tbuckley/cabot-search huggingface dataset:
Hypoxia‐inducible factor‐1α/interleukin‐1β signaling enhances hepatoma epithelial–mesenchymal transition through macrophages in a hypoxic‐inflammatory microenvironment
Authors: Jingying Zhang, Qi Zhang, Yu Lou, Qihan Fu, Qi Chen, Tao Wei, Jiaqi Yang, Jinlong Tang, Jianxin Wang, Yiwen Chen, Xiaoyu Zhang, Jian Zhang, Xueli Bai, Tingbo Liang
Journal: Hepatology (2017)

The development and progression of hepatocellular carcinoma (HCC) are dependent on its local microenvironment. Hypoxia and inflammation are two critical factors that shape the HCC microenvironment; however, the interplay between the two factors and the involvement of cancer cells under such conditions remain poorly understood. We found that tumor‐associated macrophages, the primary proinflammatory cells within tumors, secreted more interleukin 1β (IL‐1β) under moderate hypoxic conditions due to increased stability of hypoxia inducible factor 1α (HIF‐1α). Under persistent and severe hypoxia, we found that the necrotic debris of HCC cells induced potent IL‐1β release by tumor‐associated macrophages with an M2 phenotype. We further confirmed that the necrotic debris–induced IL‐1β secretion was mediated through Toll‐like receptor 4/TIR domain–containing adapter‐inducing interferon‐β/nuclear factor kappa‐light‐chain‐enhancer of activated B cells signaling in a similar, but not identical, fashion to lipopolysaccharide‐induced inflammation. Using mass spectrometry, we identified a group of proteins with O ‐linked glycosylation to be responsible for the necrotic debris–induced IL‐1β secretion. Following the increase of IL‐1β in the local microenvironment, the synthesis of HIF‐1α was up‐regulated by IL‐1β in HCC cells through cyclooxygenase‐2. The epithelial–mesenchymal transition of HCC cells was enhanced by overexpression of HIF‐1α. We further showed that IL‐1β promoted HCC metastasis in mouse models and was predictive of poor prognosis in HCC patients. Conclusion : Our findings revealed an HIF‐1α/IL‐1β signaling loop between cancer cells and tumor‐associated macrophages in a hypoxic microenvironment, resulting in cancer cell epithelial–mesenchymal transition and metastasis; more importantly, our results suggest a potential role of an anti‐inflammatory strategy in HCC treatment. (H epatology 2018;67:1872‐1889)
Changes in Outcomes of Cardiac Allograft Vasculopathy Over 30 Years Following Heart Transplantation
Authors: Maxime Tremblay-Gravel, Normand Racine, Simon de Denus, Anique Ducharme, Guy B. Pelletier, Geneviève Giraldeau, Mark Liszkowski, Marie-Claude Parent, Michel Carrier, Annik Fortier, Michel White
Journal: JACC Heart Failure (2017)
Meditation as a doula-delivered intervention for underserved late-stage cancer patients: A feasibility trial.
Authors: Alyson B. Moadel, Fernando J. Camacho, Nicolas Schlecht
Journal: Journal of Clinical Oncology (2017)

188 Background: Socioeconomic disparities in psychosocial outcomes among cancer patients have been documented. High interest in peer support and mind-body therapies across diverse populations presents an opportunity for enhancing end-of-life care in the underserved setting. We present the results of a psychosocial needs assessment, and the findings from a feasibility trial in which peer navigators (PN; cancer survivor volunteers) were taught to deliver Loving Kindness (LK) Meditation in preparation for their role as end-of-life “Doulas”. Methods: (1) A survey of psychosocial symptoms and needs was administered to a convenience sample of 56 stage IV patients from an NCI-designated cancer center in Bronx, NY. Patients were female (75%), African American (43%), Hispanic (45%), and 56 M years old. (2) A feasibility trial randomly assigned 9 patients to receive LK meditation delivered by 1 of 4 trained PNs or a professional meditation instructor. The trial was rated on 8 measures of feasibility as set forth by Bowen et al 2009. Results: Patients reported high sadness (66%), anxiety (54%), anger (41%), and spiritual distress (18%) with 70% endorsing an interest in mind-body therapies “such as meditation”, and 46% an interest in a PN. In the LK meditation feasibility trial, patients reported improved positive affect scores by a clinically significant margin of 13%, with equivalent impact and satisfaction for PN relative to professional instructor. Conclusions: Inner city late stage cancer patients endorse high distress, and high interest in peer support and mind-body interventions. Feasibility testing demonstrates that LK meditation is responsive to patient preference and demonstrates preliminary efficaciousness. Findings suggest that Doula-delivered meditation for underserved patients presents a unique resource in the palliative care setting.
Oncology providers, patients, and caregivers reflect: Applying "big data" for better supportive outcomes.
Authors: Marie C. Haverfield, Adam Singer, Karl Lorenz
Journal: Journal of Clinical Oncology (2017)

