tbuckley/cabot-search huggingface dataset:
Associations of Fetal Growth Outcomes with Measures of the Combined Xenoestrogenic Activity of Maternal Serum Perfluorinated Alkyl Acids in Danish Pregnant Women
Authors: Christian Bjerregaard-Olesen, Cathrine Carlsen Bach, Manhai Long, Maria Wielsøe, Bodil Hammer Bech, Tine Brink Henriksen, Jørn Olsen, Eva Cecilie Bonefeld-Jørgensen
Journal: Environmental Health Perspectives (2019)

Background: Higher concentrations of single perfluorinated alkyl acids (PFAAs) have been associated with lower birth weight (BW), but few studies have examined the combined effects of PFAA mixtures. PFAAs have been reported to induce estrogen receptor (ER) transactivity, and estrogens may influence human fetal growth. We hypothesize that mixtures of PFAAs may affect human fetal growth by disrupting the ER. Objectives: We aimed to study the associations between the combined xenoestrogenic activity of PFAAs in pregnant women's serum and offspring BW, length, and head circumference. Methods: We extracted the actual mixture of PFAAs from the serum of 702 Danish pregnant women (gestational wk 11–13) enrolled in the Aarhus Birth Cohort (ABC) using solid phase extraction, high-performance liquid chromatography (HPLC), and weak anion exchange. PFAA-induced xenoestrogenic receptor transactivation (XER) was determined using the stable transfected MVLN cell line. Associations between XER and measures of fetal growth were estimated using multivariable linear regression with primary adjustment for maternal age, body mass index (BMI), educational level, smoking, and alcohol intake, and sensitivity analyses with additional adjustment for gestational age (GA) (linear and quadratic). Results: On average, an interquartile range (IQR) increase in XER was associated with a 48 g [95% confidence interval (CI): −90, −6] decrease in BW and a 0.3 cm (95% CI: 0.1, 0.5) decrease in birth length. Upon additional adjustment for GA, the estimated mean differences were −28g (95% CI: −60, 4) and −0.2cm (95% CI: −0.4, 0.0), respectively. Conclusion: Higher-serum PFAA-induced xenoestrogenic activities were associated with lower BW and length in offspring, suggesting that PFAA mixtures may affect fetal growth by disrupting ER function. https://doi.org/10.1289/EHP1884
Transmission Patterns in a Low HIV-Morbidity State — Wisconsin, 2014–2017
Authors: Katarina M. Grande, Casey L. Schumann, M. Cheryl Bañez Ocfemia, James M. Vergeront, Joel O. Wertheim, Alexandra M. Oster
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

Most human immunodeficiency virus (HIV) molecular linkages in Wisconsin were among persons within the same racial/ethnic, risk, and age groups. Among named partner linkages where both persons had an HIV virus sequence available, 33.8% also had a molecular linkage and were deemed plausible transmission partners.
Phase Ib trial of cabozantinib (C) in combination with atezolizumab (A) in patients (pts) with advanced hepatocellular carcinoma (HCC), gastric or gastroesophageal junction cancer (GC/GEJC), or colorectal cancer (CRC).
Authors: Kristen Renee Spencer, Giridharan Ramsingh, Nehal Mohamed, Sumanta K. Pal, Lorenza Rimassa
Journal: Journal of Clinical Oncology (2019)

