tbuckley/cabot-search huggingface dataset:
Weekly methotrexate in squamous cell cancers of head and neck
Authors: A. B. Pathak, H. Kulkarni
Journal: Journal of Clinical Oncology (2006)

15539 Background: The aim was to evaluate response rates and toxicity of weekly methotrexate in locally advanced or recurrent squamous cell cancers of the head and neck region. Methotrexate, oldest non-platinum drugs active in squamous cell cancer of head and neck, was selected for its cost-effectiveness and ease of administration. Methods: Patients with locally advanced, inoperable or recurrent squamous cancers were selected. Sites included anterior two-third tongue, buccal mucosa, alveolus, base tongue, larynx and maxilla. Methotrexate 1 mg/Kg was given intramuscularly on outpatient basis once a week for 6 to 8 weeks along with hydration. Patients who responded well and became resectable were encouraged to undergo surgery. All patients were followed up in the clinic every monthly. Results: Total 19 patients were entered on the study over a duration of 24 months. 12 out of 19 patients had partial response (63%), 5 had stable disease (26%) and 2 patients had disease progression. Symptomatic relief ranged from 25% to 100%. Maximum response duration was 12 weeks. Treatment naïve patients had rapid response. In 5 patients disease became clearly resectable. Toxicity was grade II-III oral mucositis in patients with previous radiation. Sample size is small for a subset analysis. Conclusions: Weekly methotrexate is a simple, cost-effective regimen for palliation in advanced recurrent squamous cell cancers of head and neck region. It should also be evaluated further in large scale trials and especially in neo-adjuvant setting in locally advanced squamous cell cancers of the head and neck region given its rapidity of response and brief duration of therapy. No significant financial relationships to disclose.
The game-theoretic innocence of experimental behavioral psychology
Authors: Don Ross
Journal: Behavioral and Brain Sciences (2001)

Hertwig and Ortmann imply that failure of many behavioral psychologists to observe several central methodological principles of experimental economics derives mainly from differences in disciplinary culture. I suggest that there are deeper philosophical causes, based (ironically) on a legacy of methodological individualism in psychology from which economists have substantially cured themselves through use of game theory. Psychologists often misidentify their objects of study by trying to wrench subjects out of their normal behavioral contexts in games.
Where are object properties? In the world or in the mind?
Authors: James Tanaka
Journal: Behavioral and Brain Sciences (2001)

This commentary questions whether the category properties of an object can be determined independent of the experience of the categorizer. Expertise studies have shown that the judged properties of an object can differ from expert to novice and from expert to expert. The expertise findings indicate that object properties exist not only in the world, but in the mind of the categorizer.
P14.36 Treatment patterns by O6-methylguanine DNA methyltransferase promoter (MGMT) status in newly-diagnosed glioblastoma multiforme (GBM): a multi-country chart review study
Authors: A Z Fu, G J Thompson, J P Hall, A Bailey, J Kemp, C Lee
Journal: Neuro-Oncology (2019)

Abstract INTRODUCTION This study explored the relationship between MGMT testing and treatment patterns of patients with newly-diagnosed GBM from France, Germany, Italy, Spain, the UK (EU5), and Canada. MATERIALS AND METHODS Medical oncologists and neuro-oncologists across EU5 and Canada completed a point in time, cross-sectional survey for the next eight GBM patients seen between May and July 2016 (GBM Disease-specific ProgrammeTM). Statistically significant differences (p&lt;0.05) between groups are presented. RESULTS A total of 241 physicians reported on 1,747 GBM patients. 1L patients had mean age 59.7 years (SD=12.3) and 36% were female. Of 1,113 (64%) patients who had an MGMT test performed with results recorded (tested), 58% (n=651) were methylated and 42% (n=462) were unmethylated. The remaining 634 patients (36%) were MGMT untested or awaiting MGMT results at time of survey (untested). Overall, 63% of patients received surgery prior to their 1L drug therapy, 78% received radiotherapy (RT; mean 4.3 sessions) in conjunction with 1L drug therapy, 90% received corticosteroids during RT, and 89% received temozolomide (TMZ). Patients who received corticosteroids during RT received similar drug treatments to those that did not, but were less likely to receive surgery prior to 1L treatment (65% vs 83%). MGMT-tested patients were more likely to receive surgery (66% vs 57%) and RT (81% vs 71%) than untested patients. Tested patients were also more likely to receive TMZ (92% vs 83%), and less likely to receive procarbazine+/lomustine+/vincristine (PCV; 3% vs 7%) or other chemotherapies (5% vs 11%). For 1L patients that experienced side effects, the most common effects included fatigue (74%), nausea (60%), and appetite loss (59%). Untested patients were more likely to stop their 1L drug treatment due to progression/recurrence of GBM (44% vs 36%). Patients who received surgery prior to 1L treatment were more likely to receive TMZ than those who did not (93% vs 82%). Among MGMT tested patients at 1L, methylated patients were more likely to receive RT (84% vs 78%) and TMZ (95% vs 89%) than unmethylated patients, and less likely to receive PCV (2% vs 5%) or other chemotherapy (4% vs 7%). Methylated patients with reported treatment-related side effects were less likely to experience dehydration (0% vs 10%), loss of strength/unusual weakness (5% vs 25%), memory problems (16% vs 35%), and nausea (51% vs 75%). CONCLUSIONS More than one-third of GBM patients in EU5 and Canada are not tested for MGMT-methylation. Untested patients are less likely to receive standard treatments than tested patients. Generally, TMZ is used in most patients regardless of MGMT testing and status. MGMT-methylated patients are more likely to receive standard treatments and experience fewer side effects than MGMT-unmethylated patients.
Reduction of false alarms in the intensive care unit using an optimized machine learning based approach
Authors: Wan-Tai M. Au-Yeung, Ashish K. Sahani, Eric M. Isselbacher, Antonis A. Armoundas
Journal: npj Digital Medicine (2019)