59 Background: The development of “big data” methods offers an opportunity to more precisely predict patient outcomes. We explored physicians, patients, and caregivers’ perspectives about the use of predictive models in oncology practice. Methods: We conducted 12 patient, 12 provider, and 12 caregiver interviews (N = 36) from Stanford University outpatient oncology clinics. We queried participants about patient and family-centered applications of predictive models for prognosis, cost, and novel patient and family-centered outcomes. Two trained coders iteratively examined transcripts for consistent topics and used the constant comparative methods to establish themes and sub-themes. Results: Several overlapping themes emerged: 1) Outcomes of Interest, [provider] “Predictive information about side effects or adverse effects of treatment would be helpful”: 2) Barriers to Using Predictions, [patient] “If it seems too sort of set in stone, without…you know, everything has grey areas”; 3) Benefits to Using Predictions, [provider] “Some people…their cancer may be cured, but they live with these really horrible chronic illnesses and some people would say, ‘I would have rather have just died from my disease than be in this shape’; and 4) Communication Strategy, [provider] “I’m not even sure if I would bring up the models…I would kind of fall back on what I normally discuss with patients”. A theme specific to the provider group was 5) Accuracy of Model Information, [provider] “It’s hard to know whether to use in the clinical setting just the results of the model or whether you would really want to go down to the root level and actually access the raw data”. A theme specific to the patient and caregiver groups was 6) Privacy, [caregiver] “I would want to be able to have the patient authorize that”. Conclusions: There is consistency between provider strategies to communicate prognostic information and patients’ perceptions of how they would like prognostic information to be communicated to them. While providers are concerned with accuracy of predictive models, patients and caregivers are more concerned with privacy.
The Role of Nanomechanics in Healthcare
Authors: Pranjal Nautiyal, Fahad Alam, Kantesh Balani, Arvind Agarwal
Journal: Advanced Healthcare Materials (2017)

Nanomechanics has played a vital role in pushing our capability to detect, probe, and manipulate the biological species, such as proteins, cells, and tissues, paving way to a deeper knowledge and superior strategies for healthcare. Nanomechanical characterization techniques, such as atomic force microscopy, nanoindentation, nanotribology, optical tweezers, and other hybrid techniques have been utilized to understand the mechanics and kinetics of biospecies. Investigation of the mechanics of cells and tissues has provided critical information about mechanical characteristics of host body environments. This information has been utilized for developing biomimetic materials and structures for tissue engineering and artificial implants. This review summarizes nanomechanical characterization techniques and their potential applications in healthcare research. The principles and examples of label-free detection of cancers and myocardial infarction by nanomechanical cantilevers are discussed. The vital importance of nanomechanics in regenerative medicine is highlighted from the perspective of material selection and design for developing biocompatible scaffolds. This review interconnects the advancements made in fundamental materials science research and biomedical technology, and therefore provides scientific insight that is of common interest to the researchers working in different disciplines of healthcare science and technology.
Strategies to Achieve High-Value Oncology Care—A Beginning
Authors: Harold C. Sox, Ethan M. Basch, Donald Berwick
Journal: JAMA Oncology (2017)

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Abstract 18547: Feedback Devices During Laypeople's CPR Courses: Are They Able to Eliminate Anthropometric Variables Effect?
Authors: Enrico Baldi, Alberto Somaschini, Stefano Cornara, Michela Tonani, Amedeo Cutuli, Daniele Bertaia, Alice Gabbrielli, Luca Magarotto, Guido Giardini, Mauro Marzolla, Gianluca Mantovan, Gaia Massino, Gianni Bruno, Enrico Contri
Journal: Circulation (2017)

