tbuckley/cabot-search huggingface dataset:
Osteocyte morphology and orientation in relation to strain in the jaw bone
Authors: Vivian Wu, René F. M. van Oers, Engelbert A. J. M. Schulten, Marco N. Helder, Rommel G. Bacabac, Jenneke Klein-Nulend
Journal: International Journal of Oral Science (2018)

Bone mass is important for dental implant success and is regulated by mechanoresponsive osteocytes. We aimed to investigate the relationship between the levels and orientation of tensile strain and morphology and orientation of osteocytes at different dental implant positions in the maxillary bone. Bone biopsies were retrieved from eight patients who underwent maxillary sinus-floor elevation with β-tricalcium phosphate prior to implant placement. Gap versus free-ending locations were compared using 1) a three-dimensional finite-element model of the maxilla to predict the tensile strain magnitude and direction and 2) histology and histomorphometric analyses. The finite-element model predicted larger, differently directed tensile strains in the gap versus free-ending locations. The mean percentage of mineralised residual native-tissue volume, osteocyte number (mean ± standard deviations: 97 ± 40/region-of-interest), and osteocyte shape (~90% elongated, ~10% round) were similar for both locations. However, the osteocyte surface area was 1.5-times larger in the gap than in the free-ending locations, and the elongated osteocytes in these locations were more cranially caudally oriented. In conclusion, significant differences in the osteocyte surface area and orientation seem to exist locally in the maxillary bone, which may be related to the tensile strain magnitude and orientation. This might reflect local differences in the osteocyte mechanosensitivity and bone quality, suggesting differences in dental implant success based on the location in the maxilla.
Intensive first-line triplet chemotherapy plus cetuximab FIr-C/FOx-C in <i>RAS</i> wild-type MCRC: Preliminary phase II data and prediction of individual limiting toxicity syndromes by pharmacogenomic biomarkers.
Authors: Gemma Bruera, Silvia Massacese, Antonella Dal Mas, Corrado Ficorella, Eugenio Ciacco, Giuseppe Calvisi, Maurizio Simmaco, Enrico Ricevuto
Journal: Journal of Clinical Oncology (2018)

