tbuckley/cabot-search huggingface dataset:
Impact of physical activity on insulin levels in breast cancer survivors
Authors: J. A. Ligibel, N. Campbell, H. Chen, T. Salinardi, W. Chen, A. Partridge, C. Mantzoros, E. Winer
Journal: Journal of Clinical Oncology (2007)

555 Background: Accumulating data suggest that body weight and physical activity may affect breast cancer risk and outcomes. Biological mechanisms underlying these relationships are not clear. Studies have demonstrated that high levels of insulin, often seen in obese and sedentary individuals, are also associated with an increased risk of breast cancer recurrence and breast cancer-related death. We sought to analyze whether exercise lowers insulin levels in a population of breast cancer survivors. Methods: Inactive women with early stage breast cancer who had completed adjuvant treatment were randomized to a 16 week, mixed cardiovascular and strength training exercise intervention, or to a normal care control group. Target exercise goals included 2 supervised strength training sessions and 90 minutes of unsupervised cardiovascular exercise each week. Fasting insulin and glucose levels, as well as measurement of weight, body composition, and circumference at the waist and hip, were collected at baseline and after 16 weeks in both groups, and changes in these measures were assessed. Results: One hundred and one women were randomized. Comparison of changes in anthropometric measures are presented in Table 1 . Baseline insulin levels were similar in the 2 groups. After the 16-week exercise or control period, insulin levels decreased by 2.86 μIU/ml in the exercise group (p=0.03), and by 0.27 μIU/ml in the control group (p=0.65). A comparison of the change in insulin levels across time in the 2 groups approached statistical significance (p=0.07). There was also a trend toward improvements in insulin sensitivity in the exercise group (p=0.09), with no change seen in fasting glucose levels. Conclusions: Physical activity was associated with a decrease in insulin levels and in hip circumference in breast cancer survivors. The relationship between physical activity and breast cancer prognosis may be mediated, at least partially, through changes in insulin levels and/or changes in fat mass or deposition. [Table: see text] No significant financial relationships to disclose.
Gene predictors for extrathoracic metastases (EM) in advanced bronchioloalveolar carcinoma (BAC) of the lung obtained from formalin-fixed, paraffin-embedded tissue (FFPE)
Authors: G. J. Weiss, W. A. Franklin, C. Zeng, Z. V. Tran, C. D. Coldren, L. Magree, M. Sugita, P. A. Bunn, K. Kelly
Journal: Journal of Clinical Oncology (2007)

7622 Background: Advanced BAC is typically a more indolent tumor confined to the lungs, thus raising the question of the role for bilateral lung transplantation (BLT). In a small series, BLT produced a 5-year survival rate of 50%. Determining biological predictors of EM could identify the most ideal candidates for curative BLT. Methods: We retrospectively reviewed patient records from 1/1/98–10/1/06. RNA was extracted from FFPE tissue. RNA was amplified using Arcturus kits and profiled by Affymetrix X3P chips, which contain 47,000 transcripts and 61,000 probe sets. Chi-square and t-tests were used to compare clinical characteristics. Log-rank and Cox hazards modeling were used to determine clinical factors that predict either overall survival or time to EM. Logistic regression modeling was used to examine clinical factors predicting rate of EM. Hybridization signals and detection calls were generated in BioConductor, using gcrma and affy tools, and normalized to benign tissue. Univariate analysis was performed to identify genes of interest. Results: Patients with advanced BAC/adenocarcinoma with BAC features at diagnosis, (T any N any M 1 [lung only]; n=20), and matched cohort of locally-advanced adenocarcinoma (T any N 2–3 M 0 ) and pure adenocarinoma with pulmonary metastases only, (T any N any M 1 [lung only]), were identified (n=45). There was no significant difference for age, gender, smoking history, survival, or EM between the 2 groups. Arrays have been performed on 12 samples (4 BAC, 5 lung adenocarcinoma, 2 benign lung, and 1 benign lymph node). Preliminary analysis shows 27 genes were significantly up- and down-regulated vs. benign tissue (p&lt;0.01). Seven of these genes were highly altered and may differentiate risk for EM. Conclusions: Gene expression profiling may discern risk for EM not readily apparent from clinical characteristics and could serve to identify advanced BAC patients with low risk for EM that may benefit from BLT. Gene profiling of 12 additional tumor samples is ongoing and results will be updated. We plan future validation of candidate genes in collaboration with cooperative groups or other multi-center sites. Supported by a grant from Cancer League of Colorado. No significant financial relationships to disclose.
Bevacizumab (Bev) in combination with XELOX or FOLFOX4: Updated efficacy results from XELOX-1/ NO16966, a randomized phase III trial in first-line metastatic colorectal cancer
Authors: L. Saltz, S. Clarke, E. Diaz-Rubio, W. Scheithauer, A. Figer, R. Wong, S. Koski, M. Lichinitser, T. Yang, J. Cassidy
Journal: Journal of Clinical Oncology (2007)

