bluuebunny/crossref_metadata_2025 huggingface dataset:
The Virtuous, the Critical and the Trustworthy: Citizen Ideals and Forms of Democratic Participation
Authors: Holdo Markus
Published: December 2017

A vibrant democratic society requires continuous innovation to actualize and encourage democratic ideals through participation, but no universal answers exist as to which kinds of participation are best suited to achieve this. This article demonstrates that different types of participation correlate with different citizen ideals, implying that the remedies to democratic deficits depend on which ideals need to be strengthened. Citizen survey data is used to examine the relationships between two types of citizen participation – in voluntary associations and workplaces – and three empirical citizen ideals: the virtuous citizen, the critical citizen and the trustworthy citizen. The results suggest that voluntary associations make space for all three ideals, while workplace participation tends to be characterized specifically by the critical citizen's ideal of reason‐giving and critical reflection. The article ends by discussing the implications of these results: new democratic designs should be more effective if tailored to address context‐dependent weaknesses in democratic practices.
Targeting Albumin Binding Function as a Therapy Goal in Liver Failure: Development of a Novel Adsorbent for Albumin Dialysis
Authors: Dominik Adrian , Stange Jan , Baumann Anja K , Pfensig Claudia , Suraj Matthias , Ibrahim Badr , Eggert Martin
Published: December 2017

Liver failure results in impaired hepatic detoxification combined with diminished albumin synthesis and is associated with secondary organ failure. The accumulation of liver toxins has shown to saturate albumin binding sites. This was previously demonstrated by an in vitro test for albumin binding capacity (ABiC) that has shown to inversely correlate with the established MELD (Model for End‐Stage Liver Disease) score. In this study, we introduced a new adsorbent material for albumin dialysis treatments that improves albumin binding capacity. The new charcoal adsorbent was developed by an evolutionary test schedule. Batch testing of charcoals was performed as steady‐state experiments. The charcoal reflecting the highest increase in albumin binding capacity was then introduced to kinetic models: Perfusion tests were designed to evaluate adsorption capacity and kinetics for liver failure marker toxins. A dynamic recirculation model for liver failure was used for upscaling and comparison against conventional MARS adsorbents as the gold standard in an albumin dialysis setting. Batch tests revealed that powdered activated Hepalbin charcoal displayed the highest ABiC score. Hepalbin charcoal also demonstrated higher adsorptive capacity and kinetics for liver failure marker toxins as determined by perfusion tests. These findings translated to tests of upscaled adsorbents in a dynamic model for liver failure: upscaled Hepalbin adsorbent removes bile acids, direct bilirubin and indirect bilirubin significantly better than MARS adsorbents and significantly increases ABiC. The novel adsorbent Hepalbin offers a significant improvement over both MARS adsorbents concerning liver failure marker toxin removal and ABiC improvement.
Inadequate sunlight exposure in patients with inflammatory bowel disease
Authors: Vernia Piero , Burrelli Scotti Giorgia , Dei Giudici Anna , Chiappini Ambra , Cannizzaro Santi , Afferri Maria Teresa , de Carolis Aurora
Published: December 2017

OBJECTIVE

Inadequate sun exposure impairs vitamin D activity and favors low bone density, especially in patients at increased risk for osteoporosis, such as those affected by inflammatory bowel disease (IBD). In this study, sun exposure was investigated in a large series of patients with IBD in a Mediterranean country, Italy, where this risk is considered less likely to occur than in higher latitudes.

METHODS

This is a case‐control study of 292 patients with IBD [132 with Crohn's disease (CD) and 160 with ulcerative colitis (UC)], 80 diseased and 540 healthy controls, conducted via a validated questionnaire to quantify sunlight exposure. Data were also compared with controls matched by age and gender.

RESULTS

In total 78 of the 292 patients with IBD had low, 169 had moderate and 45 had high exposure to sunlight, significantly differing from controls (P < 0.001). The 132 patients with CD were more likely to have abnormal levels of sunlight exposure (49 low, 72 moderate and 11 high) than those with UC (29 low, 97 moderate and 34 high) (P < 0.001). The controls were significantly more exposed to sunlight than both men and women with IBD (P < 0.001 and 0.004, respectively).

CONCLUSIONS

IBD patients are significantly less exposed to sunlight than matched controls in Italy, often to an extent that may impair vitamin D activation. Increasing responsible sunlight exposure, thus promoting adequate vitamin D concentrations, may prove beneficial in IBD, in geographical areas in which this risk factor is not generally taken into consideration.
Dual drive coexistence of EML4‐ALK and TPM3‐ROS1 fusion in advanced lung adenocarcinoma
Authors: Zhu You‐cai , Liao Xing‐hui , Wang Wen‐xian , Xu Chun‐wei , Zhuang Wu , Wei Jian‐guo , Du Kai‐qi
Published: December 2017