TPS478 Background: C is an inhibitor of tyrosine kinases involved in tumor growth, angiogenesis, and immune regulation, including MET, VEGFR, and TAM family kinases (Tyro3, AXL, MER). Preclinical and clinical studies suggest that C promotes an immune-permissive tumor environment which may enhance response to checkpoint inhibitors such as the anti-PD-L1 mAb A. C significantly improved overall survival vs placebo in previously treated advanced HCC, and the combination of A and bevacizumab has shown synergistic activity in advanced HCC. Checkpoint inhibitors have shown clinical activity in advanced CRC primarily in pts with high microsatellite instability (MSI); combination with immune-modulating agents may enhance activity in pts with stable or low MSI. Likewise, combination therapy may improve response in pts with GC/GEJC resistant to standard chemotherapy. Here, we present the study design of an ongoing phase 1b trial which includes cohorts with advanced HCC, GC/GEJC, or CRC. Methods: This global, phase 1b, open-label trial will assess the safety, tolerability, preliminary efficacy, and pharmacokinetics of C in combination with A (NCT03170960). The study consists of a dose-escalation stage and an expansion stage. In the dose-escalation stage (3+3 design), a recommended C dose for combination with a standard dose of A will be established. In the expansion stage, 18 cohorts will be enrolled at the recommended dose of C + A including 3 cohorts with gastrointestinal cancers: (1) advanced HCC not previously treated with systemic therapy; (2) advanced GC/GEJC after progression on platinum- or fluoropyrimidine-containing therapy; and (3) advanced CRC after progression on fluoropyrimidine combined with oxaliplatin or irinotecan. Pts will continue treatment as long as they experience clinical benefit as judged by the investigator or until unacceptable toxicity. The primary objective of the expansion stage is the objective response rate for each cohort. Exploratory objectives include correlation of tumor and plasma biomarkers, immune cell profiles, and MSI status with clinical outcome. Clinical trial information: NCT03170960.
N-myristoyltransferase deficiency impairs activation of kinase AMPK and promotes synovial tissue inflammation
Authors: Zhenke Wen, Ke Jin, Yi Shen, Zhen Yang, Yinyin Li, Bowen Wu, Lu Tian, Stanford Shoor, Niall E. Roche, Jorg J. Goronzy, Cornelia M. Weyand
Journal: Nature Immunology (2019)
Phase I/II study of panitumumab (PANI) combined with trifluridine/tipiracil (FTD/TPI) in patients (pts) with previously treated <i>RAS</i> wild-type (wt) metastatic colorectal cancer (mCRC): Final results of APOLLON study.
Authors: Yoshito Komatsu, Takeshi Kato, Yoshinori Kagawa, Takayuki Yoshino, Yasutoshi Kuboki, Makio Gamoh, Hirofumi Yasui, Kentaro Yamazaki, Hironaga Satake, Masahiro Goto, Hiroaki Tanioka, Eiji Oki, Masahito Kotaka, Akitaka Makiyama, Tadamichi Denda, Junpei Soeda, Kazunori Shibuya, Masaru Iwata, Koji Oba, Kensei Yamaguchi
Journal: Journal of Clinical Oncology (2019)

624 Background: Previous preclinical study reported that a combination of PANI with FTD/TPI demonstrated synergistic antitumor activity (Baba, 2017); however, no clinical study has been reported in this combination yet. Therefore, we conducted a phase I/II study to evaluate the efficacy and safety of this combination in pts with RAS wt mCRC. Here, we report the results of final analysis, including follow-up. Methods: Eligible pts had RAS wt mCRC refractory or intolerant to fluoropyrimidines, irinotecan, oxaliplatin, or angiogenesis inhibitors, and had never been treated with anti-EGFR antibodies, FTD/TPI, or regorafenib (REG).Pts received four-week cycles of PANI (every two weeks) and FTD/TPI (twice daily, days 1 to 5 and 8 to 12). The primary endpoint was frequency of dose-limiting toxicity (DLT) in phase I and progression-free survival (PFS) rate at 6 months (M) in phase II. With a PFS rate at 6 M of 48% deemed promising and 29% judged unacceptable, and assuming a one-sided significance level of 5%, the necessary sample size to achieve a power of 80% was estimated to be 47 pts (target sample size, 52 pts). Results: Since no DLT occurred in phase I, the recommended dose was determined to be 6 mg/kg for PANI and 35 mg/m 2 for FTD/TPI. In phase II with a median follow-up of 16.5 M, the PFS rate at 6 M (n = 54) was 33.3% (90% CI: 22.8–45.3; p = 0.24), and median PFS and overall survival were 5.8 M (95% CI: 4.5–6.5) and 14.1 M (95% CI: 12.2–19.3), respectively. The response rate and disease control rate were 37.0% and 81.4%, respectively. The most common grade 3 or higher adverse events (n = 55) were neutropenia (10.9%), febrile neutropenia (9.1%), stomatitis (9.1%), and dermatitis acneiform (9.1%). Subsequent therapy was given to 39 pts (72.2%), including 25 pts (46.3%) treated with REG. Subgroup analyses stratified by age, PS, and primary lesion will be reported at the time of conference presentation. Conclusions: PANI combined with FTD/TPI showed favorable antitumor activity with an acceptable safety profile for previously treated RAS wt mCRC, although the primary endpoint of PFS rate at 6 M did not meet the prespecified threshold. Clinical trial information: NCT02613221.
Development and validation of a more accurate estimating equation for glomerular filtration rate in a Chinese population
Authors: Dai-yang Li, Wen-jun Yin, Yi-hu Yi, Bi-kui Zhang, Jun Zhao, Chao-nan Zhu, Rong-rong Ma, Ling-yun Zhou, Yue-liang Xie, Jiang-lin Wang, Shan-ru Zuo, Kun Liu, Can Hu, Ge Zhou, Xiao-cong Zuo
Journal: Kidney International (2019)
Abstract 05: Association of 25-Year Body Mass Index Trajectories Throughout Early Adulthood With Nonalcoholic Fatty Liver Disease in Middle Age: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Lisa B VanWagner, Sadiya Khan, Hongyan NIng, Juned Siddique, Cora E Lewis, John Jeffery Carr, Miriam Vos, Elizabeth Speliotes, Norah Terrault, Mary Rinella, Donald M Lloyd-Jones, Norrina B Allen
Journal: Circulation (2017)