Introduction:  It has been demonstrated that anthropometric variables affect layperson’s chest compression quality, especially chest compression depth. Furthermore, there are evidences that the use of feedback devices during CPR/AED course improve layperson’s CPR quality after the course.   Hypothesis:  We wanted to verify whether the use of feedback devices during BLS/AED course for laypeople could mitigate the effect of anthropometric variables on chest compression depth.   Methods:  We prospectively enrolled 329 participants attending 5-h CPR/AED courses with the use of feedback devices in 2 training centers (feedback group - FG) and we matched them with 329 participants of a previous study conducted in the same centers with the same type of course, but without any feedback devices (no feedback group - NFG), using a propensity score matching adjusted for age, sex, weight and height. The feedback device used in this study was the Laerdal ResusciAnne QCPR. In both group we evaluated the percentage of compression performed with a depth between 5 and 6 cm in 1 minute of chest-compression only CPR on a ResusciAnne QCPR. We divided the populations in quartiles for weight, height and age, and we evaluated differences among the quartiles by analysis of variance (ANOVA).   Results:  FG showed an improvement in the percentage of compressions performed with correct depth compared to NFG (70.7 ± 36.1 vs 62.5 ± 40.1, p   Conclusions:  Our study confirm that feedback device are able to improve chest compression depth in laypeople. However, feedback devices are not able to eliminate anthropometric variables effect, so instructors should tailor their attention during training, in particular for chest compression depth, depending on the physical characteristics of the attendee.
Variation in the 12-Month Treatment Trajectories of Children and Adolescents After a Diagnosis of Depression
Authors: Nina R. Joyce, Megan S. Schuler, Scott E. Hadland, Laura A. Hatfield
Journal: JAMA Pediatrics (2017)

<h3>Importance</h3> Depression during childhood and adolescence is heterogeneous. Treatment patterns are often examined in aggregate, yet there is substantial variability across individual treatment trajectories. Understanding this variability can help identify treatment gaps among youths with depression. <h3>Objective</h3> To characterize heterogeneity in 12-month trajectories of psychotherapy and antidepressant treatment in youths with depression. <h3>Design, Setting, and Participants</h3> This is a longitudinal-cohort study of youths 18 years or younger with a new diagnosis of depression and at least 12 months of follow-up following diagnosis, as determined from commercial insurance claims filed from 2007 to 2014. Latent class models were fit to summary measures of psychotherapy and antidepressant use in the 12 months following the index diagnosis. We examined variation in baseline health, health care utilization, and health outcomes across classes with similar patterns of psychotherapy and antidepressant use. Data analysis took place between June 2016 and March 2017. <h3>Main Outcomes and Measures</h3> Psychotherapy and antidepressant use. <h3>Results</h3> The cohort included 84 909 individuals with a mean (SD) age at index diagnosis of 15.0 (2.6) years, of whom 49 995 (59%) were female. Attention-deficit/hyperactivity disorder (n = 14 625; 17%) and anxiety (n = 12 358; 15%) were the most common comorbid diagnoses. During the assessment period, 59 023 individuals (70%) received psychotherapy at any point, and 33 997 individuals (40%) were dispensed antidepressants at any point. Eight classes with distinct treatment trajectories were identified, which we classified into 4 broad groups: 3 classes that received dual therapy (n = 18 710; 22%), 2 classes that received antidepressant monotherapy (n = 15 287; 18%), 2 classes that received psychotherapy monotherapy (n = 40 313; 48%) and 1 class that received no treatment (n = 10 599; 13%). The most common class received psychotherapy monotherapy (n = 35 243; 42%) and had the lowest incidence of attempted suicide (0.8 per 100 person-years [PY]) and inpatient hospitalization (3.5 per 100 PY) during the assessment period and postassessment period (0.5 per 100 PY and 1.3 per 100 PY, respectively). The group receiving dual therapy had the highest incidence of attempted suicide during the assessment period (4.7-7.1 per 100 PY, depending on the class) and postassessment period (1.5-1.7 per 100 PY). <h3>Conclusions and Relevance</h3> In our sample, 13% of youths received no treatment, and 18% received antidepressants without concomitant psychotherapy. Summary measures of treatment can mask informative patterns of psychotherapy and antidepressant use. Latent class analysis can be used to identify subgroups of individuals with similar treatment trajectories and help identify treatment gaps under current practice patterns.
Abstract #2671: Antitumor activity and mode of action of pentacyclic oxindole alkaloids from Uncaria tomentosa
Authors: Yoshihiko Fujita, Kazuko Matsumoto, Kaoru Tanaka, Hiroyasu Kaneda, Kanae Kudo, Mari Maegawa, Daisuke Tamura, Keiichi Aomatsu, Marco DeVelasco, Tokuzo Arao, Kazuto Nishio
Journal: Cancer Research (2009)