4028 Background: NO16966 is the first phase III trial to evaluate the combination of Bev with oxaliplatin-based chemotherapy (FOLFOX4 or the XELOX regimen) in the first-line setting. Methods: 1401 pts were randomized to receive FOLFOX4 (oxaliplatin, 5-FU, leucovorin as described previously) or XELOX (oxaliplatin 130mg/m 2 iv, capecitabine 1000mg/m 2 bid oral d1–14, q3w) plus Bev (5mg/kg q 2 weeks for FOLFOX, 7.5mg/kg q 3 weeks for XELOX) or Placebo in a 2x2 factorial design. Results: The addition of Bev to oxaliplatin-based chemotherapy demonstrated a significant benefit in terms of PFS in the primary analysis (HR 0.83; 97.5% CI 0.72- 0.95, p=0.0023). Prespecified analysis of PFS on treatment (defined as progressive disease or death within 28 days from the last dose of study treatment) and PFS analysis based on tumor assessments by an independent review committee (IRC) were consistent with the benefit observed in the primary analysis. PFS results are shown in Table 1 . 34% of patients have died and the median follow-up for survival at this time is 18.6 months. Mature overall survival data will be presented at the meeting. Conclusions: This large, international phase III trial demonstrates that the addition of Bev to oxaliplatin-based chemotherapy regimens significantly improves PFS. [Table: see text] [Table: see text]
Primary Atopic Disorders
Authors: Joshua D. Milner
Journal: Annual Review of Immunology (2020)

