bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic impact of the tumor immune microenvironment in synovial sarcoma
Authors: Oike Naoki , Kawashima Hiroyuki , Ogose Akira , Hotta Tetsuo , Hatano Hiroshi , Ariizumi Takashi , Sasaki Taro , Yamagishi Tetsuro , Umezu Hajime , Endo Naoto
Published: August 2018

The association between the immune status within the tumor microenvironment and prognosis in synovial sarcoma is not well understood. We aimed to investigate the tumor immune microenvironment and analyze its prognostic impact for patients with synovial sarcoma. A total of 36 primary patients who were treated in our institution were retrospectively evaluated. Infiltration of lymphocytes (CD4+, CD8+, and FOXP3+), CD163+ macrophages, and expression of human leukocyte antigen (HLA) class I and programmed death ligand 1 (PD‐L1) were evaluated by immunohistochemistry. Moreover, we investigated PD‐L1 and programmed death ligand 2 (PD‐L2) mRNA expression in 19 of the 36 cases, using real‐time PCR. The Kaplan‐Meier method was used to estimate overall survival and progression‐free survival. Infiltration of lymphocytes and macrophages varied among the patients. Furthermore, the expression of HLA class I was negative or downregulated in 11 specimens. No PD‐L1 expression was observed using immunohistochemistry. Moreover, although PD‐L1 mRNA expression was observed in 18 of 19 specimens, the expression level was low. A higher infiltration of CD8+ or FOXP3+ lymphocytes in patients was associated with a favorable overall survival. In addition, a higher infiltration of CD163+ macrophages indicated a significantly worse overall and progression‐free survival. Infiltration of CD4+ lymphocytes, HLA class I, PD‐L1, and PD‐L2 expression were not associated with patient prognosis. This represents the first report investigating the tumor immune microenvironment as a prognostic factor in synovial sarcoma, indicating that CD163+ macrophages are associated with tumor progression. Our results underscore the clinical significance of the tumor immune microenvironment in synovial sarcoma.
Birch pollen‐specific subcutaneous immunotherapy reduces ILC2 frequency but does not suppress IL‐33 in mice
Authors: van Rijt Leonie S. , Logiantara Adrian , Canbaz Derya , van Ree Ronald
Published: August 2018

Background

The underlying mechanism of allergen‐specific subcutaneous immunotherapy (SCIT) is not yet fully understood, but suppression of allergen‐specific Th2 cells and production of allergen‐specific IgG4 antibodies are two hallmarks. The impact on the innate arm of the immune system is far less clear.

Objective

The aim of this study was to investigate the effect of birch pollen (BP) SCIT on the innate immune response in a BP SCIT mouse model.

Methods

Mice with birch pollen‐induced allergic airway inflammation received weekly subcutaneous immunotherapy injections with birch pollen extract (BPE) adsorbed to alum. The effect of the BP SCIT on innate cytokine levels in lung, the number and the functionality of ILC2s and the airway inflammation was determined.

Results

Mice with BP allergy had an increased level of the innate cytokines IL‐33, IL‐25, GM‐CSF and IL‐5+ ILC2s in the lungs. BP SCIT suppressed the number of IL‐5+ ILC2s, mast cell tryptase release, Th2 cytokine production, eosinophil recruitment and peribronchial inflammatory infiltrates. In contrast, innate cytokine production and collagen deposition in the airways were not affected.

Conclusion and Clinical Relevance

BP SCIT is able to suppress the adaptive and part of the innate immune response, but this is not sufficient to inhibit collagen deposition and the IL‐33 expression in the airways in mice.
High‐ and low‐dose oral immunotherapy similarly suppress pro‐allergic cytokines and basophil activation in young children
Authors: Kulis Michael , Yue Xiaohong , Guo Rishu , Zhang Huamei , Orgel Kelly , Ye Ping , Li Quefeng , Liu Yutong , Kim Edwin , Burks Arvil Wesley , Vickery Brian P.
Published: August 2018

Background

Mechanisms underlying oral immunotherapy (OIT) are unclear and the effects on immune cells at varying maintenance doses are unknown.

Objective

We aimed to determine the immunologic changes caused by peanut OIT in preschool aged children and determine the effect on these immune responses in groups ingesting low or high‐dose peanut OIT (300 mg or 3000 mg, respectively) as maintenance therapy.

Methods

Blood was drawn at several time‐points throughout the OIT protocol and PBMCs isolated and cultured with peanut antigens. Secreted cytokines were quantified via multiplex assay, whereas Treg and peanut‐responsive CD4 T cells were studied with flow cytometry. Basophil activation assays were also conducted.

Results

Th2‐, Th1‐, Th9‐ and Tr1‐type cytokines decreased over the course of OIT in groups on high‐ and low‐dose OIT. There were no significant differences detected in cytokine changes between the high‐ and low‐dose groups. The initial increase in both the number of peanut‐responsive CD4 T cells and the number of Tregs was transient and no significant differences were found between groups. Basophil activation following peanut stimulation was decreased over the course of OIT and associated with increased peanut‐IgG4/IgE ratios. No differences were found between high‐ and low‐dose groups in basophil activation at the time of desensitization or sustained unresponsiveness oral food challenges.