673 Background: Intensive first line bevacizumab added to triplet, and cetuximab (CET) to doublet in RAS wild-type MCRC significantly increased outcomes. We investigated safety/activity of FIr-C/FOx-C adding CET to triplet in RAS wild-type. Methods: Phase II study according to Simon two-step design: delta 15% (p070%, p185%), power80%, α5%, β20%; projected ORR I step 14/19. FIr-C/FOx-C: 5-fluorouracil (5-FU) 12h-TFI 900 mg/m2 days (d) 1-2,8-9,15-16,22-23 associated to weekly alternating irinotecan (CPT-11) 160 mg/m2 d1,15 or oxaliplatin 80 mg/m2 d8,22; CET loading dose, then 250 mg/m2 d1,8,15,22; every 28d. Toxicity, LTS evaluated/compared by chi-square test; activity/efficacy by log-rank. Pharmacogenomic biomarkers of 5-FU/CPT-11, 5-FU degradation rate (5-FUDR), Single Nucleotide Polimorphisms (SNP) ABCB1, CYP3A4, DYPD, UGT1A1, evaluated in individual patients with limiting toxicity syndromes (LTS) and at recommended dose. Results: 29 patients &lt; 75 years, primary/intermediate CIRS. From April 2014, KRAS/NRAS wild-type eligible: median age 59; young-elderly (yE) 7, 24%; liver-limited (L-L) 7, 24%. Recommended CPT-11/5-FU doses 120/750 mg/m2. Activity met primary endpoint: OR 14/18 evaluable as-treated (76%), confirmed in preliminary phase II, 17/23 intent-to-treat (74%). Liver metastasectomies 14%, 57% L-L. At median follow-up 18 months, PFS 12, OS 23 months. At recommended doses, received DI &gt; 80% for each drug; cumulative G3-4 toxicities: diarrhea 23%, asthenia 15%, vomiting 8%, hypertransaminasemy 8%; LTS, consisting of the LT, associated or not to G2 or other LT, in 19 patients (65.5%), 83% yE. LTS prevalently multiple than single site (59 vs 7% p0.006). Reduced FUDR, CYP3A4 and UGT1A1 SNPs, frequently associated, prevalently in patients with gastrointestinal LTS, while not without LTS. Conclusions: Intensive first-line FIr-C/FOx-C at recommended dose is tolerable, highly effective in RAS wild-type. Reduced FUDR, CYP3A4, UGT1A1 SNPs may predict individual LTS to select fit patients. Prospective studies will confirm efficacy and personalization by companion toxicity biomarkers. Clinical trial information: EudraCT 2009-016793-32.
Phase 1 study of the PI3Kδ inhibitor INCB040093 ± JAK1 inhibitor itacitinib in relapsed/refractory B-cell lymphoma
Authors: Tycel J. Phillips, Andres Forero-Torres, Taimur Sher, Catherine S. Diefenbach, Patrick Johnston, Moshe Talpaz, Jennifer Pulini, Li Zhou, Peggy Scherle, Xuejun Chen, Paul M. Barr
Journal: Blood (2018)
Low-moderate alcohol use is associated with a lower prevalence of non-alcoholic fatty liver disease in Hispanics/Latinos living in the US: Results from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)
Authors: A. Unalp-Arida, C. Ruhl, E. Kallwitz, M. Daviglus, D. Sotres-Alvarez, D. Vidot, D. Lee, G. Talavera, L. Aviles-Santa
Journal: Journal of Hepatology (2018)
Preventing Atopic Dermatitis and <scp>ALL</scp>ergies in Children—the Prevent<scp>ADALL</scp> study
Authors: Karin C. Lødrup Carlsen, Eva Maria Rehbinder, Håvard O. Skjerven, Monica Hauger Carlsen, Thea Aspelund Fatnes, Pål Fugelli, Berit Granum, Guttorm Haugen, Gunilla Hedlin, Christine Monceyron Jonassen, Linn Landrø, Jon Lunde, Benjamin J Marsland, Björn Nordlund, Knut Rudi, Katrine Sjøborg, Cilla Söderhäll, Anne Cathrine Staff, Riyas Vettukattil, Kai‐Håkon Carlsen
Journal: Allergy (2018)

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Troubled rebuild of Stockholm’s landmark hospital has cost twice as much as planned
Authors: Marta Paterlini
Journal: BMJ (2018)

An ambitious project to establish one of the most advanced and specialised hospitals in Europe has cost twice as much as planned and remains unfinished because of financial and operational problems.

The New Karolinska Hospital in Stockholm, Sweden, is now described as the most expensive hospital ever built. Current costs stand at Kr22.8bn (£1.91bn; €2.19bn; $2.67bn), and by 2040 the entire project is estimated to cost Swedish taxpayers Kr61.4bn.

The political debate about hugely over-running costs and operational problems at the hospital is intensifying ahead of Sweden’s national elections.

As well as moving the Karolinska’s location to new buildings, the project is designed to create a more patient oriented organisation. Karolinska has been using so called value based healthcare since 2014, under the highly criticised “patient first” …
Impact of Type 2 Diabetes Susceptibility Loci on Variation in Physiologic Glycaemic Traits in Non-Diabetic Individuals
Authors: A S Dimas, V I Gomes, J Knowles, R Maegi, A Barker, Hivert M-F., A Benazzo, D Rybin, T I Assimes, T Ouertermous, M Walker, J C Florez, I Barroso, C Langenberg, J Dupuis, R Watanabe, M McCarthy, E Ingelsson, I Prokopenko
Journal: Circulation (2012)
Relapse of porphyria cutanea tarda after treatment with phlebotomy or 4-aminoquinoline antimalarials: a meta-analysis
Authors: H. Salameh, H. Sarairah, M. Rizwan, Y.-F. Kuo, K.E. Anderson, A.K. Singal
Journal: British Journal of Dermatology (2018)

