bluuebunny/crossref_metadata_2025 huggingface dataset:
Expression of interleukin (IL)‐10 family cytokines in aqueous humour of patients with specific endogenous uveitic entities: elevated levels of IL‐19 in human leucocyte antigen‐B27‐associated uveitis
Authors: Abu El‐Asrar Ahmed M. , Berghmans Nele , Al‐Obeidan Saleh A. , Gikandi Priscilla W. , Opdenakker Ghislain , Van Damme Jo , Struyf Sofie
Published: February 2019

Purpose

Evidence exists that the interleukin (IL)‐10 family of cytokines is involved in autoimmune diseases. The aim of this study was to analyse the levels of the IL‐10 family cytokines IL‐10, IL‐19, IL‐20, IL‐22, IL‐26, IL‐28A and IL‐29 in aqueous humour (AH) samples from patients with specific uveitic entities. In addition, we correlated their levels with the levels of the proinflammatory cytokines tumour necrosis factor‐α (TNF‐α) and IL‐1β.

Methods

Aqueous humour (AH) samples from patients with active uveitis associated with Behçet's disease (BD; n = 13), sarcoidosis (n = 8), human leucocyte antigen (HLA)‐B27‐related inflammation (n = 12), Vogt–Koyanagi–Harada (VKH) disease (n = 12) and control subjects (n = 9) were assayed with the use of a multiplex assay.

Results

Of all the IL‐10 family cytokines studied, only IL‐19 levels were significantly higher in AH samples of patients (n = 45) than in controls (p = 0.022). When comparing the four individual disease groups to controls, IL‐19 levels were only significantly higher in HLA‐B27‐associated uveitis (p < 0.001). IL‐19 levels were significantly higher in patients with HLA‐B27‐associated uveitis than in patients with BD, sarcoidosis and VKH disease (p < 0.001; p = 0.002; p < 0.001, respectively). Significant correlations were found between AH levels of IL‐19 and AH levels of TNF‐α, (r = 0.3; p = 0.03) and IL‐1β (r = 0.56; p < 0.001).

Conclusions

Among the IL‐10 family cytokines analysed, IL‐19 demonstrated the highest expression in endogenous uveitis, particularly in HLA‐B27‐associated uveitis. IL‐19 thus might assist in the regulation of inflammation in HLA‐B27‐associated uveitis.
Systematic review with meta‐analysis: mycophenolate mofetil as a second‐line therapy for autoimmune hepatitis
Authors: Santiago Priscila , Schwartz Ingrid , Tamariz Leonardo , Levy Cynthia
Published: February 2019

Background

First‐line treatment for autoimmune hepatitis (AIH) typically includes corticosteroids in combination with azathioprine. Mycophenolate mofetil (MMF) is often used as a rescue therapy in patients who are intolerant of, or nonresponsive to, standard therapy.

Aim

To systematically review studies and perform a meta‐analysis on the efficacy and safety of MMF as a second‐line therapy for AIH patients.

Methods

MEDLINE, EMBASE and Cochrane Central were searched for studies that reported data on efficacy and safety of MMF as a second‐line therapy in AIH. We calculated the pooled response rate, adverse events rate and discontinuation rate due to side effects, with their corresponding 95% confidence intervals.

Results

Twelve studies comprising 397 patients, followed for a median of 34 months (range, 12‐47 months), were included. MMF doses ranged from 0.5‐4.0 g/d. Pooled response rate was 0.58 (95% CI 0.54‐0.63). Pooled adverse events rate was 0.14 (95% CI 0.11‐0.17), and pooled discontinuation rate due to side effects was 0.08 (95% CI 0.06‐0.11). Five studies (n = 309) specified response rates according to reason for using MMF. Pooled response rate in the subgroup with intolerance to standard therapy was 0.82 (95% CI 0.77‐0.87) and pooled response rate among nonresponders was 0.32 (95% CI 0.24‐0.39).

Conclusions

The overall efficacy of MMF as second‐line therapy in AIH was high. Response rate was greater in patients who started the medication due to intolerance to standard therapy as opposed to nonresponse. Overall, MMF was well tolerated, with a low discontinuation rate due to side effects.
Conscientious Objections to Corporate Wrongdoing
Authors: Solas John
Published: February 2019

In recent years, there has been increasing concern about unethical conduct within corporate business, not least because of the scandalous behavior of former chief executives at top blue chip companies such as Enron, Worldcom, Parmalat, and Volkswagen. These scandals have not only threatened the privileged position of senior corporate employees but also the solvency of the companies they manage and lead. The high profile cases of corporate crime and corruption that occurred in the early 2000s together with the 2008 Wall Street bailouts and the growth in criminal prosecutions since have raised the profile of business ethics to an unprecedented level. Greater public sensitivity toward and awareness about the unlawful and immoral conduct of firms in the United States and elsewhere, has created demand for organizations to become more accountable and socially responsible and prompted greater regulatory scrutiny. It has also served to highlight the embryonic and delimited state of research and scholarship on business ethics, where the focus has tended to remain on leadership. A neglected, though important, line of ethical enquiry concerns followership. Corporate wrongdoing would be less formidable and extensive if it was not aided and abetted. Two key questions arise. First, what prompts followers to support rather than oppose bad leaders? Second, what can be done to stem or at least curtail their allegiance to bad leaders?
The injustice of fat stigma
Authors: Nath Rekha
Published: February 2019

