tbuckley/cabot-search huggingface dataset:
Abstract 21307: Beta-Blockers Inferior to Calcium Channel Blockers in Hypertrophic Cardiomyopathy
Authors: Saurabh Gombar, Kegan J Moneghetti, Alison Callahan, Ken Jung, Matthew T Wheeler
Journal: Circulation (2017)

Introduction: There have been no large, randomized comparison trials in the medical treatment of hypertrophic cardiomyopathy (HCM). Beta-blockers (BB) have been used as first line therapy based on evidence from small studies (combined N&lt;500). Preclinical evidence suggests calcium channel blockers (CCB) may have beneficial molecular effects in sarcomere-mutation driven HCM. We hypothesized that HCM patients treated with CCB would have improved outcomes versus patients treated with BB. Methods: We queried claims data of 115 million unique patients from 2007 to 2014 for records with a HCM diagnosis. We divided HCM patients into those prescribed only beta-blockers (N=5141) or those prescribed only calcium-channel blockers (N=993) during the follow up period (4.4 +/- 2.1 years). We evaluated the time to event of atrial fibrillation, ventricular arrhythmia, heart failure, myectomy, ICD implant, or sudden cardiac arrest as well as a combined endpoint. Survival analysis was performed on cohorts matched for age, gender, year of entry, and length of record; logrank test was used to compare groups. Results: The cohort treated with BB, when compared to matched patients treated with CCB (n=984 each group), were found to have a significant increase in the rate of new diagnoses of atrial fibrillation, ventricular arrhythmia, heart failure, or myectomy (logrank p all &lt;0.01). Overall (Figure), 152 of 984 patients treated with CCB as compared to 283 of 984 patients treated with BB met the combined endpoint (p&lt;0.001), driven by fewer diagnoses of atrial fibrillation (58 vs 109 outcomes) and ventricular arrhythmias (43 vs 105 outcomes). Conclusion: We find that treatment of HCM patients with calcium channel blockers is associated with fewer adverse outcomes when compared to a matched cohort treated with beta-blockers. Further investigation is necessary to determine if these findings warrant a change of current clinical practice. Figure.
Publisher Correction: Stimulation of 3D osteogenesis by mesenchymal stem cells using a nanovibrational bioreactor
Authors: Penelope M. Tsimbouri, Peter G. Childs, Gabriel D. Pemberton, Jingli Yang, Vineetha Jayawarna, Wich Orapiriyakul, Karl Burgess, Cristina González-García, Gavin Blackburn, Dilip Thomas, Catalina Vallejo-Giraldo, Manus J. P. Biggs, Adam S. G. Curtis, Manuel Salmerón-Sánchez, Stuart Reid, Matthew J. Dalby
Journal: Nature Biomedical Engineering (2017)
A phase II trial of carboplatin plus S-1 for elderly patients with advanced non-small cell lung cancer with wild-type EGFR: The Okayama Lung Cancer Study Group Trial 1202 (OLCSG1202)
Authors: A. Bessho, N. Ochi, S. Kuyama, T. Umeno, G. Ikeda, D. Harada, N. Nogami, K. Ninomiya, D. Kishino, K. Chikamori, N. Fujimoto, K. Hotta, N. Takigawa, K. Kiura
Journal: Annals of Oncology (2017)
Phase 3, randomized KEYNOTE-240 study of pembrolizumab (Pembro) versus best supportive care (BSC) for second-line advanced hepatocellular carcinoma (HCC)
Authors: S.L. Chan, R.S. Finn, A.X. Zhu, J. Knox, A-L Cheng, A.B. Siegel, O. Bautista, M. Kudo
Journal: Annals of Oncology (2017)
Motifs de la nette augmentation des infections génitales à chlamydia signalée au cours des premiers mois de l’année 2007 en Suède
Authors: I Velicko, S Kühlmann-Berenzon, A Blaxhult
Journal: Eurosurveillance (2007)

Apres une augmentation continue de l’incidence declaree du chlamydia au cours des 10 dernieres annees en Suede, l’incidence a connu une baisse de 2 % en 2006.
Brexit and wage caps are blamed for UK doctor and nurse shortage
Authors: Rory Watson
Journal: BMJ (2017)

Existing “resilience challenges” in the UK’s healthcare workforce could become increasingly serious, the European Commission and the Organisation for Economic Co-operation and Development have warned in a joint analysis of the state of healthcare in the UK,1 one of 28 individual EU country studies released last week.