This work attempts to reduce the number of false alarms generated by bedside monitors in the intensive care unit (ICU), as a majority of current alarms are false. In this study, we applied methods that can be categorized into three stages: signal processing, feature extraction, and optimized machine learning. At the stage of signal processing, we ensured that the heartbeats were properly annotated. During feature extraction, besides extracting features that are relevant to the arrhythmic alarms, we also extracted a set of signal quality indices (SQIs), which we used to distinguish noise/artifact from normal physiological signals. When applying a machine learning algorithm (Random Forest), we performed feature selection in order to reduce the complexity of the models and improve the efficiency of the algorithm. The dataset used is from Reducing False Arrhythmia Alarms in the ICU: the PhysioNet/Computing in Cardiology Challenge 2015. Using the performance metric "score" from the Challenge, we achieved a score of 83.08 in the real-time category on the hidden test set, which is the highest in all published work.
Killers 2.0: NK cell therapies at the forefront of cancer control
Authors: Jonathan J. Hodgins, Sarwat T. Khan, Maria M. Park, Rebecca C. Auer, Michele Ardolino
Journal: Journal of Clinical Investigation (2019)

Natural killer (NK) cells are innate cytotoxic lymphocytes involved in the surveillance and elimination of cancer. As we have learned more and more about the mechanisms NK cells employ to recognize and eliminate tumor cells, and how, in turn, cancer evades NK cell responses, we have gained a clear appreciation that NK cells can be harnessed in cancer immunotherapy. Here, we review the evidence for NK cells' critical role in combating transformed and malignant cells, and how cancer immunotherapies potentiate NK cell responses for therapeutic purposes. We highlight cutting-edge immunotherapeutic strategies in preclinical and clinical development such as adoptive NK cell transfer, chimeric antigen receptor-expressing NK cells (CAR-NKs), bispecific and trispecific killer cell engagers (BiKEs and TriKEs), checkpoint blockade, and oncolytic virotherapy. Further, we describe the challenges that NK cells face (e.g., postsurgical dysfunction) that must be overcome by these therapeutic modalities to achieve cancer clearance.
Abstract 16: Spatiotemporally-Controlled Ultrasound-Triggered Release of Nitric Oxide Using Nano Au-Polymersomes/S-Nitrosoglutathione Mitigates Post-Resuscitation Cerebral Vasoconstriction and Neuronal Apoptosis via Reciprocating Akt-eNOS-NO Signaling
Authors: Wei-Tien Chang, Woan-Yi Wang, Min-Hsuan Hsu, Po-Tsung Kao, Chih-Hung Wang, Min-Shan Tsai, Hsiao-Ju Cheng, Chien-Hua Huang, Wen-Shiang Chen, Ian Liau, Chen-Sheng Yeh, Wen-Jone Chen
Journal: Circulation (2018)