Fatness stigma is pervasive. Being fat is widely regarded a bad thing, and fat persons suffer numerous social and material disadvantages in virtue of their weight being regarded that way. Despite the seriousness of this problem, it has received relatively little attention from analytic philosophers. In this paper, I set out to explore whether there is a reasoned basis for stigmatizing fatness, and, if so, what forms of stigmatization could be justified. I consider two lines of reasoning that might be advanced to defend fat stigma. The first is broadly consequentialist. It seeks to justify stigmatizing fatness based on the public health benefits that might be produced by doing so. The second argument takes stigmatizing fatness to be a warranted response to the morally blameworthy failure to slim down exhibited by fat persons. Clarifying and assessing each of these two lines of reasoning is the main task of this paper. I argue that, upon careful examination, both these attempts to justify the stigmatization of fatness fail.
Taxane‐based chemohormonal therapy for metastatic hormone‐sensitive prostate cancer: a Cochrane Review
Authors: Sathianathen Niranjan J. , Philippou Yiannis A. , Kuntz Gretchen M. , Konety Badrinath R. , Gupta Shilpa , Lamb Alastair D. , Dahm Philipp
Published: February 2019

To provide a precis of the Cochrane Collaboration Review of taxane‐based chemohormonal therapy for metastatic hormone‐sensitive prostate cancer by Sathianathen NJ, Philippou YA, Kuntz GM et al. Cochrane Database of Systematic Reviews 2018, Issue 10. Art. No.: CD012816. https://doi.org/10.1002/14651858.cd012816.pub2.
Mate choice in a changing world
Authors: Candolin Ulrika
Published: February 2019

Human activities by altering environmental conditions are influencing the mate choice of animals. This is by impacts on: (i) the production and expression of traits evaluated by mate choosers; (ii) the transmission of information about potential mates to choosers; (iii) the reception and processing of the information by choosers; and (iv) the final mate choice. Here, I first discuss how these four stages of the mate‐choice process can be altered by environmental change, and how these alterations, in turn, can influence individuals, populations, and communities. Much evidence exists for human‐induced environmental changes influencing mate choice, but the consequences for the fitness of courters and choosers are less well known, and even less is known about the impact on population dynamics, species interactions and community composition. More evidence exists for altered mate‐choice systems influencing interspecific matings and thereby community composition and biodiversity. I then consider whether plastic adjustments and evolutionary changes can rescue adaptive mate‐choice systems, and reflect on the possibility of non‐adaptive mate‐choice systems becoming less maladaptive under environmental change. Much evidence exists for plastic adjustments of mate‐choice systems, but whether these are adaptive is seldom known, as is the contribution of genetic changes. Finally, I contemplate the possibility of mate‐choice systems rescuing populations from decline in changing environments. I explain how this is context dependent with both positive and negative outcomes possible. In summary, while much evidence exists for human‐induced environmental changes influencing mate‐choice systems, less is known about the consequences for ecological and evolutionary processes. Considering the importance that mate choice plays in determining individual fitness and population viability, the effects of environmental change on mate‐choice systems should be considered in studies on the ecological and evolutionary consequences of human disturbances to habitats.
Death domain of p75 neurotrophin receptor: a structural perspective on an intracellular signalling hub
Authors: Yuan Wensu , Ibáñez Carlos F. , Lin Zhi
Published: February 2019

The death domain (DD) is a globular protein motif with a signature feature of an all‐helical Greek‐key motif. It is a primary mediator of a variety of biological activities, including apoptosis, cell survival and cytoskeletal changes, which are related to many neurodegenerative diseases, neurotrauma, and cancers. DDs exist in a wide range of signalling proteins including p75 neurotrophin receptor (p75NTR), a member of the tumour necrosis factor receptor superfamily. The specific signalling mediated by p75NTR in a given cell depends on the type of ligand engaging the extracellular domain and the recruitment of cytosolic interactors to the intracellular domain, especially the DD, of the receptor. In solution, the p75NTR‐DDs mainly form a symmetric non‐covalent homodimer. In response to extracellular signals, conformational changes in the p75NTR extracellular domain (ECD) propagate to the p75NTR‐DD through the disulfide‐bonded transmembrane domain (TMD) and destabilize the p75NTR‐DD homodimer, leading to protomer separation and exposure of binding sites on the DD surface. In this review, we focus on recent advances in the study of the structural mechanism of p75NTR‐DD signalling through recruitment of diverse intracellular interactors for the regulation and control of diverse functional outputs.
Primär kutane CD4+ klein‐ bis mittelgroßzellige pleomorphe T‐Zell‐Lymphoproliferation: Wo stehen wir? Eine systematische Übersicht
Authors: Salah Eman
Published: February 2019

Die primär kutane CD4+ klein‐ bis mittelgroßzellige pleomorphe T‐Zell‐Lymphoproliferation (PCSMP‐TLPD) ist nach der neuesten Auflage der WHO‐Klassifikation der lymphatischen Neoplasien eine vorläufige Entität mit unbekanntem malignem Potenzial. Wir führten eine systematische Literaturanalyse aller bisher publizierten Fälle von PCSMP‐TLPD durch, um ihre typischen und atypischen Merkmale herauszuarbeiten. Die wichtigsten Charakteristika der PCSMP‐TLPD und ihre mögliche klinisch‐pathologische Überlappung mit ähnlichen Erkrankungen werden ebenfalls diskutiert. Dieser Übersichts‐Artikel soll einen Überblick über diese Störung und die wichtigsten Differenzialdiagnosen bieten. Schließlich empfehlen wir, dass Experten für kutane Lymphome einen rigorosen Konsens hinsichtlich der Formulierung diagnostischer Kriterien und der besten Falldefinition finden.
Phänomen „grüner Nagel“ in der ICG‐gestützten fluoreszenzoptischen Bildgebung – ein möglicher differenzialdiagnostischer Hinweis auf Psoriasisarthritis
Authors: Wiemann Oliver , Werner Stephanie G. , Langer Hans‐Eckhard , Backhaus Marina , Chatelain René
Published: February 2019

Hintergrund und Zielsetzung

Die Frühdiagnostik der Psoriasisarthritis stellt eine besondere Herausforderung dar. Das Xiralite®‐System, ein neueres fluoreszenzoptisches Bildgebungsverfahren kann dazu mittels Darstellung von Mikrovaskularität und Perfusion einen wichtigen Beitrag leisten. In der vorliegenden Studie wurden erstmals extraartikuläre fluoreszenzoptische Signale an einer großen Psoriasisarthritis‐Kohorte systematisch untersucht.

