tbuckley/cabot-search huggingface dataset:
Abstract P1-05-11: Breaking “vicious cycle”? The role of miR-223 in breast cancer metastasis to bone
Authors: Zhen Shan, Wen Li, Ying Lin, Huijuan Zeng, Yunling Qi, Zefei Lin, Yuanjian Fan
Journal: Cancer Research (2020)

Abstract The “seed and soil” theory of metastasis was proposed by Stephen Paget in 1889. The theory suggests that bone acts as a fertile environment (soil) for cancer cells (seeds) colonization and growth. The theory successfully explains how bone and breast cancer cells interact to support breast cancer cell growth within the bone microenvironment.Breast cancer cells that metastasize to bone secrete growth factors and cytokines into the bone microenvironment that promote the production of receptor activator nuclear factor κ β ligand (RANKL), which, in turn, leads to osteoclast formation. The osteoclasts then cause bone resorption and the subsequent release of growth factors, include transforming growth factor-beta (TGF-β), bone morphogenetic proteins (BMPs), insulin-like growth factors (IGFs), fibroblast growth factors (FGFs), and platelet-derived growth factors (PDGF) into the bone microenvironment, which further stimulate the growth of breast cancer cells. Growth factors and cytokines produced by both breast cancer cells and bone cells result in a “vicious cycle” of bone breakdown: factors released from the bone promote breast cancer cell proliferation, which leads to more bone loss, and the subsequent release of more growth factors from the bone. The concept of the “vicious cycle” was proposed in 1997 by Mundy and Guise. Currently, the “vicious cycle” model provides the best description of our understanding of the interaction between breast cancer and bone. We found in miR-223 knockout mice, the bone volume of lowe limb bones is significantly lower than C57BL/6 mice (wild type), the osteoclastic resorption is more severe in miR-223 knockout mice according to H&amp;E sections. Then, we hypothesized miR-223 may inhibit osteoclast formation. In vitro study, We found miR-223 can suppress RANKL activating osteocalst formation by targeting NF1A protein. These results indicated miR-223 may disturb the establishment of osteolytic lesion, which may destroy the “soil” in bone microenvironment. Besides, we also found in miR-223 knockout mice, the IGF-1R is over expressed and the PI3K-Akt pathway was excessively activated. miR-223 up-regulation can inhibit MDA-231 cell proliferation but enhance apoptosis, which may destroy the “seed” in bone microenvironment. In conclusion, we hypothesized that miR-223 may break the “vicious cycle” and suppress breast cancer metastasis to bone. Citation Format: Zhen Shan, Wen Li, Ying Lin, Huijuan Zeng, Yunling Qi, Zefei Lin, Yuanjian Fan. Breaking “vicious cycle”? The role of miR-223 in breast cancer metastasis to bone [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-05-11.
Abstract P334: The Relationship Between Urinary Sodium-to-Potassium Ratio And High Blood Pressure: TMM CommCohort Study
Authors: Mana Kogure, Tomohiro Nakamura, Naho Tsuchiya, Takumi Hirata, Akira Narita, Naoki Nakaya, Masahiro Kikuya, Hirohito Metoki, Taku Obara, Kozo Tanno, Junichi Sugawara, Shinichi Kuriyama, Ichiro Tsuji, Shigeo Kure, Atsushi Hozawa
Journal: Circulation (2020)

