tbuckley/cabot-search huggingface dataset:
The Efficacy and Safety of First-line Chemotherapy in Advanced Esophagogastric Cancer: A Network Meta-analysis
Authors: Emil ter Veer, Nadia Haj Mohammad, Gert van Valkenhoef, Lok Lam Ngai, Rosa M. A. Mali, Maarten C. Anderegg, Martijn G. H. van Oijen, Hanneke W. M. van Laarhoven
Journal: JNCI Journal of the National Cancer Institute (2016)

Background: A globally accepted standard first-line chemotherapy regimen in advanced esophagogastric cancer (AEGC) is not clearly established. We conducted a systematic review to investigate the efficacy and safety of first-line chemotherapy using Network meta-analysis (NMA). Methods: Medline, EMBASE, CENTRAL, and conferences were searched until June 2015 for randomized controlled trials that compared regimens containing: fluoropyrimidine (F), platinum (cisplatin [C] and oxaliplatin [Ox]), taxane (T), anthracycline (A), irinotecan (I), or methotrexate (M). Direct and indirect evidence for overall survival (OS) and progression-free-survival (PFS) were combined using random-effects NMA on the hazard ratio (HR) scale and calculated as combined hazard ratios and 95% credible intervals (CrIs). Results: The NMA incorporated 17 chemotherapy regimens with 37 direct comparisons between regimens for OS (50 studies, n = 10 249) and 29 direct comparisons for PFS (34 studies, n = 7795). Combining direct and indirect effects showed increased efficacy for fluoropyrimidine noncisplatin doublets (F-doublets) over cisplatin doublets (C-doublets): FI vs CF (combined HR = 0.85, 95% CrI = 0.71 to 0.99), FOx vs CF (combined HR = 0.83, 95% CrI = 0.71 to 0.98) in OS and FOx vs CF (combined HR = 0.82, 95% CrI = 0.66 to 0.99) in PFS. Anthracycline-containing triplets (A-triplets: ACF, AFOx, AFM) and TCF triplet showed no benefit over F-doublets in OS and PFS. The triplet FOxT showed increased PFS vs F-doublets FT (combined HR = 0.61, 95% CrI = 0.38 to 0.99), FI (combined HR = 0.62, 95% CrI = 0.38 to 0.99), and FOx (combined HR = 0.67, 95% CrI = 0.44 to 0.99). Increased grade 3 to 4 toxicity was found for CF vs F-doublets, for ACF vs FI for TCF vs CF, and for FOxT vs FOx. Conclusions: Based on efficacy and toxicity, F-doublets FOx, FI, and FT are preferred as first-line treatment for AEGC compared with C-doublets, A-triplets, and TCF. FOxT is the most promising triplet.
Abstract 5551: Anti-tumorigenic function of polyphenolic compounds on gefitinib resistant lung cancer
Authors: Ai N. H. Phan, Yangsik Jeong
Journal: Cancer Research (2015)