Patienten und Methodik

In der Hauptstudie untersuchten und analysierten wir extraartikuläre fluoreszenzoptische Signalmuster bei 241 Sequenzen von 187 Psoriasisarthritis‐Patienten. Als Kontrolle dienten 36 fluoreszenzoptische Sequenzen bei 31 Patienten mit rheumatoider Arthritis. In einer Folgestudie wurden 203 konsekutive fluoreszenzoptische Sequenzen bei 54 Psoriasisarthritis‐Patienten und 149 Kontrollen mit entzündlich‐rheumatischen Erkrankungen retrospektiv ausgewertet, um die Ergebnisse der Hauptstudie hinsichtlich der identifizierten Muster zu validieren.

Ergebnisse

In Projektion auf den Nagelbereich ließen sich bei Psoriasisarthritis insgesamt drei fluoreszenzoptische Signalmuster differenzieren, die in bisherigen Untersuchungen nicht beschrieben wurden, darunter insbesondere das von uns so bezeichnete „Green Nail“‐Phänomen, das hohe Spezifität (97 %) für die Psoriasisarthritis zeigte. In der Folgestudie lag die Spezifität bei 87 % für die Psoriasisarthritis in Bezug zur Kontrollkohorte.

Schlussfolgerungen

In den vorliegenden Untersuchungen erwiesen sich fluoreszenzoptische Signale im Bereich der Nägel als hochspezifisch für die Psoriasisarthritis. Dabei scheint der „Green Nail“ von besonderem diagnostischem Interesse zu sein als möglicher Hinweis auf eine Mikrozirkulationsstörung im Bereich des Nagelbettes.
S2k‐Leitlinie Basalzellkarzinom der Haut – Teil 2: Therapie, Prävention und Nachsorge
Authors: Lang Berenice M. , Balermpas Panagiotis , Bauer Andrea , Blum Andreas , Brölsch G. Felix , Dirschka Thomas , Follmann Markus , Frank Jorge , Frerich Bernhard , Fritz Klaus , Hauschild Axel , Heindl Ludwig M. , Howaldt Hans‐Peter , Ihrler Stephan , Kakkassery Vinodh , Klumpp Bernhard , Krause‐Bergmann Albrecht , Löser Christoph , Meissner Markus , Sachse Michael M. , Schlaak Max , Schön Michael P. , Tischendorf Lutz , Tronnier Michael , Vordermark Dirk , Welzel Julia , Weichenthal Michael , Wiegand Susanne , Kaufmann Roland , Grabbe Stephan
Published: February 2019

Das Basalzellkarzinom (BZK) ist der häufigste maligne Tumor der hellhäutigen Bevölkerung mit jährlich steigender Inzidenz. Eine Aktualisierung der S2k‐Leitlinie unter Beteiligung aller mit dem Krankheitsbild vertrauten Fachgesellschaften sowie vorangegangener Literaturrecherche ist für die Qualität der Versorgung der betroffenen Patienten von essentieller Bedeutung. Im vorliegenden Teil 2 wird zunächst eine Risikostratifizierung aufgezeigt, bevor die verschiedenen Therapieoptionen diskutiert werden. Zudem werden Prävention und Nachsorge der Erkrankung behandelt.
Superior efficacy of insulin degludec/liraglutide versus insulin glargine U100 as add‐on to sodium‐glucose co‐transporter‐2 inhibitor therapy: A randomized clinical trial in people with uncontrolled type 2 diabetes
Authors: Philis‐Tsimikas Athena , Billings Liana K. , Busch Robert , Portillo Cristobal Morales , Sahay Rakesh , Halladin Natalie , Eggert Sarah , Begtrup Kamilla , Harris Stewart
Published: February 2019

Aim

To investigate the efficacy and safety of insulin degludec/liraglutide (IDegLira) versus insulin glargine 100 units/mL (IGlar U100) as add‐on to sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor therapy.

Materials and methods

In this 26‐week, phase IIIb, open‐label, parallel‐group, treat‐to‐target trial, conducted at 74 sites in 11 countries, insulin‐naïve people aged ≥18 years with glycated haemoglobin (HbA1c) 53–97 mmol/mol (7.0–11.0%), body mass index 20–40 kg/m2 and inadequately controlled type 2 diabetes (T2D) on SGLT2 inhibitor ± oral antidiabetic drugs were randomized 1:1 to once‐daily IDegLira or IGlar U100, both as add‐on to existing therapy. The primary endpoint was change in HbA1c from baseline to week 26.

Results

A total of 210 participants were randomized to each treatment arm. Mean HbA1c reductions were 21 mmol/mol (1.9%‐points) with IDegLira and 18 mmol/mol (1.7%‐points) with IGlar U100; confirming non‐inferiority (P < 0.0001) and superiority of IDegLira (difference in HbA1c change –3.90 mmol/mol; 95% confidence interval [CI] –5.45; –2.35 (−0.36%‐points; 95% CI –0.50, –0.21)). Superiority for IDegLira over IGlar U100 was also confirmed for: body weight (difference −1.92 kg; 95% CI –2.64, –1.19); severe or blood‐glucose‐confirmed symptomatic hypoglycaemia (rate ratio 0.42; 95% CI 0.23, 0.75); total daily insulin dose (difference −15.37 U; 95% CI –19.60, −11.13). The overall treatment‐emergent adverse event rate was higher with IDegLira as a result of higher increased lipase and nausea rates.