Conclusions and Clinical Relevance

Peanut OIT leads to decreases in pro‐allergic cytokines, including IL‐5, IL‐13, and IL‐9 and decreased basophil activation. No differences in T cell or basophil responses were found between subjects on low or high‐dose maintenance OIT, which has implications for clinical dosing strategies.
Impact of dental cement on the peri‐implant biofilm‐microbial comparison of two different cements in an in vivo observational study
Authors: Korsch Michael , Marten Silke‐Mareike , Walther Winfried , Vital Marius , Pieper Dietmar H. , Dötsch Andreas
Published: August 2018

Background

The type of cement used in cemented fixed implant‐supported restorations influences formation of undetected excess cement and composition of the peri‐implant biofilm. Excess cement and dysbiosis of the biofilm involve the risk of peri‐implant inflammation.

Purpose

The aim of the study was to investigate the impact of two different cements on the peri‐implant biofilm and inflammation.

Materials and Methods

In an observational study, the suprastructures of 34 patients with cemented fixed implant‐supported restorations were revised. In 20 patients, a methacrylate cement (Premier Implant cement [PIC]) and in 14 patients, a zinc oxide eugenol cement (Temp Bond [TB]) were used. After revision, TB was used for recementation. During revision and follow‐up after 1 year, microbial samples were obtained.

Results

Excess cement was found in 12 (60%) of the 20 patients with PIC. Suppuration was observed in two (25%) implants with PIC without excess cement (PIC−) and in all 12 (100%) implants with PIC and excess cement (PIC+). Implants cemented with TB had neither excess cement nor suppuration. The taxonomic analysis of the microbial samples revealed an accumulation of periodontal pathogens in the PIC patients independent of the presence of excess cement. Significantly, fewer oral pathogens occurred in patients with TB compared to patients with PIC. TB was used in all cases (PIC and TB) for recementation. In the follow‐up check, suppuration was not found around any of the implants with PIC−, only around one implant with PIC+ and around one implant with TB. Bacterial species associated with severe periodontal infections that were abundant in PIC− and PIC+ samples before the revision were reduced after 1 year to levels found in the TB samples.

Conclusions

The revision and recementation with TB had a positive effect on the peri‐implant biofilm in cases with PIC. The cementation of suprastructures on implants with TB is an alternative method to be considered.
European position paper on drug‐induced sleep endoscopy: 2017 Update
Authors: De Vito Andrea , Carrasco Llatas Marina , Ravesloot Madeline J. , Kotecha Bhik , De Vries Nico , Hamans Evert , Maurer Joachim , Bosi Marcello , Blumen Marc , Heiser Clemens , Herzog Michael , Montevecchi Filippo , Corso Ruggero Massimo , Braghiroli Alberto , Gobbi Riccardo , Vroegop Anneclaire , Vonk Patty Elisabeth , Hohenhorst Winfried , Piccin Ottavio , Sorrenti Giovanni , Vanderveken Olivier M. , Vicini Claudio
Published: August 2018

Background

The first edition of the European position paper (EPP) on drug‐induced sleep endoscopy (DISE) was published in 2014 with the aim to standardise the procedure, to provide an in‐depth insight into the main aspects of this technique and to have a basis for future research. Since 2014, new studies have been published concerning new sedative agents or new insights into the pattern/levels of the obstruction depending on the depth of sedation. Therefore, an enlarged group of European experts in the field of sleep breathing disorders (SBD), including the most of the first DISE EPP main authors, has decided to publish an update of the European position paper on DISE, in order to include new evidence and to find a common language useful for reporting the findings of this endoscopic evaluation in adult population affected by SBD.

Methods

The authors have evaluated all the available evidence reported in the literature and have compared experience among various departments in leading European centres in order to provide an update regarding the standardisation of the DISE procedure and an in‐depth insight into the main aspects of this technique.

Results

After the first European Position Consensus Meeting on DISE and its update, consensus was confirmed for indications, required preliminary examinations, where to perform DISE, technical equipment required, staffing, local anaesthesia, nasal decongestion, other medications, patient positioning, basics and special diagnostic manoeuvres, drugs and observation windows. So far, no consensus could be reached on a scoring and classification system. However, regarding this aim, the idea of an essential classification, such as VOTE with the possibility of its graded implementation of information and descriptions, seems to be the best way to reach a universal consensus on DISE classification at this stage. A common DISE language is mandatory, and attempts to come to a generally accepted system should be pursued.
Fabrication of magnetic nanochains linked with CTX and curcumin for dual modal imaging detection and limitation of early tumour
Authors: Yang Yuedi , Huang Zhongbing , Pu Ximing , Yin Guangfu , Wang Lei , Gao Fabao
Published: August 2018

Objective

Five‐year survival rate at early lung tumour was about 70%; however, its early diagnosis rate was still at a low level, so the enhancement of diagnosis level for early lung tumour is the key factor to increase the survival rate. Diagnosis and therapy of early lung tumour are still challenged.

Methods

The magnetic nanochains (NCs) with biocompatibility and transverse relaxivity (r2 = 231 Fe mmol l−1 s−1) were fabricated through a co‐precipitation method in the assistance of dextran, and then, linked with chlorotoxin (CTX) and curcumin (Cur) via the PEGylation and carbodiimide technique (named as CTX‐NCs‐Cur).

Results

The results of cell test indicated that CTX‐conjugated NCs could obviously target non–small‐cell lung cancer cells and limit their growth. The in vivo results of magnetic resonance imaging and fluorescence imaging indicated that the CTX‐NCs‐Cur significantly targeted the tumour site and enhanced images contrast of the small‐size tumour. Moreover, the results of everyday tail‐vein injection confirmed that CTX‐NCs‐Cur could significantly limit the growth of early tumour, due to blocking Cl ion channels from CTX‐NCs‐Cur‐MMP‐2 composite and intracellular ROS increase from Cur treatment.