We report a case of concomitant EML4‐ALK and TPM3‐ROS1 fusion in non‐small cell lung cancer (NSCLC) in a 47‐year‐old Chinese man and review the clinical characteristics of this type double of fusion. The patient presented with a local tumor of the left upper lobe and underwent thoracoscopy. Postoperative surgical pathologic staging revealed T1aN0M0 stage IA. Histological examination of the tumor showed lung adenocarcinoma. Ventana ALK (D5F3) assay of the left lung tissue was ALK negative; however, immunohistochemical assay was positive for ROS1 protein. Using next generation sequencing, we found that the tumor had concomitant EML4‐ALK and TPM3‐ROS1 fusion. No recurrence was observed during seven months of follow‐up. Precise diagnostic techniques allow the detection of concomitant ROS1 fusion and other driver genes, including ALK or EGFR; therefore oncologists should consider this rare double mutation in NSCLC patients. Further exploration of treatment models is required to provide additional therapeutic options.
Optimal cumulative cisplatin dose in nasopharyngeal carcinoma patients receiving additional induction chemotherapy
Authors: Lv Jia‐Wei , Qi Zhen‐Yu , Zhou Guan‐Qun , He Xiao‐Jun , Chen Yu‐Pei , Mao Yan‐Ping , Chen Lei , Tang Ling‐Long , Li Wen‐Fei , Lin Ai‐Hua , Ma Jun , Sun Ying
Published: December 2017

To clarify the optimal cumulative cisplatin dose (CCD) in locoregionally‐advanced nasopharyngel carcinoma (NPC) patients receiving induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT). Using the NPC‐specific database from the established big‐data intelligence platform at Sun Yat‐Sen University Cancer Center, 583 non‐disseminated, locoregionally‐advanced NPC patients receiving IC plus CCRT were enrolled. Propensity score matching (PSM) analysis was conducted to control for confounding factors. The median CCD was 160 mg/m2 after IC (range, 40‐300 mg/m2); only 74 patients (12.7%) achieved CCD >200 mg/m2. Patients receiving >200 mg/m2 CCD did not show significantly improved 5‐year overall survival (OS) (HR = 1.19; 95% confidence intervals [CI] 0.69‐2.06, P = .53) and progression‐free survival (PFS) (HR = 1.03; 95% CI: 0.63‐1.68, P = .92) compared with patients receiving <200 mg/m2 CCD. Further investigations of the potential of median CCD (160 mg/m2) to yield survival benefits revealed that there were no significant differences in survival endpoints between patients receiving CCD >160 mg/m2 and CCD < 160 mg/m2 in both the original and PSM cohorts. In addition, subgroup analysis indicated a favorable PFS, but not OS, with higher cisplatin administration in patients with pretreatment Epstein–Barr virus deoxyribonucleic acid (EBV DNA) <1000 copies/mL (HR = 0.26, 95% CI: 0.07‐0.93, P = .03) and receiving <3 IC cycles (HR = 0.59, 95% CI 0.33‐1.07, P = .08). Our analysis of real world data provided references for the optimal CCD in locoregionally‐advanced NPC receiving additional IC. The causal relationship between 200 mg/m2 CCD and improved survival was not defined; 160 mg/m2 CCD might be enough. However, for patients with EBV DNA <1000 copy/mL and receiving <3 IC cycles, a higher dose might be necessary.
Proteochemometric modeling of the origin of thymidylate synthase inhibition
Authors: Rasti Behnam , Shahangian Seyyedeh Shirin
Published: December 2017

Due to its crucial role in DNA synthesis, thymidylate synthase (TS) has been considered as a potential therapeutic target. Inhibition of the enzyme is a promising strategy for the treatment of some hyperproliferative diseases, including infections. As TS species‐specific inhibitors would be able to distinguish between the host and the pathogens, developing highly selective inhibitors is of great clinical importance. TS is among the most highly conserved enzymes over evolutionary history, making the design of its species‐selective inhibitor significantly challenging. The chemical interaction space, governed by a set of non‐selective TS inhibitors, has been explored for human TS and its homologous proteins in both Toxoplasma gondii and Escherichia coli using proteochemometrics modeling (PCM). Validity, robustness, and prediction power of the PCM model have been assessed applying a diverse set of internal/external validation approaches. Our PCM model has provided major structural information, which is indeed of great help to design new TS species‐specific inhibitors with the simultaneous inhibition ability toward both T. gondii and E. coli. To show applicability of the PCM model, new compounds have been designed based on structural information provided by the constructed model. Final results have been very promising with regard to selectivity ratios of the designed compounds for different TS isoforms, confirming the applicability of the PCM model.
Differential Associations of Distinct Forms of Childhood Adversity With Neurobehavioral Measures of Reward Processing: A Developmental Pathway to Depression
Authors: Dennison Meg J. , Rosen Maya L. , Sambrook Kelly A. , Jenness Jessica L. , Sheridan Margaret A. , McLaughlin Katie A.
Published: December 2017

Childhood adversity is associated with altered reward processing, but little is known about whether this varies across distinct types of adversity. In a sample of 94 children (6–19 years), we investigated whether experiences of material deprivation, emotional deprivation, and trauma have differential associations with reward‐related behavior and white matter microstructure in tracts involved in reward processing. Material deprivation (food insecurity), but not emotional deprivation or trauma, was associated with poor reward performance. Adversity‐related influences on the integrity of white matter microstructure in frontostriatal tracts varied across childhood adversity types, and reductions in frontostriatal white matter integrity mediated the association of food insecurity with depressive symptoms. These findings document distinct behavioral and neurodevelopmental consequences of specific forms of adversity that have implications for psychopathology risk.
Gaming to improve vision: 21st century self‐monitoring for patients with age‐related macular degeneration
Authors: Razavi Hessom , Baglin Elizabeth , Sharangan Pyrawy , Caruso Emily , Tindill Nicole , Griffin Susan , Guymer Robyn
Published: December 2017

Importance

Improved vision self‐monitoring tools are required for people at risk of neovascular complications from age related macular degeneration (AMD).

