julilili42/papers huggingface dataset:
The Petrology of the Kaiserstuhl Volcanic Complex, SW Germany: The Importance of Metasomatized and Oxidized Lithospheric Mantle for Carbonatite Generation
2018-08-02

Abstract The Miocene Kaiserstuhl Volcanic Complex (Southwest Germany) consists largely of tephritic to phonolitic rocks, accompanied by minor nephelinitic to limburgitic and melilititic to haüynitic lithologies associated with carbonatites. Based on whole-rock geochemistry, petrography, mineralogy and mineral chemistry, combined with mineral equilibrium calculations and fractional crystallization models using the Least Square Fitting Method, we suggest that the Kaiserstuhl was fed by at least two distinct magma sources. The most primitive rock type of the tephritic to phonolitic group is rare monchiquite (basanitic lamprophyre) evolving towards tephrite, phonolitic tephrite, phonolitic noseanite, nosean phonolite and tephritic phonolite by fractional crystallization of variable amounts of clinopyroxene, amphibole, olivine, spinel/magnetite, garnet, titanite, plagioclase and nosean. During this evolution, temperature and silica activity (aSiO2) decrease from about 1100°C and aSiO2 = 0·6–0·8 to 880°C and aSiO2 = ∼0·2. At the same time, oxygen fugacity (fO2) increases from ΔFMQ* = +2–3 to ΔFMQ* = +3–5, with ΔFMQ* being defined as the log fO2 deviation from the silica activity-corrected FMQ buffer curve. Nephelinitic rocks probably derive by fractionation of mostly olivine, spinel/magnetite, melilite, perovskite and nepheline from an olivine melilititic magma. The nephelinitic rocks were formed at similarly high crystallization temperatures (&amp;gt;1000°C) and evolve towards limburgite (hyalo-nepheline basanite) by an increase of silica activity from about aSiO2 = 0·4–0·5 to aSiO2 = 0·5–0·9, whilst redox conditions are buffered to ΔFMQ* values of around +3. Haüyne melilitite and the more evolved (melilite) haüynite may equally be derived from an olivine melilitite by more intense olivine and less melilite fractionation combined with the accumulation of haüyne, clinopyroxene and spinel. These rocks were crystallized at very low silica activities (aSiO2 ≤0·2) and highly oxidized conditions (ΔFMQ* = +4–6). Even higher oxygen fugacities (ΔFMQ* = +6–7) determined for the carbonatite suggests a close genetic relation between these two groups. The assemblage of carbonatites with highly oxidized silicate rocks is typical of many carbonatite occurrences worldwide, at least for those associated with melilititic to nephelinitic silicate rocks. Therefore, we suggest that the existence of highly oxidized carbonate-bearing sublithospheric mantle domains is an important prerequisite to form such complexes.
Effect of a 1-week intense myofunctional training on obstructive sleep apnoea in children with Down syndrome
2018-08-02

Background Obstructive sleep apnoea (OSA) is common in children with Down syndrome (DS), yet difficult to treat. As muscular hypotonia of the upper airway may cause OSA and is also common in DS, we tested whether intense myofunctional therapy improves OSA in children with DS. Patients and methods Forty-two children underwent cardiorespiratory sleep studies immediately before and after a 1-week intensive training camp consisting of three daily 45 min sessions of myofunctional exercises according to Padovan. Primary outcome was the mixed-obstructive-apnoea/hypopnoea index (MOAHI), secondary outcomes the ≤3% oxygen desaturation index (DI 3 ), the ≤90% desaturation index (DI 90 ) and the lowest pulse oximeter saturation (SpO 2nadir ). Results Eighteen recordings had ≥3 hours of artefact-free recording in both the pretreatment and post-treatment sleep study and were therefore included in the analysis. Mean age was 6.3 years (SD 2.5); 83% had OSA prior to intervention. Mean MOAHI was 6.4 (SD 8.6) before and 6.4 (SD 10.8) after the intervention (p&gt;0.05); the DI 3 and SpO 2nadir also did not change. Only the DI 90 decreased significantly from 2.7 (SD 4.5) to 2.1 (SD 3.7) (p&lt;0.05). Conclusion The 1-week intense myofunctional training camp evaluated here in children with DS had only a marginal effect on OSA. Whether a longer follow-up period or duration of intervention would yield stronger effects remains to be determined.
The State of the Field of Global Taiwan Studies Institutions: A Time for Optimism or Pessimism?
2018-08-02

