tbuckley/cabot-search huggingface dataset:
Aberrant T cell-mediated immunity in untreated schizophrenic patients: deficient interleukin-2 production
Authors: F Villemain, L Chatenoud, A Galinowski, F Homo-Delarche, D Ginestet, H Loo, E Zarifian, J F Bach
Journal: American Journal of Psychiatry (1989)

The authors examined the immune status at the cellular and humoral levels of 16 untreated schizophrenic patients. No abnormality in the distribution of T cell subsets (CD4+, CD8+) was detected. The proliferative response to the T cell mitogen phytohemagglutinin was normal. No increase in the number of T cells showing activation markers, such as human leukocyte antigens and interleukin-2 receptors, was noted. Conversely, function studies revealed a clear deficiency in interleukin-2 production by purified T cells. This lower production was probably intrinsic to the patients' T cells, since interleukin-2 production showed normal sensitivity to prostaglandin E2-mediated down-regulation by autologous monocytes.
THU0117 Low-Risk Patients Also Benefit from Remission Induction Treatment in Early Rheumatoid Arthritis: Week 52 Results from the Carera Trial
Authors: D. De Cock, L. Corluy, R. Joos, C. Langenaken, V. Taelman, F. Raeman, I. Ravilingien, K. Vandevyvere, J. Lenaerts, E. Geens, P. Geusens, J. Vanhoof, A. Durnez, J. Remans, B. Vander Cruyssen, E. Van Essche, A. Sileghem, G. De Brabanter, J. Joly, S. Meyfroidt, K. Van der Elst, R. Westhovens, P. Verschueren
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Early intensive treatment to target is recommended in severe early Rheumatoid Arthritis (eRA). However, data are lacking in patients presenting without markers of poor prognosis. <h3>Objectives</h3> To compare Methotrexate (MTX) with or without Glucocorticoid (GC) remission induction in a tight control setting over 52 weeks in low-risk patients with eRA. <h3>Methods</h3> CareRA is a two year prospective investigator-initiated multicenter RCT rooted in daily practice. DMARD naïve eRA patients were stratified into a high or low-risk group according to classical prognostic markers (presence of erosions, rheumatoid factor, anti-cyclic citrullinated protein and disease activity). In the low-risk arm, 43 patients were randomized to 15mg MTX monotherapy following a Tight Step Up (MTX-TSU) approach and 47 patients to a Cobra Slim schedule (MTX+30mg prednisone tapered to 5mg daily from W6). GCs were tapered from W28 and stopped at W34. A predefined treat to target approach was applied. Efficacy measures were proportions of DAS28(CRP) remission, good EULAR response, clinically meaningful HAQ response, HAQ=0 and Area Under the Curve (AUC) for DAS28(CRP) (ITT analysis). Radiographic progression was measured via the Sharp Van der Heijde (SvH) method. Adverse events related to therapy (AEs) were registered. No power was calculated in this explorative study. Missing data were imputed via last observation carried forward. <h3>Results</h3> Remission rates at week 52 were 57.4% and 67.4% in the MTX-TSU and Cobra Slim group respectively (p=0.329). MTX-TSU patients had a higher AUC for DAS28(CRP) than Cobra Slim patients over 52 weeks of treatment (p=0.017). No other efficacy scores differed between groups. 76% of X-ray images were available at baseline. Radiographic progression was minimal. SvH scores were 0.7±1.1 and 0.9±1.5 at baseline and changed over 52 weeks 0.2±0.3 and 0.3±0.4 in the MTX-TSU and Cobra Slim group respectively (p=0.184). The numbers of AEs were 48 in 27 MTX-TSU patients and 49 in 20 Cobra Slim patients (p=0.871). Two serious AEs (pulmonary infection and anemia) were registered in the Cobra Slim group. We observed numerically more treatment adaptations and IM/IA GC injections in MTX-TSU patients. <h3>Conclusions</h3> Both RA therapies achieved high remission rates in a tight control setting at week 52. However, remission induction with Cobra Slim resulted in a more rapid and sustained disease control. MTX with or without GC remission induction showed a comparable safety profile. <h3>Disclosure of Interest</h3> None declared
Overcoming Instability of Antibody‐Nanomaterial Conjugates: Next Generation Targeted Nanomedicines Using Bispecific Antibodies
Authors: Christopher B. Howard, Nicholas Fletcher, Zachary H. Houston, Adrian V. Fuchs, Nathan R. B. Boase, Joshua D. Simpson, Lyndon J. Raftery, Tim Ruder, Martina L. Jones, Christopher J. de Bakker, Stephen M. Mahler, Kristofer J. Thurecht
Journal: Advanced Healthcare Materials (2016)