Conclusions

We provided a mechanism about the effect of CTX‐NCs‐Cur on the targeting and limiting early tumour, and these results indicated the application foreground of CTX‐NCs‐Cur in tumour diagnosis and therapy.
Computer‐aided identification of a novel pyruvate kinase M2 activator compound
Authors: Li Yuanyuan , Bao Minyue , Yang Chunlan , Chen Jiao , Zhou Shu , Sun Rong , Wu Chuanfang , Li Xin , Bao Jinku
Published: August 2018

Objectives

The aim of this study was to obtain antitumour molecules targeting to activate PKM2 through adequate computational methods combined with biological activity experiments.

Methods

The structure‐based virtual screening was utilized to screen effective activator targeting PKM2 from ZINC database. Molecular dynamics simulations were performed to evaluate the stability of the small molecule‐binding PKM2 complex systems. Then, cell survival experiments, glutaraldehyde crosslinking reaction, western blot, and qPCR experiments were used to detect the effects of top hits on various cancer cells and the targeting specificity of PKM2.

Results

Two small molecules in 1,5‐2H‐pyrrole‐dione were obtained after virtual screening. In vitro experiments demonstrated that ZINC08383544 specifically activated PKM2 and affected the expression of upstream and downstream genes of PKM2 during glycolysis, leading to the inhibition of tumour cell growth. These results indicate that ZINC08383544 conforms to the characteristics of PKM2 activator and is potential to be a novel PKM2 activator as antitumour drug.

Discussion

This work proves that ZINC08383544 promotes the formation of PKM2 tetramer, effectively blocks PKM2 nuclear translocation, and inhibits the growth of tumour, and ZINC08383544 may be a novel activator of PKM2. This work may provide a good choice of drug or molecular fragments for the antitumour strategy targeting PKM2. Screening of targeted drugs by combination of virtual screening and bioactivity experiments is a rapid method for drug discovery.
Hepatitis C viremia as a risk factor for opportunistic infections in kidney transplant recipients
Authors: Bodro Marta , Londoño Maria C. , Esforzado Nuria , Sanclemente Gemma , Linares Laura , Solano María Fernanda , Cofan Federico , Marcos María Angeles , Diekmann Fritz , Moreno Asuncion
Published: August 2018

The aim of the present study was to determine the clinical characteristics, frequency of opportunistic infections (OI) in HCV‐positive kidney recipients, and to evaluate HCV replication as a risk factor for developing an OI. We conducted a retrospective study of all kidney recipients from 2003 to 2014. A total of 1203 kidney transplants were performed during the study period. Opportunistic infections were recorded in 251 patients (21%) and nucleic acid amplification testing (NAAT) positivity in 75 (6%). Patients who are HCV NAAT positive were more likely to present an OI than those who are HCV NAAT negative (45% vs 20%, P < 0.001). Multivariate analysis showed the factors that were independently associated with the development of OI to be acute rejection, graft loss, post‐transplantation hemodialysis, and HCV replication. Liver cirrhosis after transplantation could not be considered a risk factor to develop OI. To conclude, a high index of suspicion of OI must be maintained in the case of kidney recipients with HCV replication. Active surveillance of cytomegalovirus infection and other prophylactic strategies against OI should be considered after 6 month post‐transplantation. Prompt initiation of DAA therapies may be a useful option aiming to decrease the incidence of OI after transplantation.
Use of hepatitis C‐positive grafts in hepatitis C‐negative liver transplant recipients is cost effective
Authors: Saab Sammy , Kardashian Ani , Saggi Satvir , Choi Gina , Agopian Vatche , Tong Myron J.
Published: August 2018

Background

The number of patients needing liver transplantation (LT) exceeds the number of available allografts. The current opioid epidemic in this country has increased the number of potential donors infected with hepatitis C (HCV).

Methods

We assessed the incremental cost‐effectiveness ratio (ICER) by comparing the costs and number of liver transplants performed using HCV‐positive and HCV‐negative grafts into patients without HCV infection in a decision analysis model with a 1‐year time horizon.

Results

The use of HCV‐positive grafts was found to have an ICER below $50 000 across all MELD scores. Using our baseline cohort with a model for end‐stage liver disease (MELD) score of 15‐22, the ICER was $21 233/additional LT performed. As the MELD scores increased, the ICER decreased. Above a MELD score of 23, the use of HCV‐positive grafts became cost saving (‐$115 419). Our model was robust to all variables tested in the sensitivity analyses, except drug costs.

Conclusion

The results of our decision analysis model highlight the potential pharmacoeconomic benefit of utilizing HCV‐positive grafts in LT candidates who are not infected with HCV. The use of HCV‐positive grafts is at least cost effective and even cost saving in patients with MELD scores above 23.
A metabolic approach during normothermic regional perfusion in uncontrolled donors after circulatory death—A pilot study
Authors: Peris Adriano , Lazzeri Chiara , Bonizzoli Manuela , Guetti Cristiana , Tadini Buoninsegni Laura , Fulceri Giorgio , Ticali Pier Francesco , Chiostri Marco , Li Marzi Vincenzo , Serni Sergio , Migliaccio Maria Luisa
Published: August 2018