Porphyria cutanea tarda (PCT) is the most common human porphyria. It is caused by hepatic deficiency of uroporphyrinogen decarboxylase activity, which is acquired in the presence of multiple susceptibility factors. PCT presents clinically with cutaneous blistering photosensitivity and is readily treatable with either repeated phlebotomy or 4-aminoquinoline antimalarials.To perform a systematic review and meta-analysis to compare the effectiveness of these quite different treatment approaches, especially on relapse rates (RRs) after achieving remission.Published studies that included follow-up for at least 1 year after treatment of PCT were included. The primary study outcome was PCT relapse. Pooled data are reported as the RRs per person-year of follow-up with 95% confidence intervals (CIs).Of 375 articles identified as pertaining to PCT treatment, 12 were eligible for analysis. Of these, five used high-dose 4-aminoquinoline regimens (two combined with phlebotomy and three without phlebotomy), five used low-dose 4-aminoquinoline regimens and three used phlebotomy. RRs during the year after treatment were similar for the high- and low-dose 4-aminoquinoline groups (35-36%) and lower in the phlebotomy group (20%). The pooled RRs with their 95% CIs were 8·6 (3·9-13·3) per 100 person-years in the high-dose 4-aminoquinoline group, 17·1 (8·9-25·3) per 100 person-years in the low-dose 4-aminoquinoline group and 5·1 (0·5-10·6) per 100 person-years in the phlebotomy group. Subgroup and sensitivity analyses showed similar results.Clinical or biochemical RRs ranged from 5 to 17 per 100 person-years after remission of PCT. Relapses were somewhat more frequent after remission with 4-aminoquinoline regimens than after remission following phlebotomy. Prospective studies are needed to define better how often relapses occur with these treatments after documenting both clinical and biochemical remission of PCT.
NGM282 improves fibrosis and NASH-related histology in 12 weeks in patients with biopsy-confirmed NASH, which is preceded by significant decreases in hepatic steatosis, liver transaminases and fibrosis markers at 6 weeks
Authors: S. Harrison, S. Rossi, M. Bashir, C. Guy, R. Banerjee, M. Jaros, S. Owers, B. Baxter, L. Ling, A. Depaoli
Journal: Journal of Hepatology (2018)
P349Platelet turnover in ST segment myocardial infarction: regulation, kinetics and clinical impact
Authors: L Malinova, N Furman, P Dolotovskaya, N Puchinyan, T Denisova
Journal: Cardiovascular Research (2018)

expression of the down-stream proteins including transforming growth factor-b1 (TGF-b1), connective tissue growth factor (CTGF), collagen I and collagen VIII in HCSMCs exposed to AGEs.Conclusions: ASK1/MKKs/p38 MAPK pathway was activated by AGEs, leading to fibrotic response in VSMCs.AGI-1067 reversed this process by maintaining the inactive state of ASK1.
Risk of early de-novo hepatocellular carcinoma (HCC) in patients with genotype-1b HCV compensated cirrhosis treated with 3 direct-acting antivirals (DAAs) – a real life, multicenter study
Authors: C.-M. Muzica, C. Stanciu, O. Stoica, I. Girleanu, L. Huiban, C. Alexandru, T. Cuciureanu, A.-M. Singeap, S. Chiriac, A. Trifan
Journal: Journal of Hepatology (2018)
Annularity of Aorto-Iliac Arterial Calcification and Risk of All-Cause and Cardiovascular Mortality
Authors: Eva J.E. Hendriks, Pim A. de Jong, Joline W.J. Beulens, Yvonne T. van der Schouw, Nketi I. Forbang, C. Michael Wright, Michael H. Criqui, Matthew A. Allison, Joachim H. Ix
Journal: JACC. Cardiovascular imaging (2018)
TCTAP A-111 Comparison of Early Clinical Outcomes of Transcatheter Aortic Valve Replacement Between Low to Intermediate and High Surgical Risk Patients with Severe Aortic Stenosis
Authors: Hyungdon Kook, Cheol Woong Yu, Han Saem Jeong, Duck-Hyun Jang, Seung Hun Lee, Hyung Joon Joo, Jae Hyoung Park, Soon Jun Hong, Seung Hyuk Choi, Kiyuk Chang, Young Jin Choi, Do-Sun Lim
Journal: Journal of the American College of Cardiology (2018)
TCTAP C-071 The Neointimal Formation of Everolimus-eluting Stent Implanted in the Subintimal Space at Chronic Phase with Optical Coherence Tomography
Authors: Akinori Sumiyoshi, Atsunori Okamura, Mutsumi Iwamoto, Hiroyuki Nagai, Tomohiro Yamasaki, Takamasa Tanaka, Kota Tanaka, Kenshi Fujii
Journal: Journal of the American College of Cardiology (2018)
Abstract 20068: Enhanced Pyruvate Dehydrogenase Activity Improves Myocardial Hemodynamics and Return to Spontaneous Circulation in a Murine Model of Cardiac Arrest
Authors: Lin Piao, Yonghu Fang, Willard Sharp
Journal: Circulation (2016)

