin U. Jansen, Lynne S. Newbold, Annaliesa S. Anderson, Ray Borrow
Journal: Journal of Infection (2016)
Origin of Carcinoma of the Bronchus
Authors: B K DIJKSTRA
Journal: JNCI Journal of the National Cancer Institute (1963)

A study of 330 cases of bronchial cancer occurring from January 1, 1950, to January 1, 1960, diagnosed by biopsy, cytology, operation, or autopsy revealed: 1) Not every birth year contributed equally to the number of cases; 2) the month of birth was an important factor, with a high peak late in winter (March). This seasonal influence could be explained by the absence of vitamin A at birth, when the lungs begin to function. Lack of vitamin A at that critical time causes an irreversible metaplasia. Later, this tissue cannot cope with the normal stimuli of life and predisposes the individual to various pulmonary diseases, including cancer.
Shifts in attitudes among psychiatric residents: serial measures over 10 years
Authors: W Coryell
Journal: American Journal of Psychiatry (1987)

Psychiatric residents completing their training in 1976, 1978, 1980, and 1986 were sent surveys on their attitudes toward treatment and training among a "dynamic-organic continuum." Their responses indicated decreasing antagonism toward the medical model and increasing endorsement of medical education, experience in neurology, and the internship as essential aspects of psychiatric education. The rankings of various treatment modalities for each of four disorders were remarkably stable across surveys. Except for megavitamin therapy, residents in 1986 were at least somewhat more likely to consider essential each of six therapies for each of the four disorders, indicating a general increase in therapeutic optimism.
Proteolytic Enzymes in Tumor Metastasis. II. Collagenase Type IV Activity in Subcellular Fractions of Cloned Tumor Cell Populations&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: L Eisenbach, S Segal, M Feldman
Journal: JNCI Journal of the National Cancer Institute (1985)

Collagenase type IV degradation activity was examined in metastatic and nonmetastatic clones of the Lewis lung carcinoma (3LL) and of the T10 sarcoma. Conditioned media prepared from cells of both tumors grown in vitro contained low degradation activities, whereas conditioned media from organ cultures of the same clones grown as solid tumors in animals exhibited higher degradation activities. Analysis of subcellular fractions of tumor cells showed that collagenase type IV activity was localized mainly in the cytoplasmic fraction. Crude homogenates or detergent lysates manifested low degradation activities. Little activity was associated with purified plasma membrane preparations and endoplasmic reticular fractions. However, addition of plasma membrane to conditioned media and to cytoplasmic fractions reduced the degradation activities of the cytoplasmic fractions. Possibly a factor that inhibits collagenase type IV exists in the cells in a vesicular form. No correlation between degradation activity and metastatic capacity was demonstrated in the models used in this study. Both metastatic and nonmetastatic clones of the same tumor similarly could degrade basement membrane components.
Evolution of Radiation Therapy Within the German Hodgkin Study Group Trials
Authors: Hans Theodor Eich, Jan Kriz, Rolf-Peter Müller
Journal: Journal of the National Comprehensive Cancer Network (2011)

Since its beginning, more than 16,000 patients have been enrolled in the multicentric randomized trials of the German Hodgkin Study Group (GHSG) for adult patients. Within 6 study generations, the treatment of Hodgkin lymphoma has been developed stepwise by using the results of the completed protocols. Now the sixth generation is active. According to the role of radiotherapy, the study group successfully evaluated different dose–effect relationships and could also prove the efficacy of involved-field radiotherapy in early stages in combination with effective chemotherapy. Currently, a radiation dose of 20 Gy to the involved field after a mildly aggressive chemotherapy (2 cycles of adriamycin, bleomycin, vinblastine, and dacarbazine [ABVD]) should be the standard for early-favorable stages according to the GHSG classification. In early-unfavorable or intermediate-risk stages, involved-field radiation therapy with 30 Gy is sufficient; the optimal chemotherapy has to be fixed. For the advanced stages, the question of radiotherapy is still unclear. Preliminary results of the GHSG and others show that additive radiotherapy after intensive chemotherapy might be useful for elective subgroups of patients. The extensive radiotherapy quality assurance program, performed by the GHSG and its radiotherapy reference center, has proven to be successful and necessary to ensure that, with reduced radiation doses and reduced radiation volumes, precise radiotherapy, as defined by the protocol, will be performed by the participating radiotherapy departments.
Abstract 1856: Preclinical effects of dual AKT/MAPK inhibition in PTEN-deficient prostate cancer
Authors: Marco A. De Velasco, Yutaka Yamamoto, Yurie Kura, Emiko Fukushima, Naomi Ando, Barry Davies, Yuji Hatanaka, Takashi Oki, Nobutaka Shimizu, Masahiro Nozawa, Kazuhiro Yoshikawa, Kazuhiro Yoshimura, Kazuto Nishio, Hirotsugu Uemura
Journal: Cancer Research (2015)