The use of donation after circulatory death (DCD) has increased significantly to face the persistent mismatch between supply and demand of organs for transplantation. While controlled (c) DCDs have warm ischemic time (WIT) that can be estimated, the WIT is often inexact and extended in uncontrolled DCD (uDCD), making assessment of injury difficult. We aimed at investigating the effects of cold ischemia on potential donor organ damage in the course of nRP by assessing the dynamic variations of transaminases and creatinine values in 17 uDCD donors. In our series, lactate values did not show significant changes during the study period (P = 0.147). Creatinine values did not significantly changed while transaminases progressive increased throughout the study period, even if it was significant only for AST (P = 0.035). According to our data, nRP duration affects splanchnic organs, being the liver sensitive to hypoperfusion, and serial biochemical measurements could help in detecting organ functional status.
Silvery hair with dyschromatosis: Griscelli syndrome type 3 or familial gigantic melanocytosis
Authors: Batrani Meenakshi , Thole Akhilesh , Kubba Asha , Mahajan Khushbu
Published: August 2018

We herein illustrate a case of an adult male presenting with silvery hair and generalized guttate hypopigmented macules on a background of diffuse cutaneous hyperpigmentation, since birth. Histopathology showed enlarged melanocytes with abundant melanin. Based on these clinicopathological features, differential diagnoses considered were Griscelli syndrome 3 (GS3) and familial giagantic melanocytosis. GS3 belongs to a group of inherited autosomal recessive (AR) disorders of partial albinism, known as silvery hair syndromes, while familial gigantic melanocytosis (FGM) is a putative disorder of dyschromia with silvery hairs. A pertinent literature search revealed hyperpigmentation or dyschromatosis as a rare manifestation of silvery hair syndromes, especially in dark‐skin populations. A comparative analysis of previously reported cases depicted close morphological similarities between GS3 and FGM. We discuss the uncertainty pertaining to cases described in literature as FGM, to be truly representative of a distinctive entity, or merely a morphological variation of GS3.
Neurodevelopmental difficulties in children with idiopathic clubfoot
Authors: Lööf Elin , Andriesse Hanneke , Broström Eva W , André Marie , Bölte Sven
Published: August 2018

Aim

To evaluate neurodevelopmental difficulties in children with idiopathic clubfoot.

Method

A cross‐sectional study of 106 children (29 females, 77 males; aged 8–10y) with idiopathic clubfoot and 109 age‐, sex‐, and residential area‐parallelized children from the general population. Neurodevelopmental difficulties were assessed using the parent‐report Five to Fifteen (FTF) questionnaire. Group differences were analysed for FTF domains, subdomains, and items. The 90th centile cut‐off of the general population on FTF and the parent‐based disease‐specific instrument (DSI) were used to evaluate clinical relevance of neurodevelopmental symptoms in idiopathic clubfoot.

Results

Modest group differences were found for several FTF domains (motor skills, perception, and language) and subdomains (gross and fine motor skills, relation in space, comprehensive and expressive language skills). Thirty‐one per cent of the children with idiopathic clubfoot scored in the clinically significant range on 2 or more FTF domains. DSI scores were lower in this subgroup.

Interpretation

Findings indicate a moderate and selective increase of neurodevelopmental difficulties in children with idiopathic clubfoot as a whole, especially in the areas of motor skills, perception, and language. Idiopathic clubfoot with marked neurodevelopmental symptoms are associated with less satisfaction of the clubfoot treatment. Our results recommend awareness of neurodevelopmental difficulties in the assessment and treatment of idiopathic clubfoot.

What this paper adds

A substantial minority of children with idiopathic clubfoot show neurodevelopmental difficulties.

Children with idiopathic clubfoot might present additional difficulties in motor skills, perception, and language.

Children with idiopathic clubfoot and marked neurodevelopmental symptoms show poorer parent‐reported clubfoot treatment satisfaction.

Neurodevelopmental difficulties should be considered in clinical practice of idiopathic clubfoot.
RELEASING THE TRAP: A METHOD TO REDUCE INATTENTION BIAS IN SURVEY DATA WITH APPLICATION TO U.S. BEER TAXES
Authors: Malone Trey , Lusk Jayson L.
Published: August 2018

This study uses discrete choice experiments to explore the efficacy of prompts targeted at reducing inattention bias. Upon receiving feedback, inattentive respondents are given the opportunity to reanswer a so‐called “trap question” that checks for attentiveness. We find that individuals who miss trap questions and do not correctly revise their responses have significantly different choice patterns as compared to individuals who correctly answer the trap question. Adjusting for these inattentive responses has a substantive impact on policy impacts. Results, based on attentive participant responses, indicate that a minimum beer price would have to be substantial to substantially reduce beer demand. (JEL C83, Q18, Q51)
Mate‐searching behavior in the invasive German wasp, Vespula germanica, in Patagonia
Authors: Martínez Andrés S. , Masciocchi Maité , Pisman Natalia , Villacide José M. , Corley Juan C.
Published: August 2018

In order to increase the probability of reproduction, social insects can adopt various mate‐finding strategies, such as increasing densities of males at specific locations, and/or visual and chemical cues that attract the opposite sex. In field and laboratory studies we investigated strategies used by the invasive eusocial wasp Vespula germanica (Fabricius) (Hymenoptera: Vespidae). In tethered flight assays, we established contrasting flight patterns in females and males that may partly explain how related individuals distribute spatially during the mating period. We also determined experimentally, in the field and in the laboratory via olfactometer assays, that gynes produce airborne pheromonal cues that attract drones and are important during mate location. Our field trials also suggest that visual cues play a role in mate location. We conclude that in addition to aspects of the social biology of the species, an efficient mate‐location strategy can partly explain the invasion success of the species. Tools to mitigate the damage caused by yellowjackets may be developed by focusing on reproductive castes, in addition to workers.
Effects of a low dose of ethanol on mating success of Drosophila melanogaster males: implications for the evolution of ethanol resistance?
Authors: Zhu Jing , Fry James D.
Published: August 2018