Rationale: Post-ischemic changes in cellular metabolism alter myocardial and neurological function. Pyruvate dehydrogenase (PDH), the limiting step in mitochondrial glucose oxidation, is inhibited ...
A Glial Signature and Wnt7 Signaling Regulate Glioma-Vascular Interactions and Tumor Microenvironment
Authors: Amelie Griveau, Giorgio Seano, Samuel J. Shelton, Robert Kupp, Arman Jahangiri, Kirsten Obernier, Shanmugarajan Krishnan, Olle R. Lindberg, Tracy J. Yuen, An-Chi Tien, Jennifer K. Sabo, Nancy Wang, Ivy Chen, Jonas Kloepper, Louis Larrouquere, Mitrajit Ghosh, Itay Tirosh, Emmanuelle Huillard, Arturo Alvarez-Buylla, Michael C. Oldham, Anders I. Persson, William A. Weiss, Tracy T. Batchelor, Anat Stemmer-Rachamimov, Mario L. Suvà, Joanna J. Phillips, Manish K. Aghi, Shwetal Mehta, Rakesh K. Jain, David H. Rowitch
Journal: Cancer Cell (2018)
Efficacy of pharmacological therapies for the treatment of opioid-induced constipation: systematic review and network meta-analysis
Authors: Pavit Luthra, Nicholas E Burr, Darren M Brenner, Alexander C Ford
Journal: Gut (2018)

Objective Opioids are increasingly prescribed in the West and have deleterious GI consequences. Pharmacological therapies to treat opioid-induced constipation (OIC) are available, but their relative efficacy is unclear. We performed a systematic review and network meta-analysis to address this deficit in current knowledge. Design We searched MEDLINE, EMBASE, EMBASE Classic and the Cochrane central register of controlled trials through to December 2017 to identify randomised controlled trials (RCTs) of pharmacological therapies in the treatment of adults with OIC. Trials had to report a dichotomous assessment of overall response to therapy, and data were pooled using a random effects model. Efficacy and safety of pharmacological therapies was reported as a pooled relative risk (RR) with 95% CIs to summarise the effect of each comparison tested and ranked treatments according to their P-score. Results Twenty-seven eligible RCTs of pharmacological therapies, containing 9149 patients, were identified. In our primary analysis, using failure to achieve an average of ≥3 bowel movements (BMs) per week with an increase of ≥1 BM per week over baseline or an average of ≥3 BMs per week, to define non-response, the network meta-analysis ranked naloxone first in terms of efficacy (RR=0.65; 95% CI 0.52 to 0.80, P-score=0.84), and it was also the safest drug. When non-response to therapy was defined using failure to achieve an average of ≥3 BMs per week, with an increase of ≥1 BM per week over baseline, naldemedinewas ranked first (RR=0.66; 95% CI 0.56 to 0.77, P score=0.91) and alvimopan second (RR=0.74; 95% CI 0.57 to 0.94, P-score=0.71). Conclusion In network meta-analysis, naloxone and naldemedine appear to be the most efficacious treatments for OIC. Naloxone was the safest of these agents.
De novo hepatocellular carcinoma in patients with cirrhosis due hepatitis C virus infection after treatment with direct antiviral agents
Authors: P. Ruiz, L. Deiss, L. Buendía, I. Erdozain, C. Álvarez, P. Gutiérrez, J. José Pascual, A. Baranda, S. Blanco, F. Menéndez, Ángel José Calderón, A. Esain
Journal: Journal of Hepatology (2018)
WHO recommends additional tests for Sanofi’s dengue vaccine after safety concerns
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Sanofi Pasteur’s vaccine against dengue fever should be used only by people already infected with the virus, subject to additional testing, the World Health Organization has said.