Abstract Targeting signal molecules with single agent monotherapy is met with limited or transient clinical benefits. Therefore, establishing effective rational combinatorial treatment strategies provides a better option for achieving improved clinical outcomes. The AKT/PI3K and MAPK signaling pathways have been identified as key compensatory signal transduction pathways in prostate cancer. We have used genetically engineered mouse models of prostate cancer to show the treatment efficacy of monotherapy with the AKT inhibitor AZD5363 and the MAP/ERK kinase (MEK) inhibitor selumetinib (AZD6244, ARRY142886). We hypothesized that a rational combinatorial approach utilizing both of these inhibitors would improve treatment efficacy compared to single agent monotherapy. To test this hypothesis, we evaluated the treatment effects of AZD5363 and selumetinib in preclinical models of prostate cancer. In vitro experiments were carried out using a panel of human prostate cancer cell lines, and mouse prostate cancer cell lines, derived from PTEN-deficient castration-naïve prostate cancer (CNPC) and castration-resistant prostate cancer (CRPC). Treatments with AZD5363 and selumetinib demonstrated a synergistic combination effect in both human and mouse prostate cancer cell lines. We evaluated the antitumor effects in vivo by comparing the effects of AZD5363 and selumetinib alone or in combination in PTEN-deficient mice. Our studies show that combination therapy of AZD5363/selumetinib was well-tolerated by the mice and demonstrated significantly improved inhibition of tumor growth compared to single agent therapy. In the CNPC model, mice showed 16.7, 10.0 and 24.9% reductions in tumor burden after treatments with AZD5363, selumetinib and AZD5363/selumetinib, respectively (P&amp;lt;0.001). In the CRPC model, mice showed 15.8, 3.8 and 27.0% reductions in tumor burden after treatments with AZD5363, selumetinib and AZD5363/selumetinib, respectively (P&amp;lt;0.001). Target validation studies confirmed the inhibition of downstream targets. Overall, our findings suggest a potential role for targeting the PI3K/AKT and MAPK signaling pathways with AZD5363 and selumetinib for treatment of PTEN-deficient prostate cancer. Citation Format: Marco A. De Velasco, Yutaka Yamamoto, Yurie Kura, Emiko Fukushima, Naomi Ando, Barry Davies, Yuji Hatanaka, Takashi Oki, Nobutaka Shimizu, Masahiro Nozawa, Kazuhiro Yoshikawa, Kazuhiro Yoshimura, Kazuto Nishio, Hirotsugu Uemura. Preclinical effects of dual AKT/MAPK inhibition in PTEN-deficient prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1856. doi:10.1158/1538-7445.AM2015-1856
Protection of the elite athlete is the responsibility of all of us in sports medicine
Authors: Lars Engebretsen, Kathrin Steffen
Journal: British Journal of Sports Medicine (2015)

<h3>Abstract</h3> To achieve their therapeutic effect on the brain, molecules need to pass the blood-brain-barrier (BBB). Many pharmacological treatments of neuropathologies encounter the BBB as a barrier, hindering their effective use. Pharmaceutical nanotechnology based on optimal physicochemical features and taking advantage of naturally occurring permeability mechanisms, nanocarriers such as liposomes offer an attractive alternative to allow drug delivery across the BBB. Liposomes are spherical bilayer lipid-based nanocapsules that can load hydrophilic molecules in their inner compartment and on their outer surface can be functionally modified by peptides, antibodies and polyethyleneglycol (PEG). When composed of cationic lipids, liposomes can serve as gene delivery devices, encapsulating and protecting genetic material from degradation and promoting nonviral cell transfection. In this study, we aimed to develop a liposomal formulation to encapsulate a plasmid harbouring brain-derived neurotrophic factor (BDNF) and infuse these liposomes via the peripheral bloodstream into the brain. To this end, liposomes were tagged with PEG, transferrin, and arginine and characterized regarding their physical properties, such as particle size, zeta-potential and polydispersity index (PDI). Moreover, we selected liposomes preparations for plasmid DNA (pDNA) encapsulation and checked for loading efficiency, in vitro cell uptake, and transfection. The preliminary results from this pilot study revealed that we were able to replicate the liposomes synthesis described in literature, achieving compatible size, charge, PDI, and loading efficiency. However, we could not properly determine whether the conjugation of the surface ligands transferrin and arginine to PEG worked and whether they were attached to the surface of the liposomes. Additionally, we were not able to see transfection in SH-SY5Y cells after 24 or 48 hours of incubation with the pDNA loaded liposomes. In conclusion, we synthesized liposomes encapsulation pBDNF, however, further research will be necessary to address the complete physicochemical characterization of the liposomes. Furthermore, preclinical studies will be helpful to verify transfection efficiency, cytotoxicity, and in the future, safe delivery of BDNF through the BBB.
IMPS-30NOVEL AND SHARED NEOANTIGEN FOR GLIOMA T CELL THERAPY DERIVED FROM HISTONE 3 VARIANT H3.3 K27M MUTATION
Authors: Yafei Hou, Gary Kohanbash, Kaori Okada, Shruti Shrivastav, Matthew Smith-Cohn, Theodore Nicolaides, Sabine Mueller, Angel Carcaboso, Ian Pollack, Hideho Okada
Journal: Neuro-Oncology (2015)