Background

to report the self‐monitoring habits of participants with intermediate AMD using the Amsler grid chart, and the use of personal electronic devices and gameplay in this over 50 year old cohort.

Design

single‐centre descriptive study carried out at the Centre for Eye Research (CERA), Melbourne, Australia.

Participants

140 participants over 50 years of age, with a diagnosis of intermediate AMD and best‐corrected visual acuity (BCVA) of ≥6/12 in each eye.

Methods

structured questionnaire survey of participants who were enrolled in natural history of AMD studies at CERA.

Main outcome measures

frequency of vision self‐monitoring using the Amsler grid chart, and frequency of general use of personal electronic devices and gameplay.

Results

Of 140 participants with mean age of 70.5 years, 83.6% used an Amsler grid chart, but only 39.3% used it once per week. Most participants (91.4%) used one or more personal electronic devices. Of these, over half (54.7%) played games on them, among whom 39% played games once a day. Of participants aged 50–69 years, 92% (95%CI 85.1–98.9) were willing to play a game to monitor their vision, compared to 78% (95%CI 69.0–87.0) of those aged 70 years and older (P < 0.05).

Conclusions and Relevance

a large proportion of AMD patients already use personal electronic devices. Gamification techniques are likely to increase compliance with self‐monitoring, leading to earlier detection in the next generation of patients with neovascular AMD.
Corneal hysteresis and anterior segment optical coherence tomography anatomical parameters in primary angle closure suspects
Authors: Hussnain Syed Amal , Kovacs Kyle D , Warren Joshua L , Teng Christopher C
Published: December 2017

Importance

Corneal hysteresis (CH) is a dynamic marker of structural and functional changes in the cornea associated with intraocular pressure (IOP) and central corneal thickness, but its utility in assessing primary angle closure suspects (PACS) has not been fully elucidated.

Background

This study assesses if anterior segment measurements correlate with CH in PACS patients.

Design

IRB‐approved retrospective review of imaging and records at a university practice.

Participants

Sixty‐three eyes from 37 patients diagnosed as PACS, without other ocular pathology.

Methods

Every eye underwent measurements including: ocular response analyzer (ORA), anterior segment optical coherence tomography (OCT) and a clinical evaluation. ORA measurements were correlated with other anatomic parameters using a mixed effects multivariable linear regression framework.

Main Outcome Measures

ORA measurements included: CH, corneal resistance factor, Goldmann IOP (IOPg) and corneal compensated IOP (IOPcc). Anterior segment OCT measurements included: central corneal thickness (CCTOCT), nasal and temporal peripheral corneal thicknesses (PCT1 and PCT2), anterior chamber depth (ACD), nasal angle to temporal angle distance (ATA) and temporal and nasal angle measurements. Clinical measurements included: central corneal thickness via pachymetry, IOP measured by Goldmann applanation, axial length by A‐scan ultrasound and spherical equivalent.

Results

CH was negatively correlated with IOPcc, and ACD CH was positively correlated with CCTOCT, CCTp, CRF, PCT1 and PCT2. Females were found to have lower CH. In multivariable regression controlling for gender, CCT, PCT, IOP and ACD, no correlation was seen between CH and anatomic measurements.

Conclusions and Relevance

CH values in PACS do not correlate with anterior segment anatomy.
De novo variants in KLF7 are a potential novel cause of developmental delay/intellectual disability, neuromuscular and psychiatric symptoms
Authors: Powis Z. , Petrik I. , Cohen J.S. , Escolar D. , Burton J. , van Ravenswaaij‐Arts C.M.A. , Sival D.A. , Stegmann A.P.A. , Kleefstra T. , Pfundt R. , Chikarmane R. , Begtrup A. , Huether R. , Tang S. , Shinde D.N.
Published: December 2017

Due to small numbers of reported patients with pathogenic variants in single genes, the phenotypic spectrum associated with genes causing neurodevelopmental disorders such as intellectual disability (ID) and autism spectrum disorder is expanding. Among these genes is KLF7 (Krüppel‐like factor 7), which is located at 2q33.3 and has been implicated in several developmental processes. KLF7 has been proposed to be a candidate gene for the phenotype of autism features seen in patients with a 2q33.3q34 deletion. Herein, we report 4 unrelated individuals with de novo KLF7 missense variants who share similar clinical features of developmental delay/ID, hypotonia, feeding/swallowing issues, psychiatric features and neuromuscular symptoms, and add to the knowledge about the phenotypic spectrum associated with KLF7 haploinsufficiency.
Injectable simvastatin gel for minimally invasive periosteal distraction: In vitro and in vivo studies in rat
Authors: Hao Jia , Chou Joshua , Kuroda Shinji , Otsuka Makoto , Kasugai Shohei , Lang Niklaus P.
Published: December 2017

Objectives

To evaluate whether the subperiosteal injection of simvastatin (SIM) with a novel in situ gel‐forming system, SrHA/Alg (strontium hydroxyapatite/alginate), can stimulate vertical bone augmentation in a rat calvarial model.