Introduction: Recently, the balance between sodium and potassium intake, i.e. sodium-to-potassium (Na/K) ratio, has received significant attention for prevention of hypertension. Previous studies reported the positive association between urinary Na/K (uNa/K) ratio and hypertension. However, even the same uNa/K ratio value, there might be high Na/ high K ratio or low Na/ low K ratio. Hypothesis: We assessed the hypothesis that blood pressure (BP) is higher in high Na/ high K group than that in low Na/ low K group even at the same uNa/K ratio in general population in cross-sectional study. Methods: The subjects were 20 to 74 years old who participated in The Tohoku Medical Megabank Project Community-based Cohort Study. Of these participants, we targeted 54,011 subjects (men: 20,505 women: 33,506 mean age: 59.9 years) who had information of BP, urinary Na and K. We estimated 24-h urinary excretion of Na and K using Tanaka formula. Urinary Na and K were each classified into quartiles (Na; Q1~Q4, K; Q1~Q4), and set all 16 groups of uNa/K ratio by combining Na and K respectively. To assess the relationship between casual uNa/K ratio and BP, we performed an analysis of covariance to calculate the adjusted mean systolic BP (SBP). We included covariate factors as age, sex, BMI and alcohol intake. We also assessed the relationship between uNa/K ratio and SBP using multiple regression analyses adjusted for covariate factors. We stratified the participants into two groups: ‘under treatment for hypertension’ (n=17,091) and ‘without treatment for hypertension (n=36,920)’. Results: The mean of uNa/K ratio for each group of Na (Q1)/K(Q1), Na (Q2)/K(Q2), Na (Q3)/K(Q3) and Na (Q4)/K(Q4) was all 4.0. As previous report showed, higher uNa/K ratio group showed higher SBP and lower uNa/K group showed lower BP. When we compared adjusted mean SBP of Na (Q1)/K(Q1) and Na (Q4)/K(Q4) the value were comparable, but the value were significantly higher in Na (Q4)/K(Q4) group (The adjusted mean SBP of Na (Q1)/K(Q1), Na (Q2)/K(Q2), Na (Q3)/K(Q3) and Na (Q4)/K(Q4) was 123.6, 124.9, 124.7 and 125.5 mmHg, respectively). The uNa/K was significantly positively associated with SBP independently of age, sex, BMI, and alcohol intake. The finding was unchanged the results in under treatment group. Conclusions: BP was significantly higher in high Na/ high K group than in low Na/ low K group even at the same uNa/K ratio. We suggested that not only increasing K intake but also reducing salt is important for preventing hypertension.
First cases of coronavirus disease 2019 (COVID-19) in the WHO European Region, 24 January to 21 February 2020
Authors: Gianfranco Spiteri, James Fielding, Michaela Diercke, Christine Campese, Vincent Enouf, Alexandre Gaymard, Antonino Bella, Paola Sognamiglio, Maria José Sierra Moros, Antonio Nicolau Riutort, Yulia V. Demina, Romain Mahieu, Markku Broas, Malin Bengnér, Silke Buda, Julia Schilling, Laurent Filleul, Agnès Lepoutre, Christine Saura, Alexandra Mailles, Daniel Levy-Bruhl, Bruno Coignard, Sibylle Bernard-Stoecklin, Sylvie Behillil, Sylvie van der Werf, Martine Valette, Bruno Lina, Flavia Riccardo, Emanuele Nicastri, Inmaculada Casas, Amparo Larrauri, Magdalena Salom Castell, Francisco Pozo, Rinat A. Maksyutov, Charlotte Martin, Marc Van Ranst, Nathalie Bossuyt, Lotta Siira, Jussi Sane, Karin Tegmark-Wisell, Maria Palmérus, Eeva K. Broberg, Julien Beauté, Pernille Jorgensen, Nick Bundle, Dmitriy Pereyaslov, Cornelia Adlhoch, Jukka Pukkila, Richard Pebody, Sonja Olsen, Bruno Christian Ciancio
Journal: Eurosurveillance (2020)

In the WHO European Region, COVID-19 surveillance was implemented 27 January 2020. We detail the first European cases. As at 21 February, nine European countries reported 47 cases. Among 38 cases studied, 21 were linked to two clusters in Germany and France, 14 were infected in China. Median case age was 42 years; 25 were male. Late detection of the clusters’ index cases delayed isolation of further local cases. As at 5 March, there were 4,250 cases.
Chemotherapy in gallbladder cancer: Improving survival
Authors: J. Gallardo, B. Rubio, M. Ahumada, L. Villanueva, O. Barajas
Journal: Journal of Clinical Oncology (2007)

