tbuckley/cabot-search huggingface dataset:
Abstract P241: Psychosocial Profiles and Cardiovascular Disease Risk Factor Control: The Coronary Artery Risk Development in Young Adults (cardia) Study
Authors: Emily A Vargas, Kiarri N Kershaw, Mercedes R Carnethon, Diana Chirinos, Allison J Carroll, Catarina I KIEFE, April P Carson, Mandy Wong
Journal: Circulation (2020)

Introduction: Psychosocial factors are associated with the onset of chronic disease, however few studies have examined the association between these factors and cardiovascular disease risk factor (CVDRF) control over time in individuals who already have a chronic disease. Thus, the goal of this study was to evaluate associations of psychosocial factors with a composite measure of CVDRF control. Methods: This study includes 1,018 CARDIA participants (51.6% Black; 41.6% Male) with prevalent hypertension (n = 604), hypercholesterolemia (n = 636), and/or diabetes (n = 210) in 2000-2001 (Year 15 follow-up exam). Latent Profile Analysis (LPA) was used to identify distinct psychosocial profiles based on a combination of personality, social life, and psychological health factors (Table). We used generalized estimating equations to determine associations of the psychosocial profiles with composite control, defined as HbA1c &lt; 7.0%, systolic blood pressure (SBP) &lt; 140 mm Hg, and LDL-cholesterol &lt; 100 mm/dl, all measured in 2005-2016. Results: The LPA revealed an optimal model of three psychosocial profile groups (AIC 87,467.545; entropy = .895) namely “Healthy”, “Depressed Mood” and “Discriminated Against”. There were no significant differences in composite control across the profiles. Looking at HbA1C, SBP, and LDL separately in the unadjusted models, we found participants in the Depressed and Discriminated Against profiles were less likely to meet guidelines for SBP compared to individuals in the Healthy profile. Participants in the Discriminated profile were significantly less likely to meet the guidelines for HbA1C levels compared to the Healthy profile. These associations were attenuated with adjustment for sociodemographic covariates. Conclusions: Psychosocial profiles were associated with CVDRF control in unadjusted models, but not independent of socio-demographic characteristics.
Molecular profiling of lineage-related androgen-sensitive (LNCaP) and insensitive (C4-2) prostate cancer cell lines
Authors: Qian Chen, Jeffery T. Watson, William N. Brennen, Susan R. Marengo, Delisha A. Stewart, Robert C. Kelly, Keith S. Decker, Peter S. Nelson, Robert A. Sikes
Journal: Cancer Research (2004)

1659  As prostate cancer (PCa) progresses it becomes increasingly more metastatic and ultimately independent of the normal growth and differentiation controls imposed by androgens. Given the hypothesis that gene expression changes account for changes in tumor cell behavior, we used the LNCaP human prostate cancer progression model cell lines, to perform microarray analysis on the differences in gene expression between the poorly tumorigenic, androgen sensitive LNCaP cells and the highly tumorigenic, spontaneously metastatic in vivo-derived variant, C4-2. Our microarrays were performed on the prostatome, or prostate expressed genome, as defined at the Prostate Expression Database (http://www.pedb.org/). This cDNA microarray contains 6388 nonredundant cDNAs or ESTs. LNCaP or C4-2 cells were plated at 2 x 10e6 cells per 60 mm dish in 5% FBS and allowed recover overnight. The media was changed the next day to serum and phenol red free RPMI 1640. The cells were grown for 24 hours before isolation of RNA. This was repeated 4 times for each cell line. The RNAs were reverse transcribed and labeled with Cy3 or Cy5 for dye swap experiments. Hybridization to tandem spotted chips was performed on duplicate chips with the corresponding dye swap. Pooled RNA from LNCaP, DU-145 and PC-3 PCa cells was used as a driver. This yielded 16 hybridization data points for each cell line. Statistical analysis of the microarray data was performed using BRB microarray tools and SAM. Sequences having expression differences above the 95% CI from both lists were pooled. This yielded 51 sequences, 20 of which were down regulated from LNCaP to C4-2 and 31 that were up regulated. Twelve genes from this list of statistically valid changes were chosen for validation based on the predicted genetic function and the level of expression difference. We have used both conventional RT-PCR and Q-RT-PCR to validate the microarray results. Of the 12 genes, 11 have been successfully validated, 7 of which (63.6%) followed the direction of gene expression change observed in our microarray results. They include TMEFF2, IL8, BChE, NKX3.1 (these are higher in LNCaP than in C4-2); TM4SF1, AMACR, UCHL1 (these are higher in C4-2 than in LNCaP). Recent publications have confirmed these results in prostate cancer for Nkx-3.1 and TMEFF2. Western blot analysis and immunohistochemistry is underway to confirm expression profiles at the protein level. Further studies are warranted based on these results to determine if these genes are useful diagnostic targets or contribute to PCa progression.
Preliminary results of a multicenter phase II trial of vinflunine (with trastuzumab in HER2+ pts) as first-line treatment in metastatic breast cancer
Authors: N. W. Peacock, D. R. Spigel, M. G. Mainwaring, D. S. Thompson, L. Simons, M. S. Rubin, M. McCleod, W. N. Harwin, F. J. Schreiber, D. A. Yardley
Journal: Journal of Clinical Oncology (2007)