Abstract EGFR-mutant non-small cell lung cancer (NSCLC) is initially very sensitive to EGFR tyrosine kinase inhibitors (TKIs). Even with the remarkable effect of EGFR TKIs, patients eventually acquire resistance to gefitinib or elortinib, leading to a clinical challenge for overcoming TKI resistance. Some polyphenolic compounds are known as potential anti-tumorigenic compounds, such as resveratrol, curcumin or EGCG. However the function of these natural compounds in resistant NSCLC remains to be elucidated. Here, we identified a polyphenolic compound (named as compound A) from screening a set of natural compounds for anti-cancer effects on NSCLC. We found that compound A is a potential anticancer agent both in vivo and in vitro. Moreover, the growth inhibition of compound A turns out to be selective for cancer cells. Next, we further evaluated the growth inhibitory effect of compound A in two sets of NSCLC panels which are either sensitive or resistant to gefitinib treatment. Interestingly, the cell lines which are resistant to gefitinib are highly sensitive to compound A treatment, whereas the gefitinib-sensitive (GS) cell lines are not responsive to the compound A treatment. In gefitinib resistant (GR) cells, compound A increases expression of autophagy markers, p62 and LC3, which might result in the growth inhibition of the GR panel of cells but not in the GS cell panel. Moreover, we profiled the metabolic genes in the GR and GS cell lines. Surprisingly, compound A treatment significantly reduces the expression of a subset of enzymes associated with Warburg effect, which includes GLUT1, LDHA, PDK1, HK1, and HK2. As a result, compound A decreases Warburg effect, subsequently suppressing cell proliferation, especially of the GR cell lines. Taken together, compound A decreases Warburg effect and up-regulates autophagy process that may contribute to tumor suppression function of compound A in gefitinib-resistant cancer. Citation Format: Ai N. H. Phan, Yangsik Jeong. Anti-tumorigenic function of polyphenolic compounds on gefitinib resistant lung 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 5551. doi:10.1158/1538-7445.AM2015-5551
Aerobic Fitness and Neurocognitive Function Scores in Young Faroese Adults and Potential Modification by Prenatal Methylmercury Exposure
Authors: Youssef Oulhote, Frodi Debes, Sonja Vestergaard, Pal Weihe, Philippe Grandjean
Journal: Environmental Health Perspectives (2016)

Exposure to methylmercury was shown to decrease neural stem cell populations, whereas aerobic fitness has beneficial effects on the adult brain that relies on improved neurogenesis in the hippocampus.We examined the association between aerobic fitness and neurocognitive outcomes at young adult age, along with the potential moderating effect of prenatal exposure to methylmercury.At age 22 years, 262 members of a Faroese birth cohort, established in 1986-1987, underwent a graded exercise test of aerobic fitness to measure maximal oxygen uptake (VO2Max). Their prenatal methylmercury exposure had been assessed from the mercury concentration in cord blood. We estimated cross-sectional associations between VO2Max and multiple measures of neurocognitive function. In addition, we compared groups with low and high prenatal methylmercury exposure.A 1 standard deviation (SD) increase in VO2Max was associated with better scores on short-term memory and cognitive processing speed by 0.21 SD (95% CI: -0.04, 0.46) and 0.28 SD (95% CI: 0.02, 0.54), respectively. In the group with lower prenatal methylmercury exposure, a 1 SD increase in VO2Max was associated with increased scores on cognitive processing speed by 0.45 SD (95% CI: 0.08, 0.81) and with a slightly lesser benefit in short-term memory. No such association was observed in the group with high prenatal methylmercury exposure.Higher aerobic capacity was associated with better performance in short-term memory and processing speed. However, prenatal methylmercury exposure seemed to attenuate these positive associations.
Oral polymorphonuclear neutrophil characteristics in relation to oral health: a cross-sectional, observational clinical study
Authors: Patrick Rijkschroeff, Ineke D C Jansen, Fridus A van der Weijden, Bart J F Keijser, Bruno G Loos, Elena A Nicu
Journal: International Journal of Oral Science (2016)

