bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic review with network meta‐analysis: comparative assessment of tofacitinib and biological therapies for moderate‐to‐severe ulcerative colitis
Authors: Bonovas S. , Lytras T. , Nikolopoulos G. , Peyrin‐Biroulet L. , Danese S. 
Published: December 2017

SummaryBackgroundBiological therapies have improved the care of patients with ulcerative colitis (UC). Tofacitinib, an oral small‐molecule Janus kinase inhibitor, is potentially a new treatment option.AimTo comparatively assess efficacy and harm of tofacitinib and biologics (infliximab, adalimumab, golimumab and vedolizumab) in adult patients not previously exposed to TNF antagonists.MethodsWe performed a comprehensive search of PubMed, Embase, Scopus, clinical trial registries, regulatory authorities' websites and major conference proceedings, through August 2017, to identify randomised, placebo‐controlled or head‐to‐head trials assessing tofacitinib or biologics as induction and/or maintenance therapy in moderate‐to‐severe UC. Two reviewers independently extracted study data and outcomes, and investigated each trial's risk‐of‐bias. We used conventional meta‐analysis to synthesise direct evidence, and network meta‐analysis for adjusted indirect treatment comparisons.ResultsFifteen randomised, double‐blind, placebo‐controlled trials (n = 3130) contributed data for induction: All treatments are superior to placebo. Indirect treatment comparisons showed that infliximab is better than adalimumab (OR: 2.01, 95% CI: 1.36‐2.98) and golimumab (1.67, 1.08‐2.59) in clinical response, better than adalimumab (2.10, 1.21‐3.64) in clinical remission, and better than adalimumab (1.87, 1.26‐2.79) and golimumab (1.75, 1.13‐2.73) in mucosal healing. No indirect comparisons between tofacitinib and biologics reached statistical significance. Nine studies (n = 1776) contributed maintenance data showing that all treatments have higher clinical efficacy than placebo. Safety analyses indicated no increased rates of adverse events for the treatments under evaluation (except for infliximab), while vedolizumab may have an advantage regarding the occurrence of serious adverse events.ConclusionsTofacitinib and biologics are efficacious and safe for UC. Further high‐quality research is warranted to establish the best therapeutic option.
Systematic review: human gut dysbiosis induced by non‐antibiotic prescription medications
Authors: Le Bastard Q. , Al‐Ghalith G. A. , Grégoire M. , Chapelet G. , Javaudin F. , Dailly E. , Batard E. , Knights D. , Montassier E. 
Published: December 2017

SummaryBackgroundGlobal prescription drug use has been increasing continuously for decades. The gut microbiome, a key contributor to health status, can be altered by prescription drug use, as antibiotics have been repeatedly described to have both short‐term and long‐standing effects on the intestinal microbiome.AimTo summarise current findings on non‐antibiotic prescription‐induced gut microbiome changes, focusing on the most frequently prescribed therapeutic drug categories.MethodsWe conducted a systematic review by first searching in online databases for indexed articles and abstracts in accordance with PRISMA guidelines. Studies assessing the intestinal microbiome alterations associated with proton pump inhibitors (PPIs), metformin, nonsteroidal anti‐inflammatory drugs (NSAIDs), opioids, statins and antipsychotics were included. We only included studies using culture‐independent molecular techniques.ResultsProton pump inhibitors and antipsychotic medications are associated with a decrease in α diversity in the gut microbiome, whereas opioids were associated with an increase in α diversity. Metformin and NSAIDs were not associated with significant changes in α diversity. β diversity was found to be significantly altered with all drugs, except for NSAIDs. PPI use was linked to a decrease in Clotridiales and increase in Actinomycetales, Micrococcaceae and Streptococcaceae, which are changes previously implicated in dysbiosis and increased susceptibility to Clostridium difficile infection. Consistent results showed that PPIs, metformin, NSAIDs, opioids and antipsychotics were either associated with increases in members of class Gammaproteobacteria (including Enterobacter, Escherichia, Klebsiella and Citrobacter), or members of family Enterococcaceae, which are often pathogens isolated from bloodstream infections in critically ill patients. We also found that antipsychotic treatment, usually associated with an increase in body mass index, was marked by a decreased ratio of Bacteroidetes:Firmicutes in the gut microbiome, resembling trends seen in obese patients.ConclusionsNon‐antibiotic prescription drugs have a notable impact on the overall architecture of the intestinal microbiome. Further explorations should seek to define biomarkers of dysbiosis induced by specific drugs, and potentially tailor live biotherapeutics to counter this drug‐induced dysbiosis. Many other frequently prescribed drugs should also be investigated to better understand the link between these drugs, the microbiome and health status.
Switching from infliximab innovator to biosimilar in patients with inflammatory bowel disease: a 12‐month multicentre observational prospective cohort study
Authors: Schmitz E. M. H. , Boekema P. J. , Straathof J. W. A. , van Renswouw D. C. , Brunsveld L. , Scharnhorst V. , van de Poll M. E. C. , Broeren M. A. C. , Derijks L. J. J. 
Published: December 2017