Conclusions

The favourable safety and efficacy profile of IDegLira in people with uncontrolled T2D on SGLT2 inhibitors, and lower weight gain and hypoglycaemia risk versus IGlar U100, suggest that clinicians should consider IDegLira initiation in this population.
The effects of land abandonment and long‐term afforestation practices on the organic carbon stock and lignin content of Mediterranean humid mountain soils
Authors: Campo Julian , Stijsiger Romy J. , Nadal‐Romero Estela , Cammeraat Erik L.H.
Published: February 2019

Afforestation is an important strategy that can decrease atmospheric carbon by sequestering carbon in biomass and soil. In Spain, an active afforestation programme was adopted in the 1950s when the soil was severely eroded after widespread abandonment of arable land. The Araguás catchment (Central Spanish Pyrenees) is a good example of this programme because it was afforested with both Pinus sylvestris L. (PS) and Pinus nigra J.F.Arnold (PN). The soil organic carbon (SOC) stock and lignin content (based on the vanillyl, syringyl and cinnamyl contents) of these afforested soils were examined and compared to those of bare soil, secondary succession and meadow soils. Both the SOC stock and lignin content were used to evaluate the effects of land‐use changes on soil. Curie‐point pyrolysis with tetramethylammonium hydroxide was used to assess the lignin content. In the bare soil, there was none of the lignin compounds. The largest SOC stock and lignin content occurred under PN and secondary succession sites. A decreasing trend for the lignin content, related to the limited organic matter input and the longer degradation period, was observed at deeper horizons in all soils except meadows. These meadow soils also showed increased SOC stocks in deeper horizons. Land abandonment reduced the SOC stock although no significant differences were observed in the organic carbon incorporation assessed through lignin content (and if this was so it was restricted to the top centimetre or so). According to the results, PN was the best afforestation practice for increasing SOC stock and lignin content in soil. Pinus sylvestris afforestation was less successful than secondary succession at increasing SOC sequestration and lignin content.

Highlights

Effects of long‐term afforestation and land abandonment assessed in Mediterranean humid mountain soils.

Soil organic carbon (SOC) stock and lignin content were used as indicators.

Bare soil had the smallest SOC stock and lignin content.

Afforestation with Pinus nigra was the best practice, increasing SOC stock and lignin content.
Natalizumab, rituximab and fingolimod as escalation therapy in multiple sclerosis
Authors: Boremalm M. , Juto A. , Axelsson M. , Novakova L. , Frisell T. , Svenningsson A. , Lycke J. , Piehl F. , Salzer J.
Published: February 2019

Background and purpose

Breakthrough disease on first‐line injectables in relapsing‐remitting multiple sclerosis (RRMS) is a common clinical situation where comparative studies between different escalation therapies are lacking. The aim of this study was to compare the efficacy, safety and medication persistence of natalizumab (NTZ), rituximab (RTX) and fingolimod (FGL) as escalation therapy in RRMS.

Methods

Patients switching from interferon or glatiramer acetate to NTZ, RTX or FGL due to breakthrough disease were identified through the Swedish multiple sclerosis (MS) registry at four large MS centers in this retrospective observational study. Data were collected from the MS registry and medical charts. Hazard ratios (HRs) for relapses, adverse events and drug discontinuation with 95% confidence interval (CI) were calculated using multivariable confounder‐adjusted Cox proportional hazard models.

Results

A total of 241 patients were included. The annualized relapse rates were 0.02 for NTZ, 0.03 for RTX and 0.07 for FGL. Compared with NTZ, the adjusted HR for relapse was 1.0 (95% CI, 0.2–5.6) for RTX and 3.4 (95% CI, 1.3–9.2) for FGL. The annualized drug discontinuation rates were 0.15, 0.01 and 0.15 for NTZ, RTX and FGL, respectively. The adjusted HR for drug discontinuation was 0.05 (95% CI, 0.01–0.38) for RTX and 1.0 (95% CI, 0.6–1.7) for FGL vs. NTZ.

Conclusions

In patients with RRMS on interferon/glatiramer acetate with breakthrough disease, switching to NTZ or RTX was associated with less disease activity compared with FGL. RTX displayed superior medication persistence compared with both NTZ and FGL.
Price discovery and persistent arbitrage violations in credit markets
Authors: Lin Hai , Man Kasing , Wang Junbo , Wu Chunchi
Published: February 2019

This paper investigates price violations in credit markets using a data sample spanning from 2002 to 2016. We find that price violations are highly persistent during the crisis period, particularly for speculative‐grade bonds. There is evidence that price distortions and market disintegration are linked to market‐wide and firm‐level impediments to arbitrage and limited capital provision. Higher firm‐level impediments to arbitrage lead to less market integration, and more severe and persistent pricing discrepancies. Moreover, we find that the negative CDS basis persists in the postcrisis period, which is attributable to dealers’ lower capital commitment and deterioration in market‐making quality.
Spatial and habitat variation in aphid, butterfly, moth and bird phenologies over the last half century
Authors: Bell James R. , Botham Marc S. , Henrys Peter A. , Leech David I. , Pearce‐Higgins James W. , Shortall Chris R. , Brereton Tom M. , Pickup Jon , Thackeray Stephen J.
Published: February 2019