Polymorphonuclear neutrophils (PMNs) have a major role in the innate immune system. However, little is known about PMN contribution in relation to oral health. The objective of this study was to investigate the numbers and functional characteristics of oral PMNs (oPMNs) compared with circulatory PMNs (cPMNs). Oral rinse and venous blood samples were obtained from 268 systemically and orally healthy volunteers in a cross-sectional observational study. PMN counts, cell cycle analysis and cellular activation state were investigated. Also, reactive oxygen species (ROS) production was analyzed, with and without bacterial stimulation (Fusobacterium nucleatum). In males, 1.2 × 10(6)±1.0 × 10(6) oPMNs were collected, and showed a tendency to correlate with the levels of gingival bleeding (r=0.215, P=0.008). Comparable oPMNs counts were found among females (1.0 × 10(6)±0.7 × 10(6)). More late-stage apoptotic/necrotic cells were found among the oPMNs (53.1%) compared with the cPMNs (8.5%; P<0.001). Without additional stimulation, oPMNs were more activated than cPMNs, as indicated by higher expression of CD11b, CD63 and CD66b, and higher constitutive ROS levels (P<0.001). Notably, in response to bacterial stimulation, oPMNs released comparable ROS levels as cPMNs (P=0.042). In conclusion, this study provides data on viable oPMNs showing high levels of activation in orally and systemically healthy individuals, free of apparent caries lesions and periodontal disease. These data suggests that although the oPMNs are in a more mature stage of their life cycle compared with the cPMNs, oPMNs are still responsive to stimulation, which indicates their functional potential and possible contribution to a healthy oral ecosystem.
Remaining Questions Concerning Wearable Devices
Authors: Paul H. Lee
Journal: JAMA Internal Medicine (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Drug deaths hit record high in England and Wales, figures show
Authors: Anne Gulland
Journal: BMJ (2016)

New figures from the Office for National Statistics show that there were 3674 deaths related to illegal and legal drug use in England and Wales in 2015, the highest number since 1993. The number of deaths has risen sharply in recent years, up from 2652 in 2011.1 Drug charities have blamed the record number of drug poisoning deaths recorded in 2015 on the government’s “ideological” drug policy.

Of these deaths 2479 (67%) involved illegal drugs only. The number of deaths involving heroin or morphine (or both) continues to rise,2 and is now the highest on record. It has doubled in the past three years, from 579 in 2012 to 1201 in 2015. The ONS report said that an increase in the purity of heroin over recent years could partly explain the increase in the number of deaths, …
Sevoflurane for Sedation in Acute Respiratory Distress Syndrome. A Randomized Controlled Pilot Study
Authors: Matthieu Jabaudon, Pierre Boucher, Etienne Imhoff, Russell Chabanne, Jean-Sébastien Faure, Laurence Roszyk, Sandrine Thibault, Raiko Blondonnet, Gael Clairefond, Renaud Guérin, Sébastien Perbet, Sophie Cayot, Thomas Godet, Bruno Pereira, Vincent Sapin, Jean-Etienne Bazin, Emmanuel Futier, Jean-Michel Constantin
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Rationale: Sevoflurane improves gas exchange, and reduces alveolar edema and inflammation in preclinical studies of lung injury, but its therapeutic effects have never been investigated in acute respiratory distress syndrome (ARDS).Objectives: To assess whether sevoflurane would improve gas exchange and inflammation in ARDS.Methods: We did a parallel, open-label single-center randomized controlled trial at three intensive care units from a French university hospital between April 2014 and February 2016. Adult patients were randomized within 24 hours of moderate-to-severe ARDS onset to receive either intravenous midazolam or inhaled sevoflurane for 48 hours. The primary outcome was the PaO2/FiO2 ratio on Day 2. Secondary endpoints included alveolar and plasma levels of cytokines and soluble form of the receptor for advanced glycation end-products, and safety. Investigators who did the analyses were masked to group allocation. Analysis was by intention to treat.Measurements and Main Results: Twenty-five patients were assigned to the sevoflurane group and 25 to the midazolam group. On Day 2, PaO2/FiO2 ratio was higher in the sevoflurane group than in the midazolam group (mean ± SD, 205 ± 56 vs. 166 ± 59, respectively; P = 0.04). There was a significant reduction over time in cytokines and soluble form of the receptor for advanced glycation end-products levels in the sevoflurane group, compared with the midazolam group, and no serious adverse event was observed with sevoflurane.Conclusions: In patients with ARDS, use of inhaled sevoflurane improved oxygenation and decreased levels of a marker of epithelial injury and of some inflammatory markers, compared with midazolam.Clinical trial registered with www.clinicaltrials.gov (NCT 02166853).
Conflicts of interest common among US cancer guideline authors, study finds
Authors: Michael McCarthy
Journal: BMJ (2016)

More than 85% of the authors of national cancer guidelines had at least one financial conflict of interest in 2014, a US study has found.1 The researchers found that the authors received an average of more than $10 000 (£7600, €8900) from the drug and device industry in general payments relating to such things as consulting, meals, and lodging and $236 000 in payments relating to research, including funding associated with clinical trials.