1043 Background: Vinflunine (VFL) is a new and innovative microtubule inhibitor of the vinca alkaloid class that achieves high intracellular concentrations. By inhibition of tubulin polymerization, cell proliferation is arrested leading to apoptotic death. Demonstrating anti- angiogenic and vascular disrupting activities, VFL has demonstrated significant efficacy as 2 nd line chemotherapy in MBC (M. Campone, BJC 2006). This trial was designed to evaluate the response rate and safety of VFL as 1st line therapy in MBC as well as its activity in combination with trastuzumab in HER2+ MBC pts. Methods: Eligibility: 0 prior regimens for MBC, &gt; 6 mo from adjuvant therapy, RECIST measurable disease, ECOG PS 0–2, adequate organ function, &lt; G2 neuropathy. Treatment: 320 mg/m 2 IV over 20 minutes q3 weeks; 280 mg/m 2 with trastuzumab 6 mg/kg q3 weeks in HER2+ pts. Response evaluations q9 weeks; treatment continued until progression or toxicity. A total of 96 pts will be enrolled, 48 pts per each of 2 cohorts, HER2- and HER2+. Results: 18 pts are enrolled, 13 pts evaluable for toxicity and 12 pts for response. 3 pts received VFL monotherapy and 10 pts were treated with VFL + trastuzumab. Median age: 59 years (43–78). ECOG PS 0: 9 pts, 1: 3 pts, 2: 1 pt. Prior adjuvant chemo: 7 pts (54%), with 5 prior anthracyclines and 6 prior taxanes. 2 pts received adjuvant hormonal therapy only. 4 pts presented with de novo stage IV HER2+ MBC. Metastatic disease sites: liver: 6 pts, lung: 7 pts, bone: 5 pts, lymph nodes: 6 pts. 46% had 3 or more sites of organ involvement. Median of 3 cycles (range:1 - 11) was delivered. 7 pts (58%, all HER2+) had a PR and 4 pts (33%) achieved SD. Only 1 pt progressed. Heme toxicity: G3/4 neutropenia: 2 pts (16%); no febrile neutropenia was noted. G3 non-heme toxicity consisted of N/V: 2 pts and myalgia, 2 pts. There were no G4 events. 4 pts were hospitalized (vomiting: 2, cerebro-vascular accident: 1, back pain: 1 pt). 92% of pts remain free of progression at 6 months. Median TTP has not been reached. Conclusions: Vinflunine is a promising new drug with a high level of activity as first line MBC therapy, especially in combination with trastuzumab. VFL is well tolerated in this patient population with a manageable toxicity profile. Accrual to this trial continues. [Table: see text]
Abstract P130: Risk Factors for Progression to Type 2 Diabetes Mellitus From Prediabetes
Authors: Margareta Hellgren, Ulf Lindblad, Bledar Daka
Journal: Circulation (2020)