Using 2015 data, the report on the UK noted that, despite steady increases in recent decades, the number of doctors in the country was the third lowest in the EU, at 2.8 per 1000 population (the EU average is 3.6 per 1000). Nursing numbers …
Abstract 194: Neurological Prognosis Of Infliximab Therapy Against Immunoglobulin Refractory Kawasaki Disease
Authors: Nobuyuki Katsumata, Yoshimi Kaga, Keiichi Koizumi, Takako Toda, Hiroaki Kise, Youhei Hasebe, Kanji Sugita, Minako Hoshiai
Journal: Circulation (2015)

Background: Infliximab (IFX) which is an anti-TNFα monoclonal antibody is effective in the treatment of gamma globulin treatment (IVIG) resistance Kawasaki disease (KD) . It has been reported that TNFα adjusts the gene expression of myelin protein components and cause demyelination. Furthermore, at IFX treatment, the possibility of onset of the demyelinating disease in rheumatic diseases, and the exacerbation of the underlying disease in demyelinating disease have been suggested. Objective: To evaluate the neurological prognosis in pediatric cases who underwent treatment with IFX against IVIG resistant KD, were examined for the presence or absence of demyelination and delayed myelination. Methods: It is targeted for the 10 cases of IVIG refractory KD patients who received IFX 5mg/kg administration. Informed consent was obtained from the parents of all participants. We evaluated the candidate child’s mental development by the intelligence test (WISC-IV) and investigated the presence of demyelination and delayed myelination by brain MRI. Results: All cases were above 6 years old, and more than a year had passed since they received medication of IFX. In all cases, abnormalities of neurological findings and psychomotor developmental delay after treatment were not observed. There was no obvious abnormality in eight cases (boys of 5 cases, girls of 3 cases, 6-11 years of age at the investigation) who underwent the WISC- IV; Full Scale IQ 97.4 ± 12.5, Verbal Comprehension Index 92.8 ± 11.9, Perceptual Reasoning Index 103.9 ± 17.9, Working Memory Index 97.1 ± 15.5, Processing Speed Index 100.9 ± 9.7. In addition, in nine cases (boys of 4 cases, girls of 5 cases, 6-16 years of age at the investigation) who underwent brain MRI, there was no evidence of demyelination and delayed myelination. Conclusion: In this study, there were not existed the findings of demyelination, delayed myelination, and mental retardation in IFX administration cases. However, it is necessary to repeat examination how the IFX medication to children make adverse effects on central nervous system.
New test in tribunal cases could find more doctors acted dishonestly
Authors: Clare Dyer
Journal: BMJ (2017)

A new test for dishonesty has been adopted by medical practitioners tribunals that could increase the chances that doctors will be found to have acted dishonestly.

Tribunals will no longer follow the two stage “Ghosh” test for dishonesty, which was said in a UK Supreme Court judgment last month to be wrong, but will use the simpler test that is now applied in civil cases.

The new test was followed when the General Medical Council won an appeal on 20 November overturning a tribunal finding that Kennedy Krishnan, a doctor who worked for a locum agency while on sick leave from his main employers, was not dishonest. …
ERα Binding by Transcription Factors NFIB and YBX1 Enables FGFR2 Signaling to Modulate Estrogen Responsiveness in Breast Cancer
Authors: Thomas M. Campbell, Mauro A. A. Castro, Kelin Gonçalves de Oliveira, Bruce A. J. Ponder, Kerstin B. Meyer
Journal: Cancer Research (2017)