Ethanol occurs naturally in the decaying fruit in which many species of Drosophila (Diptera: Drosophilidae) breed, potentially generating selection for resistance to its toxic and sedating effects. Studies measuring mortality of flies exposed to a range of ethanol concentrations have shown that within Drosophila melanogaster Meigen, populations from temperate regions are more ethanol resistant than ancestral tropical African populations. The high ethanol resistance of temperate D. melanogaster presents a puzzle, however, because breeding and feeding sites in the wild seldom contain enough ethanol to kill even more ethanol‐sensitive Afrotropical genotypes. We hypothesize that the ethanol concentrations encountered by temperate populations, though usually sub‐lethal, are nonetheless high enough to reduce fitness in other ways, potentially generating indirect selection for genotypes that can survive exposure to unnaturally high ethanol concentrations. As a first step in testing this hypothesis, we compared the effects of a sub‐lethal dose of ethanol, comparable to that obtainable from fermenting fruit, on the mating success of males from one European and one Afrotropical population. Ethanol significantly reduced mating success of males from the Afrotropical population, but had no effect on that of males from the European population. We also show that when flies are placed on medium with a realistic concentration of ethanol, considerably more ethanol is absorbed through vapor than through feeding, suggesting that courting males may be unable to avoid being exposed to ethanol. We hypothesize that the higher resistance of temperate populations to being killed by high, unnatural ethanol concentrations may have evolved in part as a correlated response to selection for behavioral insensitivity to natural concentrations.
Evolutionarily distinct amphibians are disproportionately lost from human‐modified ecosystems
Authors: Greenberg D. A. , Palen W. J. , Chan K. C. , Jetz W. , Mooers A. Ø.
Published: August 2018

Humans continue to alter terrestrial ecosystems, but our understanding of how biodiversity responds is still limited. Anthropogenic habitat conversion has been associated with the loss of evolutionarily distinct bird species at local scales, but whether this evolutionary pattern holds across other clades is unknown. We collate a global dataset on amphibian assemblages in intact forests and nearby human‐modified sites to assess whether evolutionary history influences susceptibility to land conversion. We found that evolutionarily distinct amphibian species are disproportionately lost when forested habitats are converted to alternative land‐uses. We tested the hypothesis that grassland‐associated amphibian lineages have both higher diversification and are pre‐adapted to human landscapes, but found only weak evidence supporting this. The loss of evolutionarily distinct amphibians with land conversion suggests that preserving remnant forests will be vital if we aim to preserve the amphibian tree of life in the face of mounting anthropogenic pressures.
Working with nature to improve the environment and profitability of irrigated cotton production at ‘Kilmarnock’, Namoi Valley, New South Wales
Authors: Smith Rhiannon , Watson Andrew
Published: August 2018

Several environmentally positive farming innovations at ‘Kilmarnock’ near Boggabri, New South Wales, have been monitored over time and have revealed a positive impact upon this irrigated cotton farming enterprise's financial sustainability and environmental footprint. This study demonstrates economic benefits from environmental approaches to farm management.
Matching effort to threat: Strategies to increase the scale and effectiveness of revegetation in southern Australia
Authors: Freudenberger David
Published: August 2018

The past 30 years of restoration activities in Australia has been mere cautious fiddling in the face of continental‐wide native habitat loss, fragmentation and degradation. A fundamental principle of conservation is to address threats at the scale of the threatening processes. This is still not happening for two reasons: we do not know how to effectively restore at scale, and if we did, there is no demand because it does not pay. The first problem of developing the technologies needed for large‐scale revegetation will largely be solved if we collectively demand revegetation at scale. Such a scale of demand by Australian governments (taxpayers) is only likely if a permanent Natural Heritage Trust is created for long‐term funding complemented by a price on carbon pollution. That will take a lot of political will. The other big opportunity is to create demand for large‐scale revegetation cofunded by farmers to improve their farm's long‐term productivity, resilience and economic viability. This requires sustained R&D supported by novel partnerships with the massive Australian agricultural market. Native vegetation must move from the margins to the mainstream if scale is to be achieved.
Turquoise is the new green: Restoring and enhancing riparian function in the Anthropocene
Authors: Capon Samantha J. , Pettit Neil E.
Published: August 2018

Riparian ecosystems are hotspots for ecological restoration globally because of the disproportionately high value and diversity of the ecological functions and services which they support and their high level of vulnerability to anthropogenic pressures, including climate change. Degraded riparian ecosystems are associated with many serious anthropogenic problems including increased river bank erosion, water quality decline, increased flood risk and biodiversity loss. Conventional approaches to riparian restoration, however, are frequently too narrow in focus – spatially, temporally, ecologically and socially – to adequately or equitably address the goals to which they aspire. Climate change, along with the intensification of other human pressures, means that static, historically oriented restoration objectives focused solely on prior ecological composition and structure are unlikely to be defensible, achievable or appropriate in the Anthropocene. Conversely, open‐ended restoration strategies lacking clear objectives and targets entail substantial risks such as significant biodiversity losses, especially of native species. A functional approach to planning and prioritising riparian restoration interventions offers an intermediate alternative that is still framed by measurable targets but allows for greater consideration of broader temporal, spatial and cultural influences. Here, we provide an overview of major riparian functions across multiple scales and identify key drivers of, and threats to, these. We also discuss practical approaches to restoring and promoting riparian functions and highlight some key concerns for the development of policy and management of robust riparian restoration in the Anthropocene.
Statistical and Methodological Myths and Urban Legends in Strategic Management Research: The Case of Moderation Analysis
Authors: Li Ming , Sharp Barton M. , Bergh Donald D. , Vandenberg Robert
Published: August 2018