15140 Background: Since 1999 we had been studying the effect of chemotherapy in gallbladder cancer, a disease frequent in low economical income area of the world, orphan of research, traditionally considered chemotherapy-resistant. Previous studies included 5- FU regimen and communicated response rate of 10–26 %, and no changes on survival. We first conducted a phase II study with gemcitabine (Gem), and later, another study (with support of GOCCHI) using Gem and cisplatin (C). Since 2001 we had treated patients out of clinical trial. We compare median survival observed in all series. Methods: Patients file of both 2 phase II studies and clinical record of all patients treated out of clinical trial were retrieved and median survival was calculated. The both phase two trials had a similar population, and inclusion criteria, both were multicenters. The third cohort is a one center experience. The regimens used were: Gem 1,000 mg/m 2 on days 1,8 and 15 every 28 days (first trial), Gem 1,250 mg/m 2 +C 35 mg/m 2 on the 1 and 8 days every 21 days (second trial), only maximum 6 courses were planned. The third group, most frequently, received Gem 1.000 mg/m 2 (10mg/m 2 /min)+C 40 mg/m 2 days 1 and 8 every 21 days, until disease progression and/or toxicity; second line chemotherapy was allowed. Among whole group 7 pts, who had significant response, underwent a surgical resection. Survival was also calculated and comparison is included. The toxicity was evaluated every 2 weeks and response was assessed every two cycles using CT scan. Overall survival was calculated from beginning of chemotherapy until death or last follow up. Survival analysis was also done using Kaplan Meier’s tables Results: For Gem monotherapy (26 pts) median survival was 30 weeks, for Gem+C (44 pts) median survival was 28 weeks. For third group (29 pts) median survival was 56 weeks. Until now, for the 7 pts who underwent a surgical resection median survival is 92 weeks, with one pt alive, without evidence of disease, at 112 weeks of follow up Conclusions: Both regimens showed better efficacy than 5-FU based chemotherapy, the combination did not show better survival. The third group has better median survival, probable due to the use of second line therapies. Combining chemotherapy + surgical resection may be a better treatment for some few, well selected patients. No significant financial relationships to disclose.
Phase I study of amrubicin (AMR) for patients (pts) with previously treated small cell lung cancer (SCLC)
Authors: N. Katakami, A. Hata, H. Yoshioka, Y. Higashi, T. Nishimura, S. Sakaguchi, M. Hayashi, K. Tomii, R. Naya, K. Ishihara
Journal: Journal of Clinical Oncology (2007)

18209 Background: Amrubicin, a totally synthetic 9-amino-anthracycline, has been demonstrated to have excellent antitumor activity against previously untreated SCLC. However, severe hematological toxicities were observed in previously treated SCLC when given at doses of 40 to 45 mg/m 2 , days 1–3. We sought to determine the maximum tolerable dose (MTD) and toxicity of amrubicin for pts with previously treated SCLC. Methods: Pts with confirmed SCLC, ECOG PS 0–1, and 20 to 74 years of age, with a history of receiving one or two regimens were eligible for the study. Pts were divided into two groups. Group R (-) consisted of pts without history of radiotherapy except prophylactic cranial irradiation. Group R (+) consisted of pts with history of irradiation up to two fields including thoracic radiotherapy. AMR was initially given at 35 mg/m 2 , iv, days 1–3, every 3 weeks in both groups. The dose was then increased to 40 and 45 mg/m 2 . Three pts were treated at each dose level in the absence of a dose limiting toxicity (DLT). All pts received prophylactic hG- CSF between days 8–13. DLT was defined as neutrophil nadir &lt;500/μL lasting more than 4 days, neutropenic fever and neutrophil nadir &lt;1000/μL, platelet nadir &lt;20,000/μL or ≥ grade 3 non-hematologic toxicities. Results: Fourteen pts were enrolled, 10m/4f. The median age was 62 years (range 34–82). Two of 6 pts in the first cohort in group R (-) had dose-limiting neutropenia. The dose escalation is ongoing. Three pts in the first cohort in group R (+) had no dose-limiting toxicities. A subsequent 5 pts were treated at dose-level 2, and 3 pts had dose-limiting neutropenia. The MTD in group R (+) was 40 mg/m 2 . A response rate of 62% was observed. Median survival time was 12 months. No treatment-related death was observed. Conclusions: The MTD in group R (-) was not determined. The MTD in group R (+) was determined as 40 mg/m 2 . Further data will be presented. No significant financial relationships to disclose.
Serum free light chain level at diagnosis in myeloma cast nephropathy—a multicentre study
Authors: Punit Yadav, Insara Jaffer Sathick, Nelson Leung, Elizabeth E. Brown, Mark Cook, Paul W. Sanders, Paul Cockwell
Journal: Blood Cancer Journal (2020)