In the study, researchers from Chapel Hill School of Medicine at the University of North Carolina determined the financial conflicts of interest of 125 authors contributing to the …
340TiP Phase III study of afatinib vs methotrexate (MTX) for second-line recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) patients after platinum-based chemotherapy (CT) in Asia/Middle East/North Africa: LUX-Head &amp; Neck 3 (LUX-H&amp;N3)
Authors: P.Z. Tang, M.-J. Ahn, Q. Zhang, A. Chan, S.-B. Kim, C.-H. Wang, X. He, W. Guo, J.H. Kang, A. Dechaphunkul, P. Li, A. Kandil, E. Cohen, G.-Q. Hu, Y. Geng, E. Ehrnrooth, Y. Guo
Journal: Annals of Oncology (2015)
Brain Atrophy on Magnetic Resonance Imaging as a Biomarker of Neurodegeneration
Authors: Clifford R. Jack
Journal: JAMA Neurology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Hunger-Dependent Enhancement of Food Cue Responses in Mouse Postrhinal Cortex and Lateral Amygdala
Authors: Christian R. Burgess, Rohan N. Ramesh, Arthur U. Sugden, Kirsten M. Levandowski, Margaret A. Minnig, Henning Fenselau, Bradford B. Lowell, Mark L. Andermann
Journal: Neuron (2016)
Busulfan Targeted Dose In Hematopoietic Stem Cell Transplantation: The Impact In Toxicity, Sinusoidal Obstructive Syndrome and Survival
Authors: Fabio P S Santos, Morgani Rodrigues, Jairo Jose, Nascimento Sobrinho, Physician, Juliana F Fernandes, Andreza Alice Feitosa Ribeiro, Jose Mauro Kutner, José Salvador Rodrigues Oliveira, Adriana Seber, Ricardo Helman, Guilherme Fleury Perini, Leonardo Raul Morelli, Reijane Alves de Assis, Claudio Galvao de Castro Junior, Claudia Mac Donald Bley Nascimento, Paulo Vidal Campregher, Nelson Hamerschlak, Fabio Rodrigues Kerbauy
Journal: Blood (2013)
Increased Oxidative Stress In Sickle Cell Disease Activates The Renin-Angiotensin-TGF-β Pathway To Mediate Sickle Nephropathy
Authors: Swarnava Roy, Diamantis G. Konstantinidis, Tilat Rizvi, Kyung-Hee Chang, Nambirajan Sundaram, Michael Wourms, Loberg Anastacia, Lanxi Song, Katie Burke, Tadashi Inagami, Nancy Ratner, David Witte, Theodosia A. Kalfa, Jose A Cancelas, Shiva Kumar Shanmukhappa, Punam Malik
Journal: Blood (2013)
Witches and Warts
Authors: Eric Laurent Maranda, Victoria M. Lim, Richa Taneja, Brian J. Simmons, Penelope J. Kallis, Joaquin J. Jimenez
Journal: JAMA Dermatology (2016)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Impact of Severe Infections during Induction Therapy on Dosage, Response and Survival in Newly Diagnosed Multiple Myeloma - a Subgroup Analysis from the Randomized Phase III Trial GMMG-HD4
Authors: Elias Karl Mai, Christina Kunz, Uta Bertsch, Hans-Juergen Salwender, Michael Pfreundschuh, Ulrich Duehrsen, Peter Brossart, Norma Peter, Kai Neben, Thomas Hielscher, Jens Hillengass, Hans Martin, Hans Walter Lindemann, Christof Scheid, Katja C. Weisel, Igor W. Blau, Hartmut Goldschmidt
Journal: Blood (2015)
Neuroanatomical correlates of happiness, sadness, and disgust
Authors: R D Lane, E M Reiman, G L Ahern, G E Schwartz, R J Davidson
Journal: American Journal of Psychiatry (1997)