Primary atopic disorders describes a series of monogenic diseases that have allergy- or atopic effector-related symptoms as a substantial feature. The underlying pathogenic genetic lesions help illustrate fundamental pathways in atopy, opening up diagnostic and therapeutic options for further study in those patients, but ultimately for common allergic diseases as well. Key pathways affected in these disorders include T cell receptor and B cell receptor signaling, cytokine signaling, skin barrier function, and mast cell function, as well as pathways that have not yet been elucidated. While comorbidities such as classically syndromic presentation or immune deficiency are often present, in some cases allergy alone is the presenting symptom, suggesting that commonly encountered allergic diseases exist on a spectrum of monogenic and complex genetic etiologies that are impacted by environmental risk factors.
Early detection of diabetic kidney disease by urinary proteomics and subsequent intervention with spironolactone to delay progression (PRIORITY): a prospective observational study and embedded randomised placebo-controlled trial
Authors: Nete Tofte, Morten Lindhardt, Katarina Adamova, Stephan J L Bakker, Joachim Beige, Joline W J Beulens, Andreas L Birkenfeld, Gemma Currie, Christian Delles, Ingo Dimos, Lidmila Francová, Marie Frimodt-Møller, Peter Girman, Rüdiger Göke, Tereza Havrdova, Hiddo J L Heerspink, Adriaan Kooy, Gozewijn D Laverman, Harald Mischak, Gerjan Navis, Giel Nijpels, Marina Noutsou, Alberto Ortiz, Aneliya Parvanova, Frederik Persson, John R Petrie, Piero L Ruggenenti, Femke Rutters, Ivan Rychlík, Justyna Siwy, Goce Spasovski, Marijn Speeckaert, Matias Trillini, Petra Zürbig, Heiko von der Leyen, Peter Rossing, Silke Zimmermann, Brit Rädisch, Anika Hävemeier, Annette Busmann, Ulrike Wittkop, Barbara Neuhaus, Regina Ax-Smolarski, Veit Zieglschmid, Eva Bollweber, Heidrun Wölk, Viktor R. Curovic, Ninna H. Tougaard, Mie K. Eickhoff, Sascha Pilemann-Lyberg, Signe A. Winther, Signe V. Rosenlund, Tine W. Hansen, Bernt J. von Scholten, Christian S. Hansen, Emilie H. Zobel, Jens C. Laursen, Simone Theilade, Lone Jelstrup, Tina R. Juhl, Dorthe Riis, Jessie A. Hermann, Anne G. Lundgaard, Maja L.D. Halkjær, Lene Aabo, Therese Frost Lerche, Maria Lajer, Rikke J. Stefansen, Maria A. Campbell, Annika Durban, Julia Raad, Michael Prigge, Marco Schiemann, Robbie Wilson, Sharon Kean, Elizabeth Douglas, Pamela Surtees, Christina Gant, Stanley M.H. Yeung, Ilse Hagedoorn, Joanne Flynn, Joe Galloway, Katriona Brooksbank, Carolina Aparicio, Ilian P. Iliev, Francesco Nones, Francesca Lo Bue, Daniela Melacini, Daniela Cugini, Silvia Prandini, Verusca Lecchi, Svitlana Yakymchuk, Giulia Gherardi, Alessandro Villa, Davide Villa, Flavio Gaspari, Antonio N. Cannata, Silvia Ferrari, Nadia Stucchi, Šárka Albrechtová, Elina Eldeik, Renata Amanaki, Beatriz Fernandez-Fernandez, Jinny Sanchez-Rodriguez, Clotilde Vázquez, Ana B. Sanz, Maria D. Sanchez-Niño, Adrian M. Ramos, Maria Á. Gonzalo, Ulrike Schmidt, Gjulsen Selim, Tatjana Gjorgovski, Slavica S. Stratrova, Olivera Stojceva-Taneva, Petra Schutten-Westerneng, Brenda Wierbos, Frank Huvers, Anneke K. De Bruin, Bruno Lapauw, Elsie de Man, Kelly Rokegem, Sabien Inion, Kristin Kreutzmann, Isabelle Dewettinck, Caroline Boukens-de Graaf, Ferrina Clerc-de Jong, Jannet Entius, Marian Nannings, Suzy van Steenderen, Friedrich W. Petry, Ceyda Kilic
Journal: The Lancet Diabetes & Endocrinology (2020)
ATTAX: Randomised phase II study evaluating weekly docetaxel-based chemotherapy combinations in advanced esophago- gastric cancer, final results of an AGITG trial
Authors: N. Tebbutt, T. Sourjina, A. Strickland, G. Van Hazel, V. Ganju, D. Gibbs, V. Gebski, S. Munro, M. Cummins
Journal: Journal of Clinical Oncology (2007)