Abstract Myeloma cast nephropathy (MCN) is a common cause of severe renal impairment in multiple myeloma (MM). The level of free light chain (FLC) that causes MCN varies substantially and there is uncertainty about the threshold level that should be used to inform clinical practice. In a multicentre cohort study of 103 patients with a diagnosis of MM and biopsy-confirmed MCN made between 2002–2014, we report prospectively measured levels of serum FLC at diagnosis obtained using a single nephelometric assay (Freelite®) and we explore the relationship between serum FLC level at diagnosis with renal outcome and patient survival. Using a landmark approach, overall survival (OS) was compared between patients who achieved independence from dialysis compared to those who remained dialysis dependent at 3-month, 6-month, 9-month, and 12-month time points. The median serum FLC level at diagnosis was 7531 mg/L (range 107–114600). Serum creatinine was 535 μmol/L (range 168–2993) and eGFR 7 ml/min/1.73 m 2 (range 1–34). Six patients (5.8%) had an FLC level &lt;1500 mg/L, which is the International Myeloma Working Group threshold for MCN and two patients were below the International Kidney and Monoclonal Gammopathy working group threshold of 500 mg/L; one was hypercalcaemic, and one had high-normal serum calcium level and had received a non-steroidal anti-inflammatory agent. Sixty-nine (67%) patients required haemodialysis treatment of whom 36 (52.1%) recovered independent renal function. Sixty-six (64%) patients died with a median OS of 2.5 years (95% CI 1.8–3.3). A landmark analysis revealed that independence from dialysis was associated with improved survival at 3-months ( P = 0.003), 6-months ( P = 0.035) and 9-months ( P = 0.014); there was no survival benefit observed beyond 12 months ( P = 0.146). Serum FLC level at diagnosis was neither associated with renal function recovery nor with OS. This is the largest reported cohort of patients with biopsy-confirmed MCN and prospectively measured serum FLC levels. These results indicate that a serum monoclonal FLC &gt; 500 mg/L should be considered the threshold level associated with the development of MCN.
Preoperative diagnosis of malignant pulmonary nodules in lung cancer screening with a radiomics nomogram
Authors: Ailing Liu, Zhiheng Wang, Yachao Yang, Jingtao Wang, Xiaoyu Dai, Lijie Wang, Yuan Lu, Fuzhong Xue
Journal: Cancer Communications (2020)

Abstract Background Lung cancer is the most commonly diagnosed cancer worldwide. Its survival rate can be significantly improved by early screening. Biomarkers based on radiomics features have been found to provide important physiological information on tumors and considered as having the potential to be used in the early screening of lung cancer. In this study, we aim to establish a radiomics model and develop a tool to improve the discrimination between benign and malignant pulmonary nodules. Methods A retrospective study was conducted on 875 patients with benign or malignant pulmonary nodules who underwent computed tomography (CT) examinations between June 2013 and June 2018. We assigned 612 patients to a training cohort and 263 patients to a validation cohort. Radiomics features were extracted from the CT images of each patient. Least absolute shrinkage and selection operator (LASSO) was used for radiomics feature selection and radiomics score calculation. Multivariate logistic regression analysis was used to develop a classification model and radiomics nomogram. Radiomics score and clinical variables were used to distinguish benign and malignant pulmonary nodules in logistic model. The performance of the radiomics nomogram was evaluated by the area under the curve (AUC), calibration curve and Hosmer‐Lemeshow test in both the training and validation cohorts. Results A radiomics score was built and consisted of 20 features selected by LASSO from 1288 radiomics features in the training cohort. The multivariate logistic model and radiomics nomogram were constructed using the radiomics score and patients’ age. Good discrimination of benign and malignant pulmonary nodules was obtained from the training cohort (AUC, 0.836; 95% confidence interval [CI]: 0.793‐0.879) and validation cohort (AUC, 0.809; 95% CI: 0.745‐0.872). The Hosmer‐Lemeshow test also showed good performance for the logistic regression model in the training cohort ( P = 0.765) and validation cohort ( P = 0.064). Good alignment with the calibration curve indicated the good performance of the nomogram. Conclusions The established radiomics nomogram is a noninvasive preoperative prediction tool for malignant pulmonary nodule diagnosis. Validation revealed that this nomogram exhibited excellent discrimination and calibration capacities, suggesting its clinical utility in the early screening of lung cancer.
Abstract P480: The Distinct Role of Occupational Therapy in Addressing the Self-care Management Needs of Patients With Heart Failure
Authors: Amber Bennett, Kristin Nxumalo, Whitney Pike, Olivia Carroll
Journal: Circulation (2020)