The updated recommendations of WHO’s Strategic Advisory Group of Experts on Immunization (SAGE) on the use of Dengvaxia were made on 19 April after a meeting in Geneva, Switzerland.

The move follows the disclosure of new data by Sanofi …
Unending story of the indirect immunofluorescence assay on HEp-2 cells: old problems and new solutions?
Authors: Pier Luigi Meroni, Edward K Chan, Jan Damoiseaux, Luís Eduardo Coelho Andrade, Xavier Bossuyt, Karsten Conrad, Xavier Mariette, Joanna Sheldon, Johan Rönnelid, Marvin J Fritzler
Journal: Annals of the Rheumatic Diseases (2018)

The paper by Pisetsky et al raised some critical points on the indirect immunofluorescence assay (IFA) on HEp-2 cells (HEp-2 IFA): (1) the low antinuclear antibodies (ANA) pretest and post-test probability, and (2) the variability of the IFA ANA result depending on the method type and reagent source.1 One consequence of these points is the heterogeneity in the classification criteria for systemic lupus erythematosus and/or the inclusion criteria in clinical trials or in specific treatment protocols.

Unfortunately, the paper by Pisetsky et al conveys no practical suggestions on how to minimise these issues, and the impact on the readers could be one of confusion rather than resolution.

Several international committees are joining their efforts in order to avoid misdiagnosis and …
Maternal Smoking during Pregnancy and Early Childhood and Development of Asthma and Rhinoconjunctivitis – a MeDALL Project
Authors: Jesse D. Thacher, Ulrike Gehring, Olena Gruzieva, Marie Standl, Göran Pershagen, Carl-Peter Bauer, Dietrich Berdel, Theresa Keller, Sibylle Koletzko, Gerard H. Koppelman, Inger Kull, Susanne Lau, Irina Lehmann, Dieter Maier, Tamara Schikowski, Ulrich Wahn, Alet H. Wijga, Joachim Heinrich, Jean Bousquet, Josep M. Anto, Andrea von Berg, Erik Melén, Henriette A. Smit, Thomas Keil, Anna Bergström
Journal: Environmental Health Perspectives (2018)

Background: The role of tobacco smoke exposure in the development and persistence of asthma and rhinoconjunctivitis through childhood into adolescence is unclear. Objectives: We assessed the associations of parental smoking from fetal life through adolescence with asthma and rhinoconjunctivitis during childhood and adolescence. Methods: We analyzed data for 10,860 participants of five European birth cohort studies from the Mechanisms of the Development of Allergy (MeDALL) consortium. Parental smoking habits and health outcomes (early transient, persistent, and adolescent-onset asthma and rhinoconjunctivitis) were based on questionnaires covering the period from pregnancy to 14–16 y of age. Data were combined and analyzed using a one-stage and two-stage individual participant data meta-analysis. Results: Overall, any maternal smoking during pregnancy tended to be associated with an increased odds of prevalent asthma [adjusted odds ratio (aOR)=1.19 (95% CI: 0.98, 1.43)], but not prevalent rhinoconjunctivitis [aOR=1.05 (95% CI: 0.90, 1.22)], during childhood and adolescence. In analyses with phenotypes related to age of onset and persistence of disease, any maternal smoking during pregnancy was associated with early transient asthma [aOR=1.79 (95% CI: 1.14, 2.83)]. Maternal smoking of ≥10 cigarettes/day during pregnancy was associated with persistent asthma [aOR=1.66 (95% CI: 1.29, 2.15)] and persistent rhinoconjunctivitis [aOR=1.55 (95% CI, 1.09, 2.20)]. Tobacco smoke exposure during fetal life, infancy, childhood, and adolescence was not associated with adolescent-onset asthma or rhinoconjunctivitis. Conclusions: Findings from this combined analysis of five European birth cohorts strengthen evidence linking early exposure to tobacco smoke with asthma during childhood and adolescence. Children with high early-life exposure were more likely than unexposed children to have early transient and persistent asthma and persistent rhinoconjunctivitis. https://doi.org/10.1289/EHP2738
Abstract 19531: Effect of Mainstream Cigarette Smoke and Its Constituents on Immune Cells
Authors: Marina V Malovichko, Srinivas D Sithu, Iris Zeller, Abhinav Agarwal, Timothy E O’Toole, Aruni Bhatnagar, Daniel J Conklin, Sanjay Srivastava
Journal: Circulation (2016)