4528 Background: Docetaxel (T), cisplatin (C) and 5FU(F) are active agents in esophago-gastric cancer. A recent phase III study evaluating 3-weekly TCF demonstrated a survival advantage over standard therapy, but TCF was associated with high rates of hematological toxicity (30% incidence of febrile neutropenia/neutropenic infection) as well as non-hematological side effects (Van Cutsem et al, J. Clin Oncol. 24 4991–4997 2006). Weekly docetaxel is associated with a lower incidence of hematological toxicity. This randomized phase II study aimed to test weekly docetaxel based combination chemotherapy regimens with the aim of maintaining the activity of such regimens but reducing toxicity. Methods: Eligibility included; histologically confirmed, metastatic esophageal or gastric (OG) carcinoma, measurable disease, PS0–2, adequate organ function, no prior treatment, informed consent. Patients (Pts) were randomized to receive weekly (w) T 30mg/m2 d1,8 C 60 mg/m2 d1 F 200 mg/m2/d continuously q 3w or wT 30 mg/m2 d1,d8 and capecitabine (X)1,600 mg/m2/d d1–14 q3w. The primary endpoint is confirmed response rate (RR), with each arm analyzed independently. Simon’s 2-stage design was used, with 5/21 responses required in the first stage to allow continuation to 50 pts per arm. Results: Response rates in each arm satisfied the first stage, and complete accrual of 106 pts was completed in May 2006. Demographics, toxicity and response rates are shown in the table . With a median follow-up of 14.6 months, progression free and overall survival times are 5.9 m and 12.8 m, and 4.2m and 10.1 m for wTCF and wTX, respectively. Conclusions: wTCF and wTX have encouraging activity and a far more favorable toxicity profile than TCF administered 3-weekly. Weekly docetaxel-based combination regimens should be evaluated further in this disease. [Table: see text] [Table: see text]
Abstract P175: Systolic Blood Pressure Trajectory Across Childhood to Adolescence Predicts Self-reported Htn in Adults: <i>I3c CV Outcomes Study</i>
Authors: Elaine M Urbina, Philip R Khoury, Tian Hu, Lydia A Bazzano, Trudy Burns, Terence Dwyer, Markus Juonala, Ronald J PRINEAS, Olli T Raitakari, Alan R Sinaiko, Julia STEINBERGER, Alison Venn, Jessica G WOO, David R Jacobs
Journal: Circulation (2020)

Levels of systolic blood pressure (SBP) in youth tend to predict adult SBP levels, but whether the trajectory of SBP over time predicts adult HTN is not known. In the International Childhood CV Cohort (i3C) Consortium, we constructed SBP trajectories in 9515 participants who had ≥2 SBPs in youth, and who reported HTN status (by questionnaire) at mean age 47 years. We used measured SBP from age 3-19 years to form trajectories using a mixed model with spline for age and random intercept and slope. The intercept and slope form personal trajectories during age 3-19 after removing the overall curve (spline) common to all participants. Trajectory groupings were formed by stratifying the intercept and slope by tertiles, forming 9 nearly equal sized groups, each having a consistent intercept and slope combination, among either a low, mid or high intercept and low (declining), mid (flat) or high (increasing) slope. The average SBP for all measurements in 6 age categories characterized the trajectories (Figure left panel). This characterization is reiterated using ages 3-11 and 12-19 years in the right panel which displays the adult HTN prevalence across the trajectories. Logistic models evaluated whether SBP trajectory group predicted adult HTN after adjustment for age and year at first childhood SBP measurement, age and BMI at adult HTN, smoking, sex, cohort, and race. Overall adult HTN prevalence was 30.9% increasing across SBP trajectories. All SBP trajectories compared to the highest intercept/slope group remained significant predictors of adult HTN even after adjustments (odds ratios 0.24 for lowest intercept/slope trajectory and 0.75 for highest intercept/intermediate slope trajectory both compared to highest intercept/highest slope, all P&lt;0.0001). We conclude that baseline (intercept) and slope of SBP changes from childhood to adolescence can assist providers in identifying potential for modifying the development of hypertension in adulthood.
Abstract P100: Improving Ideal Cardiovascular Health in a Pediatric Preventive Cardiology Practice
Authors: Holly C Gooding, Kimberlee Gauvreau, Jennifer Bachman, Annette Baker, Skylar Griggs, Jacob Hartz, YIsong Huang, Michael Mendelson, Hannah Palfrey, Sarah D De Ferranti
Journal: Circulation (2020)