This paper examines whether methodological precedence in applying moderation analysis to strategic management research relies on myths and urban legends, and if doing so affected empirical conclusions, implications for theory development, and practical recommendations. An in‐depth analysis of 69 studies published in the Strategic Management Journal between 2000 and 2014 using moderation analysis finds that strategic management scholars typically rely on statistical myths and urban legends when applying moderation analysis including: (1) interpreting main effects separately from their significant interaction with other variables; (2) failing to report reliability values of interaction terms; and (3) relying on hierarchical approaches that can lead to interpretation errors. Further examples illustrate how these practices could lead researchers to draw incomplete and possibly inaccurate conclusions. Overall, problematic precedents have become the gold standards for testing and interpreting moderation models. Best practice recommendations for redirecting future research to more solid methodological grounding are provided.
Thrombolysis and adjunct anticoagulation in patients with acute basilar artery occlusion
Authors: Ritvonen J. , Strbian D. , Silvennoinen H. , Virtanen P. , Salonen O. , Lindsberg P. J. , Sairanen T.
Published: August 2018

Background and purpose

Patients suffering from basilar artery occlusion (BAO) and treated with intravenous thrombolysis are, in some centers, started on adjunct anticoagulation in hyperacute settings. We aimed to assess the outcome of such patients and to compare low‐molecular weight heparin (LMWH) and unfractionated heparin (UFH) in this context.

Methods

We examined 211 patients with angiography‐proven BAO treated with intravenous thrombolysis and either adjunct UFH or LMWH. Main outcome variables were rate of symptomatic intracranial hemorrhage (sICH) according to European Cooperative Acute Stroke Study II criteria and modified Rankin Scale (mRS) at 3 months.

Results

The overall rate of sICH was 11.4% and driven by the UFH group (13.3%). None of the LMWH group developed sICH. Recanalization rate did not significantly differ between the LMWH and UFH groups. An additional propensity analysis was made to balance anticoagulation groups regarding baseline characteristics. Propensity analysis showed a significant difference in sICH rate (0.0% vs. 14.8%, P = 0.044) in favor of LMWH. Independent outcome (mRS score 0–2) was achieved in a total of 31.0% and in 44.8% and 29.1% in the LMWH and UFH group, respectively (P = 0.09). Propensity analysis showed a significant difference in the risk of ending up bedridden or dead (mRS score 5–6; 34.5% vs. 63.0%, P = 0.033) in favor of LMWH.

Conclusions

Our study showed a lower rate of sICH and a shift towards improved outcome in thrombolysed patients with BAO treated with LMWH as compared with UFH.
Self‐reported cognitive function in a large international cohort of people with multiple sclerosis: associations with lifestyle and other factors
Authors: Jelinek P. L. , Simpson S. , Brown C. R. , Jelinek G. A. , Marck C. H. , De Livera A. M. , O'Kearney E. , Taylor K. L. , Neate S. L. , Weiland T. J.
Published: August 2018

Background and purpose

We aimed to estimate the prevalence of perceived cognitive impairment (PCI) and explore its associations with lifestyle and disease characteristics in a large international cohort of people with multiple sclerosis (MS).

Methods

This study was a cross‐sectional analysis. Participants rated their cognitive function over the preceding 4 weeks using four questions in a subscale within the Multiple Sclerosis Quality of Life questionnaire (MSQOL‐54). These questions assessed perceived concentration, attention and memory by the patient and family/friends. Four definitions of PCI were derived, ranging from lowest to highest specificity. Associations with PCI were assessed by log‐binomial regression.

Results

The prevalence of PCI in our sample ranged from 41.0% (95% confidence interval, 39.0–43.0) using the least‐specific definition to 11.6% (95% confidence interval, 10.3–12.9) using the most specific definition. A number of factors were associated with PCI, increasing in magnitude as the definition specificity increased, including positive associations for smoking and body mass index, whereas physical activity, dietary quality and use of vitamin D/omega‐3 supplements were inversely associated with PCI.

Conclusions

Our study reports associations between healthy lifestyle behaviours and PCI in people with MS. Although reverse causality is a potential explanation for our findings, previous studies have shown comparable associations with healthy lifestyle and MS onset and progression. Subject to external validation, these results suggest benefits realized from a healthy lifestyle in people with MS.
No association of DNM3 with age of onset in Asian Parkinson's disease
Authors: Foo J. N. , Tan L. C. , Au W.‐L. , Prakash K.‐M. , Liu J. , Tan E.‐K.
Published: August 2018

Background and purpose

Genetic variability in DNM3 has been shown to modify age of onset of Parkinson's disease (PD) among LRRK2 Gly2019Ser carriers in North African Arab–Berber populations. In Asian populations, the Gly2019Ser mutation is rare or absent but two other LRRK2 variants, Gly2385Arg and Arg1628PPro, increase PD risk. We aimed to determine whether the DNM3 locus was associated with age of PD onset in both carriers and non‐carriers of LRRK2 risk variants in Asians.

