tbuckley/cabot-search huggingface dataset:
Antonio Vallejo-Nágera (1889–1960) and Juan Antonio Vallejo-Nágera Botas (1926–1990)
Authors: Ethan Pearlstein, Javier I. Escobar
Journal: American Journal of Psychiatry (2018)

Spanish psychiatrist, played a pivotal role toward the end of Spain's civil war, as General Francisco Franco, the country's caudillo (leader), began to consolidate his regime.During the Spanish Civil War (1936War ( -1939))-a conflict between the Republicans, who were loyal to Spain's first democratic republic, and the Nationalists, a rebel group led by Franco-Spanish physicians and mental health professionals aligned themselves on either side of the ideological conflict.Vallejo-Nágera, an academic psychiatrist, had studied medicine at the University of Valladolid in northern Spain and spent time in Germany, where he met leading psychiatrists of that period, such as Gruhle, Schwalb, Kretschmer, and others (1).On his return to Spain, Vallejo-Nágera took teaching positions in the military academy and practiced at a public mental hospital in Ciempozuelos, near Madrid.During these early years, Vallejo-Nágera published various texts on psychopathology, some of them emphasizing racial elements and eugenic doctrines, his writings clearly influenced by Kretschmer's biotypologies (1-3)In 1938, Franco instituted the Gabinete de Investigaciones Psicológicas de Inspección de Campos de Concentración de Prisioneros de Guerra ("Cabinet for Psychiatric Inspection of Concentration Camps of Prisoners of War") and appointed Vallejo-Nágera to lead it.As part of this official assignment, Vallejo-Nágera initiated a research project entitled "Biopsiquismo del Fanatismo Marxista" ("The Biopsychism of Marxist Fanaticism"), the results of which were published in 1938 and 1939 (4, 5).The second of these papers, focusing on female prisoners, was entitled "Psiquismo del Fanatismo Marxista: Investigaciones Psicológicas en Marxistas Femeninos Delincuentes" ("Psyche of Marxist Fanaticism: Psychological Investigations on Delinquent Marxist Feminists").The paper documented "the threat of the psychiatrically degenerate Republican enemy," based on a study of 50 female political prisoners.A 200question survey administered to these women included psychological tests assessing IQ as well as brief assessments of personality and temperament (6).The presentation of the data is preceded by a brief introduction stating that the purpose of the paper was "to understand the very active female participation in the Marxist revolt, their characteristic psychic lability, the weakness of their mental equilibrium, their lower
Abstract 3405: A mutational signature associated with alcohol consumption and prognostically mutated driver genes in esophageal squamous cell carcinoma
Authors: Xiangchun Li, Mengyao Wang, Meng Yang, Hongji Dai, Baifeng Zhang, Wei Wang, Xinlei Chu, Xin Wang, Hong Zheng, Ruifang Niu, Wei Zhang, Kexin Chen
Journal: Cancer Research (2018)

Abstract Aim: Esophageal squamous cell carcinoma (ESCC) is often diagnosed at advanced and incurable stage. Information on driver genes and prognosticators in ESCC remains incomplete. Herein, we elucidated significantly mutated genes (SMGs), mutational signatures, and prognosticators in ESCC. Methods: Three MutSig algorithms (i.e. MutSigCV, MutSigCL and MutSigFN) and “20/20” ratio-metric were employed to identify SMGs. Nonnegative matrix factorization was used to decipher mutational signatures. Kaplan-Meier survival analysis, multivariate Cox and logistic regression models were applied to analyze association between mutational features and clinical parameters. Results: We identified 26 SMGs, including 8 novel (NAV3, TENM3, PTCH1, TGFBR2, RIPK4, PBRM1, USP8 and BAP1) and 18 previously reported. Three mutational signatures were identified to be prevalent in ESCC including clocklike C&amp;gt;T at CpG, APOBEC overactive C&amp;gt;T at TpCp[A/T], and a signature featured by T&amp;gt;C substitution. The T&amp;gt;C mutational signature was significantly correlated with alcohol consumption (OR: 3.59; 95% CI: 2.30-5.67; P &amp;lt; 0.001). This alcohol consumption signature was also observed in liver cancer and head and neck squamous cell carcinoma, and its mutational activity was substantially higher in samples with mutations in TP53. Survival analysis revealed that TENM3 mutations (HR: 5.54; CI: 2.68-11.45; P &amp;lt; 0.001) and TP53 hotspot mutation p.R213* (HR: 3.37; CI: 1.73-8.06; P &amp;lt; 0.001) were significantly associated with shortened survival outcome. The association remained statistically significant after controlling for age, gender, TNM stage and tumor grade. Conclusions: We have uncovered several new SMGs in ESCC and defined an alcohol consumption related mutational signature. TENM3 mutation and TP53 hotspot mutation p.R213* are independent prognosticators for poor survival in ESCC. Citation Format: Xiangchun Li, Mengyao Wang, Meng Yang, Hongji Dai, Baifeng Zhang, Wei Wang, Xinlei Chu, Xin Wang, Hong Zheng, Ruifang Niu, Wei Zhang, Kexin Chen. A mutational signature associated with alcohol consumption and prognostically mutated driver genes in esophageal squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3405.
Abstract 5319: Genetic regulation of DNA methylation in breast cancer
Authors: Nan Lin, Aditi Shendre, JinPeng Liu, Chi Wang, Yunlong Liu, Chunyan He
Journal: Cancer Research (2018)