Recent genetic studies have revealed that malignant gliomas in children and young adults often show shared missense mutations, which encodes the replication-independent histone 3 variant H3.3. Approximately 30 % of overall glioblastoma (GBM) and over 70% of diffuse intrinsic pontine gliomas (DIPG) cases harbor the amino-acid substitution from lysine (K) to methionine (M) at the position 27 of H3.3. T-cells are normally tolerant to wild-type self-proteins, but can recognize mutated peptide epitopes as non-self. Hence, tumor-specific missense mutations can be suitable targets (i.e. neoantigens) for cancer immunotherapy. We evaluated whether H3.3-derived peptides that encompass the H3.3 K27M mutation can induce specific cytotoxic T lymphocyte (CTL) responses in human leukocyte antigen (HLA)-A2+ CD8+ T-cells. Four candidate peptides encompassing different amino-acid positions around the H3.3 K27M mutation were synthesized, and peptide-specific CTL lines and clones were generated from peripheral blood mononuclear cells of HLA-A2+ donors by in vitro stimulation with each of the synthetic peptides. One of the 4 peptides (the H3.3.K27M epitope, hereafter) induced CTL lines which recognized not only the synthetic peptide loaded on T2 cells but also lysed HLA-A2+ DIPG cell lines which endogenously harbor the H3.3.K27M mutation. On the other hand, CTL lines did not react to HLA-A2+, H3.3 K27M mutation-negative cells or HLA-A2-negative, H3.3 K27M mutation+ cells. Furthermore, CTL clones with high and specific affinities to HLA-A2-H3.3.K27M-tetramer were successfully obtained, and α- and β-chain cDNAs from high-affinity T cell receptor (TCR)s were cloned into a lentiviral vector. Additional studies are underway to determine antigen specificity, key epitope residues in the epitope and possible cross-reactivity to naturally existing variants using T-cells transduced with the lentiviral vector encoding the TCR. These data provide us with a strong basis for developing peptide-based vaccines as well as adoptive transfer therapy using autologous T-cells transduced with the TCR.
ASA must be given to classify multiple NSAID-hypersensitivity patients as selective or cross-intolerant
Authors: N. Blanca-López, G. Bogas, I. Doña, M. J. Torres, M. Blanca, J. A. Cornejo-García, G. Canto, S. Demir, M. Olgac, D. Unal, A. Gelincik, B. Colakoglu, S. Buyukozturk
Journal: Allergy (2016)
A feasibility study of an intensive combined modality smoking cessation program in the radiation oncology clinic
Authors: D. J. Hoopes, D. M. Hudson, M. P. Langer, B. Sinha, H. Pai, A. M. McDaniel
Journal: Journal of Clinical Oncology (2007)

19604 Background: Radiotherapy (RT) patients present for daily treatment over many weeks, often accompanied by friends and family. This represents a unique opportunity for intensive smoking intervention concurrently with RT in both cancer patients and their companions. Methods: Eligible participants included smoking cancer patients scheduled to receive = 3 weeks of RT and their smoking family/friends. All participants received bupropion and 9 individualized behavioral interventions (BI) in the RT clinic with an addiction professional, followed by 9–12 scheduled intensive relapse prevention encounters (in person or by telephone). The primary endpoint was feasibility determined by accrual and program completion. Other endpoints included carbon-monoxide (CO) confirmed and participant-reported tobacco abstinence. During 4 months of enrollment, smoking and basic eligibility data were prospectively collected on consultations seen in clinic. Results: Over 8 months 20 cancer patients and 3 family members were enrolled. Based on our sampling, this represented greater than 40% of eligible smokers seen in clinic. Six cancer patients withdrew, all on or before the third BI. 13 participants completed all 9 BIs while 4 patients completed 7–8 BIs. 11 participants reported compliance with bupropion therapy. One participant discontinued bupropion citing increased depression. No other possible adverse events to bupropion or BI were discovered. At the completion of BI, 16 participants had exhaled CO concentrations &lt; 10ppm and 14 participants self-reported tobacco abstinence. Of the 17 participants completing 7–9 behavioral interventions, the median number of relapse prevention sessions was 4 (range 0–8). With a median follow-up of 5.85 months, the 3-month crude self-reported abstinence rate was 41% (7/17). Conclusions: Tobacco cessation with bupropion and intensive BI for cancer patients and their companions during RT was feasible. A significant number of eligible smokers enrolled and completed BI during RT. However, few participants completed scheduled prevention encounters following RT. No significant financial relationships to disclose.
New Era of Lipid-Lowering Drugs
Authors: Philip J. Barter, Kerry-Anne Rye
Journal: Pharmacological Reviews (2016)