Conference' at SOAS, University of London.The conference aimed to bring together representatives from the leading Taiwan studies programmes in Europe and North America to discuss our experiences and how to make our programmes more sustainable.Following the conference, I published an upbeat essay in the Taiwan Sentinel arguing that we are now experiencing a golden era of Taiwan studies (Fell, 2017).This was followed by two more
Functional dynamics underlying near-threshold perception of facial emotions: a magnetoencephalography investigation
2018-08-02

Abstract Conscious perception of emotional valence of faces has been proposed to involve top-down and bottom-up information processing. Yet, the underlying neuronal mechanisms of these two processes and the implementation of their cooperation is still unclear. We hypothesized that the networks activated during the interaction of top-down and bottom-up processes are the key substrates responsible for perception. We assessed the participation of neural networks involved in conscious perception of emotional stimuli near the perceptual threshold using a visual-backward-masking paradigm in 12 healthy individuals using magnetoencephalography. Providing visual stimulation near the perceptual threshold enabled us to compare correctly and incorrectly recognized facial emotions and assess differences in top-down modulation for these stimuli using coherence analysis. We found a fronto-parietal network oscillating in the lower gamma band and exerting top-down control as determined by the causality measure of phase slope index. We demonstrated that correct recognition of facial emotions involved high-beta and low-gamma activity in parietal networks, Incorrect recognition was associated with enhanced coupling in the gamma band between left frontal and right parietal regions. Our results indicate that fronto-parietal control of the perception of emotional face stimuli relies on the right-hemispheric dominance of synchronized gamma band activity.
Faculty Opinions recommendation of Efficacy of Sterile Fecal Filtrate Transfer for Treating Patients With Clostridium difficile Infection.
2018-08-02

BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridium difficile infection (CDI). However, transferring undefined living bacteria entails uncontrollable risks for infectious and metabolic or malignant diseases, particularly in immunocompromised patients. We investigated whether sterile fecal filtrates (containing bacterial debris, proteins, antimicrobial compounds, metabolic products, and oligonucleotides/DNA), rather than intact microorganisms, are effective in patients with CDI.METHODS: We performed a clinical case series to investigate the effects of fecal filtrate transfer (FFT) in 5 patients with symptomatic chronic-relapsing CDI at the Department of Internal Medicine I at the University Hospital Schleswig-Holstein (Kiel, Germany). Patients were followed up for at least 6 months and for up to 33 months. Stool was collected from 5 donors selected by the patients, and fully characterized according to FMT standards. Stool was sterile-filtered to remove small particles and bacteria; the filtrate was transferred to patients in a single administration via nasojejunal tube. Fecal samples were collected from patients before and at 1 week and 6 weeks after FFT. Microbiome, virome, and proteome profiles of donors and patients were compared.RESULTS: In all 5 patients, FFT restored normal stool habits and eliminated symptoms of CDI for a minimum period of 6 months. Proteome analyses of selected FFT filtrates showed no obvious protein candidates associated with therapeutic efficacy. 16S ribosomal RNA gene sequencing detected diverse bacterial DNA signatures in the filtrates. Analysis of virus-like particles from a filtrate found to reduce symptoms of CDI showed a complex signature of bacteriophages. Bacterial phylogeny and virome profile analyses of fecal samples from recipients indicated longitudinal changes in microbial and viral community structures after FFT.CONCLUSIONS: A preliminary investigation of 5 patients with CDI shows that transfer of sterile filtrates from donor stool (FFT), rather than fecal microbiota, can be sufficient to restore normal stool habits and eliminate symptoms. This finding indicates that bacterial components, metabolites, or bacteriophages mediate many of the effects of FMT, and that FFT might be an alternative approach, particularly for immunocompromised patients.Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved. PMID: 27866880
Faculty Opinions recommendation of Evolution After Anti-TNF Discontinuation in Patients With Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study.
2018-08-02