Abstract Aberrant DNA methylation plays an important role in breast cancer initiation and progression. It is believed that changes in DNA methylation occur early in breast cancer development or even in normal tissue before tumor occurrence, and these changes could be a useful source for early detection, prognosis, and targeted therapy. DNA methylation is tissue-specific and is influenced by inherited genetic variations in the human genome. Genome-wide association studies (GWAS) have identified more than 600 single nucleotide polymorphisms (SNPs) associated with breast cancer risk and outcome. However, how these germline genetic variants influence DNA methylation in breast tissue, especially in normal breast tissue, remains largely unknown. We performed a methylation quantitative trait loci (meQTL) analysis to examine the association between the GWAS identified breast cancer risk loci and DNA methylation in 48 women with paired blood and breast tissue samples. Genotyping of SNPs was performed using blood-derived DNA and the Illumina HumanOmni 2.5-4v1_D array chip. Genome-wide DNA methylation was measured using breast tissue derived genomic DNA and the new Illumina TruSeq Methyl Capture EPIC sequencing technology. We found that GWAS-identified breast cancer risk loci were associated with DNA methylation sites close to genes enriched in pathways related to cell differentiation and morphogenesis, DNA damage, cell movement, and hormonal signaling pathways. We identified more cis-acting than trans-acting meQTLs, and the peak enrichment for meQTLs was in close proximity to transcription start sites. We further compared our results with those from the meQTL studies conducted with lymphoblastoid cell lines and peripheral blood samples. We found more than 60% of the identified association between genetic variants and DNA methylation in our study are tissue-type specific. Our study may provide a post-GWAS functional characterization of breast cancer risk loci and shed light on epigenetic mechanisms that underlie the observed GWAS association. Citation Format: Nan Lin, Aditi Shendre, JinPeng Liu, Chi Wang, Yunlong Liu, Chunyan He. Genetic regulation of DNA methylation in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5319.
Function and clinical significance of circRNAs in solid tumors
Authors: Yiting Geng, Jingting Jiang, Changping Wu
Journal: Journal of Hematology & Oncology (2018)

Circular RNA (circRNA) is a new type of endogenous non-coding RNAs (ncRNAs). circRNA regulates gene expression in many biological processes, and it also participates in the initiation and development of various diseases, including tumors, which are the focus of present research. With the development of high-throughput sequencing technique, an increasing number of circRNAs closely related to tumors have been discovered. According to numerous studies, there is a significant difference in the expressions of circRNAs among a variety of tumor tissues and para-carcinoma normal tissues. Some specifically expressed circRNAs may potentially serve as new biomarkers for tumor diagnosis and prognosis. This systemic review briefly introduces the characteristics, biogenesis, and functions of circRNAs, as well as discusses their relationship with cancer in detail. In addition, this article also describes several research strategies for circRNAs.
Maternally Inherited Essential Hypertension Is Associated With the Novel 4263A>G Mutation in the Mitochondrial tRNAIle Gene in a Large Han Chinese Family
Authors: ShiwenWang, RonghuaLi, AndreaFettermann, ZongbinLi, YapingQian, YuqiLiu, XinjianWang, AnnaZhou, Jun QinMo, LiYang, PingpingJiang, AndreasTaschner, WalterRossmanith, Min-XinGuan
Journal: Circulation Research (2011)