Material and methods

The SrHA/Alg solution was synthesized and combined with different doses of SIM (0.01, 0.02, 0.1, and 0.2 mg) to form the following groups: (1) SrHA/Alg only, (2) SrHA/Alg/0.01, (3) SrHA/Alg/0.02, (4) SrHA/Alg/0.1, and (5) SrHA/Alg/0.2. The SIM release pattern was analyzed, and rat primary periosteum‐derived cell (PDC) responses were investigated. Twenty male Wistar rats were enrolled in the calvarial subperiosteal injection experiment with each animal receiving a 200‐μl single subperiosteal injection of SrHA/Alg with different amounts of SIM (0, 0.01, 0.02, and 0.1 mg) incorporated (n = 5). The 0.2 mg dose group was not tested in vivo due to the severe toxicity found in vitro. The new bone formation was assessed histologically and radiologically at 8 weeks.

Results

The slow release of SIM was confirmed, and PDC viability decreased in the SrHA/Alg/0.2 group. Alkaline phosphatase positive areas and mineralization areas were significantly greater in the SrHA/Alg/0.01 and SrHA/Alg/0.02 groups (p < .05). The mRNA expression level of Runx2 significantly increased in the SrHA/Alg/SIM‐0.02 group by day 7 (p < .05) and significantly higher levels of VEGF were found in the SrHA/Alg/0.01 and SrHA/Alg/0.02 groups at different time points (p < .05). In vivo, no prominent clinical sign of inflammation was observed, and the most significant bone gain was shown in the SrHA/Alg/0.02 group (p < .05). The osteoclast formation within the newly formed bone area was reduced in the SrHA/Alg/0.1 group (p < .05).

Conclusions

When combined with SrHA/Alg system, the 0.02 mg SIM seemed to be the optimal dose to stimulate subperiosteal bone formation without inducing inflammation. This combination may hold potential therapeutic benefits for clinical bone augmentation in a minimally invasive manner.
YOUR LANGUAGE OR MINE? THE NONCOMMUNICATIVE BENEFITS OF LANGUAGE SKILLS
Authors: Caminal Ramon , Di Paolo Antonio
Published: December 2017

Do languages matter beyond their communicative benefits? We explore the potential role of preferences over the language of use, theoretically and empirically. We focus on Catalonia, a bilingual society where everyone is fully proficient in Spanish, to isolate linguistic preferences from communicative benefits. Moreover, we exploit the language‐in‐education reform of 1983 to identify the causal effects of language skills. Results indicate that the policy change has improved the Catalan proficiency of native Spanish speakers, which in turn increased their propensity to find Catalan‐speaking partners. Hence, the acquisition of apparently redundant language skills has reduced endogamy. (JEL C26, C78, I28, J12, J15, Z13)
Leverage Ratio and Central Bank Operations in the Euro Area
Authors: Baldo Luca , Bucalossi Annalisa , Scalia Antonio
Published: December 2017

Using estimates of the Basel III leverage ratio (LR), we show that banks in the euro area were largely in compliance with the preliminary 3 per cent threshold already in 2013 and that they continued improving their ratio up to an average of 4.7 per cent in 2016. Contrary to predictions that the new requirement might interfere with the implementation of monetary policy, the evidence shows that, in a context of extraordinary monetary policy stimulus, this conflict has not materialized. First, the LR discourages participation in central bank refinancing operations only to a very limited extent and for a specific category of banks. Second, the surge in central bank reserves created by the Asset Purchase Programme has not prompted banks to deleverage by reducing other asset classes. Finally, although banks' balance sheets report a decrease in outstanding repos and reverse repos, the overall activity outside reporting dates does not seem to have decreased as much.
Temporal coupling of field potentials and action potentials in the neocortex
Authors: Watson Brendon O. , Ding Mingxin , Buzsáki György
Published: December 2017

The local field potential (LFP) is an aggregate measure of group neuronal activity and is often correlated with the action potentials of single neurons. In recent years, investigators have found that action potential firing rates increase during elevations in power high‐frequency band oscillations (50–200 Hz range). However, action potentials also contribute to the LFP signal itself, making the spike–LFP relationship complex. Here, we examine the relationship between spike rates and LFP in varying frequency bands in rat neocortical recordings. We find that 50–180 Hz oscillations correlate most consistently with high firing rates, but that other LFP bands also carry information relating to spiking, including in some cases anti‐correlations. Relatedly, we find that spiking itself and electromyographic activity contribute to LFP power in these bands. The relationship between spike rates and LFP power varies between brain states and between individual cells. Finally, we create an improved oscillation‐based predictor of action potential activity by specifically utilizing information from across the entire recorded frequency spectrum of LFP. The findings illustrate both caveats and improvements to be taken into account in attempts to infer spiking activity from LFP.
Decreased cerebral Irp‐1B limits impact of social isolation in wild type and Alzheimer's disease modeled in Drosophila melanogaster
Authors: Ruland C. , Berlandi J. , Eikmeier K. , Weinert T. , Lin F. J. , Ambree O. , Seggewiss J. , Paulus W. , Jeibmann A.
Published: December 2017