Background and Aims: Individuals with prediabetes, impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT), have approximately 50% risk to develop type 2 diabetes mellitus (T2DM) within ten years. This paper examines risk factors for development of T2DM in individuals with prediabetes. Materials and Methods: A total of 2816 individuals were randomly selected and completed a careful physical examination and an oral glucose tolerance test. IFG and IGT was defined according to WHO. A representative sample of 1327 individuals were re-examined in a follow-up study after ten years. This study focuses on the participants who were diagnosed with prediabetes, IFG (n=67) and/or IGT (n=89) at baseline and who were re-examined at follow-up. Insulin resistance was estimated by HOMA-ir (Homeostatic Model Assessment for Insulin Resistance). Differences between the participants with prediabetes who developed T2DM and those who did not, were analyzed with general linear models and adjusted for age, sex and BMI. The risk to progress to T2DM in ten years was explored using binary logistic regression, adding the risk-factors one after another. Results: Of the 156 individuals with prediabetes 28% progressed to T2DM. Individuals who developed T2DM had higher BMI (α=3.2kg/m 2 , P&lt;0.001), higher HbA1c (α=0.2 mmol/mol, P=0.047), higher C-reactive protein (α=3.3 mmol/L, P=0.040) and also significantly higher HOMAir (α=2.8, P&lt;0.001) at base-line. The risk to develop T2DM increased in a step-wise manner in individuals with prediabetes when successively adding the risk-factors. Having a BMI ≥30kg/m 2 , a known family history for T2DM, HbA1c ≥37mmol/mol, HOMAir ≥2.8 and a low level of physical activity increased the risk to develop T2DM 5.6 times. Table 1. Conclusion: In individuals with prediabetes, those with additional risk-factors like obesity, HbA1c and HOMAir above mean values, family history for T2DM and a low level of physical activity require extra attention and intensive lifestyle interventions should be initiated.
Clinical features of COVID-19 in elderly patients: A comparison with young and middle-aged patients
Authors: Kai Liu, Ying Chen, Ruzheng Lin, Kunyuan Han
Journal: Journal of Infection (2020)

Due to the general susceptibility of new coronaviruses, the clinical characteristics and outcomes of elderly and young patients may be different.To analyze the clinical characteristics of elderly patients with 2019 new-type coronavirus pneumonia (COVID-19).This is a retrospective study of patients with new coronavirus pneumonia (COVID-19) who were hospitalized in Hainan Provincial People's Hospital from January 15, 2020 to February 18, 2020. Compare the clinical characteristics of elderly with Young and Middle-aged patients.A total of 56 patients were enrolled 18 elderly patients (32.14%), and 38 young and middle-aged patients (67.86%). The most common symptoms in both groups were fever, followed by cough and sputum. Four patients in the elderly group received negative pressure ICU for mechanical ventilation, and five patients in the young and middle-aged group. One patient died in the elderly group (5.56%), and two patients died in the young and middle-aged group (5.26%). The PSI score of the elderly group was higher than that of the young and middle-aged group (P < 0.001). The proportion of patients with PSI grades IV and V was significantly higher in the elderly group than in the young and middle-aged group (P < 0.05). The proportion of multiple lobe involvement in the elderly group was higher than that in the young and middle-aged group (P < 0.001), and there was no difference in single lobe lesions between the two groups. The proportion of lymphocytes in the elderly group was significantly lower than that in the young and middle-aged group (P < 0.001), and the C-reactive protein was significantly higher in the young group (P < 0.001). The Lopinavir and Ritonavir Tablets, Chinese medicine, oxygen therapy, and mechanical ventilation were statistically different in the elderly group and the young and middle-aged group, and the P values were all <0.05.The mortality of elderly patients with COVID-19 is higher than that of young and middle-aged patients, and the proportion of patients with PSI grade IV and V is significantly higher than that of young and middle-aged patients. Elderly patients with COVID-19 are more likely to progress to severe disease.
De-implementation strategy to reduce inappropriate use of intravenous and urinary catheters (RICAT): a multicentre, prospective, interrupted time-series and before and after study
Authors: Bart J Laan, Jolanda M Maaskant, Ingrid J B Spijkerman, Marjon J Borgert, Mieke H Godfried, Berend C Pasmooij, Brent C Opmeer, Margreet C Vos, Suzanne E Geerlings
Journal: The Lancet Infectious Diseases (2020)
Abstract MP60: Do Adults With Metabolic Healthy Obesity Maintain Their Health Over Time? Results From The Atherosclerosis Risk In Communities (ARIC) Study
Authors: Yvonne Commodore-Mensah, Chiadi E Ndumele, Justin B Echouffo Tcheugui, Dan Wang, Elizabeth Selvin
Journal: Circulation (2020)