Introduction: Cerebral vasoconstriction in the post-resuscitation phase worsens neurological outcome. Nitric oxide (NO) plays important roles mediating vasodilatation and anti-apoptotic protection. We therefore designed an Au-polymersomes/S-nitrosoglutathione (Au-PLGA/GSNO) nanoparticle that can be triggered by ultrasound (US) to release NO, and investigated its roles in mitigating cerebral vasoconstriction and neuronal apoptosis post-CPR. Hypothesis: Spatiotemporally controlled, US-triggered NO release by Au-PLGA/GSNO improves post-CPR cerebral perfusion and confers anti-apoptotic neuroprotection. Methods: Using an established rat model of asphyxia cardiac arrest and CPR, Au-PLGA/GSNO (7500 PPM, 0.4 ml) was infused with simultaneous US (1 MHz) stimulation at the brain 10 min after ROSC. Brain tissue perfusion was continuously recorded by OxyFLO probe and cerebral vasculature videoed by CytoCam. The blood was sampled 2 h post-CPR for measurement of nitrate/nitrite, and the brain harvested for measurement of casepase-3, endothelial NO synthase (eNOS) and protein kinase B (Akt). In a subgroup the brain was harvested at 24 h for TUNEL stain. Results: After CPR, marked cerebral vasoconstriction was noted on CytoCam while brain perfusion significantly reduced to ~0.5 folds that of baseline. After Au-PLGA/GSNO infusion and US stimulation, cerebral vasoconstriction was ameliorated and the brain perfusion significantly enhanced ( P &lt; 0.05 vs. CPR control). The plasma NO indicated by nitrate/nitrite 2 h post-CPR was significantly increased ( P &lt; 0.01) while cleaved caspase-3/caspase-3 of the brain markedly reduced ( P &lt; 0.001). TUNEL stain of the hippocampus CA1 and CA3 regions were also remarkably abrogated, suggesting anti-apoptotic neuroprotection. Specifically, the phosphorylated (p)-eNOS/eNOS and p-Akt/Akt were also increased ( P &lt; 0.01 and 0.001, respectively), indicating reciprocating activation of Akt-eNOS signaling upstream of NO. Conclusion: Spatiotemporally controlled US-triggered NO release by Au-PLGA/GSNO mitigates cerebral vasoconstriction, improves brain perfusion and confers anti-apoptotic neuroprotection post-CPR via reciprocating Akt-eNOS-NO signaling.
P11.65 Insights into the mechanisms of primary brain tumor invasion
Authors: A Bikfalvi, T Daubon, C Billottet
Journal: Neuro-Oncology (2019)

Abstract We have made progress in unravelling the mechanisms of tumor cell invasion by focusing the attention on two molecular pathways including chemokines and extracellular matrix molecules. Chemokines are important mediators of cell signaling that operate both on normal cells and tumor cells and in the immune-cell compartment (Billottet et al, 2013). Among the chemokine receptors, CXCR3 mediate diverse biological functions and comes in two major isoforms the A and B isoform. We found that ligand affinities and conformational changes are very different for the A and B form. We have recently elucidated the role and mechanism of CXCR3A in GBM invasion (Boyé et al, 2017b). We demonstrated that agonist stimulation enhances in vitro cell migration and invasion in GBM cells. A major finding was that CXCR3A forms a complex with the trafficking receptor Lipoprotein-related receptor-1 (LRP1). Silencing of LRP1 leads to an increase in the magnitude of ligand-induced conformational change with CXCR3-A focalized at the cell membrane, leading to sustained receptor activity and increase in the migration. This was also clinically validated. Our study defines LRP1 as a new regulator of CXCR3 and indicates that targeting CXCR3-A in GBM may constitute a promising strategy to halt tumor cell invasion. The extracellular matrix (ECM) has morphogenic roles in tumors. Important ECM components are the matricellular proteins, called thrombospondins(THBS1-5) (Adams and Lawler 2011). We recently elucidated the complex role of THSB1 in GBM invasion (Daubon et al.2019). Global expression analysis revealed that THBS1 is up-regulated in GBMs and associated with a poor prognosis. We, furthermore, demonstrated that THBS1 did not activate TGFβ in GBM but that TGFβ1 induced the expression of THBS1 via SMAD3. Furthermore, GBM invasion is compromised when THBS1 is silenced in tumor cells. Thus, our data clearly show that THBS1 is not only involved in the regulation of angiogenesis in GBM, but also impacts the invasive behaviour of glioma cells by interacting with a molecule called CD47 expressed on the surface of GBM cells. RNA-sequencing after microdissection of central and peripheral tumour areas in a human PDX model demonstrated that THBS1 was the gene with the highest connectivity in the peripheral invasive tumour areas. Taken together, these data indicate that THBS1 plays important role in the infiltrative process in GBM. REFERENCES: Adams JC, Lawler J. Cold Spring Harb Perspect Biol. 2011;3:a009712 Billottet C, Quemener C, Bikfalvi A. Biochim Biophys Acta. 2013;1836:287- Boyé K et al. Sci Rep. 2017;7:10703 Boyé K et al. Nat Commun. 2017;8:1571 Daubon T et al, Nature Communications. Nat Commun. 2019 Mar 8;10(1):1146 Murphy-Ullrich JE, Poczatek M. Cytokine Growth Factor Rev. 2000 11:59
Recreating the Hematopoietic Microenvironment in Vitro Using Microfluidic “on-a-Chip” Technology Enables the Study of Interactions of Normal and Malignant HSPC with Specific Bone Marrow Niches
Authors: Sunil George, Julio Aleman, M. Graca Almeida-Porada, Aleksander Skardal, Christopher D Porada
Journal: Blood (2017)
Opioid Prescribing After Surgery—Cause for Concern?
Authors: Lesley A. Colvin
Journal: JAMA Network Open (2019)