Uncaria tomentosa  (cat\#8217;s claw), a South American Rubiaceae, has been recently more and more popular as an immunomodulatory, anti-inflammatory and anti-cancer remedy. Here we show that the antiproliferative and apoptotic effects of pentacyclic oxindole alkaloids (POAs) purified from  U. tomentosa , namely pteropodine, isopteropodine, mitraphylline, isomitraphylline and speciophylline on various types of human cancer cell lines. MTT assay revealed that, with the exception of mitraphylline, all alkaloids tested inhibited the growth of several cells. Pteropodine and isopteropodine, particularly, were the most potent with the IC50 of ~5 \#956;M on PC3 (prostate cancer) and WiDr (colon cancer) cells. A549 (lung cancer), Hela (cervical cancer) and MCF7 (breast cancer) cells were also sensitive to these two POAs, although to a lesser extent. Interestingly, T98G (glioblastoma) cells showed no response to these POAs, suggesting the cell-specific inhibitory effect of the POAs. Flow cytometry and immunoblotting analyses of PC3 and WiDr showed that pteropodine arrested these cells at G1 phase and reduced the expression levels of G1-specific cdks (cdks 2 and 4). Annexin-V staining of PC3 suggested that pteropodine induced apoptosis of the cells in a concentration-dependent manner. These findings suggest that the specific POAs from  U. tomentosa  may be a possible candidate for anti-tumor agent.  In vivo  antitumor activity of the POAs will be also presented.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 2671.
Abstract 21042: Cardiovascular Risk Stratification Using Off-the-Shelf Wearables and a Multi-Task Deep Learning Algorithm
Authors: Geoffrey H Tison, Avesh C Singh, Daniel A Ohashi, Johnson T Hsieh, Brandon M Ballinger, Jeffrey E Olgin, Gregory M Marcus, Mark J Pletcher
Journal: Circulation (2017)

Introduction: We aimed to evaluate whether a novel deep neural network (DNN) can predict cardiovascular risk factors from off-the-shelf wearables with a photoplethysmographic (PPG) heart rate sensor and accelerometer. Longitudinal heart rate variability and activity patterns have previously been associated with incident hypertension, diabetes, and sleep apnea, conditions which are frequently undiagnosed. Methods: Health eHeart, an IRB-approved UCSF study, enrolled 6,115 active users of the Cardiogram app for Apple Watch. Heart rate and step counts were collected for a period of 1 to 53 weeks (mean=8.9). Data from 70% of participants (33,628 person-weeks of data) was used to train a semi-supervised, multi-task DNN with both convolutional and recurrent layers to simultaneously predict prevalent hypertension, sleep apnea, and diabetes. Test performance characteristics were estimated using the remaining 30% of participants. Results: Mean age was 42.3 ± 12.1, 69% male. 2,230 (36.5%) of participants had hypertension, 1,016 (16.6%) had sleep apnea, and 462 (7.6%) had diabetes. In the validation set, the DNN outperformed a baseline logistic regression model incorporating age, sex, and beta blocker use, predicting prevalent hypertension with a c-statistic of 0.819 (95% CI 0.76-0.88; with an optimal operating point yielding 84.8% sensitivity and 63.6% specificity) vs a baseline c-statistic of 0.682 (95% CI 0.60-0.76), and prevalent sleep apnea with a c-statistic of 0.902 (95% CI 0.85-0.95; with an optimal operating point yielding 90.4% sensitivity and 59.8% specificity) vs a baseline c-statistic of 0.459 (95% CI 0.39-0.53). Results were not statistically significant for diabetes. Conclusions: Our DNN demonstrates surprisingly good prediction of hypertension and sleep apnea given that its only inputs are heart rate and step count. Whether such DNNs can provide durable and portable predictions for these conditions in other study samples is worth pursuing.
Exploratory analysis of multiprotein serum predictors at baseline of progression-free survival of ipilimumab or ipilimumab and nivolumab in the Checkmate-069 study.
Authors: Krisztian Homicsko, Michel A. Cuendet, Agata Mlynska, Bianca Moura, Christine Horak, Douglas Hanahan, Olivier Michielin
Journal: Journal of Clinical Oncology (2017)