Targeted nanomaterials promise improved therapeutic efficacy, however their application in nanomedicine is limited due to complexities associated with protein conjugations to synthetic nanocarriers. A facile method to generate actively targeted nanomaterials is developed and exemplified using polyethylene glycol (PEG)-functional nanostructures coupled to a bispecific antibody (BsAb) with dual specificity for methoxy PEG (mPEG) epitopes and cancer targets such as epidermal growth factor receptor (EGFR). The EGFR-mPEG BsAb binds with high affinity to recombinant EGFR (KD : 1 × 10(-9) m) and hyperbranched polymer (HBP) consisting of mPEG (KD : 10 × 10(-9) m) and demonstrates higher avidity for HBP compared to linear mPEG. The binding of BsAb-HBP bioconjugate to EGFR on MDA-MB-468 cancer cells is investigated in vitro using a fluorescently labeled polymer, and in in vivo xenograft models by small animal optical imaging. The antibody-targeted nanostructures show improved accumulation in tumor cells compared to non-targeted nanomaterials. This demonstrates a facile approach for tuning targeting ligand density on nanomaterials, by modulating surface functionality. Antibody fragments are tethered to the nanomaterial through simple mixing prior to administration to animals, overcoming the extensive procedures encountered for developing targeted nanomedicines.
WORK OF COMMISSION ON FINANCING OF HIGHER EDUCATION
Authors: Laird Bell
Journal: JAMA (1952)

The Commission on Financing of Higher Education is a private agency sponsored by the Association of American Universities and created to study and report on the present situation in meeting the financial needs of higher education in this country. Our three year study was made possible by grants from the Rockefeller Foundation and the Carnegie Corporation of New York. Our final reports, to be issued some time this year, are addressed to all those interested in the well-being of American higher education. Our commission is made up of 12 men, 8 of whom are university administrators and 4 of whom are laymen who are serving on boards of trustees. The Survey of Medical Education, conducted by a survey committee sponsored by the Council on Medical Education and Hospitals and the Association of American Medical Colleges, is interested in more than costs. The commission has met with the survey committee, and
Increased Risk for Gastrointestinal Cancer in Childhood Cancer Survivors
Authors: T O Henderson, K C Oeffinger, J Whitton, W Leisenring, J Neglia, A Meadows, C Crotty, D T Rubin, L Diller, P Inskip, S A Smith, M Stovall, L S Constine, S Hammond, G T Armstrong, L L Robison, P C Nathan
Journal: Annals of Internal Medicine (2012)
Obsessive-compulsive symptoms in panic disorder
Authors: T A Mellman, T W Uhde
Journal: American Journal of Psychiatry (1987)

Previous reports have noted an increased prevalence of obsessive-compulsive symptoms in patients with panic disorder. The authors found a prevalence of obsessive-compulsive symptoms in 19 (27%) of 70 patients with panic disorder. Compared to a subgroup of 25 patients with classic features of panic disorder and no obsessive-compulsive symptoms, the subgroup with obsessive-compulsive symptoms had an earlier onset of illness, were more likely to have personal and family histories of major depression and substance abuse, and showed a poorer outcome after treatment.
Prenatal Polybrominated Diphenyl Ether Exposure and Body Mass Index in Children Up To 8 Years of Age
Authors: Ann M. Vuong, Joseph M. Braun, Andreas Sjödin, Glenys M. Webster, Kimberly Yolton, Bruce P. Lanphear, Aimin Chen
Journal: Environmental Health Perspectives (2016)