Background: Obesity is a heterogeneous condition, and there is debate about whether adults with “metabolically healthy obesity” (MHO) are protected from health complications. It is also unclear if MHO is a transient state. Objective: To examine transition from the MHO to metabolically unhealthy obese (MUO) phenotype during 6 years of follow-up among middle-aged adults. Methods: We conducted a prospective analysis of 9,672 adults in the ARIC Study who were free of cardiovascular disease (CVD) at Visit 2 (1990-1992) and attended Visit 4 (1996-1998). Obesity phenotypes were cross-classified using two body mass index subgroups 18.5-29.9 kg/m 2 (non-obese) and ≥ 30 kg/m 2 (obese). The NCEP Adult Treatment Panel III criteria were used to define metabolic health (without waist circumference). We used logistic regression to evaluate risk factors for transition from MHO at Visit 2 to MUO at Visit 4 among those with MHO at Visit 2(N=692). Results: At baseline (mean age 57, 21% black, 57% female), 18%, 54%, 7%, and 21% were metabolically healthy non-obese, metabolically unhealthy non-obese, MHO, and MUO, respectively. More adults with the MHO phenotype transitioned to MUO (48.3%) than maintained MHO status (43.4%) during the 6-year period). Most (71%) of those who transitioned from MHO to MUO were women. Adults with higher waist-to-hip ratio were more likely to transition to MUO (HR 2.67, 95% CI 1.09-6.58) than those who maintained their metabolic health during follow-up. (Table) . Conclusions: Almost 50% of adults who are MHO will transition to higher cardiometabolic risk over 6 years. High waist-to-hip ratio, lower socioeconomic status and smoking were linked to greater likelihood of transition to MUO. Persons with MHO should receive early behavioral interventions to prevent worsening metabolic health.
Characteristics of Hodgkin lymphoma in Hispanics compared to other ethnic groups
Authors: S. Ofori-Ntow, B. Ciobanu, M. Telfer, A. Jajeh, P. Kovarik, S. Nathan, R. Kouz, D. S. Griza, R. Catchatourian
Journal: Journal of Clinical Oncology (2007)