Abstract Two opposing clusters of transcription factors (TF) have been associated with the differential risks of estrogen receptor positive or negative breast cancers, but the mechanisms underlying the opposing functions of the two clusters are undefined. In this study, we identified NFIB and YBX1 as novel interactors of the estrogen receptor (ESR1). NFIB and YBX1 are both risk TF associated with progression of ESR1-negative disease. Notably, they both interacted with the ESR1-FOXA1 complex and inhibited the transactivational potential of ESR1. Moreover, signaling through FGFR2, a known risk factor in breast cancer development, augmented these interactions and further repressed ESR1 target gene expression. We therefore show that members of two opposing clusters of risk TFs associated with ESR1-positive and -negative breast cancer can physically interact. We postulate that this interaction forms a toggle between two developmental pathways affected by FGFR2 signaling, possibly offering a junction to exploit therapeutically. Significance: Binding of the transcription factors NFIB and YBX1 to the estrogen receptor can promote an estrogen-independent phenotype that can be reverted by inhibiting FGFR2 signaling. Cancer Res; 78(2); 410–21. ©2017 AACR.
Sorveglianza europea delle infezioni sessualmente trasmesse - un intervento tempestivo ed appropriato
Authors: K. A. Fenton, J Giesecke, F F Hamers
Journal: Eurosurveillance (2001)

Le infezioni sessualmente trasmesse (IST), compreso l’HIV, rappresentano una minaccia significativa per la salute e il benessere degli europei e richiedono un intervento concertato e sostenuto. Negli ultimi dieci anni, e considerevolmente aumentato il numero di casi di IST notificati, tra i quali la Neisseria gonorrhoeae resistente agli antimicrobici (1), e recentemente sono state notificate in molti stati membri dell'Unione Europea (UE) epidemie di sifilide (2, 3). Sembrano particolarmente colpiti i giovani, omosessuali maschi e coloro che hanno difficile accesso all'assistenza sanitaria (tra cui i servizi di prevenzione e di educazione sanitaria). I fattori determinanti sembrano essere l'aumento dei viaggi e delle migrazioni, i comportamenti sessuali ad alto rischio, e un deterioramento delle risposte di sanita pubblica al controllo delle IST (per esempio la notifica del partner). Molti di questi trend demografici e comportamentali sono simili per tutti gli stati dell'UE, cosi come lo e il desiderio di sviluppare e implementare programmi efficaci di prevenzione e controllo delle IST.
The uncontrollable nature of early learning experiences
Authors: Katelyn Kurkul, Kathleen Corriveau
Journal: Behavioral and Brain Sciences (2017)

Abstract Early learning experiences shape the development of the behavioral constellation of deprivation (BCD) proposed by Pepper &amp; Nettle (P&amp;N). There is considerable variability in early learning experiences across diverse socioeconomic status (SES) backgrounds, particularly when it comes to language. Here, we discuss how early learning experiences are beyond the control of the individual and subsequently contribute to behaviors in P&amp;N's constellation.
Rapidly growing, moderately differentiated HCC: A clinicopathological characteristic of HCC occurrence after IFN-free DAA therapy?
Authors: Yasuhiko Nakao, Satoru Hashimoto, Seigo Abiru, Atsumasa Komori, Kazumi Yamasaki, Shinya Nagaoka, Akira Saeki, Shigemune Bekki, Yuki Kugiyama, Tamotsu Kuroki, Masahiro Ito, Kazuhiko Nakao, Hiroshi Yatsuhashi
Journal: Journal of Hepatology (2017)