Background: Nonalcoholic Fatty Liver Disease (NAFLD) has increased in parallel with obesity, is a risk factor for cirrhosis and liver cancer, and has few effective treatments. Identifying modifiable risk factors for NAFLD development is essential to effectively design prevention programs. We tested whether trajectories of body mass index (BMI) change throughout early adulthood were associated with risk of prevalent NAFLD in midlife independent of current BMI. Methods: Participants from the CARDIA study, a prospective multicenter population-based biracial cohort of adults (baseline age 18-30 years), underwent BMI measurement at exam years 0, 2, 5, 7, 10, 15, 20, and 25. At Year 25 (Y25, 2010-2011), liver fat was assessed by computed tomography. NAFLD was identified after exclusion of other causes of liver fat (alcohol/hepatitis). Latent mixture modeling was used to identify 25-year trajectories in BMI percent (%) change relative to baseline BMI over time. Multivariable logistic regression models were used to assess associations between BMI trajectory group and prevalent NAFLD with adjustment for baseline or current Y25 BMI. Results: Among 4,423 participants, we identified 4 distinct trajectories of BMI %change: stable BMI (26.2% of the cohort, 25-year mean BMI Δ=0.7 kg/m 2 ), mild increase (46.0%, BMI Δ=5.2 kg/m 2 ), moderate increase (20.9%, BMI Δ=10.0 kg/m 2 ), and extreme increase (6.9%, BMI Δ=15.1 kg/m 2 ) (Figure). NAFLD prevalence at Y25 was higher with increasing BMI trajectory: 4.1%, 9.3%, 13.0%, and 17.6% (p-trend &lt;0.0001). At baseline, 34.6% of participants had overweight or obesity. After adjustment for confounders, trajectories of greater BMI increase were associated with greater NAFLD prevalence independent of baseline or current Y25 BMI (Figure). Conclusion: Weight gain throughout adulthood is associated with greater prevalence of NAFLD in midlife independent of baseline or current BMI. These findings highlight weight maintenance throughout adulthood as a potential target for primary prevention of NAFLD.
Protective Effects of Activated Myofibroblasts in the Pressure-Overloaded Myocardium Are Mediated Through Smad-Dependent Activation of a Matrix-Preserving Program
Authors: Ilaria Russo, Michele Cavalera, Shuaibo Huang, Ya Su, Anis Hanna, Bijun Chen, Arti V. Shinde, Simon J. Conway, Jonathan Graff, Nikolaos G. Frangogiannis
Journal: Circulation Research (2019)