Environmental factors, such as housing conditions and cognitively stimulating activities, have been shown to affect behavioral phenotypes and to modulate neurodegenerative conditions such as Alzheimer's disease (AD). AD is a progressive neurodegenerative disorder affecting cognitive functions. Epidemiological evidence and experimental studies using rodent models have indicated that social interaction reduces development and progression of disease. Drosophila models of Aβ42‐associated AD lead to AD‐like phenotypes, such as long‐term memory impairment, locomotor and survival deficits, while effects of environmental conditions on AD‐associated phenotypes have not been assessed in the fly. Here, we show that single housing reduced survival and motor performance of Aβ42 expressing and control flies. Gene expression analyses of Aβ42 expressing and control flies that had been exposed to different housing conditions showed upregulation of Iron regulatory protein 1B (Irp‐1B) in fly brains following single housing. Downregulating Irp‐1B in neurons of single‐housed Aβ42 expressing and control flies rescued both survival and motor performance deficits. Thus, we provide novel evidence that increased cerebral expression of Irp‐1B may underlie worsened behavioral outcome in socially deprived flies and can additionally modulate AD‐like phenotypes.
Biome stability in South America over the last 30 kyr: Inferences from long‐term vegetation dynamics and habitat modelling
Authors: Costa Gabriel C. , Hampe Arndt , Ledru Marie‐Pierre , Martinez Pablo A. , Mazzochini Guilherme G. , Shepard Donald B. , Werneck Fernanda P. , Moritz Craig , Carnaval Ana Carolina
Published: December 2017

Aim

The aim was to examine the links between past biome stability, vegetation dynamics and biodiversity patterns.

Location

South America.

Time period

Last 30,000 years.

Major taxa studied

Plants.

Methods

We classified South America into major biomes according to their dominant plant functional groups (grasses, trees and shrubs) and ran a random forest (RF) classification with data on current climate. We then fitted the algorithm to predict biome distributions for every 1,000 years back to 21,000 yr BP and estimated biome stability by counting how many times a change in climate was predicted to shift a grid cell from one biome to another. We compared our model‐based stability map with empirical estimates from selected pollen records covering the past 30 kyr in terms of vegetation shifts, changes in species composition and time‐lag of vegetation responses.

Results

We found a strong correlation between our habitat stability map and regional vegetation dynamics. Four scenarios emerged according to the way forest distribution shifted during a climate change. Each scenario related to specific regional features of biome stability and diversity, allowing us to formulate specific predictions on how taxonomic, genetic and functional components of biodiversity might be impacted by modern climate change.

Main conclusions

Our validated map of biome stability provides important baseline information for studying the impacts of past climate on biodiversity in South America. By focusing exclusively on climatic changes of manifested relevance (i.e., those resulting in significant habitat changes), it provides a novel perspective that complements previous datasets and allows scientists to explore new questions and hypotheses at the local, regional and continental scales.
Attitudes towards childcare policies, policy feedback and path dependency: Czech Republic contrasted to Norway
Authors: Sirovátka Tomáš , Válková Jana
Published: December 2017

This article explores the recent changes in mothers’ employment, childcare policies and attitudes towards gender equality in the labour market, in the Czech Republic and Norway, how these factors interact and what impact they have on the provision of childcare. Analysis suggests that there is convergence of the Czech Republic with Norway in terms of female employment, but divergence in childcare policies. The policy feedback – the mutual interrelatedness of attitudes towards mothers’ employment and childcare policies – has shaped refamilialising policies in the Czech Republic, whereas in Norway policies that support gender equality in work and family have emerged.
Management of high risk chronic lymphocytic leukaemia (CLL) patients in Australia
Authors: Kuss Bryone J. , Tam Constantine S.
Published: December 2017

Background

Chronic lymphocytic leukaemia (CLL) frequently responds to chemoimmunotherapy combining cytotoxic chemotherapy and monoclonal antibodies. However, CLL is associated with significant genetic heterogeneity, and some high‐risk forms are known to be chemo‐resistant and associated with early relapse.

Aims

To review the current treatment paradigm of patients with high‐risk disease, in particular those with del(17p) and TP53 variants.

Results

A ‘watch and wait’ approach is recommended for all patients who are asymptomatic. When symptomatic, fluorescence in situ hybridisation testing should be performed and gene sequencing considered subsequently to identify del(17p) and TP53 variants respectively. In the front‐line setting, treatment within a clinical trial is the preferred option. In the relapsed or refractory setting, patients with del(17p) or TP53 aberrations should be offered treatment with a novel agent, such as ibrutinib, idelalisib‐rituximab or venetoclax. However, of note, at the date of this publication venetoclax is not PBS reimbursed, and ibrutinib will not be reimbursed until 1 December 2017.

Conclusion

Testing for del(17p) and TP53 variants identifies high‐risk CLL that requires specialist management.
Suppression of inflammation and acquired immunity by IL‐37
Authors: Cavalli Giulio , Dinarello Charles A.
Published: December 2017