Global warming has advanced the timing of biological events, potentially leading to disruption across trophic levels. The potential importance of phenological change as a driver of population trends has been suggested. To fully understand the possible impacts, there is a need to quantify the scale of these changes spatially and according to habitat type. We studied the relationship between phenological trends, space and habitat type between 1965 and 2012 using an extensive UK dataset comprising 269 aphid, bird, butterfly and moth species. We modelled phenologies using generalized additive mixed models that included covariates for geographical (latitude, longitude, altitude), temporal (year, season) and habitat terms (woodland, scrub, grassland). Model selection showed that a baseline model with geographical and temporal components explained the variation in phenologies better than either a model in which space and time interacted or a habitat model without spatial terms. This baseline model showed strongly that phenologies shifted progressively earlier over time, that increasing altitude produced later phenologies and that a strong spatial component determined phenological timings, particularly latitude. The seasonal timing of a phenological event, in terms of whether it fell in the first or second half of the year, did not result in substantially different trends for butterflies. For moths, early season phenologies advanced more rapidly than those recorded later. Whilst temporal trends across all habitats resulted in earlier phenologies over time, agricultural habitats produced significantly later phenologies than most other habitats studied, probably because of nonclimatic drivers. A model with a significant habitat‐time interaction was the best‐fitting model for birds, moths and butterflies, emphasizing that the rates of phenological advance also differ among habitats for these groups. Our results suggest the presence of strong spatial gradients in mean seasonal timing and nonlinear trends towards earlier seasonal timing that varies in form and rate among habitat types.
Take Your Time to Grow: A Field Experiment on the Hiring of Youths
Authors: Kübler Dorothea , Stüber Robert , Schmid Julia
Published: February 2019

We investigate the effect of spells of no formal employment of young Germans on their chances of entering the labor market through an apprenticeship. We also study whether the potential negative effects of such spells can be mitigated by publicly provided training measures. In a field experiment, the fictitious applications of three young women were sent to firms advertising apprenticeships for the position of office manager. One application was from a fresh school-leaver and two from applicants who had been out of school for two years, where one of them had participated in a training measure. We find that applicants who have been out of school for two years and have participated in the training are more successful than older applicants without additional training. We do not find a significant difference between older applicants with or without training and fresh school leavers. Our findings show that training measures increase the attractiveness of applicants and that the potential stigma of spells of no formal employment after school are compensated by informal work experience or age or a combination of both.
Associations of number of teeth with medical costs and hospitalization duration in an older Japanese population
Authors: Saito Mizuki , Shimazaki Yoshihiro , Nonoyama Toshiya , Tadokoro Yasushi
Published: February 2019

Aim

Many studies have reported close relationships between oral and systemic health. We explored the association of the number of remaining teeth with medical costs and hospitalization duration in people aged 75 and 80 years.

Methods

Oral health examinations were carried out at dental clinics in 2014. Medical cost and hospitalization duration data for fiscal year 2015 were obtained from the Mie Prefecture health insurer. We analyzed the data of 4700 individuals who met our inclusion criteria: 2745 75‐year‐olds and 1955 80‐year‐olds. The effects of remaining tooth numbers on medical costs and hospitalization days were analyzed using a generalized linear model with log link adjustment for confounders.

Results

Total medical costs for all diseases were significantly higher in those with 20–27, 10–19 and 1–9 teeth, and in edentulous older individuals, compared with those with 28 teeth. Outpatient medical costs for diabetes were significantly higher in those with 20–27 and 1–9 teeth. Inpatient medical costs for digestive cancers were significantly higher in those with 10–19 and 1–9 teeth, and in edentulous older individuals. Hospitalization for digestive cancer was significantly longer in those with 20–27, 10–19 and 1–9 teeth, and in edentulous older individuals, than in those with 28 teeth. The number of teeth as a continuous variable was significantly inversely associated with medical costs for cerebrovascular disease and digestive cancer, and hospitalization days for digestive cancer.

Conclusion

Small numbers of teeth were associated with higher medical costs and longer hospital stays for older Japanese. Geriatr Gerontol Int 2019; 19: 335–341.
Influence of the phenotype on mycosis fungoides prognosis, a retrospective cohort study of 160 patients
Authors: Jaque Alejandra , Mereniuk Alexandra , Walsh Scott , Shear Neil H. , Sade Shachar , Zagorski Brandon , Alhusayen Raed
Published: February 2019

Background

Mycosis fungoides (MF) typically has a CD4+CD8− T‐cell phenotype. Rare cases of CD4−CD8+, CD4−CD8−, or CD4+CD8+ immunophenotypes have been described. Little is known about the impact of MF immunophenotypes on disease behavior.

Methods

We conducted a retrospective cohort study to review all cases of MF from 2007 to 2017 from Sunnybrook Health Sciences Centre, Toronto, Canada. CD4+CD8− (Group 1) was compared to the three less common subtypes (Group 2) with respect to stage at diagnosis, progression, and transformation. Potential confounding factors (demographic, clinical, and laboratory parameters) were assessed.

Results

A total of 160 patients with confirmed MF were analyzed, including 126 CD4+CD8− MF (79%), 26 CD4−CD8+ MF (16%), six CD4+CD8+ MF (4%), and two CD4−CD8− MF (1%). Both groups were similar with respect to demographics and laboratory parameters at the time of diagnosis. There was no difference between patients with late stage disease (10% vs. 9%) for groups 1 and 2, respectively (P = 0.901). There was no statistically significant difference either in 5‐year progression (27.7% vs. 23.5%, P = 0.283) or transformation (16.2% vs. 17.3%, P = 0.350) estimates. We did find that atypical immunophenotypes presented with different clinical morphologies and were less likely to require systemic therapy.