Introduction: Achieving ideal cardiovascular health (iCVH) for children necessitates both public health and individual interventions. Hypothesis: We hypothesized that children referred to a multidisciplinary preventive cardiology clinic would demonstrate improved iCVH after clinic-based lifestyle counseling. Methods: We analyzed data from youth ages 8-19 years seen for ≥2 consecutive visits in the Boston Children’s Hospital Preventive Cardiology clinic between 2010-2017. Demographic information, smoking status, diet, and physical activity were self-reported. Anthropometric data, blood pressure, fasting cholesterol, and fasting glucose were measured using standard protocols. We applied AHA definitions of ideal, intermediate, and poor iCVH with minor adaptations to data extracted from a clinical registry. Each iCVH metric had a possible range of 0 (poor) to 2 (ideal); the total iCVH score could range from 0 (all poor) to 14 (all ideal). Results: Median age of the 767 children in the study was 12.5 years [IQR 10.2,15.9]; 414 (54%) were female and 32 (5%) had a moderate or high CVD risk condition (diabetes, renal disease, Kawasaki, congenital heart disease, or heart transplant). Over a median of 3.9 [IQR 3.2, 6.0] months from initial assessment to first follow-up, mean iCVH score improved from 7.7 (SD 2.2) to 8.1 (SD 2.2) (p &lt; 0.001). Females had higher iCVH scores at baseline and follow-up (females 7.9 to 8.4 vs. males 7.5 to 7.9, p&lt;0.001), as did children younger than 14 years of age (data not shown). iCVH score improved to a mean of 8.3 (SD 2.4) for the 449 children returning for a third visit. The largest improvement was observed in total cholesterol and dietary habits (Figure); only 61 (8%) of children were prescribed statin therapy. Conclusion: Multidisciplinary clinical care can improve the iCVH of children who present with non-optimal levels, largely without the use of medications. Further work is needed to determine the scalability and long-term effectiveness of cardiovascular health promotion efforts in pediatric care.
Abstract 54: Addressing Cardiovascular Health Using Artificial Intelligence: Randomized Clinical Trial to Increase Physical Activity in Cancer Survivors Using Intelligent Voice Assist (Amazon Alexa) for Patient Coaching
Authors: Ahmed Hassoon, Yasmin Baig, Daniel Naimann, David Celentano, Dina Lansey, Vered Stearns, Jennifer Schrack, Seth S Martin, Lawrence J Appel
Journal: Circulation (2020)

Importance: Physical Activity (PA) has numerous health benefits to cancer survivors, but motivation remains problematic. Coaching may increase PA and improve survivorship outcomes, but it is challenging to deliver personalized coaching at scale Objective: To determine if the use of a novel Artificial Intelligence (AI) agent delivered by smart speaker (Amazon Echo) increases PA among overweight or obese cancer survivors compared to autonomous SMS or standard health education publications Method: A single center 3-arm randomized clinical trial in Maryland, USA with 1:1:1 allocation. One-week base-line period followed by 4-week interventions. Participants were adult overweight or obese physically inactive cancer survivors (who completed their active treatments three or more months prior to the time of recruitment) with an emphasis on racial/ethnic minorities. Interventions were: (A) on-demand AI coaching using interactive digital voice assist on Amazon Echo; (B) autonomous data-driven text message via mobile phone; or (C) NCI health education materials about the benefit of PA for cancer survivors (Control). Outcome was the change in average steps per day from baseline to the end of follow-up Results: Of 90 candidates, 42 were enrolled and randomized (N=14 in each arm). 90.5% of the participants were female, 36% Black/African American, average age was 62.1(SD 9.8) years, with average BMI of 32.9(SD 5.0). The majority were breast cancer survivors (85.7%). No differences in baseline characteristics or baseline PA levels found between the groups. After 4-week intervention, only group (A) achieved significant gain in PA adding 3618.2 steps/day (95% CI: 2490.1 - 4764.2, P &lt;0.001). Group (A) also achieved significant net gain in PA compared to group (B) &amp; (C), table 1. Group (A) also peaked around 10k steps/day each week, figure 1. Conclusions: Using AI voice-assist may be a practical method to deliver scalable individualized behavioral health coaching to address cardiovascular health in cancer survivors.
Abstract P483: Living Arrangement Affects Urine Na/k Ratio Among 44,085 Residents: Tohoku Medical Megabank Project Community-based Cohort Study
Authors: Takahiro Mikami, Kozo Tanno, Ryouhei Sasaki, Nobuyuki Takanashi, Yuka Kotozaki, Mana Kogure, Atsushi Hozawa, Kiyomi Sakata, Makoto Sasaki
Journal: Circulation (2020)