IL‐37 is a unique member of the IL‐1 family of cytokines, which functions as a natural suppressor of inflammatory and immune responses. Immune and non‐immune cells produce IL‐37 precursor following pro‐inflammatory stimuli. Following activating cleavage by caspase‐1, mature IL‐37 translocates to the nucleus, where it suppresses transcription of pro‐inflammatory genes. Both precursor and mature IL‐37 are also secreted in the extracellular space, where they bind IL‐18Rα and recruit the IL‐1R8 (formerly TIR8 or SIGIRR), which transduces anti‐inflammatory signals by suppressing NF‐kB and MAPK and by activating Mer‐PTEN‐DOK pathways. During inflammation, IL‐37 restores the metabolism of the cell by reducing succinate, inhibiting mTOR, and activating AMPK. Transgenic mice expressing human IL‐37 and wild type mice treated with recombinant human IL‐37 are protected from several experimental models of inflammation, including endotoxin shock, colitis, lung and spinal cord injury, coronary artery disease, arthritis and inflammation‐induced fatigue, while also exhibiting reduced adaptive immune responses. In humans, IL‐37 likely functions to limit excessive inflammation: accordingly, IL‐37 levels are abnormal in patients with inflammatory and autoimmune diseases. In this review, we provide an overview of the discovery and biology of IL‐37, and discuss the potential for development of this cytokine as a therapeutic agent.
The intra‐ and extracellular functions of ASC specks
Authors: Franklin Bernardo S , Latz Eicke , Schmidt Florian Ingo
Published: December 2017

Inflammasomes are the central signaling hubs of the inflammatory response. They process cytosolic evidence of infection, cell damage, or metabolic disturbances, and elicit a pro‐inflammatory response mediated by members of the interleukin‐1 family of cytokines and pyroptotoic cell death. On the molecular level, this is accomplished by the sensor‐nucleated recruitment and oligomerization of the adapter protein ASC. Once a tunable threshold is reached, cooperative assembly of ASC into linear filaments and their condensation into macromolecular ASC specks promotes an all‐or‐none response. These structures are highly regulated and provide a unique signaling platform or compartment to control the activity of caspase‐1 and likely other effectors. Emerging evidence indicates that ASC specks are also released from inflammasome‐activated cells and accumulate in inflamed tissues, where they can continue to mature cytokines or be internalized by surrounding cells to further nucleate ASC specks in their cytosol. Little is known about the mechanisms governing ASC speck release, uptake, and endosomal escape, as well as its contribution to inflammation and disease. Here, we describe the different outcomes of inflammasome activation and discuss the potential function of extracellular ASC specks. We highlight gaps in our understanding of this central process of inflammation, which may have direct consequences on the modulation of host responses and chronic inflammation.
Function and regulation of IL‐1α in inflammatory diseases and cancer
Authors: Malik Ankit , Kanneganti Thirumala‐Devi
Published: December 2017

The interleukin (IL)‐1 family of cytokines is currently comprised of 11 members that have pleiotropic functions in inflammation and cancer. IL‐1α and IL‐1β were the first members of the IL‐1 family to be described, and both signal via the same receptor, IL‐1R. Over the last decade, much progress has been made in our understanding of biogenesis of IL‐1β and its functions in human diseases. Studies from our laboratory and others have highlighted the critical role of nod‐like receptors (NLRs) and multi‐protein complexes known as inflammasomes in the regulation of IL‐1β maturation. Recent studies have increased our appreciation of the role played by IL‐1α in inflammatory diseases and cancer. However, the mechanisms that regulate the production of IL‐1α and its bioavailability are relatively understudied. In this review, we summarize the distinctive roles played by IL‐1α in inflammatory diseases and cancer. We also discuss our current knowledge about the mechanisms that control IL‐1α biogenesis and activity, and the major unanswered questions in its biology.
The role of the interleukin‐1 family in trained immunity
Authors: Moorlag Simone J.C.F.M. , Röring Rutger Jan , Joosten Leo A.B. , Netea Mihai G.
Published: December 2017

Immunological memory was long considered a trait exclusive to cells of the adaptive immune system. However, recent studies have shown that after activation of the innate immune system, innate immune cells may undergo long‐term functional reprogramming characterized by the ability to mount either a stronger or attenuated inflammatory response upon reactivation. This phenomenon, which has been termed trained immunity and is a de facto innate immune memory, is regulated by a network of integrated metabolic and epigenetic rewiring. The endogenous mediators that modulate trained immunity in the host are only partially understood, but increasing evidence supports the concept that the interleukin (IL)‐1 family of cytokines plays an important role. In this review, we will highlight key findings from studies that provide insight into the multifaceted roles of members of the IL‐1 family for trained immunity. Finally, we will discuss how the recent advances of our understanding on the role of IL‐1 cytokines in this field may lead to new therapeutic strategies for treatment of common conditions, such as IL‐1‐driven autoinflammatory diseases.
Differential root responses in two cultivars of winter wheat (Triticum aestivum L.) to elevated ozone concentration under fully open‐air field conditions
Authors: Kou T.‐J. , Yu W.‐W. , Lam S. K. , Chen D.‐L. , Hou Y.‐P. , Li Z.‐Y.
Published: December 2017

The effect of elevated tropospheric ozone concentration [O3] on root processes in wheat systems of different O3 sensitivity is not well understood. Two wheat cultivars (cv. Y15 and YN19) with contrasting O3 tolerance were grown in a fully open‐air O3 enrichment platform for one season. We found that elevated O3 (EO3) (50% above the ambient O3) significantly decreased the total biomass at all key growth stages and the yield of the O3‐sensitive cultivar YN19 but did not affect those of the O3‐tolerant cultivar Y15. EO3 significantly decreased the root biomass of two wheat cultivars at the jointing and grain‐filling stages. EO3 significantly decreased the root length, length density, surface area and volume of the two cultivars at the jointing stage but increased those of YN19 at the grain‐filling stage. EO3 significantly increased the root activities (specific root respiration rates) of Y15 and YN19 at the jointing, heading and grain‐filling stages. EO3 significantly decreased the contribution of fresh root respiration to soil respiration (CRS) of YN19 at the jointing stage but increased it at the heading stage; however, it did not change the CRS of Y15 at any growth stages. This study indicates that the effects of EO3 on root morphology and activity varied among wheat cultivars, and suggest that we can breed O3‐tolerant cultivars to maintain crop yield under higher [O3] scenarios.
Lead‐free (K,Na)NbO3‐based ceramics with high optical transparency and large energy storage ability
Authors: Chai Qizhen , Yang Dong , Zhao Xumei , Chao Xiaolian , Yang Zupei
Published: December 2017