We read with great interest the report by Reig et al. describing unexpected early tumor recurrence in patients with hepatitis C virus-related hepatocellular carcinoma (HCC) undergoing treatment with interferon (IFN)-free direct-acting antivirals (DAA).1 There is some debate as to whether DAA therapy increases the risk of liver cancer. We report herein a clinicopathological case series of patients who experienced HCC occurrence after DAA therapy, in order to shed some light on this emerging issue.
Diminished microRNA-29b level is associated with BRD4-mediated activation of oncogenes in cutaneous T-cell lymphoma
Authors: Rebecca Kohnken, Jing Wen, Bethany Mundy-Bosse, Kathleen McConnell, Ashleigh Keiter, Leah Grinshpun, Alex Hartlage, Max Yano, Betina McNeil, Nitin Chakravarti, Basem William, James E. Bradner, Michael A. Caligiuri, Pierluigi Porcu, Anjali Mishra
Journal: Blood (2017)
P2.07-006 Irinotecan Augmented Anti-Tumor Activity of Anti-PD-L1 through Enhancing CD8 Proliferation Regardless of Its Hematotoxicity
Authors: T. Iwai, M. Sugimoto, D. Wakita, K. Yorozu, M. Kurasawa, K. Yamamoto
Journal: Journal of Thoracic Oncology (2017)
CNS distribution of WP744; A novel anthracyclines with activity against glioblastoma multiforme
Authors: Neil Thapar, Catherine R. Scholz, Mary J. Johansen, Charles Conrad, Waldemar Priebe, Jay Thapar, Izabela Fokt, Kirk Culotta, Timothy Madden
Journal: Cancer Research (2004)

5406   WP744 differs from clinically available anthracyclines in than it is able to circumvent P-gp and MRP1-mediated cellular efflux while possessing enhanced activity in cells overexpressing Bcl-2 and its homolog Bcl-X L . This compound demonstrates substantial activity against GBM cell lines in vitro and in vivo. To complement preclinical dose-finding, PK and toxicology trials we investigated the CNS distribution of WP744 following single IV and oral (PO) doses in both orthotopic tumor bearing (TB) and non-tumor bearing (NTB) mice. NTB CD 1  or TB NuNu nude-U87MG bearing mice (M ≈ 38 gm) were administered WP744 at 20 mg/kg as an IV bolus via the tail vein (0.2 ml; vehicle, DMSO:D5W, 5:95, v/v) or by oral gavage (0.5 ml; vehicle, DMSO:D5W, 5:95, v/v). In the NTB CD-1 mice blood samples (collected in heparin containing tubes) and brain tissue from groups of animals (8 per timepoint) prior to and at selected timepoints between 1 and 24 hr following IV bolus drug administration. In the TB mice blood, tumor, and contralateral brain samples were harvested at 0.5, 1, and 3 hrs post dose. WP744 was extracted from plasma using a solid phase extraction method and in tissues using a liquid-liquid extraction method. Standard curves were generated for each tissue type. All samples were analyzed using LC/MS/MS with ES ionization operating in positive ion mode. This method has an LLQ of 0.25 ng/ml and was linear throughout a dynamic range of 0.25 ng/ml to 1.0 μg/ml in blood and tissues. Comparison of AUC data from both IV and PO dosing in the NTB mice yielded an estimated fraction absorbed of 0.04; therefore no further tissue distribution studies following PO dosing were performed. In the groups receiving IV drug the peak plasma WP744 concentration was > 1 μg/ml declining to 360 ng/ml in one hour. The mean measured brain tissue concentration at one hour was 65% of the simultaneously measured plasma concentration. Mean WP744 concentrations declined linearly over time in both the plasma and CNS, however CNS tissue concentrations of WP744 were >25 ng/gm tissue at 24 hours and up to 2-fold > that measured simultaneously in plasma. Preliminary studies in the TB model demonstrate similar findings. In these studies brain and tumor concentrations were up to 52 % of the simultaneously measured plasma concentration (≈500 ng/ml) 30 minutes after injection, and at one hour tumor concentrations were > those measured in the surrounding CNS tissue. These data, coupled with the initial efficacy and toxicology data suggest that WP744 may be an excellent new agent for the treatment of brain tumors.
Abstract 12011: Time in Therapeutic Range and Major Adverse Outcomes in Anticoagulated Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention on Triple Antithrombotic Therapy: The Atrial Fibrillation Undergoing Coronary Artery Stenting (AFCAS) Registry
Authors: Marco Proietti, K.E. Juhani Airaksinen, Andrea Rubboli, Axel Schlitt, Tuomas Kiviniemi, Pasi P Karjalainen, Gregory Y Lip
Journal: Circulation (2016)