Introduction: High dietary sodium-to-potassium (Na/K) ratio contributes to increased risk of cardiovascular disease (CVD) events. Previous studies on Japanese people suggested that women living in a multi-generational household (i.e., with spouse-children-parents; or spouse-parents) had a 2-3 fold higher risk of CVD events than women living with spouses only. However, few studies have examined the effect of living arrangement on urinary (U) Na/K. We clarified whether those living in a multi-generational household had higher UNa/K than those living with spouses only. Methods: We analyzed data of 44,085 residents (20-74 years), enrolled in the Tohoku Medical Megabank Project Community-based Cohort (TMM CommCohort) Study. UNa/K ratios were derived by dividing urinary Na levels (mEq/L) by urinary K levels (mEq/L) using spot urine samples. Participants were categorized into “living with spouse only”, “living with spouse and children”, “living with spouse and parents”, “living with parents and children”, “living with child only”, and “living with spouse, children and parents”. Using analysis of covariance, multivariate-adjusted geometric means of UNa/K ratios in each group were calculated by sex, with adjustments for other variables. Results: Those in a multi-generational household with spouse-children-parents had significantly higher multivariate-adjusted geometric means of UNa/K ratios in both sexes than those living with spouses. In male, those in a multi-generational household with spouse-childrenhad significantly higher multivariate-adjusted geometric means of UNa/K ratios than those living with spouses. In female those in a multi-generational household with spouse-parents or with children-parents had significantly higher multivariate-adjusted geometric means of UNa/K ratios than those living with spouses. Conclusions: This study suggests that those living in a multi-generational household have higher UNa/K ratios, which might contribute to an increased risk of CVD events.
Abstract 12342: LEGACY: Phase 2a Trial to Evaluate the Safety, Pharmacokinetics and Pharmacodynamic Effects of the Anti-Endothelial Lipase Antibody MEDI5884 in Subjects With Stable CAD
Authors: Christian T Ruff, Joe S Grimsby, Anton Rosenbaum, ChaoYu Jin, Lan-Feng Tsai, Sotirios Karathanasis, Judith Falloon, Tim Hummer, Xiao Tu, Judith A Hsia, Boaz Hirshberg, Michael J Koren, Marc S Sabatine
Journal: Circulation (2019)

Introduction: Even with marked lowering of LDL-C, patients with CAD remain at significant risk of CV events. Elevated HDL-C is one of the strongest epidemiologic surrogates for protection against C...
A regenerative peripheral nerve interface allows real-time control of an artificial hand in upper limb amputees
Authors: Philip P. Vu, Alex K. Vaskov, Zachary T. Irwin, Phillip T. Henning, Daniel R. Lueders, Ann T. Laidlaw, Alicia J. Davis, Chrono S. Nu, Deanna H. Gates, R. Brent Gillespie, Stephen W. P. Kemp, Theodore A. Kung, Cynthia A. Chestek, Paul S. Cederna
Journal: Science Translational Medicine (2020)

Peripheral nerves provide a promising source of motor control signals for neuroprosthetic devices. Unfortunately, the clinical utility of current peripheral nerve interfaces is limited by signal amplitude and stability. Here, we showed that the regenerative peripheral nerve interface (RPNI) serves as a biologically stable bioamplifier of efferent motor action potentials with long-term stability in upper limb amputees. Ultrasound assessments of RPNIs revealed prominent contractions during phantom finger flexion, confirming functional reinnervation of the RPNIs in two patients. The RPNIs in two additional patients produced electromyography signals with large signal-to-noise ratios. Using these RPNI signals, subjects successfully controlled a hand prosthesis in real-time up to 300 days without control algorithm recalibration. RPNIs show potential in enhancing prosthesis control for people with upper limb loss.