9571 Background: Checkpoint inhibitors have revolutionized the treatment of stage IV melanoma patients. Selection of patients for PD-1 monotherapy or CTLA4/PD1 combination remains an important challenge. We set out to perform a discovery study of pretreatment serum protein biomarkers to identify predictors of progression free survival (PFS) for ipilimumab (IPI) or ipilimumab/nivolumab (IPI/NIVO). Methods: We performed an exploratory analysis of baseline serum samples from 135 treatment-naive patients with metastatic melanoma included in the randomized phase II clinical trial, CheckMate 069 (NCT01927419). We used the RayBiotech 440 human cytokine array and evaluated the relationship of serum protein levels with 44 clinical parameters. R, Prism 7.0 and TensorFlow were used for analyses. Results: We focused on correlation of serum protein markers with PFS as a predictor of long-term benefit. In the IPI arm (n = 46), high FGF4 correlated with worse PFS outcome (p = 0.0012). However, FGF4 levels alone were unable to select responsive vs. non-responsive patients. In contrast, a set of three markers consisting of FGF4 ( &lt; 760pg/ml), CCL15 ( &gt; 2.7 ng/ml), and TACE ( &gt; 600pg/ml) separated non-progressing versus progressing patients. Moreover a small group of FGF4-high patients who were concomitantly TIM-3-low also had longer PFS (combined of both: p = 0.0004, HR logrank : 0.07, 95% CI: 0.03279 to 0.1533). The same markers did not discriminate between IPI/NIVO patients (p = 0.467, HR: 15). In the IPI/NIVO arm, three different markers could select patients. Patients either with low CCL2 ( &lt; 72 pg/ml) or alternatively with high CCL2 combined with high PDGF-AA ( &gt; 8.2 ng/ml) and low GASP-1 ( &lt; 1.3 ng/ml) had longer PFS (p &lt; 0.0001, HR: 0.115, 95% CI: 0.03848 to 0.3408). Conversely, these markers did not predict benefit for IPI-monotherapy. Conclusions: In this study we identified protein signatures in baseline serum that correlate with PFS for therapies with IPI or IPI/NIVO. The markers were exclusive for IPI or IPI/NIVO but not for both. Additional research is warranted to substantiate these results and evaluate the possibility of incorporating into clinical practice.
P2.02-006 Targeted Next Generation Sequencing Reveals Prognostic Recurrent Somatic Mutations in the GNAQ Oncogene in NSCLC
Authors: Norma Hernández-Pedro, Giovanny Soca-Chafre, Carmen Alaez-Verson, Karol Carrillo-Sánchez, Alejandro Avilés-Salas, Mario Orozco-Morales, Pedro Barrios-Bernal, Eleazar Macedo-Perez, Oscar Arrieta
Journal: Journal of Thoracic Oncology (2017)
End criminal sanctions for abortion
Authors: Richard Hurley
Journal: BMJ (2017)

The 1967 Abortion Act entitled British women to a legal termination of pregnancy, provided that certain conditions were met. It created exemptions to the 1861 Offences Against the Person Act, which is still on the statute books and makes abortion a crime punishable by life in prison.

Calls for legal reform are gathering momentum, as Sally Howard reports (doi:10.1136/bmj.j5278). Critics claim that the law is out of step with public attitudes, hinders evidence based clinical practice, and stigmatises procedures that a third of UK …
P2.03b-095 Retrospective Analysis of Correlation between ACEIs/ARBs and Clinical Outcome in Lung Cancer Patients with Bevacizumab-Based Chemotherapy
Authors: Sachi Okawa, Masanori Fujii, Naoyuki Sone, Rie Tohnai, Ryuichiro Tanaka, Yukiko Era, Yuji Yokoyama, Yusuke Ueda, Keisuke Sugimono, Kazuhiro Kajimoto, Hiroshige Yoshioka
Journal: Journal of Thoracic Oncology (2017)