Happiness, sadness, and disgust are three emotions that differ in their valence (positive or negative) and associated action tendencies (approach or withdrawal). This study was designed to investigate the neuroanatomical correlates of these discrete emotions.Twelve healthy female subjects were studied. Positron emission tomography and [15O]H2O were used to measure regional brain activity. There were 12 conditions per subject: happiness, sadness, and disgust and three control conditions, each induced by film and recall. Emotion and control tasks were alternated throughout. Condition order was pseudo-randomized and counterbalanced across subjects. Analyses focused on brain activity patterns for each emotion when combining film and recall data.Happiness, sadness, and disgust were each associated with increases in activity in the thalamus and medial prefrontal cortex (Brodmann's area 9). These three emotions were also associated with activation of anterior and posterior temporal structures, primarily when induced by film. Recalled sadness was associated with increased activation in the anterior insula. Happiness was distinguished from sadness by greater activity in the vicinity of ventral mesial frontal cortex.While this study should be considered preliminary, it identifies regions of the brain that participate in happiness, sadness, and disgust, regions that distinguish between positive and negative emotions, and regions that depend on both the elicitor and valence of emotion or their interaction.
Strain Echocardiography and Functional Capacity in Asymptomatic Primary Mitral Regurgitation With Preserved Ejection Fraction
Authors: Amgad Mentias, Peyman Naji, A. Marc Gillinov, L. Leonardo Rodriguez, Grant Reed, Tomislav Mihaljevic, Rakesh M. Suri, Joseph F. Sabik, Lars G. Svensson, Richard A. Grimm, Brian P. Griffin, Milind Y. Desai
Journal: Journal of the American College of Cardiology (2016)
Comprehensive pharmacogenetic profiling of advanced colorectal cancer.
Authors: Ayman Madi, David Fisher, Tim Maughan, James Colley, Angela M. Meade, Julie Maynard, Vikki Humpreys, Harpreet Wasan, Richard A. Adams, Shelley Idziaszczyk, Rebecca Harris, Laura L. Nichols, Richard S. Kaplan, Jeremy Cheadle
Journal: Journal of Clinical Oncology (2013)

3509 Background: Inherited genetic factors may influence a patient’s response to, and side effects from, chemotherapy and biological therapies. Here, we sought to generate a comprehensive inherited pharmacogenetic profile for advanced colorectal cancer (aCRC). Methods: We analysed 260 potentially functional coding region and promoter variants in genes within the 5-FU, capecitabine, oxaliplatin, EGFR and DNA repair pathways in 2183 patients with aCRC treated with oxaliplatin-fluoropyrimidine chemotherapy ± cetuximab (from the MRC COIN and COIN-B trials). Primary outcomes assessed were 12-week response, skin rash (SR) (for those receiving cetuximab), dose-reduction or delay in treatment due to any toxicity and peripheral neuropathy (PN). Results: For variants with minor allele frequencies &gt;20%, we had &gt;85% power to detect an effect on response / toxicity with an OR of 1.3. In patients treated with chemotherapy + cetuximab, 5 and 4 coding region variants in the EGFR pathway were associated with response and SR, respectively. The most significant associations were with variants in members of phosphatidylinositol 3-kinase regulatory subunit. In patients treated with chemotherapy ± cetuximab, 8 coding region variants in the 5-FU, capecitabine, oxaliplatin or DNA repair pathways were associated with response, 8 with any toxicity and 5 with PN. The most significant associations for response were with variants in DNA repair genes and, for any toxicity, with common variants in DPYD. Conclusions: Our study highlights the difficulty in identifying inherited biomarkers for the treatment of aCRC - despite using samples from the largest reported randomised trial for aCRC, with considerable power to detect alleles of small effects, none of the associations remained significant after rigorous correction for multiple testing.