Conclusion

Our large cohort study indicates that atypical MF immunophenotypes do not seem to influence prognosis. Hypopigmented MF was more frequent in the CD4−CD8+ group while folliculotropic MF was exclusively seen in the CD4+CD8− group. We believe that cases of CD8+ MF with aggressive behavior described in the literature represent misclassified primary cutaneous aggressive epidermotropic CD8+ T‐cell lymphoma. The small number of patients included in the study is a limiting factor.
New trends in voiding cystourethrography and vesicoureteral reflux: Who, when and how?
Authors: Arlen Angela M , Cooper Christopher S
Published: February 2019

Vesicoureteral reflux, retrograde flow of urine from the bladder into the upper urinary tract, is one of the most common urological diagnoses in the pediatric population. Diagnosis and subsequent management of urinary reflux have become increasingly debated in the past decade, with divergent opinions over which patients should be evaluated for reflux, and when detected, which children should receive intervention. Although some argue that vesicoureteral reflux is a “phenotype” that often resolves without intervention, others contest that untreated reflux has the potential to cause irreversible renal damage over time. Voiding cystourethrogram images the urethra and bladder during both bladder filling and emptying, as well as the ureters and kidneys when reflux is present, and is considered the gold standard for diagnosing vesicoureteral reflux. Once detected, therapeutic options for urinary reflux are diverse, ranging from observation with or without low‐dose antibiotic prophylaxis to a variety of operative interventions. Management should be based on a multitude of factors including patient age, risk of subsequent urinary tract infections, risk of renal parenchymal injury, a given child's projected clinical course and parental preference. Over the past two decades, investigators have elucidated many crucial voiding cystourethrogram findings in addition to grade that provide significant prognostic information and are useful in determining the best course of action for a child on a more individualized basis.
An avian influenza virus A(H7N9) reassortant that recently emerged in the United States with low pathogenic phenotype does not efficiently infect swine
Authors: Powell Joshua D. , Abente Eugenio J. , Torchetti Mia K. , Killian Mary L. , Vincent Amy L.
Published: February 2019

In 2017, outbreaks of low and highly pathogenic avian H7N9 viruses were reported in four States in the United States. In total, over 270 000 birds died or were culled, causing significant economic loss. The potential for avian‐to‐swine transmission of the U.S. avian H7N9 was unknown. In an experimental challenge in swine using a representative low pathogenic H7N9 (A/chicken/Tennessee/17‐007431‐3/2017; LPAI TN/17) isolated from these events, no infectious virus in the upper and minimal virus in the lower respiratory tract was detected, nor was lung pathology or evidence of transmission in pigs observed, indicating that the virus cannot efficiently infect swine.
How did terricolous fungi originate in the Mediterranean region? A case study with a gypsicolous lichenized species
Authors: Chiva Salvador , Garrido‐Benavent Isaac , Moya Patricia , Molins Arantzazu , Barreno Eva
Published: February 2019

Aim

The historical causes responsible for the wide distribution of terricolous, crustose lichenized fungi across the Mediterranean Basin and the Canary Islands have never been explored. Here, we used the terricolous, circum‐Mediterranean/Macaronesian species Buellia zoharyi (Caliciaceae, Ascomycota) to infer the time frame, and the climatic, geological and ecological factors influencing the origin and current spatial distribution of this species.

Location

Mediterranean Basin and Canary Islands.

Methods

Data from two nuclear markers (nrITS and tef1) obtained from 226 specimens of 23 populations covering the entire distribution range of B. zoharyi were used to calculate genetic diversity indices and haplotype networks and to investigate population size changes and structure. Three secondary calibrations were used to estimate the timing of the divergence of B. zoharyi from its hypothesized sister species, B. elegans, and the diversification of B. zoharyi.

Results

We found low nucleotide diversity and two geographically differentiated haplogroups, with a contact zone in the Iberian Peninsula. The three dating approaches established wide temporal windows for the divergence of B. zoharyi from B. elegans (Eocene‐Pliocene) and its diversification (Miocene‐Pleistocene). These intervals overlap with the origin and diversification ages found in other lichen‐forming fungi and vascular plants inhabiting the Mediterranean region.

Main conclusions

In the context of lichen biogeography, our results support ecological specialization as well as geological and climatic events as drivers of the evolutionary history of B. zoharyi in the Mediterranean. In particular, the combined effects of the Messinian salinity crisis and the subsequent Zanclean Flood on the availability of gypsum soils in the Mediterranean Basin, as well as the Quaternary climatic oscillations, seem to have collectively shaped the amount and distribution of B. zoharyi population genetic diversity.
Phylogeography and post‐glacial dynamics in the clonal‐sexual orchid Cypripedium calceolus L.
Authors: Gargiulo Roberta , Pironon Samuel , Zheleznaya Ekaterina , Sanchez Michele D. , Balázs Zoltan R. , Podar Dorina , Wilkinson Timothy , Jäkäläniemi Anne , Kull Tiiu , Väre Henry , Fay Michael F.
Published: February 2019

Aim

We investigated the phylogeographical history of a clonal‐sexual orchid, to test the hypothesis that current patterns of genetic diversity and differentiation retain the traces of climatic fluctuations and of the species reproductive system.

Location

Europe, Siberia and Russian Far East.

Taxon

Cypripedium calceolus L. (Orchidaceae).

Methods

Samples (>900, from 56 locations) were genotyped at 11 nuclear microsatellite loci and plastid sequences were obtained for a subset of them. Analysis of genetic structure and approximate Bayesian computations were performed. Species distribution modelling was used to explore the effects of past climatic fluctuations on the species range.