18510 Background: There is scant literature on the characteristics of Hodgkin’s disease in Hispanics. We studied the characteristics of this disease in Hispanics compared to other ethnic-racial groups in our large multiethnic Hodgkin’s disease caseload. Methods: A retrospective analysis of all the Hodgkin’s disease cases diagnosed between 2003 and 2006 was undertaken, using Fisher exact test. Results: Of 289 cases of lymphoma diagnosed, 65 (23%) were Hodgkin’s disease compared to SEER data of 11%; Hispanics 40%, African Americans (AA) 41%, Caucasians 19%. Median age at diagnosis: Hispanics 26, AA 27, Caucasians 38. Among the AA: 85% were men 15% women, Hispanics: 58% men 42% women, Caucasians: 33% men, 67% women (p value 0.004). Histological subtypes: Nodular sclerosis 82 % (58): AA 45%, Hispanics 34%, Caucasians 21%; Mixed cellularity 21% (8): Hispanics 75%, AA 12.5%, Caucasians12.5% (p value 0.079). Among Hispanics 62% were clinical stage 1 or 2, 38% stage 3 or 4; Caucasians 75% stage 1 or 2, 25% stage 3 or 4; AA 33% stage 1 or 2 and 66% stage 3 or 4 (p value 0.029). Among the 16 patients with limited stage disease 50% were Hispanics, 25% Caucasians and 25% AA. Of the 49 patients with advanced stage disease, 70% of the Hispanics had IPS Score 0–3, 30% had Score 4–7. Among the AA, 70% had IPS Score 0–3, 30% Score 4–7, while 33% of the Caucasians had IPS Score 0–3, 67% had Score 4–7 (p value 0.077). Conclusions: Mixed cellularity subtype is more common in the Hispanics while the nodular sclerosis subtype is relatively common in African Americans. Hispanics had early clinical and limited stage disease at diagnosis. Among the patients with advance stage disease, Caucasians had a higher IPS Score than the Hispanics. The clinical relevance of these observations remains to be determined with further studies. No significant financial relationships to disclose.
Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018
Authors: Olivier J. Wouters, Martin McKee, Jeroen Luyten
Journal: JAMA (2020)

Importance The mean cost of developing a new drug has been the subject of debate, with recent estimates ranging from $314 million to $2.8 billion. Objective To estimate the research and development investment required to bring a new therapeutic agent to market, using publicly available data. Design and Setting Data were analyzed on new therapeutic agents approved by the US Food and Drug Administration (FDA) between 2009 and 2018 to estimate the research and development expenditure required to bring a new medicine to market. Data were accessed from the US Securities and Exchange Commission, Drugs@FDA database, and ClinicalTrials.gov, alongside published data on clinical trial success rates. Exposures Conduct of preclinical and clinical studies of new therapeutic agents. Main Outcomes and Measures Median and mean research and development spending on new therapeutic agents approved by the FDA, capitalized at a real cost of capital rate (the required rate of return for an investor) of 10.5% per year, with bootstrapped CIs. All amounts were reported in 2018 US dollars. Results The FDA approved 355 new drugs and biologics over the study period. Research and development expenditures were available for 63 (18%) products, developed by 47 different companies. After accounting for the costs of failed trials, the median capitalized research and development investment to bring a new drug to market was estimated at $1141.7 million (95% CI, $888.1 million-$1480.8 million), and the mean investment was estimated at $1559.1 million (95% CI, $1271.0 million-$1893.8 million) in the base case analysis. Median estimates by therapeutic area (for areas with ≥5 drugs) ranged from $765.9 million (95% CI, $323.0 million-$1473.5 million) for nervous system agents to $2771.6 million (95% CI, $2051.8 million-$5366.2 million) for antineoplastic and immunomodulating agents. Data were mainly accessible for smaller firms, orphan drugs, products in certain therapeutic areas, first-in-class drugs, therapeutic agents that received accelerated approval, and products approved between 2014 and 2018. Results varied in sensitivity analyses using different estimates of clinical trial success rates, preclinical expenditures, and cost of capital. Conclusions and Relevance This study provides an estimate of research and development costs for new therapeutic agents based on publicly available data. Differences from previous studies may reflect the spectrum of products analyzed, the restricted availability of data in the public domain, and differences in underlying assumptions in the cost calculations.
Chromogranine A and neuron-specific enolase as the main predictors of survival for hormone-refractory prostate cancer (HRPC) patients
Authors: A. Banu, E. Banu, D. Dionysopoulos, J. Medioni, F. Scotte, E. Levy, S. Oudard
Journal: Journal of Clinical Oncology (2007)