The heart contains abundant interstitial and perivascular fibroblasts. Traditional views suggest that, under conditions of mechanical stress, cytokines, growth factors, and neurohumoral mediators stimulate fibroblast activation, inducing ECM (extracellular matrix) protein synthesis and promoting fibrosis and diastolic dysfunction. Members of the TGF (transforming growth factor)-β family are upregulated and activated in the remodeling myocardium and modulate phenotype and function of all myocardial cell types through activation of intracellular effector molecules, the Smads (small mothers against decapentaplegic), and through Smad-independent pathways.To examine the role of fibroblast-specific TGF-β/Smad3 signaling in the remodeling pressure-overloaded myocardium.We examined the effects of cell-specific Smad3 loss in activated periostin-expressing myofibroblasts using a mouse model of cardiac pressure overload, induced through transverse aortic constriction. Surprisingly, FS3KO (myofibroblast-specific Smad3 knockout) mice exhibited accelerated systolic dysfunction after pressure overload, evidenced by an early 40% reduction in ejection fraction after 7 days of transverse aortic constriction. Accelerated systolic dysfunction in pressure-overloaded FS3KO mice was associated with accentuated matrix degradation and generation of collagen-derived matrikines, accompanied by cardiomyocyte myofibrillar loss and apoptosis, and by enhanced macrophage-driven inflammation. In vitro, TGF-β1, TGF-β2, and TGF-β3 stimulated a Smad3-dependent matrix-preserving phenotype in cardiac fibroblasts, suppressing MMP (matrix metalloproteinase)-3 and MMP-8 synthesis and inducing TIMP (tissue inhibitor of metalloproteinases)-1. In vivo, administration of an MMP-8 inhibitor attenuated early systolic dysfunction in pressure-overloaded FS3KO mice, suggesting that the protective effects of activated cardiac myofibroblasts in the pressure-overloaded myocardium are, at least in part, because of suppression of MMPs and activation of a matrix-preserving program. MMP-8 stimulation induces a proinflammatory phenotype in isolated macrophages.In the pressure-overloaded myocardium, TGF-β/Smad3-activated cardiac fibroblasts play an important protective role, preserving the ECM network, suppressing macrophage-driven inflammation, and attenuating cardiomyocyte injury. The protective actions of the myofibroblasts are mediated, at least in part, through Smad-dependent suppression of matrix-degrading proteases.
Abstract 15137: Machine Learning Adds to Standard Clinical & CAC Assessments in Predicting 10-Year Coronary Heart Disease & Cardiovascular Disease Deaths: Insight From the Coronary Artery Calcium Consortium of 66,636 Patients
Authors: Rine Nakanishi, Piotr Slomka, Julian Betancur, Michael J Blaha, Khrrum Nasir, Michael D Miedema, John A Rumberger, Heidi Gransar, Leslee J Shaw, Alan Rozanski, Matthew J Budoff, Daniel S Berman
Journal: Circulation (2017)

Introduction: Assessment of coronary artery calcium (CAC) with non-contrast computed tomography (CT) is known to add to clinical risk assessment in prediction of atherosclerotic cardiovascular dise...
PRISModegib: the use of the PRISM test to assess the health‐related quality of life of patients with locally advanced basal cell carcinoma undergoing Hedgehog pathway inhibitor therapy
Authors: G. Gualdi, R. Moro, V. Regina, S. Caravello, P. Monari, P.G. Calzavara‐Pinton
Journal: British Journal of Dermatology (2019)
Comparison of international guidelines for noninvasive diagnosis of hepatocellular carcinoma: 2018 update
Authors: Tae-Hyung Kim, So Yeon Kim, An Tang, Jeong Min Lee
Journal: Clinical and Molecular Hepatology (2019)

The goal of this review is to present the similarities and differences among the latest guidelines for noninvasive diagnosis of hepatocellular carcinoma (HCC) of American Association for the Study of Liver Disease (AASLD), European Association for the Study of the Liver (EASL), Liver Imaging Reporting and Data System (LI-RADS), Asian Pacific Association for the Study of the Liver (APASL), and Korean Liver Cancer Association- National Cancer Center (KLCA-NCC) of Korea. In 2018, major guideline updates have been proposed by the AASLD, EASL and KLCA-NCC; AASLD newly incorporated LI-RADS into their HCC diagnostic algorithm. The AASLD and EASL guidelines now include magnetic resonance imaging (MRI) using hepatobiliary contrast media as a first-line diagnostic test in addition to dynamic computed tomography and MRI using extracellular contrast media and the KLCA-NCC and EASL guidelines also include contrast-enhanced ultrasound as a second-line diagnostic test. We will comprehensively review the HCC surveillance and diagnostic algorithms and compare and highlight key features for each guideline. We also address limitations of current systems for the noninvasive diagnosis of HCC.
Advanced Brain-Computer Interface for People With Paralysis
Authors: Jennifer Abbasi
Journal: JAMA (2019)

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Abstract B41: Transcriptome and proteome analyses of MCF7 cells with different expression profile of SPARC (secreted protein acidic in rich in cysteine) in the presence and absence of docetaxel
Authors: Ana Carolina Pavanelli, Luciana Pizzatti Barboza, Eliana Saul Furquim Werneck Abdelhay, Maria Aparecida Nagai
Journal: Clinical Cancer Research (2018)