Karim S. Ladha, MD, MSc; Mark D. Neuman, MD, MSc; Gabriella Broms, MD, PhD; Jennifer Bethell, PhD; Brian T. Bateman, MD, MSc; Duminda N. Wijeysundera, MD, PhD; Max Bell, MD, PhD; Linn Hallqvist, MD; Tobias Svensson, MSc; Craig W. Newcomb, MS; Colleen M. Brensinger, MS; Lakisha J. Gaskins, MHS; Hannah Wunsch, MD, MSc
Constituents of Household Air Pollution and Risk of Lung Cancer among Never-Smoking Women in Xuanwei and Fuyuan, China
Authors: Roel Vermeulen, George S. Downward, Jinming Zhang, Wei Hu, Lützen Portengen, Bryan A. Bassig, S. Katharine Hammond, Jason Y.Y. Wong, Jihua Li, Boris Reiss, Jun He, Linwei Tian, Kaiyun Yang, Wei Jie Seow, Jun Xu, Kim Anderson, Bu-Tian Ji, Debra Silverman, Stephen Chanock, Yunchao Huang, Nathaniel Rothman, Qing Lan
Journal: Environmental Health Perspectives (2019)

Background: Lung cancer rates among never-smoking women in Xuanwei and Fuyuan in China are among the highest in the world and have been attributed to the domestic use of smoky (bituminous) coal for heating and cooking. However, the key components of coal that drive lung cancer risk have not been identified. Objectives: We aimed to investigate the relationship between lifelong exposure to the constituents of smoky coal (and other fuel types) and lung cancer. Methods: Using a population-based case–control study of lung cancer among 1,015 never-smoking female cases and 485 controls, we examined the association between exposure to 43 household air pollutants and lung cancer. Pollutant predictions were derived from a comprehensive exposure assessment study, which included methylated polycyclic aromatic hydrocarbons (PAHs), which have never been directly evaluated in an epidemiological study of any cancer. Hierarchical clustering and penalized regression were applied in order to address high colinearity in exposure variables. Results: The strongest association with lung cancer was for a cluster of 25 PAHs [odds ratio (OR): 2.21; 95% confidence interval (CI): 1.67, 2.87 per 1 standard deviation (SD) change], within which 5-methylchrysene (5-MC), a mutagenic and carcinogenic PAH, had the highest individual observed OR (5.42; 95% CI: 0.94, 27.5). A positive association with nitrogen dioxide (NO2) was also observed (OR: 2.06; 95% CI: 1.19, 3.49). By contrast, neither benzo(a)pyrene (BaP) nor fine particulate matter with aerodynamic diameter ≤2.5μm (PM2.5) were associated with lung cancer in the multipollutant models. Conclusions: To our knowledge, this is the first study to comprehensively evaluate the association between lung cancer and household air pollution (HAP) constituents estimated over the entire life course. Given the global ubiquity of coal use domestically for indoor cooking and heating and commercially for electric power generation, our study suggests that more extensive monitoring of coal combustion products, including methylated PAHs, may be warranted to more accurately assess health risks and develop prevention strategies from this exposure. https://doi.org/10.1289/EHP4913
Galectin-3: A possible complementary marker to the PSA blood test.
Authors: Avraham Raz, Vitaly Balan, Yi Wang, Pratima Nangia-Makker, Dhonghyo Kho, Lance K. Heilbrun, Madhuri Bajaj, Daryn W. Smith, Elisabeth I. Heath
Journal: Journal of Clinical Oncology (2013)