SummaryBackgroundInfliximab biosimilars have become available for treatment of inflammatory bowel disease (IBD). However, data showing long‐term safety and effectiveness of biosimilars in IBD patients are limited.AimTo study prospectively the switch from infliximab innovator to biosimilar in an IBD cohort with 12 months follow‐up to evaluate safety and effectiveness.MethodsAdult IBD patients from two hospitals treated with infliximab innovator (Remicade; Janssen Biotech, Horsham , Pennsylvania, USA) were switched to infliximab biosimilar (Inflectra; Hospira, Lake Forest, Illinois, USA) as part of routine care, but in a controlled setting. Blood samples were taken just before the first, second, fourth and seventh infusion of biosimilar. Infliximab trough levels, antibodies‐to‐infliximab (ATI), CRP and ESR were measured and disease activity scores were calculated.ResultsOur cohort consisted of 133 IBD patients (64% CD, 36% UC). Before switching we found widely varying infliximab levels (median 3.5 μg/mL). ATI were detected in eight patients (6%). Most patients were in remission or had mild disease (CD: 82% UC: 90%). After switching to biosimilar, 35 patients (26%) discontinued therapy within 12 months, mostly due to subjective higher disease activity (9%) and adverse events (AE, 9.8%). AE included general malaise/fatigue (n = 7), arthralgia (n = 2), skin problems (n = 2) and infusion reactions (n = 2). No differences in IFX levels, CRP, and disease activity scores were found between the four time points (P ≥ .0917).ConclusionsWe found no differences in drug levels and disease activity between infliximab innovator and biosimilar in our IBD cohort, indicating that biosimilars are safe and effective. The high proportions of discontinuers were mostly due to elective withdrawal or subjective disease worsening.
Systematic review: ileoanal pouch microbiota in health and disease
Authors: Segal J. P. , Oke S. , Hold G. L. , Clark S. K. , Faiz O. D. , Hart A. L. 
Published: December 2017

SummaryBackgroundThe resident gut microbiota is essential for physiological processes; the disturbance of its balance is linked to intestinal inflammation. The ileoanal pouch is a model for the study of intestinal inflammation, as inflammation of the pouch is common and mostly develops within 12 months following ileostomy closure. This allows the longitudinal study of the microbiota, giving insight into the microbiota changes during transition from a normal to an inflamed pouch.AimTo explore the literature on the microbiota of the ileoanal pouch in health and disease.MethodsA systematic computer search of the on‐line bibliographic databases MEDLINE and EMBASE was performed between 1966 and February 2017. Randomised controlled trials, cohort studies and observational studies were included. Studies were included if they reported microbiota analysis on faecal samples or tissue from the ileoanal pouch.ResultsTwenty‐six papers were eligible. Following ileostomy closure, anaerobic bacteria are the abundant species in the ileoanal pouch with presence of a diverse microbiota key to maintaining a healthy ileoanal pouch. Acute pouchitis is associated with an increase in Clostridia species, while chronic pouchitis is associated with an increase in Staphylococcus aureus. In the treatment of pouchitis, a decrease in Clostridia species appears to be associated with treatment response.ConclusionThe microbiota plays an important role in both the inflamed and the healthy ileoanal pouch. A direct causal relationship between individual microbiota changes and inflammation has not yet been established, but manipulation of the ileoanal pouch microbiota may be a novel therapeutic avenue to explore.
Different games of moral bioenhancement
Authors: Rakić Vojin , Wiseman Harris 
Published: December 2017