Highly transparent lead‐free (1‐x)K0.5Na0.5NbO3–xSr(Zn1/3Nb2/3)O3 (KNN–xSZN) ferroelectric ceramics have been synthesized via a conventional pressureless sintering method. All samples are optically clear, showing high transmittance in the visible and near‐infrared regions (~70% and ~80% at 0.5 mm of thickness, respectively). This exceptionally good transmittance is due to the pseudo‐cubic phase structure as well as the dense and fine‐grained microstructure. In addition, a high energy storage density of 3.0 J/cm3 has been achieved for the 0.94K0.5Na0.5NbO3–0.06Sr(Zn1/3Nb2/3)O3 ceramics with submicron‐sized grains (~136 nm). The main reason is likely to be the typical relaxor‐like behavior characterized by diffuse phase transition, in addition to the dense and fine‐grained microstructure. This study demonstrates that the 0.94K0.5Na0.5NbO3–0.06Sr(Zn1/3Nb2/3)O3 ceramic is a promising candidate of lead‐free transparent ferroelectric ceramics for new areas beyond transparent electronic device applications.
Determinants of college students' use of online collaborative help‐seeking tools
Authors: Ding Lu , Er Erkan
Published: December 2017

Research has noted the effectiveness of online tools (e.g., discussion boards) for supporting help seeking among class members. However, help seeking is not necessarily warranted via online learning tools because some factors (e.g., low Internet self‐efficacy) may influence students' intention to use them. This study aims to identify the determinants of students' use of a web‐based help‐seeking tool called EchoLu. For this purpose, a structural model was developed based on technology acceptance model and tested using a structural equation modelling approach. According to the data analysis results, general Internet self‐efficacy, information‐search self‐efficacy, web‐based learning self‐efficacy, and EchoLu‐specific self‐efficacy play a significant role in students' intentions to use online help‐seeking tools. Contrary to the previous research, no statistically significant relationship was found between general Internet self‐efficacy and EchoLu‐specific self‐efficacy, and between web‐based learning self‐efficacy and perceived usefulness. Implications of the findings for guiding practitioners in supporting effective help‐seeking are presented. Limitations of the study and future research prospects are discussed as well.
Participation in school‐related activities that require hand use for children with and without developmental disabilities
Authors: Cho M. , Rodger S. , Copley J. , Chien C.‐W.
Published: December 2017

Background

Children with developmental disabilities (DD) may experience limited participation in school activities. Little is known about whether school participation of children with DD who attend special schools is impacted. This study specifically focused on physical engagement in school‐related activities that require hand use for the comparison between this group of children with DD and typically developing children.

Methods

The sample consisted of 97 children with DD who attended special schools (mean age 8.2 ± 2.9 years; 60 boys and 37 girls) and 105 typically developing children who attended mainstream schools/kindergartens (mean age 8.6 ± 2.4 years; 48 boys and 57 girls). Parents completed the Children's Assessment of Participation with Hands, one of the domains of which captures participation in eight school‐related activities involving hand use.

Results

Parents of children with DD reported that their children participated less, in terms of the number (χ2 = 8.45–14.97, P ≤ 0.004) and frequency (t = 4.00–6.47, P < 0.001), in four activities than typically developing children. Parents of children with DD also reported that more assistance was needed for their children's participation in all activities (t = 6.93–11.92, P < 0.001), and they wanted their children to participate in most activities more often and more independently (χ2 = 18.46–59.34, P < 0.001).

Conclusions

Differences in participation in school‐related activities requiring hand use between children with DD and typically developing children were revealed generally across all participation dimensions (does participate, frequency, independence, and desired change). This study provides information on the areas in which greater efforts are needed to support children's school participation.
Increased acetylcholine and glutamate efflux in the prefrontal cortex following intranasal orexin‐A (hypocretin‐1)
Authors: Calva Coleman B. , Fayyaz Habiba , Fadel Jim R.
Published: December 2017

Orexin/hypocretin neurons of the lateral hypothalamus and perifornical area are integrators of physiological function. Previous work from our laboratory and others has shown the importance of orexin transmission in cognition. Age‐related reductions in markers of orexin function further suggest that this neuropeptide may be a useful target for the treatment of age‐related cognitive dysfunction. Intranasal administration of orexin‐A (OxA) has shown promise as a therapeutic option for cognitive dysfunction. However, the neurochemical mechanisms of intranasal OxA administration are not fully understood. Here, we use immunohistochemistry and in vivo microdialysis to define the effects of acute intranasal OxA administration on: (i) activation of neuronal populations in the cortex, basal forebrain, and brainstem and (ii) acetylcholine (ACh) and glutamate efflux in the prefrontal cortex (PFC) of Fischer 344/Brown Norway F1 rats. Acute intranasal administration of OxA significantly increased c‐Fos expression, a marker for neuronal activation, in the PFC and in subpopulations of basal forebrain cholinergic neurons. Subsequently, we investigated the effects of acute intranasal OxA on neurotransmitter efflux in the PFC and found that intranasal OxA significantly increased both ACh and glutamate efflux in this region. These findings were independent from any changes in c‐Fos expression in orexin neurons, suggesting that these effects are not resultant from direct activation of orexin neurons. In total, these data indicate that intranasal OxA may enhance cognition through activation of distinct neuronal populations in the cortex and basal forebrain and through increased neurotransmission of ACh and glutamate in the PFC.