OBJECTIVES: The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed.METHODS: This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included.RESULTS: A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn's disease and ulcerative colitis patients, respectively. In both Crohn's disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn's disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe.CONCLUSIONS: The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe. PMID: 27958281
Faculty Opinions recommendation of Long-term outcome of infliximab treatment in chronic active ulcerative colitis: a Swedish multicentre study of 250 patients.
2018-08-02

BACKGROUND: Real-life long-term data on infliximab treatment in ulcerative colitis are limited.AIM: To study the long-term efficacy and safety of infliximab in chronic active ulcerative colitis and possible predictors of colectomy and response were also examined.METHODS: A retrospective multi-centre study of infliximab treatment in 250 patients with chronic active ulcerative colitis with inclusion criteria: age ≥18 years, ambulatory treated, steroid-dependent or intolerant and/or immunomodulator refractory or intolerant.RESULTS: Steroid-free clinical remission was achieved by 123/250 patients (49.2%) at 12 months and in 126/250 patients at a median follow-up of 2.9 years (50.4%). Primary response at 3 months was achieved by 190/250 (76.0%) patients and associated with a high probability of response 168/190 (88.4%) at 12 months and 143/190 (75.3%) at follow-up. Long-term rate of colectomy in primary responders was 6/190 (3.2%) at 12 months and 27/190 (14.2%) at last follow-up. Failure to achieve response at 3 months was associated with a high risk of subsequent colectomy, 29/60 (48.3%) at 12 months and 41/60 (68.3%) at follow-up. Response at 12 months was associated with a low risk of subsequent colectomy, 14/181 (7.7%) compared with non-response 19/34 (55.9%) (P < 0.0001). Non-response at 3 months was an independent predictor of subsequent colectomy (HR = 9.40, 95% CI = 5.10-17.35, P < 0.001). Concomitant azathioprine therapy did not influence outcome in terms of colectomy.CONCLUSIONS: Long-term efficacy of infliximab treatment in chronic active ulcerative colitis is excellent especially in patients who respond to induction treatment. Conversely, non-response at 3 months predicts a poor outcome, with a high risk of subsequent colectomy.© 2016 John Wiley & Sons Ltd. PMID: 28025840
Faculty Opinions recommendation of Vedolizumab is associated with changes in innate rather than adaptive immunity in patients with inflammatory bowel disease.
2018-08-02

OBJECTIVE: Vedolizumab, a monoclonal antibody directed against the integrin heterodimer α4β7, is approved for the treatment of Crohn's disease and ulcerative colitis. The efficacy of vedolizumab has been suggested to result from inhibition of intestinal T cell trafficking although human data to support this conclusion are scarce. We therefore performed a comprehensive analysis of vedolizumab-induced alterations in mucosal and systemic immunity in patients with inflammatory bowel disease (IBD), using anti-inflammatory therapy with the TNFα antibody infliximab as control.DESIGN: Immunophenotyping, immunohistochemistry, T cell receptor profiling and RNA sequencing were performed using blood and colonic biopsies from patients with IBD before and during treatment with vedolizumab (n=18) or, as control, the anti-TNFα antibody infliximab (n=20). Leucocyte trafficking in vivo was assessed using single photon emission computed tomography and endomicroscopy.RESULTS: Vedolizumab was not associated with alterations in the abundance or phenotype of lamina propria T cells and did not affect the mucosal T cell repertoire or leucocyte trafficking in vivo. Surprisingly, however, α4β7 antibody treatment was associated with substantial effects on innate immunity including changes in macrophage populations and pronounced alterations in the expression of molecules involved in microbial sensing, chemoattraction and regulation of the innate effector response. These effects were specific to vedolizumab, not observed in response to the TNFα antibody infliximab, and associated with inhibition of intestinal inflammation.CONCLUSION: Our findings suggest that modulation of innate immunity contributes to the therapeutic efficacy of vedolizumab in IBD.TRIAL REGISTRATION NUMBER: NCT02694588.© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2019. All rights reserved. No commercial use is permitted unless otherwise expressly granted. PMID: 29730603
Faculty Opinions recommendation of Safety and efficacy of combination treatment with calcineurin inhibitors and vedolizumab in patients with refractory inflammatory bowel disease.
2018-08-02