Abstract The SPARC (secreted protein, acidic, cysteine-rich) gene encodes a 32kDa protein that belongs to a family of matricellular proteins, which interact with cell-surface receptors, growth factors, and the ECM (extracellular matrix) components. SPARC plays a role in tissue remodeling, cell migration, angiogenesis, embryonic development, tumorigenesis, and chemosensitivity. Docetaxel is an effective chemotherapeutic drug for the treatment of advanced breast cancer. However, a considerable proportion of breast cancer patients do not respond positively to docetaxel. In a previous study, we identified SPARC as differentially expressed in mammary epithelial cells expressing different levels of HER-2. In the present study, we evaluate the effects of SPARC overexpression on the sensitivity of breast cancer cells to docetaxel. MCF7 cells were transfected with the expression vector pCMV6-SPARC or pCMV6-Neo. Real-time PCR, Western blot, and immunofluorescence were used to characterize the clones overexpressing SPARC. Using cDNA microarray and label-free approach for quantitative proteomic analysis, we evaluated the transcriptome and proteome changes in the comparison of the MCF7 cell control and overexpressing SPARC before and after docetaxel treatment. Several differentially expressed genes were identified as potentially involved in SPARC-mediated chemosensitivity to docetaxel. Among the molecular interaction networks from the differentially expressed proteins, extracellular matrix and cytoskeleton remodeling were the top pathway map observed in the comparison between MCF7 cells overexpressing SPARC and the control cells before docetaxel treatment. GTP metabolism pathway was the top pathway map observed in the comparison between MCF7 cells overexpressing SPARC and the control cells after docetaxel treatment. Transcriptome and proteome integrated data resulted in forty commonly up- and downregulated genes, with the WNT pathway represented among them. Our findings suggest that SPARC expression can influence docetaxel sensitivity in MCF7 cells by modulating genes involved in diverse biologic process that might be related to drug sensitivity. (Supported by Fapesp and CNPq.) Citation Format: Ana Carolina Pavanelli, Luciana Pizzatti Barboza, Eliana Saul Furquim Werneck Abdelhay, Maria Aparecida Nagai. Transcriptome and proteome analyses of MCF7 cells with different expression profile of SPARC (secreted protein acidic in rich in cysteine) in the presence and absence of docetaxel [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B41.
Genetic Ancestry–dependent Differences in Breast Cancer–induced Field Defects in the Tumor-adjacent Normal Breast
Authors: Harikrishna Nakshatri, Brijesh Kumar, Heather N. Burney, Mary L. Cox, Max Jacobsen, George E. Sandusky, Crislyn D'Souza-Schorey, Anna Maria V. Storniolo
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Genetic ancestry influences evolutionary pathways of cancers. However, whether ancestry influences cancer-induced field defects is unknown. The goal of this study was to utilize ancestry-mapped true normal breast tissues as controls to identify cancer-induced field defects in normal tissue adjacent to breast tumors (NATs) in women of African American (AA) and European (EA) ancestry. Experimental Design: A tissue microarray comprising breast tissues of ancestry-mapped 100 age-matched healthy women from the Komen Tissue Bank (KTB) at Indiana University (Indianapolis, IN) and tumor-NAT pairs from 100 women (300 samples total) was analyzed for the levels of ZEB1, an oncogenic transcription factor that is central to cell fate, mature luminal cell–enriched estrogen receptor alpha (ERα), GATA3, FOXA1, and for immune cell composition. Results: ZEB1+ cells, which were localized surrounding the ductal structures of the normal breast, were enriched in the KTB-normal of AA compared with KTB-normal of EA women. In contrast, in EA women, both NATs and tumors compared with KTB-normal contained higher levels of ZEB1+ cells. FOXA1 levels were lower in NATs compared with KTB-normal in AA but not in EA women. We also noted variations in the levels of GATA3, CD8+ T cells, PD1+ immune cells, and PDL1+ cell but not CD68+ macrophages in NATs of AA and EA women. ERα levels did not change in any of our analyses, pointing to the specificity of ancestry-dependent variations. Conclusions: Genetic ancestry–mapped tissues from healthy individuals are required for proper assessment and development of cancer-induced field defects as early cancer detection markers. This finding is significant in light of recent discoveries of influence of genetic ancestry on both normal biology and tumor evolution.
Individuals, traditions, and the righteous
Authors: Craig T. Palmer, Kyle J. Clark
Journal: Behavioral and Brain Sciences (2018)

Abstract Whitehouse's article posits several plausible hypotheses, but suffers from an unwarranted reliance on the importance of distinct social groups in the causation of self-sacrificing behavior. A focus on relationships between individual kin is better able to account for both the evolution of self-sacrifice and present forms of self-sacrifice. The practical importance of this point is discussed.