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Possible role of interleukin‐17 and macrophage migration inhibitory factor in cutaneous warts
Authors: El‐Hamd Mohammed Abu , Assaf Hanan A , Nada Essam A
Published: December 2017

Background/Objectives

Cutaneous warts (CW), or verrucae, are benign proliferation of skin that result from infection with human papilloma viruses. Cellular immune reactivity plays a significant role in wart regression. The aim of this study was to elucidate the cellular immune status of patients with CW through measurements of their serum levels of interleukin‐17 (IL‐17) and macrophage migration inhibitory factor (MIF,) and, identify the possible role of IL‐17 and MIF in CW. We assessed serum IL‐17 and MIF levels in patients with different forms of CW and compare the results with controls.

Patient and methods

Serum levels of IL‐17 and MIF were measured using commercially available ELISA assay kits in 60 patients with CW and 20 healthy controls.

Results

Serum levels of IL‐17 and MIF were significantly lower in patients with CW when compared with the controls (P‐value <.01, <.05, respectively). There was nonsignificant correlation between IL‐17 and MIF.

Conclusion

Low IL‐17 and MIF levels may have a contributory role in occurrence, maintenance, severity, and recurrence of different types of CW which depend mainly on the defect of cell‐mediated immunity. This may shed new light on nontraditional strategies for the future medical treatments of CW through regulation of IL‐17 and MIF.
Outcomes after drug‐coated balloon treatment for patients with calcified coronary lesions
Authors: Ito Ryuta , Ueno Katsumi , Yoshida Tamami , Takahashi Hiroshi , Tatsumi Tomohiko , Hashimoto Yasumasa , Kojima Yoshinobu , Kitamura Tomoya , Morita Norihiko
Published: December 2017

Objectives

To investigate the efficacy of drug‐coated balloon (DCB) for calcified coronary lesions.

Background

Calcified coronary lesions is associated with poor clinical outcomes after revascularization. Recently, DCB is emerging as an alternative strategy for de novo coronary lesions. However, reports describing the efficacy of DCB for calcified coronary lesions are limited.

Methods

A total of 81 patients (96 lesions) who electively underwent DCB treatment for de novo coronary lesions were enrolled: 46 patients (55 lesions) in the calcified group and 35 patients (41 lesions) in the non‐calcified group. Angiographic follow‐up data and clinical outcomes after the procedure were evaluated.

Results

The diameter of the DCB used was 2.5 ± 0.5 mm. No bail‐out stenting was observed after DCB treatment. Rotational atherectomy was used in 82% of lesions in the calcified group. Follow‐up angiography (median, 6.5 months after intervention) was performed for 59 patients (30 in the calcified group and 29 in the non‐calcified group). Late lumen loss and rates of restenosis were comparable between the groups (0.03 mm in the calcified group vs −0.18 mm in the non‐calcified group, P = 0.093 and 13.9% vs 3.03%, P = 0.095, respectively). The survival rates for target lesion revascularization free survival and major adverse cardiac events at 2 years were comparable between the groups (85.3% vs 93.4%, P = 0.64 and 81.4% vs 88.5%, P = 0.57, respectively).

Conclusion

Calcified coronary lesions might dilute the effect of DCB. However, clinical outcomes in the calcified group were similar to those in the non‐calcified group.
A Note on Quality Disclosure and Competition
Authors: Jansen Jos
Published: December 2017

Competitive pressure is lower in markets where goods are more differentiated. I analyze how a change in the degree of horizontal product differentiation affects the incentives of duopolists to disclose quality information. If disclosure is costly, then a firm discloses high qualities but conceals low qualities in equilibrium. The higher the disclosure cost, the higher the equilibrium threshold below which firms conceal quality information. I show that the effect of product differentiation on quality disclosure depends on the cost of disclosure. For low (high) disclosure costs, a firm discloses more (respectively, less) quality information if goods become more differentiated.
Tying in Two‐Sided Markets with Multi‐Homing: Corrigendum and Comment
Authors: Choi Jay Pil , Jullien Bruno , Lefouili Yassine
Published: December 2017

We identify two issues in Choi's [2010] paper on tying in two‐sided markets published in this Journal, and provide solutions to both of them. First, we point out that the equilibrium in the absence of tying requires more restrictive conditions and does not satisfy a natural equilibrium refinement criterion. We offer an alternative timing structure that validates the equilibrium derived in Choi [2010] under the conditions provided there. Second, we show that his equilibrium analysis with tying ignores a profitable deviation. We rectify this analysis under our alternative timing structure and derive the (mixed‐strategy) equilibrium with tying. We also show by means of simulations that tying is welfare‐enhancing whenever it is profitable, which is consistent with the main finding in Choi [2010].