Read the full review for this Faculty Opinions recommended article: Safety and efficacy of combination treatment with calcineurin inhibitors and vedolizumab in patients with refractory inflammatory bowel disease.
Faculty Opinions recommendation of Factors Associated with Discontinuation of Anti-TNF Inhibitors Among Persons with IBD: A Population-Based Analysis.
2018-08-02

INTRODUCTION: Antitumor necrosis factor (anti-TNF) medications are known to be highly efficacious in persons with moderate-to-severe inflammatory bowel disease (IBD). There is a paucity of data from population-based sources to elucidate persistence with these medications in the general population of IBD. Discontinuation of anti-TNF therapy is a marker of lack of effectiveness, intolerance, and patient/physician practice preferences.METHODS: We identified all persons with IBD in Manitoba who were dispensed infliximab (IFX) and adalimumab (ADA) between 2001 and 2014. Subjects were followed longitudinally to assess rates of completion of anti-TNF induction, duration of continued use, intraclass substitution, and dose adjustments. Cox proportional hazards models were used to test demographic and clinical factors associated with anti-TNF therapy discontinuation.RESULTS: Overall, 925 of 8651 persons (10.7%) with IBD were prescribed an anti-TNF drug (705 Crohn's disease: 523 IFX and 182 ADA; 220 ulcerative colitis: 214 IFX and 6 ADA). Approximately four-fifths of persons starting on anti-TNF therapy completed induction. At 1 and 5 years, persistence rates with the original anti-TNF were approximately 60% and 40%, respectively. Immunomodulator use at the time of anti-TNF dispensation was associated with a decreased likelihood of anti-TNF discontinuation in both Crohn's disease and ulcerative colitis. ADA users with Crohn's disease who reached maintenance phase had a higher risk of discontinuation than IFX users (hazard ratio 1.64, 95% confidence interval 1.15-2.37).CONCLUSIONS: Approximately two-fifths of anti-TNF users discontinue use within 1 year of initiation, and three-fifths will have discontinued at 5 years. Concomitant IM therapy has a modest effect on discontinuation rates. PMID: 28221250
Faculty Opinions recommendation of Development and Validation of a Confocal Laser Endomicroscopy-Based Score for In Vivo Assessment of Mucosal Healing in Ulcerative Colitis Patients.
2018-08-02

Read the full review for this Faculty Opinions recommended article: Development and Validation of a Confocal Laser Endomicroscopy-Based Score for In Vivo Assessment of Mucosal Healing in Ulcerative Colitis Patients.
Faculty Opinions recommendation of Systematic review with meta-analysis: endoscopic and histologic placebo rates in induction and maintenance trials of ulcerative colitis.
2018-08-02

Read the full review for this Faculty Opinions recommended article: Systematic review with meta-analysis: endoscopic and histologic placebo rates in induction and maintenance trials of ulcerative colitis.
Faculty Opinions recommendation of Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor-neutralizing therapy in patients with inflammatory bowel disease.
2018-08-02

Read the full review for this Faculty Opinions recommended article: Oncostatin M drives intestinal inflammation and predicts response to tumor necrosis factor-neutralizing therapy in patients with inflammatory bowel disease.
Faculty Opinions recommendation of Comparison of Infliximab and Adalimumab in Biologic-Naive Patients With Ulcerative Colitis: A Nationwide Danish Cohort Study.
2018-08-02