Results

Analysis of genetic diversity reveals high heterozygosity and allele diversity, with no geographical trend. Three genetic clusters are identified with extant gene pools derived from ancestral demes in glacial refugia. Siberian populations exhibit different plastid haplotypes, supporting an early divergence for the Asian gene pool. Demographic results based on genetic data are compatible with an admixture event explaining differentiation in Estonia and Romania and they are consistent with past climatic dynamics inferred through species distribution modelling. Current population differentiation does not follow isolation by distance model and is compatible with a model of isolation by colonization.

Main conclusions

The genetic differentiation observed today in C. calceolus preserves the signature of climatic fluctuations in the historical distribution range of the species. Our findings support the central role of clonal reproduction in the reducing loss of diversity through genetic drift. The dynamics of the clonal‐sexual reproduction are responsible for the persistence of ancestral variation and stability during glacial periods and post‐glacial expansion.
EIF5A regulates proliferation and chemoresistance in pancreatic cancer through the sHH signalling pathway
Authors: Wang Zheng , Jiang Jie , Qin Tao , Xiao Ying , Han Liang
Published: February 2019

Background

Pancreatic cancer (PC) has a very poor prognosis and comparatively short survival. Eukaryotic translation initiation factor 5A (EIF5A) promotes cancer metastasis. Here, we exploited the biological role of EIF5A in PC chemoresistance.

Methods

Expression of EIF5A was analysed in PC cells and tissues by real‐time PCR, Western blotting, immunohistochemistry and immunofluorescent. EIF5A expression was specifically suppressed by transfection, and subsequently the alterations of growth behaviour and resistance to anticancer treatment were tested in an orthotopic tumour model.

Results

The results showed EIF5A was increased in human PC tissues and PC cells. We found EIF5A knockdown reduced the PC proliferation ability in vivo and in vitro. In addition, sonic hedgehog (sHH) signalling pathway may be a downstream of EIF5A in PC cells. Inhibition of EIF5A and sHH signalling pathway could suppress PC cells proliferation and tumour growth. Importantly, EIF5A played an important role in gemcitabine sensitivity for PC.

Conclusion

Taken together, our results revealed that EIF5A regulated the proliferation of PC through the sHH signalling pathway and decreased the Gem sensitivity in PC, which provided a novel therapeutic strategy for PC patients.
Mutant hFGF23(A12D) stimulates osteoblast differentiation through FGFR3
Authors: Tu Yilin , Qu Taoran , Chen Fengshan
Published: February 2019

Fibroblast growth factor (FGF) 23 is a member of the FGF family involved in bone development by interacting with FGFRs. In a previous study, we discovered a mutant human FGF (hFGF) 23 (A12D) in the mandibular prognathism (MP) pedigree. However, the exact role of hFGF23(A12D) during bone formation remains unclear. The aim of this study was to identify the function of hFGF23(A12D) in bone formation. We infected isolated rat calvaria (RC) cells with the recombinant lentivirus containing mutant hFGF23(A12D) and WT hFGF23 respectively. Real‐time PCR, western blot and enzyme‐linked immunosorbent assay confirmed that hFGF23(A12D) failed to be secreted. We measured cell growth via the CCK‐8 assay based on Zsgreen expression, detected cell differentiation ability via alkaline phosphatase staining, performed RT‐PCR and found that hFGF23(A12D) inhibited proliferation of RC cells and stimulated the differentiation of RC cells to osteoblasts. Through RNA sequencing, RT‐PCR and western blot, we found increased expression of FGFR3. Through co‐immunoprecipitation assays and immunofluorescence staining, we revealed that hFGF23(A12D) activated the mitogen‐activated protein kinase signalling pathway through interactions with the intracellular domain of FGFR3. In summary, we determined the mechanisms of hFGF23(A12D) involved in osteoblast generation and formation which is specifically due to its interaction with FGFR3.
Reproductive strategy as a major factor determining female body size and fertility of a gregarious parasitoid
Authors: Samková Alena , Hadrava Jiří , Skuhrovec Jiří , Janšta Petr
Published: February 2019

The generally known “adult size‐fitness hypothesis” (ASFH) is applied to the gregarious parasitic wasp Anaphes flavipes (Foerster, 1841) (Hymenoptera: Mymaridae). ASFH is dependent on the reproductive strategy of the mother, which means the larger females have more offspring compared to smaller females. Two main factors, the mother's body size and food quantity received during larval development, can affect the body size of the offspring. For the first time, we present a study on the relative effect of both factors on fitness of the same species, wasp A. flavipes. Our data confirmed that females of A. flavipes with larger body sizes had more offspring compared to smaller ones. At the same time, mother's body size does not seem to affect the body size of the offspring. The other studied factor, quantity of food received during larval development, can be influenced by reproductive strategy (number of parasitoids developing in one host egg), host quality or the duration of development. We found only the reproductive strategy to have a statistically significant effect on body size. We demonstrated that the variable reproductive strategy (VRS) of wasp A. flavipes causes a plasticity in body size and future number of offspring. The generally known “trade‐off” scheme (more small offspring or fewer bigger offspring) does not apply to A. flavipes, because their large females have more offspring and it is their reproductive strategy that determines body size.
Zebrafish fin‐derived fibroblast cell line: A model for in vitro wound healing
Authors: Kalaiselvi Sivalingam Nathiga Nambi , Seepoo Abdul Majeed , Gani Taju , Selvam Sivakumar , Azeez Sait Sahul Hameed
Published: February 2019