Introduction: Hospitalizations for heart failure (HF) are the highest single Medicare expenditure. This cost primarily results from readmissions linked to failed self-care. Evidence suggests that effective self-care routines are equivalent to medication in preventing HF exacerbation and hospitalization. Occupational therapists (OT) are well suited to address HF self-care needs by facilitating self-efficacy and adapting patients’ routines, roles and habits. A recent study determined that OT is the only hospital spending category associated with lower HF readmission rates. Hypothesis: Occupational therapy has a significant role in addressing the self-care management needs of patients with HF throughout the continuum of care. Methods: The OT department launched a HF self-care management program as part of process improvement initiatives at an AHA-recognized teaching hospital. An assessment battery was developed which included the following: The Self-Care of Heart Failure Index (SCHFI) v.6.2, Minnesota Living With Heart Failure Questionnaire, Patient Health Questionnaire-9, and the Montreal Cognitive Assessment. Administration of the OT HF assessment battery to a pilot group of 12 inpatients revealed factors that affect patient adoption and adherence to beneficial self-care management routines. Based on assessment battery data, an outpatient OT program was established. Eleven outpatients were enrolled and completed 3-6 hours of OT treatment. The SCHFI was administered at program evaluation and completion to measure self-care maintenance and confidence. To expand service access, a telehealth self-care program was introduced and a single patient case study was assessed to determine the feasibility and effectiveness of the virtual format. Results: Assessment battery data enabled the development of outpatient treatment modules focusing on symptom monitoring, medication management, low sodium diet, activity tolerance and psychosocial strategies. All outpatients who completed the modules demonstrated improved self-care maintenance (ranging from 16-53 points) and half demonstrated improved self-care confidence (ranging from 6-39 points). The patient assessed after completing the telehealth program demonstrated improved self-care maintenance (70 points) and self-care confidence (28 points). Conclusions: In conclusion, OT has a significant role in addressing the self-care management needs of patients with HF throughout the continuum of care. The utilization of a standardized OT HF assessment battery is effective in determining the needs of this population and for guiding the implementation of targeted individualized treatment. Outpatient and telehealth delivery of OT programming is effective in improving self-care for people with HF.
Abstract MP47: Genome-wide Gene-leptin Interaction Study Identifies Loci Contributing to Leptin Resistance
Authors: Luqi Shen, Ruiyuan Zhang, José Cordero, Jia-Sheng Wang, Ye Shen, Lei Lou, Zhong-Ru Xie, Hang Yin, Yanling Qi, Lirong Liang, Changwei Li
Journal: Circulation (2020)

Background: In a preliminary candidate genes study, we robustly identified that the nicotinic acetylcholine receptor genes modified obesity’s sensitivity to leptin. However, the finding only explained a small proportion of the heritability of leptin resistance. Therefore, the current study expanded our preliminary work to the entire human genome to identify additional novel mechanisms of leptin resistance in humans. Methods: Discovery stage analyses were conducted among 3,838 White participants of the Framingham Heart Study (FHS) 3 rd generation. SNPs contributing to leptin resistance were identified by examining interactions between the SNPs and leptin on body mass index (BMI) and waist circumference (WC), controlling for age, gender, and the first 3 genetic principal components. Gene-based analyses were conducted by combining SNP-based p values using the GATES method. Promising SNPs ( P &lt;1х10 -6 ) and genes ( P &lt;1х10 -4 ) of the FHS were further evaluated for replication among 667 White participants of the Multi-Ethnic Study of Atherosclerosis (MESA) study. Analysis results of the FHS and MESA were combined using inverse-variance-weighted meta-analysis method for SNPs and Fisher’s method for genes. Genomic control was applied before meta-analysis. Results: Single SNP-based analyses identified that PCTP rs78580870, 17:53899497 (FHS P =1.90х10 -8 , MESA P =0.01, Meta P =8.23х10 -10 ) interacted with leptin on BMI. Gene-based analyses robustly identified 4 genes interacting with leptin on WC, including MED9 (FHS P =5.60х10 -6 , MESA P =1.79х10 -3 , Meta P =1.95х10 -7 ) at 17p11.2, RASD1 (FHS P =3.92х10 -6 , FHS P =1.33х10 -3 , Meta P =1.05х10 -7 ) at 17p11.2, DTX3 (FHS P =5.27х10 -7 , MESA P =3.57х10 -2 , Meta P =3.53х10 -7 ) at 12q13.3, and ARHGEF25 (FHS P =7.55х10 -7 , MESA P =4.96х10 -2 , Meta P =6.79х10 -7 ) at 12q13.3. These 4 genes have related biological functions of leptin or obesity. Conclusion: We identified 1 novel genomic locus and 4 novel genes explaining leptin resistance among White. Future large scale genomic studies of leptin resistance among multiple ethnic groups are warranted.
Short-Term Consumption of Sucralose with, but Not without, Carbohydrate Impairs Neural and Metabolic Sensitivity to Sugar in Humans
Authors: Jelle R. Dalenberg, Barkha P. Patel, Raphael Denis, Maria G. Veldhuizen, Yuko Nakamura, Petra C. Vinke, Serge Luquet, Dana M. Small
Journal: Cell Metabolism (2020)