BACKGROUND & AIMS: This study compares the effectiveness and safety of infliximab and adalimumab in biologic-naive patients with ulcerative colitis (UC), in a nationwide register-based propensity score-matched cohort study.METHODS: From 1719 adults with UC, between ages 15 and 75 years in Denmark treated with either infliximab or adalimumab as their first biologic agent, we compared rates of all-cause hospitalization, UC-related hospitalization, major abdominal surgery, and serious infections after a variable 2:1 propensity score matching, accounting for baseline clinical characteristics, disease severity, health care utilization, and use of UC-related medications.RESULTS: As compared with infliximab-treated patients, adalimumab-treated patients had higher rate of all-cause hospitalization (hazard ratio [HR], 1.84; 95% CI, 1.18-2.85) and a trend toward higher rate of UC-related hospitalization (HR, 1.71; 95% CI, 0.95-3.07), particularly in a stratum of patients on concomitant immunomodulator therapy. However, risk of abdominal surgery (HR, 1.35; 95% CI, 0.62-2.94) was not different between the 2 treatment groups. Risk of serious infection requiring hospitalization was significantly higher in adalimumab-treated patients (HR, 5.11; 95% CI, 1.20-21.80).CONCLUSIONS: In this nationwide propensity score matched-cohort study of biologic-naive adults with UC, use of adalimumab as first-line biologic over infliximab was associated with higher risk of hospitalization and serious infections, although risk of surgery was not different. In the absence of head-to-head trials, this evidence may assist patients, health care providers, purchasers, and policy makers to make informed decisions that may improve health care in UC.Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved. PMID: 27913244 Funding information This work was supported by: NLM NIH HHS, United States Grant ID: T15 LM011271
Faculty Opinions recommendation of Anti-MAdCAM antibody (PF-00547659) for ulcerative colitis (TURANDOT): a phase 2, randomised, double-blind, placebo-controlled trial.
2018-08-02

BACKGROUND: PF-00547659 is a fully human monoclonal antibody that binds to human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) to selectively reduce lymphocyte homing to the intestinal tract. We aimed to assess the efficacy and safety of PF-00547659 in patients with moderate to severe ulcerative colitis.METHODS: This phase 2, randomised, double-blind, placebo-controlled clinical trial recruited patients aged 18-65 years from 105 centres in 21 countries, with a history (≥3 months) of active ulcerative colitis extending more than 15 cm beyond the anal verge (with a total Mayo score ≥6 and a Mayo endoscopic subscore ≥2) who had failed or were intolerant to at least one conventional therapy. Patients were stratified by previous anti-TNFα treatment, and randomly assigned by a computer-generated randomisation schedule to receive a subcutaneous injection of 7·5 mg, 22·5 mg, 75 mg, or 225 mg PF-00547659 or placebo at baseline, then every 4 weeks. Patients, investigators, and sponsors were blinded to the treatment. The primary endpoint was the proportion of patients achieving remission (total Mayo score ≤2 with no individual subscore >1 and rectal bleeding subscore ≤1) at week 12. The efficacy analysis included all patients who received at least one dose of the randomised treatment; the safety analysis was done according to treatment received. All p values were one-sided and multiplicity-adjusted. This study is registered with ClinicalTrials.gov, number NCT01620255.FINDINGS: Between Nov 2, 2012, and Feb 4, 2016, we screened 587 patients; 357 were eligible and randomly assigned to receive placebo (n=73) or PF-00547659 at doses of 7·5 mg (n=71), 22·5 mg (n=72), 75 mg (n=71), or 225 mg (n=70). Remission rates at week 12 were significantly greater in three of four active-treatment groups than in the placebo group (2·7% [two of 73]): 7·5 mg (11·3% [eight of 71]), 22·5 mg (16·7% [12 of 72]), 75 mg (15·5% [11 of 71]), and 225 mg (5·7% [four of 70]). These rates corresponded to a stratum-adjusted (anti-TNFα-naive and anti-TNFα-experienced) risk difference versus placebo of 8·0% for 7·5 mg (90% CI 1·9 to 14, p=0·0425), 12·8% for 22·5 mg (5·6 to 19·9, p=0·0099), 11·8% for 75 mg (4·8 to 18·8, p=0·0119), and 2·6% for 225 mg (-1·2 to 6·4, p=0·1803). Four of 73 (5·5%) patients had a serious adverse event in the placebo group, ten of 71 (14·1%) in the 7·5 mg group, one of 70 (1·4%) in the 22·5 mg group, three of 73 (4·1%) in the 75 mg group, and three of 70 (4·3%) in the 225 mg group. No safety signal was observed for the study drug.INTERPRETATION: PF-00547659 was safe and well tolerated in this patient population, and better than placebo for induction of remission in patients with moderate to severe ulcerative colitis. The greatest clinical effects were observed with the 22·5 mg and 75 mg doses.FUNDING: Pfizer.Copyright © 2017 Elsevier Ltd. All rights reserved. PMID: 28527704