Background:Prenatal exposure to endocrine disruptors has been associated with increased risk of childhood obesity. However, epidemiologic studies on polybrominated diphenyl ethers (PBDEs) are limited despite animal studies indicating PBDEs' potential role as an obesogen.Objectives:We investigated whether maternal concentrations of BDEs 28, 47, 99, 100, 153, and ΣPBDEs during pregnancy were associated with anthropometric measures in children aged 1–8 years.Methods:We examined 318 mother–child pairs in the Health Outcomes and Measures of the Environment (HOME) Study, a birth cohort enrolled from 2003 through 2006 (Cincinnati, OH). Serum PBDEs were measured at 16 ± 3 weeks gestation. We measured child height (1–8 years), weight (1–8 years), body mass index (BMI) (2–8 years), waist circumference (4–8 years), and body fat (8 years). To account for repeated measures, we used linear mixed models and generalized estimating equations to estimate associations between maternal PBDEs and child anthropometric measures.Results:We found no statistically significant associations between prenatal PBDEs and height or weight z-score. A 10-fold increase in maternal serum BDE-153 was associated with lower BMI z-score (β = –0.36; 95% CI: –0.60, –0.13) at 2–8 years, smaller waist circumference (β = –1.81 cm; 95% CI: –3.13, –0.50) at 4–8 years, and lower percent body fat (β = –2.37%; 95% CI: –4.21, –0.53) at 8 years. A decrease in waist circumference at 4–8 years was observed with a 10-fold increase in BDE-100 (β = –1.50 cm; 95% CI: –2.93, –0.08) and ΣPBDEs (β = –1.57 cm; 95% CI: –3.11, –0.02).Conclusions:Reverse causality may have resulted in prenatal PBDEs, particularly BDE-153, and decreased BMI, waist circumference, and body fat.Citation:Vuong AM, Braun JM, Sjödin A, Webster GM, Yolton K, Lanphear BP, Chen A. 2016. Prenatal polybrominated diphenyl ether exposure and body mass index in children up to 8 years of age. Environ Health Perspect 124:1891–1897; http://dx.doi.org/10.1289/EHP139
One versus two years of elastic compression stockings for prevention of post-thrombotic syndrome (OCTAVIA study): randomised controlled trial
Authors: G C Mol, M A van de Ree, F A Klok, M J A M Tegelberg, F B M Sanders, S Koppen, O de Weerdt, T Koster, M M C Hovens, H A H Kaasjager, R E Brouwer, E Kragten, C G Schaar, W Spiering, W P Arnold, D H Biesma, M V Huisman
Journal: BMJ (2016)

<b>Objective</b>&nbsp;To study whether stopping elastic compression stockings (ECS) after 12 months is non-inferior to continuing them for 24 months after proximal deep venous thrombosis. <b>Design</b>&nbsp;Multicentre single blind non-inferiority randomised controlled trial. <b>Setting</b>&nbsp;Outpatient clinics in eight teaching hospitals in the Netherlands, including one university medical centre. <b>Participants</b>&nbsp;Patients compliant with compression therapy for 12 months after symptomatic, ultrasound proven proximal deep venous thrombosis of the leg. <b>Interventions</b>&nbsp;Continuation or cessation of ECS 12 months after deep venous thrombosis. <b>Main outcome measures</b>&nbsp;The primary outcome was the incidence of post-thrombotic syndrome 24 months after diagnosis of deep venous thrombosis, as assessed by the standardised Villalta scale in an intention to treat analysis. The predefined non-inferiority margin was 10%. The main secondary outcome was quality of life (VEINES-QOL/Sym). <b>Results</b>&nbsp;518 patients compliant with ECS and free of post-thrombotic syndrome were randomised one year after diagnosis of deep venous thrombosis to stop or continue ECS therapy for another year. In the stop-ECS group, 51 of 256 patients developed post-thrombotic syndrome, with an incidence of 19.9% (95% confidence interval 16% to 24%). In the continue-ECS group, 34 of 262 patients developed post-thrombotic syndrome (incidence 13.0%, 9.9% to 17%), of whom 85% used ECS six or seven days a week during the study period, for an absolute difference of 6.9% (95% confidence interval upper limit 12.3%). Because the upper limit of the 95% confidence interval exceeds the predefined margin of 10%, non-inferiority was not reached. The number needed to treat to prevent one case of post-thrombotic syndrome by continuing ECS was 14 (95% confidence interval lower limit 8). Quality of life did not differ between the two groups. <b>Conclusion</b>&nbsp;Stopping ECS after one year in compliant patients with proximal deep venous thrombosis seemed not to be non-inferior to continuing ECS therapy for two years in this non-inferiority trial. <b>Trial registration</b>&nbsp;Netherlands Trial Register NTR1442.
Infectivity of Friend Murine Leukemia Virus for Hamster Cells
Authors: A Ishimoto
Journal: JNCI Journal of the National Cancer Institute (1985)

Hamster-adapted Friend murine leukemia virus (F-MuLV) infected hamster cells and produced an XC-positive progeny. However, the sensitivity of hamster-adapted F-MuLV's to hamster cells was about 100 times lower than that to mouse cells. Hamster cells chronically infected with F-MuLV in vitro produced progeny virus in titers comparable to those in similarly infected mouse cells. Xenotropic and amphotropic murine leukemia virus can infect hamster cells when phenotypically mixed with the F-MuLV. Murine sarcoma virus pseudotyped with the F-MuLV easily induced sarcomas in hamsters and transformed hamster cells in vitro.
Smoking-Associated DNA Methylation Biomarkers and Their Predictive Value for All-Cause and Cardiovascular Mortality
Authors: Yan Zhang, Ben Schöttker, Ines Florath, Christian Stock, Katja Butterbach, Bernd Holleczek, Ute Mons, Hermann Brenner
Journal: Environmental Health Perspectives (2015)