Methods

We analyzed the association of DNM3 rs2421947 genotypes with age of PD onset in 3645 Chinese samples, of which 369 carried at least one of two Asian LRRK2 risk variants.

Results

DNM3 rs2421947 genotypes were not associated with age of PD onset in Chinese samples. We observed no heterogeneity in the effect of rs2421947 between the Asian LRRK2 risk variant carriers and non‐carriers.

Conclusions

DNM3 rs2421947 was not associated with age of PD onset in LRRK2 risk variant carriers and non‐carriers in Chinese samples. Further studies in other Asian populations will be of interest.
Subclinical motor impairment assessed with an engineered glove correlates with magnetic resonance imaging tissue damage in radiologically isolated syndrome
Authors: Bonzano L. , Bove M. , Sormani M. P. , Stromillo M. L. , Giorgio A. , Amato M. P. , Tacchino A. , Mancardi G. L. , De Stefano N.
Published: August 2018

Background

An engineered glove measuring finger motor performance previously showed ability to discriminate early‐stage multiple sclerosis (MS) patients from healthy controls (HCs). Radiologically isolated syndrome (RIS) classifies asymptomatic subjects with brain magnetic resonance imaging (MRI) abnormalities suggestive of multiple sclerosis.

Methods

Seventeen asymptomatic subjects with RIS and 17 HCs were assessed. They performed finger‐to‐thumb opposition sequences at their maximal velocity, metronome‐paced bimanual movements and conventional and diffusion tensor MRI.

Results

Subjects with RIS showed lower (P = 0.005) maximal velocity and higher (P = 0.006) bimanual coordination impairment than HCs. In RIS, bimanual coordination correlated with T2‐lesion volume, fractional anisotropy and radial diffusivity in the white matter.

Conclusions

These findings point out the relevance of fine hand measures as a robust marker of subclinical disability.
pckA‐deficient Porphyromonas gingivalis W83 shows reduction in hemagglutination activity and alteration in the distribution of gingipain activity
Authors: Wu Leng , Zhao Lei , Wang Jun , Liu Chengcheng , Li Yan , Wu Yafei
Published: August 2018

Bacterial metabolism during infection is related to bacterial persistence and virulence factors. Porphyromonas gingivalis is a key pathogen that contributes to chronic periodontitis. Our previous study showed that pckA, the gene encoding phosphoenolpyruvate carboxykinase, is a putative‐specific pathogenic gene of virulent strains of P. gingivalis. Here, a pckA‐deficient strain (ΔPG1676) was constructed in P. gingivalis W83. Virulence properties were compared between the mutant and wild‐type strains. Specifically, hemagglutination activity was determined by the ability to agglutinate sheep erythrocytes. Gingipain activity was detected using synthetic‐specific substrates. Gene expression levels were analyzed using RT‐qPCR, and cell surface‐associated polysaccharides were examined by silver staining and electron microscopy. Inactivation of the pckA gene did not affect bacterial growth and lipopolysaccharide formation but led to a reduction in hemagglutination activity and downregulation in expression of the hemagglutination‐associated gene, rfa, when compared with the wild‐type strain. Additionally, the ΔPG1676 mutant exhibited an alteration in the distribution of gingipain activity. Increased gingipain activity was detected on the cell surface, but a decrease in its activity in the culture supernatant was shown. Taken together, our results suggest that the pckA gene plays a role in modulating the virulence of P. gingivalis W83.
Neuroimaging alterations related to status epilepticus in an adult population: Definition of MRI findings and clinical‐EEG correlation
Authors: Giovannini Giada , Kuchukhidze Giorgi , McCoy Mark R. , Meletti Stefano , Trinka Eugen
Published: August 2018

Magnetic resonance imaging (MRI) provides an opportunity for identifying peri‐ictal MRI abnormalities (PMAs) related to status epilepticus (SE). Extremely variable MRI alterations have been reported previously during or after SE, mainly in small selected populations. In a retrospective monocentric study, we analyzed brain MRI changes observed in the ictal/postictal periods of SE in an adult population. We included all consecutive patients observed in a 5‐year period with an electroclinical diagnosis of SE and an MRI performed within 30 days from the beginning of SE. We identified 277 patients. Among them, 32 (12%) showed PMAs related to SE. The duration of SE was strongly associated with MRI alterations, showing a mean duration of 6 days vs 2 days (P = .011) in the group with and without MRI alterations, respectively. Focal electroencephalography (EEG) abnormalities (P = .00003) and in particular, lateralized periodic discharges (LPDs) (P < .0001) were strongly associated with PMAs. MRI alterations were unilateral (23 patients, 72%), located in multiple brain structures (19 patients, 59%), and involving mesiotemporal structures (17 patients, 53%). Sixteen patients (50%) had good spatial correspondence between cortical PMAs and the focal EEG pattern; 12 patients (38%) with focal EEG pattern showed cortical PMAs plus MRI signal changes also involving subcortical structures. A follow‐up MRI was available for 14 of 32 patients (44%): 10 patients presented a disappearance of PMAs, whereas in 4, PMAs were still present. This study demonstrates that a long duration SE and the presence of certain EEG patterns (LPDs) are associated with the occurrence of PMAs. A good spatial concordance was observed between cortical PMA location and the EEG focus.
Fueling the FIRES: Hemophagocytic lymphohistiocytosis in febrile infection‐related epilepsy syndrome
Authors: Farias‐Moeller Raquel , LaFrance‐Corey Reghann , Bartolini Luca , Wells Elizabeth M. , Baker Meredith , Doslea Alyssa , Suslovic William , Greenberg Jay , Carpenter Jessica L. , Howe Charles L.
Published: August 2018

Objectives

Although secondary hemophagocytic lymphohistiocytosis (HLH) has been reported in children with critical illness of various etiologies, it has not been reported in patients with febrile infection–related epilepsy syndrome (FIRES). We describe a series of patients with concurrent HLH and FIRES in an effort to establish common pathophysiologic abnormalities.