Rational:Despite maternal transmission of hypertension in some pedigrees, pathophysiology of maternally inherited hypertension remains poorly understood. Objective:To establish a causative link between mitochondrial dysfunction and essential hypertension. Method and Results:A total of 106 subjects from a large Chinese family underwent clinical, genetic, molecular, and biochemical evaluations. Fifteen of 24 adult matrilineal relatives exhibited a wide range of severity in essential hypertension, whereas none of the offspring of affected fathers had hypertension. The age at onset of hypertension in the maternal kindred varied from 20 years to 69 years, with an average of 44 years. Mutational analysis of their mitochondrial genomes identified a novel homoplasmic 4263A>G mutation located at the processing site for the tRNAIle 5′-end precursor. An in vitro processing analysis showed that the 4263A>G mutation reduced the efficiency of the tRNAIle precursor 5′-end cleavage catalyzed by RNase P. tRNA Northern ana...
Abstract 15554: Heart Failure-Related Hyperphosphorylation of Ser199 on Cardiac Troponin I Causes Divergent Effects on Cardiac Function at Baseline and During Ischemia-Reperfusion
Authors: Yuejin Li, Guangshuo Zhu, Cyrus Takahashi, Djahida Bedja, Genaro Ramirez-Correa, Nazareno Paolocci, David A Kass, Anne M Murphy
Journal: Circulation (2015)

Background: Phosphorylation of cardiac troponin I (cTnI) on Ser199 is significantly increased in human heart failure (HF), however its cardiac impact in vivo remains unknown. In addition, selective proteolysis of cTnI is a marker of myocardial injury and contributes to cardiac dysfunction in ischemia/reperfusion (I/R), and Ser199 phosphorylation affects cTnI proteolysis in vitro, thus whether Ser199 phosphorylation affects cardiac performance during I/R is of great interest. Methods and Results: We generated transgenic mice (TgS200D) carrying cTnI S200D mutation to mimic the site-specific hyperphosphorylation of murine Ser200 (equivalent to human Ser199). Cardiac function was first assessed in vivo using echocardiography. TgS200D mice demonstrated unaltered ejection fraction (EF), significantly prolonged isovolumic relaxation time, and normal left ventricular (LV) chamber size and wall thickness (n=10). LV pressure-volume studies showed preserved dp/dtmax, significantly decreased -dp/dtmin and increased relaxation time constant in TgS200D when compared to non-transgenic (NTg) control group at baseline (n=10). With increasing heart rates, the two groups showed similar enhancement in both systolic and diastolic function, suggesting the positive force-frequency relation is preserved in TgS200D (n=5). After isoproterenol injection (i.v. 40ng/min/kg), although a comparable increase in dp/dtmax was observed in both groups, there was no enhancement of -dp/dtmin in TgS200D in contrast to 15% of increase in NTg (n=5, p=0.019). After ischemia (30 min)/reperfusion (60 min), LV developed pressure was recovered by ~90% in isolated TgS200D hearts but only ~40% in NTg (n=5, p=0.003). Immunoblotting detected cTnI cleavage only in NTg hearts. Conclusions: Our results indicate that hyperphosphorylation of cTnI Ser199 1) impairs basal diastolic function but preserves systolic function, without LV hypertrophy or dilation; 2) blunts cardiac lusitropic response to β-adrenergic stimulation with isoproterenol; 3) protects heart against I/R injury, likely via preventing cTnI degradation. We propose a dual role of cTnI Ser199 hyperphosphorylaiton: contributing to HF with preserved EF but protecting heart during I/R.
Adenovirus-Mediated Transfer of Human Placental Ectonucleoside Triphosphate Diphosphohydrolase to Vascular Smooth Muscle Cells Suppresses Platelet Aggregation In Vitro and Arterial Thrombus Formation In Vivo
Authors: EijiFurukoji, MasanoriMatsumoto, AtsushiYamashita, HideoYagi, YoshihikoSakurai, KousukeMarutsuka, KintaHatakeyama, KazuhiroMorishita, YoshihiroFujimura, ShozoTamura, YujiroAsada
Journal: Circulation (2005)