BackgroundWith epigenome-wide mapping of DNA methylation, a number of novel smoking-associated loci have been identified.ObjectivesWe aimed to assess dose–response relationships of methylation at the top hits from the epigenome-wide methylation studies with smoking exposure as well as with total and cause-specific mortality.MethodsIn a population-based prospective cohort study in Germany, methylation was quantified in baseline blood DNA of 1,000 older adults by the Illumina 450K assay. Deaths were recorded during a median follow-up of 10.3 years. Dose–response relationships of smoking exposure with methylation at nine CpGs were modeled by restricted cubic spline regression. Associations of individual and aggregate methylation patterns with all-cause, cardiovascular, and cancer mortality were assessed by multiple Cox regression.ResultsClear dose–response relationships with respect to current and lifetime smoking intensity were consistently observed for methylation at six of the nine CpGs. Seven of the nine CpGs were also associated with mortality outcomes to various extents. A methylation score based on the top two CpGs (cg05575921 and cg06126421) showed the strongest associations with all-cause, cardiovascular, and cancer mortality, with adjusted hazard ratios (95% CI) of 3.59 (2.10, 6.16), 7.41 (2.81, 19.54), and 2.48 (1.01, 6.08), respectively, for participants with methylation levels in the lowest quartile at both CpGs. Adding methylation at those two CpGs into a model that included the variables of the Systematic Coronary Risk Evaluation chart for fatal cardiovascular risk prediction improved the predictive discrimination.ConclusionThe novel methylation biomarkers are highly informative for both smoking exposure and smoking-related mortality outcomes. In particular, these biomarkers may substantially improve cardiovascular risk prediction. Nevertheless, the findings of the present study need to be further validated in additional large longitudinal studies.CitationZhang Y, Schöttker B, Florath I, Stock C, Butterbach K, Holleczek B, Mons U, Brenner H. 2016. Smoking-associated DNA methylation biomarkers and their predictive value for all-cause and cardiovascular mortality. Environ Health Perspect 124:67–74; http://dx.doi.org/10.1289/ehp.1409020
Interim Safety and Efficacy of Pertuzumab, Trastuzumab and Vinorelbine for First-Line (1L) Treatment of Patients (Pts) with Her2-Positive Locally Advanced or Metastatic Breast Cancer (Mbc)
Authors: M. Andersson, J.M. Lopez-Vega, T. Petit, C. Zamagni, U. Freudensprung, S. Robb, E. Restuccia, E.A. Perez
Journal: Annals of Oncology (2014)

ABSTRACT   Aim: 1L treatment of pts with HER2-positive MBC with vinorelbine (V) + trastuzumab (T) has similar efficacy to docetaxel (D) + T but with fewer adverse events (AEs) (the HERNATA study). Pertuzumab (P) + T + D significantly improves progression-free survival (PFS) and overall survival (OS) vs. T + D in 1L HER2-positive MBC (the CLEOPATRA study). VELVET is a Phase II study of P + T + V for 1L treatment of HER2-positive advanced breast cancer (BC), with Cohort 1 (C1) receiving P + T as separate infusions and Cohort 2 (C2) receiving P + T in a single saline infusion bag after the first cycle.  Methods: Pts must have HER2-positive MBC or locally advanced BC and no prior non-hormonal anti-cancer therapy in the metastatic setting. The initial dose of P is 840 mg followed by 420 mg every 3 weeks (Q3W); the initial dose of T is 8 mg/kg followed by 6 mg/kg Q3W; V is administered at 25 mg/m2 in Cycle 1 followed by 30–35 mg/m2 on Days 1 and 8 of each subsequent cycle Q3W. The primary endpoint is objective response rate based on best overall response. Secondary endpoints include PFS, OS and safety.  Results: C1 and C2 are fully enrolled with 106 and 107 treated pts, respectively. At initial diagnosis, 32% (C1) and 25% (C2) of pts had MBC. In the neoadjuvant and adjuvant settings, 56% (C1) and 32% (C2) of pts had received chemotherapy, including a taxane (39% and 21%) or an anthracycline (39% and 26%); 41% and 18% had prior T exposure. At the data cut-off of 5 March 2014, the median number of cycles received in C1 was 15 for P + T and 9.5 for V, and in C2 was 10 for P + T and 9 for V. AEs were reported by 99% (C1) and 98% (C2) of pts. Grade ≥3 AEs were reported by 59% (C1) and 69% (C2) of pts. The grade ≥3 AEs in ≥5 pts in either cohort were neutropenia, leucopenia, diarrhoea, fatigue, febrile neutropenia, hypertension and asthenia. Serious AEs were reported by 29% (C1) and 33% (C2) of pts. Interim best overall response data from C1 will be presented.  Conclusions: These interim safety data show that P + T + V has an acceptable AE profile with no unexpected safety signals. Administration of P + T sequentially, or in a single saline infusion bag, is feasible from a safety standpoint. Interim best overall response data from C1 will be presented.  Disclosure: M. Andersson: has participated in an advisory board on behalf of Roche; T. Petit: has participated in an advisory board on behalf of Roche; U. Freudensprung: is an employee of Roche; S. Robb: is an employee of Roche; E. Restuccia: is an employee of and owns stocks in Roche. All other authors have declared no conflicts of interest.
Abstract 373: Analytical and clinical validation of an EpCAM-independent assay for CTC detection in peripheral blood of early breast cancer patients based on Cytokeratin-19 (CK-19) RT-qPCR
Authors: Areti Strati, Athina Markou, Aliki Stathopoulou, Stella Apostolaki, Dimitris Mavroudis, Vasilis Georgoulias, Evi S. Lianidou
Journal: Cancer Research (2015)