AbstractRakić has serious misgivings about Wiseman's inability to frame ethical issues in the context of transcending existing realities (the ‘is’) with the aim of achieving what we believe is morally right (the ‘ought’). This inability to think beyond the present is misguided in ethics. He also criticizes Wiseman for making the unimaginative and unsubstantiated assumption that moral bioenhancement (MBE) technologies have reached their zenith already. Rakić argues that MBE will become more effective in the time to come, that it ought to be optional for every free individual, and that it should be directed at enhancing our motivation to act in line with how we believe we ought to act. He concedes however that the enhancement of our motivation to act morally can only be effective in a limited number of morally unambiguous cases. In response, Wiseman argues that Rakić's reflections epitomize a way of articulating MBE that is unhelpful, misguidedly optimistic, and missing the most important things needing discussion. Such reflections are based on inappropriate metaphors, a too future‐oriented view detached from basic realities, and a false sense of what is possible on the global level should MBE be applied. Such ways of thinking about MBE are misguided from the outset, and indicative of the enthusiasm for a discourse in need of realignment. This should take the form of a more modest, synergistic outlook acutely aware of the inexorable limitations imposed on MBE by the internal complexity of moral goods, human agents, and the contexts in which moral action occurs.
CD34+ selected stem cell boosts can improve poor graft function after paediatric allogeneic stem cell transplantation
Authors: Mainardi Chiara , Ebinger Martin , Enkel Sigrid , Feuchtinger Tobias , Teltschik Heiko‐Manuel , Eyrich Matthias , Schumm Michael , Rabsteyn Armin , Schlegel Patrick , Seitz Christian , Schwarze Carl‐Phillip , Müller Ingo , Greil Johann , Bader Peter , Schlegel Paul‐Gerhardt , Martin David , Holzer Ursula , Döring Michaela , Handgretinger Rupert , Lang Peter 
Published: December 2017

SummaryPoor graft function (PGF) is a severe complication of haematopoietic stem cell transplantation (HSCT) and administration of donor stem cell boosts (SCBs) represents a therapeutic option. We report 50 paediatric patients with PGF who received 61 boosts with CD34+ selected peripheral blood stem cells (PBSC) after transplantation from matched unrelated (n = 25) or mismatched related (n = 25) donors. Within 8 weeks, a significant increase in median neutrophil counts (0·6 vs. 1·516 × 109/l, P < 0·05) and a decrease in red blood cell and platelet transfusion requirement (median frequencies 1 and 7 vs. 0, P < 0·0001 and <0·001), were observed, and 78·8% of patients resolved one or two of their cytopenias. 36·5% had a complete haematological response. Median lymphocyte counts for CD3+, CD3+CD4+, CD19+ and CD56+ increased 8·3‐, 14·2‐, 22.‐ and 1·6‐fold. The rate of de novo acute graft‐versus‐host disease (GvHD) grade I–III was only 6% and resolved completely. No GvHD grade IV or chronic GvHD occurred. Patients who responded to SCB displayed a trend toward better overall survival (OS) (P = 0·07). Thus, administration of CD34+ selected SCBs from alternative donors is safe and effective. Further studies are warranted to clarify the impact on immune reconstitution and survival.
Development of Episodic Prospection: Factors Underlying Improvements in Middle and Late Childhood
Authors: Coughlin Christine , Robins Richard W. , Ghetti Simona 
Published: December 2017

Episodic prospection is the mental simulation of a personal future event in rich contextual detail. This study examined age‐related differences in episodic prospection in 5‐ to 11‐year‐olds and adults (N = 157), as well as factors that may contribute to developmental improvements. Participants’ narratives of past, future, and make‐believe events were coded for episodic content, and self‐concept coherence (i.e., how coherently an individual sees himself or herself) and narrative ability were tested as predictors of episodic prospection. Although all ages provided less episodic content for future event narratives, age‐related improvements were observed across childhood, suggesting future event generation is particularly difficult for children. Self‐concept coherence and narrative ability each independently predicted the episodic content of 5‐ and 7‐year‐olds’ future event narratives.
The applications of regenerative medicine in sinus lift procedures: A systematic review
Authors: Correia Francisco , Pozza Daniel Humberto , Gouveia Sónia , Felino António , Faria e Almeida Ricardo 
Published: December 2017