Introduction: Combination of oral anticoagulation (OAC) and antiplatelet therapy is used in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention stent (PCI-S) implantation but is associated with increased bleeding, especially if triple antithrombotic therapy (TAT) is used. Hypothesis: Adverse outcomes in patients prescribed with TAT after a PCI-S are related to quality of anticoagulation control as reflected by time in therapeutic range (TTR). Methods: Subgroup analysis from the AFCAS registry in patients assigned to TAT at discharge. TTR was calculated using Rosendaal method. Outcomes were determined for TTR tertiles (T1:&lt;56.8%, T2:56.9-93.8%, T3:&gt;93.9%). Results: Of 963 patients originally enrolled, 470 (48.8%) were prescribed TAT at discharge and had all data available for this analysis. Median [IQR] TTR was 80.0% [45.3-100%]. After a mean±SD follow-up of 343±94 days, crude major bleeding rates were progressively lower with increasing TTR tertiles (T1 vs. T2 vs. T3: 10.3% vs. 4.7% vs. 2.3%, p=0.006). Kaplan Meier survival analysis demonstrated a progressively lower risk for major bleeding across TTR tertiles (p=0.006; Figure). Patients in the highest TTR tertile (T3) had a lower risk for major adverse coronary and cerebrovascular events (MACCE) compared to those in T1 and T2 (Log-Rank:4.420, p=0.036). On Cox regression analysis (adjusted for age, gender, AF type, CHA 2 DS 2 -VASc, PCI-S indication/setting), T2 and T3 were inversely associated with major bleeding (HR:0.39, 95%CI:0.15-1.00, p=0.050 and HR:0.21, 95%CI:0.07-0.63, p=0.005). Continuous TTR was also inversely associated with major bleeding (HR:0.98, 95%CI:0.97-0.99, p&lt;0.001). Patients in T3 had the lowest risk of MACCE (HR:0.58, 95%CI:0.35-0.96, p=0.033). Conclusions: In AF patients undergoing a PCI-S prescribed TAT, good quality anticoagulation control (as reflected by TTR) is related to better cardiovascular and bleeding outcomes during follow-up.
Abstract 18714: Arterial Stiffness Predicts the Increase in Systolic Blood Pressure in Adults - The ELSA-Brasil Study
Authors: Luisa C Brant, Lidyane V Camelo, Luana G Giatti, Rosane Griep, Antonio L Ribeiro, Jose G Mill, Sandhi M Barreto
Journal: Circulation (2017)

Background:  The temporal relationship between arterial stiffness and systolic blood pressure (SBP) is not completely defined and may be bidirectional. While arterial stiffness increase pulse pressure, hypertension may damage the vessels leading to higher arterial stiffness.  Objective:  To investigate whether arterial stiffness measured by carotid femoral pulse wave velocity (cfPWV) at the baseline of the ELSA-Brasil cohort study (2008-2010) predicts SBP in the second examination (2012-2014), independently of baseline SBP.   Methods:  A total of 9,626 adults from ELSA-Brasil, free of cardiovascular diseases and use of antihypertensive medication at baseline (45.1% men, age range: 35-74), with valid measures of cfPWV and SBP in both examinations were included. Blood pressure was measured three times after a resting period of 5 min and the mean of the last two readings was used. The following variables were used for adjustments: age, sex, race, education, total cholesterol/HDL, body mass index, diabetes, smoking, alcohol intake, level of physical activity, use of antihypertensives at second examination and baseline SBP. Multiple linear regression models were used.   Results:  The mean follow-up period was 3.9 years (SD: 0.57, range: 2-6 years). In the univariate analysis, a 1m/s increase in cfPWV at baseline was associated with a mean increase in SBP in the second examination of 4 mmHg (95%CI: 3.8; 4.1, p    Conclusion:  Higher arterial stiffness is an independent predictor of a longitudinal increase in SBP after a mean follow up of 3.9 years, suggesting that higher arterial stiffness may predict hypertension and may be used to identify individuals at higher risk of developing hypertension.
Updated Estimates Suggest a Much Higher Prevalence of Arthritis in United States Adults Than Previous Ones
Authors: S. Reza Jafarzadeh, David T. Felson
Journal: Arthritis & Rheumatology (2017)