15594 Background: Clinical studies suggested that the extent of neuro-endocrine differentiation in prostate cancer increases with tumor progression and the development of androgen refractory status. Chromogranine (CgA) and neuron-specific enolase (NSE) are currently explored as surrogate markers. Methods: Eligible chemonaive HRPC patients (pts) were required to have an ECOG performance status (PS) ≤ 2. Before chemotherapy initiation, we quantified NSE, CgA and PSA in the venous blood using commercial kits. We evaluated the impact of baseline NSE, CgA and PSA on overall survival (OS) using multivariate Cox regression analysis, stratified by chemotherapy regimen. Secondary, we studied the correlation between NSE, CgA, PSA and other important variables as age, Gleason score, hemoglobin, number of metastatic sites and ECOG PS. Results: Data of 39 consecutive HRPC pts treated between December 01–06 in a single French center were analyzed. Chemotherapy was docetaxel-based in 92% of pts. Median age was 71 years (range 51–86) and 79% of pts had bone metastases. Elevated NSE, CgA and PSA were observed in 6, 9 and 30% of pts and median levels were 10.8, 67 and 23.3 ng/mL, respectively. Gleason 8–10 was present in 49% of pts. Significant correlations were observed between NSE and the number of metastatic sites and between CgA and age, hemoglobin and ECOG PS. The baseline PSA was only correlated with Gleason score. Median OS for the entire cohort was 24.4 months (95% CI, 18.8–29.9). Two-year OS was 15% and only 19% of patients are dead. Univariate Cox regression analysis showed only a significant relationship between OS and baseline NSE: hazard ratio= 1.09 (95% CI, 1.03–1.16), P=0.006. No other known prognostic factors are related to outcome. A multivariate model including baseline NSE, CgA, ECOG PS and Gleason score showed a 15% rise of the risk of death related to NSE (borderline P value). Conclusions: NSE was the most powerful predictor of survival for HRPC pts. Our results emphasize the theory that cells secreting NSE are chemoresistant, with a negative impact on OS. No significant financial relationships to disclose.
Characterisation of innate lymphoid cell subsets infiltrating colorectal carcinoma
Authors: Paolo Carrega, Paola Orecchia, Linda Quatrini, Nicola Tumino, Roberta Venè, Roberto Benelli, Alessandro Poggi, Stefano Scabini, Maria Cristina Mingari, Lorenzo Moretta, Paola Vacca
Journal: Gut (2020)

Characterisation of innate lymphoid cell subsets infiltrating colorectal carcinomaWe read with great interest the paper by de Vries et al 1 which provides an interesting and unbiased characterisation of the immune contexture of colorectal cancer (CRC), the third most common cancer worldwide. 2By mass cytometric analysis together with single cell RNA sequencing, the authors identified several clusters of immune cells infiltrating CRC.They show that natural killer (NK) cells (identified as CD127 -CD56 + CD45RO + ) are the prevalent innate lymphoid cell (ILC) population.NK cells are cytotoxic cells and can be distinguished from the non-cytotoxic CD127 + 'helper' ILC subsets (hILCs), which are specialised in the secretion of different sets of cytokines. 3Because of the low numbers of CD127 + hILCs, the authors did not characterise further hILC subsets.However, given their capacity to rapidly respond to environmental signals
Neuron Culture Systems: Astrocyte‐Encapsulated Hydrogel Microfibers Enhance Neuronal Circuit Generation (Adv. Healthcare Mater. 5/2020)
Authors: Beom Jin Kim, Ji Yu Choi, Hyunwoo Choi, Sol Han, Jeongyeon Seo, Jungnam Kim, Sunghoon Joo, Hyo Min Kim, Chungik Oh, Seungbum Hong, Pilnam Kim, Insung S. Choi
Journal: Advanced Healthcare Materials (2020)

In article number 1901072 by Insung S. Choi and co-workers, a 3D neuron-culture system is fabricated by encapsulating astrocytes (green in the picture) in alginate microfibers and culturing hippocampal neurons (orange) on the aligned microfibers. The astrocyte-laden microfibers enhance neurite outgrowth and synaptic formation as well as controlling the outgrowth directionality, suggesting a cytotherapeutic platform for neural injuries. The image was designed by co-authors Sol Han and Hyunwoo Choi.