There are several established lipid-modifying agents, including statins, fibrates, niacin, and ezetimibe, that have been shown in randomized clinical outcome trials to reduce the risk of having an atherosclerotic cardiovascular event. However, in many people, the risk of having an event remains unacceptably high despite treatment with these established agents. This has stimulated the search for new therapies designed to reduce residual cardiovascular risk. New approaches that target atherogenic lipoproteins include: 1) inhibition of proprotein convertase subtilisin/kexin type 9 to increase removal of atherogenic lipoproteins from plasma; 2) inhibition of the synthesis of apolipoprotein (apo) B, the main protein component of atherogenic lipoproteins; 3) inhibition of microsomal triglyceride transfer protein to block the formation of atherogenic lipoproteins; 4) inhibition of adenosine triphosphate citrate lyase to inhibit the synthesis of cholesterol; 5) inhibition of the synthesis of lipoprotein(a), a factor known to cause atherosclerosis; 6) inhibition of apoC-III to reduce triglyceride-rich lipoproteins and to enhance high-density lipoprotein (HDL) functionality; and 7) inhibition of cholesteryl ester transfer protein, which not only reduces the concentration of atherogenic lipoproteins but also increases the level and function of the potentially antiatherogenic HDL fraction. Other new therapies that specifically target HDLs include infusions of reconstituted HDLs, HDL delipidation, and infusions of apoA-I mimetic peptides that mimic some of the functions of HDLs. This review describes the scientific basis and rationale for developing these new therapies and provides a brief summary of established therapies.
The macrophage IRF8/IRF1 regulome is required for protection against infections and is associated with chronic inflammation
Authors: David Langlais, Luis B. Barreiro, Philippe Gros
Journal: The Journal of Experimental Medicine (2016)

IRF8 and IRF1 are transcriptional regulators that play critical roles in the development and function of myeloid cells, including activation of macrophages by proinflammatory signals such as interferon-γ (IFN-γ). Loss of IRF8 or IRF1 function causes severe susceptibility to infections in mice and in humans. We used chromatin immunoprecipitation sequencing and RNA sequencing in wild type and inIRF8andIRF1mutant primary macrophages to systematically catalog all of the genes bound by (cistromes) and transcriptionally activated by (regulomes) IRF8, IRF1, PU.1, and STAT1, including modulation of epigenetic histone marks. Of the seven binding combinations identified, two (cluster 1 [IRF8/IRF1/STAT1/PU.1] and cluster 5 [IRF1/STAT1/PU.1]) were found to have a major role in controlling macrophage transcriptional programs both at the basal level and after IFN-γ activation. They direct the expression of a set of genes, the IRF8/IRF1 regulome, that play critical roles in host inflammatory and antimicrobial defenses in mouse models of neuroinflammation and of pulmonary tuberculosis, respectively. In addition, this IRF8/IRF1 regulome is enriched for genes mutated in human primary immunodeficiencies and with loci associated with several inflammatory diseases in humans.
GMC can continue to strike off doctors who miss hearings, appeal court rules
Authors: Clare Dyer
Journal: BMJ (2016)

The General Medical Council has defeated a legal challenge to rules under which scores of doctors every year are struck off the medical register in the doctor’s absence.

The UK medical regulator has successfully appealed against two High Court rulings quashing decisions to erase two doctors from the register who did not attend their own hearings.

Three appeal court judges overturned the High Court decisions that the Medical Practitioners Tribunal Service was wrong to proceed with hearings in the cases of Olufemi Adeogba and Evangelos-Efstathios Visvardis in the doctors’ absence.

The GMC rarely appeals against High Court rulings quashing such panel decisions, …
Melatonin-Induced Nocturnal Vasodilatation Contributes to Skin Regeneration
Authors: Igor B. Mekjavic, Ian A. Macdonald
Journal: JAMA Pediatrics (2016)

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