Methods

Five patients with FIRES who were assessed for HLH were identified from a neurocritical care database. All were previously healthy and had extensive diagnostic testing. All had clinical deterioration with multiorgan dysfunction prompting HLH screening 20‐29 days after hospitalization. Markers for inflammatory dysregulation were assessed in cerebrospinal fluid (CSF) and serum at various time points. Outcomes were assessed 6 months after presentation.

Results

Three patients met clinical criteria for secondary HLH. Elevation of specific cytokines/chemokines was variable. CSF neopterin, high mobility group box 1 (HMGB1), and C‐X‐C motif chemokine ligand 8 (CXCL8) were significantly elevated in all. Interleukin‐1β (IL‐1β) and IL‐18 were not elevated in any of the samples. Treatment and outcomes were variable.

Significance

We describe 3 patients with HLH and FIRES. The co‐occurrence of these 2 rare disorders suggests the possibility of a common immune dysregulation phenotype prolonging epileptogenesis. HLH screening in critically ill patients with FIRES may yield a broader understanding of shared inflammatory processes.
p53 tumor suppressor and iron homeostasis
Authors: Zhang Jin , Chen Xinbin
Published: August 2018

Iron is an essential nutrient for all living organisms and plays a vital role in many fundamental biochemical processes, such as oxygen transport, energy metabolism, and DNA synthesis. Due to its capability to produce free radicals, iron has deleterious effects and thus, its level needs to be tightly controlled in the body. Deregulation of iron metabolism is known to cause diseases, including anemia by iron deficiency and hereditary hemochromatosis by iron overload. Interestingly, dysregulated iron metabolism occurs frequently in tumor cells and contributes to tumorigenesis. In this review, we will discuss the role of p53 tumor suppressor in iron homeostasis.
A guide to quantifying membrane protein dynamics in lipids and other native‐like environments by solution‐state NMR spectroscopy
Authors: Bibow Stefan , Hiller Sebastian
Published: August 2018

Recent biochemical and technical developments permit residue‐specific solution NMR measurements of membrane protein (MP) dynamics in lipidic and chaperone‐bound environments. This is possible by combinations of improved sample preparations with suitable NMR relaxation experiments to correlate protein function to backbone dynamics on timescales from picoseconds to seconds, even for large MP–lipid assemblies above 100 kDa in molecular mass. Here, we introduce the basic concepts of different NMR relaxation experiments, individually sensitive to specific timescales. We discuss the general limitations of detergent environments and highlight the importance for native‐like environments when studying MPs. We then review three practical studies of fast‐ and slow‐timescale MP dynamics in lipid environments, as well as in a natively unfolded, chaperone‐bound state. These examples illustrate the new avenues solution NMR spectroscopy is taking to investigate MP dynamics in native‐like environments with atomic resolution.
Influence of tubificid worms on sediment structure, benthic biofilm and fauna in wetlands: A field enclosure experiment
Authors: Mermillod‐Blondin Florian , Bouvarot Morgane , Déjollat Yann , Adrien Jérome , Maire Eric , Lemoine Damien , Marmonier Pierre , Volatier Laurence
Published: August 2018

Bioturbation activities of tubificid worms play a major role in nutrient cycling and microbial processes occurring at water–sediment interfaces of freshwater environments. Nevertheless, evidence of significant contributions of worms to ecosystem functioning largely arises from experiments performed at laboratory scales, because studies exploring the role of tubificid worms in the field are scarce. Therefore, this study aimed to test the influence of tubificid worms on benthic habitat structure and functioning in field experiments. According to literature, we predicted that feeding activities of tubificid worms would increase the percentage of clay and silt particles, the bacterial growth and microbial activities in the top sediment layer.

The experiment was performed at the water–sediment interface of a shallow wetland. Enclosures with and without addition of the tubificid worm Limnodrilus hoffmeisteri were used to quantify the influences of tubificid worms on the sedimentary habitat (sediment grain size distribution, water‐filled porosity using microtomography), the biofilm (algal biomass, bacterial abundance, total organic carbon and total nitrogen, microbial enzymatic activity, photosynthetic activity and efficiency of the photosystem II) and the benthic fauna. Measures were performed before worm addition and at the end of the experiment.

After 6 weeks, the proportion of fine sediment particles (<63 μm) and the water‐filled porosity were significantly modified by the bioturbation activities of tubificid worms. The bacterial abundance was stimulated by twofold, the microbial hydrolytic activity by +35% and the algal biomass by +40%. The field enclosures with and without L. hoffmeisteri showed differences in benthic invertebrate assemblages, especially for nematodes that were excluded from enclosures with worms.

Our results indicate that bioturbation mechanisms and impacts reported from laboratory experiments with tubificid worms are not only significant at a field scale, but also highlight unpredicted interactions with other benthic organisms (autotrophic compartment of the biofilm and invertebrates).