Smoking induces/exacerbates cardiopulmonary diseases possibly via impaired immune function. Yet, little is known about what constituent(s) of mainstream cigarette smoke (MCS) affects immune functio...
FDA discounted potential risks when approving continuous glucose monitoring device, expert claims
Authors: Martha Rosenberg
Journal: BMJ (2018)

The US Food and Drug Administration (FDA) has been accused of discounting up to 30 000 medical device reports (MDR) when, in 2016, it expanded the approved use of a continuous glucose monitoring system (CGM) to replace self monitoring.1

Alan Shapiro, clinical associate professor of medicine at New York University School of Medicine, and an expert in medical statistics, said the agency had not taken account of the findings from the reports when it made the decision to approve the Dexcom G5 mobile system.

CGMs use below-the-skin sensors that continuously measure glucose levels and wirelessly send the results to a receiver and a compatible mobile device.

Shapiro has highlighted, in several journal articles,23 that the MDRs from the FDA’s Manufacturer and User Facility Device Experience (MAUDE) system showed substantial inaccuracies from the CGM device.

The FDA’s executive summary for the panel considering expanded use gave MDR data for the G5 and similar devices under …
Checkpoint inhibitor-associated immune arthritis
Authors: Laurent Arnaud, Bénédicte Lebrun-Vignes, Joe-Elie Salem
Journal: Annals of the Rheumatic Diseases (2018)

We read with interest the paper by Kostine et al .1 Immune checkpoint inhibitors (ICIs) have dramatically improved clinical outcomes in various cancer types and are increasingly being used in earlier disease settings and in combination.2 The main targets of ICIs, programmed cell death 1 (PD-1) and its ligand PD-L1 as well as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are involved in downregulating autoimmunity, with PD-1-deficient C57BL/6 mice exhibiting lupus-like features and CTLA-4 enabling Treg suppression of autoreactive T cell activation.3 It was therefore no surprise that immune-related adverse events (irAEs) such as immune arthritis, rheumatoid arthritis or systemic lupus …
The Tsinghua–Lancet Commission on Healthy Cities in China: unlocking the power of cities for a healthy China
Authors: Jun Yang, José G Siri, Justin V Remais, Qu Cheng, Han Zhang, Karen K Y Chan, Zhe Sun, Yuanyuan Zhao, Na Cong, Xueyan Li, Wei Zhang, Yuqi Bai, Jun Bi, Wenjia Cai, Emily Y Y Chan, Wanqing Chen, Weicheng Fan, Hua Fu, Jianqing He, Hong Huang, John S Ji, Peng Jia, Xiaopeng Jiang, Mei-Po Kwan, Tianhong Li, Xiguang Li, Song Liang, Xiaofeng Liang, Lu Liang, Qiyong Liu, Yongmei Lu, Yong Luo, Xiulian Ma, Bernhard Schwartländer, Zhiyong Shen, Peijun Shi, Jing Su, Tinghai Wu, Changhong Yang, Yongyuan Yin, Qiang Zhang, Yinping Zhang, Yong Zhang, Bing Xu, Peng Gong
Journal: The Lancet (2018)
The covert “C”; prevalence: Risk factors and management of hepatitis C in psychiatric in-patients
Authors: J. Ramachandran, H. Slattery, S. Budd, T. Mohan, T. Cowain, A. Baas, L. Wigg, J. Alexander, K. Muller, B. Kaambwa, R. Woodman, A. Wigg
Journal: Journal of Hepatology (2018)