Background— Platelet-rich thrombus formation is a critical event in the onset of cardiovascular disease. Because ADP plays a significant role in platelet aggregation, its metabolism is important in the regulation of platelet activation and recruitment. Ectonucleoside triphosphate diphosphohydrolase (E-NTPDase) is a key enzyme involved in vascular ADP metabolism. We recently isolated 2 isoforms of E-NTPDase from the human placenta. The present study examined whether these isoforms suppress platelet aggregation and thrombus formation after adenovirus-mediated gene transfer to vascular smooth muscle cells (SMCs). Methods and Results— We constructed adenovirus vectors expressing human placental E-NTPDase isoforms I (AdPlac I) and II (AdPlac II) or bacterial β-galactosidase (AdLacZ). Vascular SMCs infected with AdPlac I expressed significant NTPDase activity and inhibited the platelet aggregation induced by ADP and collagen in vitro. In contrast, SMCs infected with AdPlac II and AdLacZ did not exert antiplatel...
Abstract 1791: Evolutionary dynamics of non-Hodgkin's lymphoma CAR T cell therapy
Authors: Philipp M. Altrock, Gregory Kimmel, Frederick L. Locke
Journal: Cancer Research (2018)

Abstract Non-Hodgkin Lymphoma (NHL) is the most common hematologic malignancy in the United States with an estimated 72,000 new cases (4.3% of all cancer cases) and 20,000 deaths (3.4% of all cancer deaths) in 2017; the median 5-year survival rate is 71%. Despite a possible cure, with front-line chemotherapy, there exist patients that do not response or relapse and develop refractory disease. These patients have a median overall survival of less than seven months. Chimeric antigen receptor (CAR) T-cell therapy for refractory NHL relies on expansion of engineered T- cells that specifically target tumor cells expressing CD19. Here we combine mathematical modeling with statistical data-analysis based on recent results of clinical studies of CAR T-cell dynamics in individual patients. We use statistical and mathematical modeling to elucidate the key mechanisms that drive evolutionary dynamics of anti-CD19 CAR T-cell therapy. To this end, we integrate patient specific tumor burden profiles, inflammatory cytokine profiles, and CAR T cell population dynamics into our model. We find that the success of therapy may depend on dynamic regulation of inflammatory cytokines in the tumor microenvironment, as well as on specific properties of the heterogeneous CAR T-cell population. Relative abundances of juvenile and effector T cells are key factors that drive the duration of treatment response, and the tumor-killing rate of this CD19-specific immunotherapy. Our modeling framework elucidates disease and treatment specific eco-evolutionary dynamical properties, but can also quantify genetically engineered T-cell population properties related to neurological toxicity and long-term homeostatic mechanisms that determine patient survival. Citation Format: Philipp M. Altrock, Gregory Kimmel, Frederick L. Locke. Evolutionary dynamics of non-Hodgkin's lymphoma CAR T cell therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1791.
Differential Regulation of Vascular Focal Adhesion Kinase by Steady Stretch and Pulsatility
Authors: StéphanieLehoux, BrunoEsposito, RégineMerval, AlainTedgui
Journal: Circulation (2005)

Background— In vivo tensile strain in arteries comprises 2 components: steady stretch and pulsatile stretch. However, little attention has been paid to the differential transduction of these stimuli in whole vessels. Methods and Results— Using rabbit aortas maintained in organ culture for 24 hours, we found that focal adhesion kinase (FAK) was strongly activated by high intraluminal pressure (150 mm Hg), as evidenced by increased phosphorylation (P<0.01) of tyrosine residues Tyr-397 (3.06±0.17-fold), Tyr-407 (3.71±0.65-fold), Tyr-861 (1.92±0.33-fold), and Tyr-925 (2.41±0.39-fold), compared with 80 mm Hg controls. Immunohistochemistry showed positive staining for these phosphotyrosines in the endothelium and innermost smooth muscle cell layers. Total FAK phosphorylation was reduced in vessels at 150 mm Hg by treatment with the Src family kinase inhibitor PP2 or with the integrin–extracellular matrix interaction–blocking RGD peptide, attaining 1.75±0.22-fold and 2.00±0.19-fold, respectively (P<0.05), compar...
Abstract 12461: Strength of Physician Recommendation Increases Home-based Exercise Participation in Patients With Coronary Heart Disease
Authors: Nathan L Tintle, Jacob A Clark, Maureen Dunn, Madison P Buursma, Holli A DeVon, Susan L Dunn
Journal: Circulation (2015)