e22168 Background: The prostate-specific antigen (PSA) is a test widely used to detect, monitor, and predict the biology of prostate cancer (PCa). Galectin-3 (Gal-3) is a carbohydrate-binding protein and is present in the seminal fluid. It is a tumor-associated protein, which plays a role in metastasis, apoptosis, and tumor growth. We recently reported that PSA cleaves Gal-3. Cleavage status of Gal-3 in the prostate tissue might be associated with the tumor formation and progression of PCa. Therefore, we compared Gal-3 levels in the blood of non-cancer urology patients and metastatic PCa patients. Methods: Non-cancer and metastatic PCa patients were recruited from the genitourinary oncology clinics. Sixteen men (8 PCa patients and 8 controls) were recruited during their clinic visit from May to August 2012. The metastatic PCa patients could be either castrate-sensitive or castrate-resistant. The control patients could not have any history of invasive cancer. A blood sample was collected from each study patient. Levels of Gal-3 were analyzed by Western blot and ELISA. The study design was a small, prospective, single institution pre-pilot study. The primary statistical endpoint was the mean level of serum galectin-3. Within each of the two groups of patients, it was desired to estimate the mean Gal-3 level to within 0.50 standard deviations (SD’s) of the true mean, with 80% confidence. This study design required N=8 men per group. Results: The cancer-free control patients had lower levels of serum Gal-3 than did any of the 8 PCa patients (see Table). These results suggest that serum Gal-3 levels in metastatic PCa patients and cancer-free controls are quite different. The serum PSA distributions of these 2 patient groups overlap slightly, hence PSA did not distinguish them quite as well as did Gal-3. Conclusions: This is the first report to show serum Gal-3concentrations were uniformly higher in patients with metastatic PCa as compared to non-cancer control patients. [Table: see text]
Exposure to Soy-Based Formula in Infancy
Authors: Lynn R. Goldman
Journal: JAMA (2001)

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Circulating tumor cell counts is a better predictor of overall survival than dynamic tumor size changes – a quantitative modeling framework
Authors: Ida Netterberg, Mats O Karlsson, Leon Wmm Terstappen, Miriam Koopman, Cornelis Ja Punt, Lena E Friberg
Journal: Clinical Cancer Research (2019)

Purpose: Quantitative relationships between treatment-induced changes in tumor size and circulating tumor cell (CTC) counts, and their links to overall survival (OS), are lacking. We here present a ...
Daisies March: a Brazilian initiative in planetary health and gender equity
Authors: Tatiana Camargo, Enrique Falceto de Barros
Journal: The Lancet Planetary Health (2019)

Since 2000, in its first edition, the Daisies March has been consolidating itself as one of the largest social movements of women in Latin America, focusing in the fight against violence and in the search for autonomy for the women of rural areas, forests, and riversides, in a way inherently related to the socio-environmental sustainability of their communities and to the notion of planetary health. Recent studies have shown that actions that associate, for example, the reduction of carbon emissions to the promotion of gender equity, are more effective in their environmental results and in the more equitable distribution of income generated.1Cook NJ Grillos T Andersson KP Gender quotas increase the equality and effectiveness of climate policy interventions.Nat Clim Chang. 2019; 9: 330-334Crossref Scopus (36) Google Scholar In this project, we present the process of transformation of the guidelines claimed in the 2019 March in a didactic unit, suitable for popular education actions to be conducted by partners of the National Confederation of Agricultural Workers. The planned educational actions promote the voices of Rural Workers' Unions, family farmers, and public schools for the development of debates and referral of local actions aimed at more equal access to land and water; the development of local agroecological techniques; the food and energy sovereignty of rural, forest, and riversides communities; the conservation of socio-biodiversity; access to public health; economic autonomy, work, and income for women; and access to sexual and reproductive rights. As a pilot study, the actions will be conducted in five different municipalities of Rio Grande do Sul, during the year 2019, through a partnership with the Federal University of Rio Grande do Sul and have raised possible actions aiming to increase gender equity and promote planetary health. Contributors TC is an academic consultant of National Confederation of Agricultural Workers (CONTAG), for the development of activities of 2019 Daisies March. EFdB has contributed to the introduction of planetary health concept in the discussions promoted by this women's social movement. Declaration of interests We declare no competing interests.