AbstractBackgroundFindings in regenerative medicine applied to the sinus lift procedures.PurposeEvaluate the effectiveness of regenerative medicine in sinus lift.Materials and MethodsAn extensive search for manuscripts were performed by using different combinations of keywords and MeSH terms (Pub‐med; Embase; Scopus; Web of Science Core Collection; Medline; Current Contents Connect; Derwent Innovations Index; Scielo Citation Index; Cochrane library). The full text selected articles are written in English, Portuguese, Spanish, Italian, German, or French, and published until 28 of November 2016. Inclusion criteria were: implant osteointegration, radiographic, histologic, and/or histomorphometric analysis, clinical studies in humans using of regenerative medicine. This systematic review was performed by selecting only randomized controlled clinical trials and controlled clinical trials.ResultsEighteen published studies (11 CT and 7 RCT) were considered eligible for inclusion in the present systematic review. These studies demonstrated considerable variation of biomaterial and cell technics used, study design, sinus lift technic, outcomes, follow‐up, and results.ConclusionOnly few studies have demonstrated potential of regenerative medicine in sinus lift; further randomized clinical trials are needed to achieve more accurate results.
Primary cutaneous secretory carcinoma: A previously overlooked low‐grade sweat gland carcinoma
Authors: Llamas‐Velasco Mar , Mentzel Thomas , Rütten Arno 
Published: December 2017

IntroductionTwelve cases of primary cutaneous secretory carcinoma (PCSC) have been published, 9 showing ETV6‐NTRK3 translocation, a characteristic finding shared with secretory breast carcinoma and mammary analogue secretory carcinoma.Case reportA 34‐year‐old female presented a solitary nodule on the right groin. Biopsy revealed a secretory carcinoma staining positive with CK7, CAM5.2, mammaglobulin and S100 and negative with GATA3, CK20, podoplanin, calponin and CDX2. ETV6‐NTRK3 was demonstrated by Fluorescence in situ hybridization (FISH).DiscussionPCSC is a rare neoplasm, described in the skin in 2009, that affects more frequently females with a mean age of 42.3 years and it is most commonly located in axilla. Histopathologically, these tumor cells are characterized by bubbly eosinophilic secretions diastase‐resistant and bland nuclei and they are arranged in various growth patterns, including microcystic, tubular, solid and papillary. S100, mammoglobin and CK7 are usually positive. We review the main histopathological features to rule out histopathologic mimics such as breast metastasis, salivary tumors, cribriform carcinoma and primary cutaneous adenoid cystic carcinoma. GATA3 negative staining, as in our case, can help to rule out breast metastasis. Moreover, long‐term benign follow up (144 months) in this case as well as follow‐up data on outcomes from literature review support that PCSC is a low‐grade sweat gland carcinoma.
Subclinical left ventricular systolic and diastolic dysfunction in type 1 diabetic children and adolescents with good metabolic control
Authors: Yoldaş Tamer , Örün Utku Arman , Sagsak Elif , Aycan Zehra , Kaya Özkan , Özgür Senem , Karademir Selmin 
Published: December 2017

ObjectiveCardiac dysfunction is a well‐known consequence of diabetes mellitus. This study was designed to assess whether type 1 diabetic children and adolescents with good metabolic control have early echocardiographic signs of subclinical left ventricular dysfunction and whether diabetes duration has any influence, using conventional and nonconventional echocardiographic tools.MethodsA total of 100 patients with type 1 diabetes mellitus and 80 gender‐ and age‐matched healthy controls were included. The cases underwent standard conventional transthoracic echocardiography, tissue Doppler imaging, and two‐dimensional speckle tracking echocardiography. None of the diabetic patients had signs of renal, retinal, or neurological complications of the disease, and all were good metabolic control (mean HbA1c <7.5%).ResultsThere was no difference among groups in relation to age, sex, body mass index, and blood pressure. Conventional echocardiographic parameters were similar between diabetic and nondiabetic subjects except increased mitral valve peak A‐wave and significantly lower mitral E/A ratio in diabetics. Diabetic patients had more advanced diastolic dysfunction with TDI analysis. In the diabetic group, left ventricular global longitudinal, circumferential, and radial strain and strain rate were significantly lower compared with the controls. There was a positive correlation between diabetes duration and cardiac dysfunction.ConclusionThe results of this study showed that the diabetic children and adolescents with good metabolic control had diastolic dysfunction when assessed with either conventional or tissue Doppler echocardiography. Also diabetic patients had subclinical LV systolic dysfunction with a normal LVEF which can be detected with 2D speckle tracking echocardiography.
An auditory brainstem nucleus as a model system for neuronal metabolic demands
Authors: Brosel Sonja , Grothe Benedikt , Kunz Lars 
Published: December 2017