The goal of this study was to develop and characterize a cell line from the caudal fin tissue of zebrafish and also its application as an in vitro model to study the effect of H2O2 in wound healing. Fibroblastic cell line was developed using explant culture method from caudal fin tissue of zebrafish and characterized. This cell line was named as DrF cell line. The DrF cells treated with 0–10 µM/ml H2O2 were tested for viability, proliferation and motility by MTT assay, trypan blue assay and chemotaxis assay, respectively. Among the different concentrations of H2O2, 4 µM was found to be nontoxic to study cell migration in in vitro scratch wound assay. Furthermore, the expression of proliferating cell nuclear antigen (PCNA) and chemokine receptor (CXCR4) genes was carried by qPCR. The cell survival, proliferation and migration were extremely enriched at 4 µM level of H2O2. We observed accelerated wound closure in DrF cells treated with H2O2. The qPCR results indicated that H2O2 markedly up‐regulated mRNA expression of PCNA and CXCR4. The findings from our study suggest that H2O2 at low levels promotes cell survival, proliferation, migration and wound healing in DrF cells.
CAN NONLOCAL TRADERS CAPTURE THE LOCAL INFORMATION ADVANTAGE AND PROFIT?
Authors: Meshcheryakov Artem , Winters Drew B.
Published: February 2019

Market makers located in geographic proximity (local) to companies possess a local information advantage that comes from access to soft information. We study whether a nonlocal trader can capture the local information advantage and profit without relocating. We develop a trading strategy for the nonlocal trader that generates “buy” and “sell” signals for stocks based on quotes of local market makers. Our findings suggest it is possible, albeit difficult, for nonlocal traders to extract local information from local market makers’ quotes. Using limit orders from buy signals, we generate up to 7.6 basis points of abnormal return per day.
Association of low alanine aminotransferase with loss of independence or death: A 5‐year population‐based cohort study
Authors: Yamazaki Hajime , Kamitani Tsukasa , Matsui Takeshi , Yamamoto Yosuke , Fukuhara Shunichi
Published: February 2019

Background and Aim

Alanine aminotransferase (ALT) is an important enzyme for amino acid metabolism and gluconeogenesis, and low ALT is an indicator of vitamin B6 deficiency. However, it is unknown whether individuals with low ALT are likely to develop loss of independence (LOI) or death. We investigated the association of low ALT with LOI or death in the elderly.

Methods

Between 2008 and 2010, 2,484 elderly individuals (≥ 65 years old) without functional dependency from the Locomotive Syndrome and Health Outcomes in the Aizu Cohort Study were enrolled. Based on baseline ALT values, the participants were divided into the following groups: ALT < 10 (n = 73), 10–20 (n = 1,372), 20–30 (reference, n = 734), 30–40 (n = 201), and ≥ 40 (n = 104) U/L groups. LOI was defined as requiring complete support for basic activities of daily living, which is care levels 3–5 in Japanese long‐term care insurance certifications. The hazard ratios of LOI or death were estimated by Cox proportional hazard models adjusted for potential confounders.

Results

During the median follow‐up period of 5.75 (interquartile range 4.85–5.83) years, LOI or death occurred in 195 participants (7.85%). Compared with ALT 20–30 U/L, low ALT was associated with LOI or death (multivariable adjusted hazard ratios [95% confidence intervals]: 3.02 [1.57–5.81] and 1.55 [1.07–2.24] in ALT < 10 and 10–20 U/L groups, respectively), while high ALT was not (1.29 [0.72–2.31] and 1.49 [0.68–3.25] in ALT 30–40 and ≥ 40 U/L groups, respectively).

Conclusions

Clinicians should be aware of not only high ALT, indicating liver injury, but also low ALT associated with LOI or death.
The Influence of Financial Well‐Being on Pawnshop Use
Authors: Nicolini Gianni , Cude Brenda J.
Published: February 2019

This research examined the influence of financial well‐being on pawnshop use. Data from the 2015 National Financial Capability Study were used to construct a measure of financial well‐being, based on the Consumer Financial Protection Bureau's definition. A higher financial well‐being reduced the odds of pawnshop use by 17%, even after controlling for having a bank account, having a credit card, being financially overconfident, proximity to local pawnshops, and selected demographic characteristics. The authors make recommendations for future research based on changes in the pawnshop industry and its users.
Single versus multiple cervical dilation by osmotic dilator before induction of labor for second‐trimester abortion
Authors: Lee Misooja , Mimura Kazuya , Endoh Masayuki , Kawanishi Yoko , Miyake Tatsuya , Kakigano Aiko , Takiuchi Tsuyoshi , Matsuzaki Shinya , Tomimatsu Takuji , Kimura Tadashi
Published: February 2019

Aim

In this study, we aimed to investigate whether there was a significant prognostic difference between single and multiple cervical dilations when inducing second‐trimester abortion.

Methods

We conducted a retrospective review of 238 pregnant women who underwent termination of pregnancy at 12–21 weeks of gestation at Osaka University Hospital in Osaka, Japan, between January 2010 and May 2018. Termination of pregnancy was performed by vaginal administration of 1 mg gemeprost every 3 h for up to five doses per day after uterine cervical dilation using lamicel.

Results

The women were categorized into two groups: 191 women had a delivery time of <24 h, whereas 47 had delivery times >24 h. Contrasting the groups, there were significant differences with regard to numbers of primiparas (88 [46.1%] and 32 [68.1%], respectively) and lamicel exchanges ± SD (1.9 ± 0.67 for <24 h and 2.4 ± 0.87 for >24 h, respectively). Additionally, we compared the prognosis of primiparas that received just a single lamicel with that of primiparas that had ≥2 exchanged, but no significant differences were noted in the number of patients with a delivery time of >24 h and the number of used gemeprost.

Conclusion

Primipara is a risk factor for delayed delivery time of induced abortion. However, increasing the number of exchanged lamicel did not significantly reduce the delivery time; therefore, it should be performed as minimally as possible.