Abstract Introduction: The aim of our study was to evaluate the prognostic significance of our previously developed EpCAM independent RT-qPCR assay for CK-19 mRNA (Stathopoulou et al, Int J Cancer 2006) and validate its analytical and clinical performance in early breast cancer. Methods: Quality control on analytical sensitivity and specificity, linearity, intra- and inter-assay reproducibility, and stability of the external standard used for the preparation of the calibration curves was performed. Reproducibility of the assay between our labs was evaluated by analyzing 26 cDNAs. The prognostic significance of the assay in respect to DFI and OS was evaluated by analysing peripheral blood of 179 patients with stage I/II breast cancer postoperatively, before the administration of adjuvant chemotherapy. Results: The limit of detection (LOD) is 3 copies/reaction and limit of Quantitation (LOQ) 10 copies/reaction. The linear range of the calibration curve was 10-105copies/reaction and the intra- and inter-assay reproducibility are shown below: CK19 transcriptsReproducibility of the assay (n = 3)copies/reactionIntra-assay RSD (%)Inter-assay RSD (%)101.973.151020.932.241030.450.861040.122.581050.11.52 The inter-lab reproducibility of the assay was evaluated by analyzing 26 cDNA samples in both labs and there was a 100% concordance. During the follow up period (8 years) 32/179 (17.9%) patients relapsed and 18/179 (10%) patients died from the disease. 45/179 (25.1%) samples were found positive for CK-19 and 134/179 (74.9%) negative. In the group of CK-19 positive patients 15/45(33.3%) relapsed and 9/45(20.0%) died while in the group of CK-19 negative patients 17(12.7%) patients relapsed and 9(6.7%) died. Kaplan-Meier analysis showed that CK-19 mRNA positivity was significantly associated with DFI (P = 0.014) and OS (P = 0.051). Conclusions: This EpCAM independent assay can be used for a high-throughput detection of CTCs in peripheral blood and has prognostic significance in early breast cancer. Citation Format: Areti Strati, Athina Markou, Aliki Stathopoulou, Stella Apostolaki, Dimitris Mavroudis, Vasilis Georgoulias, Evi S. Lianidou. Analytical and clinical validation of an EpCAM-independent assay for CTC detection in peripheral blood of early breast cancer patients based on Cytokeratin-19 (CK-19) RT-qPCR. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 373. doi:10.1158/1538-7445.AM2015-373
The Anticipated Clinical and Economic Effects of 90–90–90 in South Africa
Authors: Rochelle P. Walensky, Ethan D. Borre, Linda-Gail Bekker, Stephen C. Resch, Emily P. Hyle, Robin Wood, Milton C. Weinstein, Andrea L. Ciaranello, Kenneth A. Freedberg, A. David Paltiel
Journal: Annals of Internal Medicine (2016)

The Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 global treatment target aims to achieve 73% virologic suppression among HIV-infected persons worldwide by 2020.
P2-141: Antitumor effect of antibody against a novel antigen (UOEH-LC-1) on lung cancer xenotransplanted into SCID mice
Authors: Makiko Mizukami, Takeshi Hanagiri, Manabu Yasuda, Yoshika Nagata, Yoshinobu Ichiki, Masakazu Sugaya, Tomoko So, Mitsuhiro Takenoyama, Kenji Sugio, Kosei Yasumoto
Journal: Journal of Thoracic Oncology (2007)