The majority of individuals with coronary heart disease (CHD) do not meet current exercise guidelines and less than half enroll in hospital-based cardiac rehabilitation (CR) exercise programs. Strength of physician referral can positively affect participation in a hospital-based CR program, but it is unknown how the strength of physician referral may impact home exercise in patients with CHD. It was hypothesized that the strength of physician recommendation would positively impact home exercise participation. A total of 251 patients with CHD completed the Cardiac Rehabilitation Exercise Participation Tool 3 months after hospital discharge. Participants were typical of the CHD population, with 165 being male (65.7%) and a mean age of 65 years (SD= 9.8). Of the total sample, 188 (75%) reported receiving physician referral for home exercise, with the mean strength of the referral being 2.9 (SD= 1.9) on a scale of 0 (none) to 5 (strong). One hundred twenty-two patients (48.6%) reported exercising 3 or more days a week at home. Logistic regression was used to evaluate the impact of the strength of physician referral on the likelihood that patients would participate in home exercise after hospital discharge. Covariates included age, sex, race, marital status, employment status, education level, insurance type, cardiac procedure type, history of CHD, history of depression, functional status, and exercise prior to hospitalization. Increased strength of physician referral was predictive of increased home exercise participation (adjusted OR 1.5, 95% CI [1.3-1.7], p&lt; 0.001). Male sex was also predictive, with 58.4% of males, as compared to 40% of females, reporting home exercise (adjusted OR 1.9, 95% CI [1.0-3.6], p= 0.049). Exercise prior to hospitalization was a final predictor, with 58.4% of prior exercisers, as compared to 41.7% of non-exercisers, reporting home exercise participation after hospital discharge (adjusted OR 2.0, 95% CI [1.1-3.6], p= 0.03). These findings demonstrate the beneficial effect of a strong physician recommendation for home-based exercise in patients with CHD. Physician referral is particularly important for women and patients who have not exercised before a cardiac event, as they reported doing less exercise after discharge home.
Poor quality reporting of screening mammography is associated with lower rates of diagnosis of early-stage breast cancer in minority-underserved women
Authors: Keith A. Dookeran, Elona Sciupokiene, Agne Mackeviciute, Gehad Elfarra, Yu Wang, Wendy A. Rogowski, Neena Muthyala, Calin Caluser, Xuezhi Gao, Karen Ferrer, Marin Sekosan, Howard A. Zaren
Journal: Cancer Research (2004)

5260   We previously demonstrated that lower rates of diagnosis of early-stage breast cancer in minority-underserved women, is in part due to inadequate screening practice, with a need for increased repeat mammography (AACR 2003). In an ongoing study, we retrospectively evaluated the quality of screening mammography reports in 439 consecutive patients with breast cancer, treated at the John Stroger Hospital of Cook County, Minority-Based Community Clinical Oncology Program, which serves the medically-indigent in Chicago. A total of 233 women (53%) had screening mammograms. Significantly more patients with early-stage breast cancer (AJCC stage 0-1) had at least one prior mammogram (74% versus 43% for 2-4; Chi-square p
A Calmodulin-Binding Site on Cyclin E Mediates Ca2+-Sensitive G1/S Transitions in Vascular Smooth Muscle Cells
Authors: JaehyunChoi, AndrewChiang, NicolasTaulier, RobertGros, AsifPirani, MansoorHusain
Journal: Circulation Research (2006)

Calcium transients are known to control several transition points in the eukaryotic cell cycle. For example, we have previously shown that a coordinate elevation in the intracellular free calcium ion concentration is required for G1- to S-phase cell cycle progression in vascular smooth muscle cells (VSMC). However, the molecular basis for this Ca2+ sensitivity was not known. Using buffers with differing [Ca2+], we found that the kinase activity of mouse and human cyclin E/CDK2, but not other G1/S-associated cell cycle complexes, was responsive to physiological changes in [Ca2+]. We next determined that this Ca2+-responsive kinase activity was dependent on a direct interaction between calmodulin (CaM), one of the major Ca2+-signal transducers of eukaryotic cells, and cyclin E. Pharmacological inhibition of CaM abrogated the Ca2+ sensitivity of cyclin E/CDK2 and retarded mouse VSMC proliferation by causing G1 arrest. We next defined the presence of a highly conserved 22 amino acid N-terminal CaM-binding mot...