National estimates of arthritis prevalence rely on a single survey question about doctor-diagnosed arthritis without using survey information on joint symptoms, even though some subjects with only the latter have been shown to have arthritis. The sensitivity of the current surveillance definition is only 53% and 69% in subjects ages 45-64 years and ages ≥65 years, respectively, resulting in misclassification of nearly one-half and one-third of subjects in those age groups. This study was undertaken to estimate arthritis prevalence based on an expansive surveillance definition that is adjusted for the measurement errors in the current definition.Using the 2015 National Health Interview Survey, we developed a Bayesian multinomial latent class model for arthritis surveillance based on doctor-diagnosed arthritis, joint symptoms, and whether symptom duration exceeded 3 months.Of 33,672 participants, 19.3% of men and 16.7% of women ages 18-64 years and 15.7% of men and 13.5% of women ages ≥65 years affirmed joint symptoms without doctor-diagnosed arthritis. The measurement error-adjusted prevalence of arthritis was 29.9% (95% Bayesian probability interval [95% PI] 23.4-42.3) in men ages 18-64 years, 31.2% (95% PI 25.8-44.1) in women ages 18-64 years, 55.8% (95% PI 49.9-70.4) in men ages ≥65 years, and 68.7% (95% PI 62.1-79.9) in women ages ≥65 years. Arthritis affected 91.2 million adults (of 247.7 million; 36.8%) in the US in 2015, which included 61.1 million persons between 18 and 64 years of age (of 199.9 million; 30.6%). Our arthritis prevalence estimate was 68% higher than the previously reported national estimate.Arthritis prevalence in the US population has been substantially underestimated, especially among adults younger than 65 years of age.
Folate: Friend or Foe? An investigation into the opposing roles of folate in glioma
Authors: Michelle Claire Rudd, Robert Lea, Jane Alder
Journal: Neuro-Oncology (2018)

Survival rates in patients with glioblastoma have shown little improvement over the last 40 years due to the heterogeneity of tumours and the difficulty of specifically targeting the tumour whilst sparing surrounding healthy tissue. Altered gene methylation is often observed in glioma cells, and methylating agents such as folate may reverse aberrant methylation. Folate treatment has shown a beneficial effect, reducing risk of certain cancers (colorectal, breast, squamous cell carcinoma), whereas other studies have shown detrimental effects following folate treatment, whereby proliferation of cancer increased (mammary, prostate). The aim of this study was to investigate the opposing roles of folate in glioma. The glioma cell lines 1321N1, U87 MG and non-cancerous glial SVGp12 cells were grown in folate deficient, folic or folinic acid supplemented media and compared to standard cell culture media. Cell viability, apoptosis and cell cycle analysis along with methylation status and protein expression of the genes of interest; PTEN, FOLR1, RFC, PCFT, and MTHFR were analysed to determine differences between cell lines following treatment. Folic and folinic acid behaved differently depending on the concentration used and the cell lines treated. Low folic acid at 5 µg/ml significantly increased cell viability and protein expression levels in the U87 MG and SVGp12 cell lines, whilst the high dose of folinic acid (35 µg/ml) resulted in significant decreased cell viability, increased apoptotic activity and down regulation of the folate transporters in the 1321N1, U87 MG and SVGp12 cell lines. Folate treatment did not significantly alter cell cycle phase. Altered methylation of genes specific for folate metabolism and transport did not explain the cytotoxic effects of folate in cell lines. In conclusion folinic acid rather than folic acid supplementation should be investigated further to elucidate the mechanism of potential cytotoxic effects in glioma.