AbstractThe correlation between neuronal activity and metabolism is essential for coding, plasticity, neurological disorders and the interpretation of functional neuroimaging data. Most likely, metabolic requirements depend upon neuron type, and macroscopic energy demands vary with brain region. However, specific needs of individual neuron types are enigmatic. Therefore, we monitored metabolic activity in the lateral superior olive (LSO), an auditory brainstem nucleus containing only one neuron type. LSO neurons exhibit extreme but well‐described biophysics with firing rates of several hundred hertz and low input resistances of a few megaohms. We recorded changes in NADH and flavin adenine dinucleotide (FAD) autofluorescence and O2 concentration in acute brainstem slices of Mongolian gerbils (Meriones unguiculatus) following electrical stimulation. The LSO shows the typical biphasic NADH/FAD response up to a physiologically relevant frequency of 400 Hz. In the same animal, we compared the LSO with the hippocampal CA1 region and the cerebral cortex. The rate of NADH/FADH2 consumption and regeneration was slowest in LSO. However, frequency dependence was only similar during the consumption phase but varied during regeneration within the three brain regions. Changes in NADH, FAD and O2 levels and blocking metabolic reactions indicate a pronounced contribution of mitochondrial oxidative phosphorylation in the LSO which is known for the other brain regions as well. Lactate transport and interconversion are involved in LSO metabolism as we found in immunohistochemical and pharmacological experiments. Our findings show that the LSO represents an apt, biophysically distinct model for brain metabolism and that neuronal properties determine metabolic needs.
The role of linear mown firebreaks in conserving butterfly diversity: Effects of adjacent vegetation and management
Authors: Ohwaki Atsushi , Hayami Sho‐ichi , Kitahara Masahiko , Yasuda Taisuke 
Published: December 2017

AbstractSemi‐natural grasslands are vital for maintaining grassland butterflies in Japan, as well as in Europe. However, severe decline in these grassland environments has recently attracted attention to linear grasslands, such as firebreaks and power‐line corridors, as alternative habitats for grassland insects. We surveyed butterflies in an abandoned grassland and nearby linear mown firebreaks adjacent to different vegetation at the northern foot of Mt. Fuji, central Japan, over 5 successive years, particularly focusing on species on the 2012 Japanese Red List of Threatened Species (“red‐list” species). We found that the firebreaks were consistently higher in species richness and abundance of butterflies than the long‐term abandoned grassland, and that species composition differed among the firebreaks depending on conditions of the adjacent vegetation. The firebreaks surrounded by forests were mainly utilized by forest and edge species, whereas the firebreaks adjacent to the grassland were essential for conserving red‐list grassland species. Thus, only the mown firebreaks adjacent to the grassland were regarded as a high‐quality alternative habitat for many grassland butterflies, but the area was limited. Therefore, creating heterogeneity in the abandoned grassland by infrequent mowing could help conserve grassland butterflies, including red‐list species.
Therapeutic and prognostic significance of PARP‐1 in advanced mycosis fungoides and Sezary syndrome
Authors: Lemchak David , Banerjee Swati , Digambar Shaunak S. , Hood Brian L. , Conrads Thomas P. , Jedrych Jaroslaw , Geskin Larisa , Akilov Oleg E. 
Published: December 2017

AbstractWhile mycosis fungoides (MF) is typically an indolent malignancy, it may infrequently undertake an aggressive course. We used proteomic analyses to identify a biomarker of the aggressive course of MF. Results of this investigation demonstrated that PARP‐1, heat‐shock protein family A (Hsp70) member 1 like (HSAP1L), Hsp70 member 1A (HSPA1A), ATP‐depending RNA helicase (DDX17) and the α‐isoform of lamina‐associated polypeptide 2 (TMPO) had higher expression in aggressive disease versus non‐aggressive. Moreover, PARP‐1 was overexpressed in patients with early stage of MF who developed later an aggressive disease. PARP‐1 was evaluated as a new target for therapy, demonstrating the selective dose‐dependent cytotoxic effect of PARP inhibitors on Sézary cells in comparison with non‐malignant lymphocytes. In conclusion, we believe that PARP‐1 may serve not only as a biomarker at initial biopsies for a disease that may become aggressive but also as a new therapeutic target of advanced MF and Sézary syndrome.