bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical impact of inflammation in dry eye disease: proceedings of the ODISSEY group meeting
Authors: Baudouin Christophe , Irkeç Murat , Messmer Elisabeth M. , Benítez‐del‐Castillo José M. , Bonini Stefano , Figueiredo Francisco C. , Geerling Gerd , Labetoulle Marc , Lemp Michael , Rolando Maurizio , Van Setten Gysbert , Aragona Pasquale ,   ODISSEY European Consensus Group Members
Published: April 2017

AbstractDry eye disease (DED) is a common, multifactorial ocular condition with major impact on vision and quality of life. It is now well recognized that the pathophysiology of chronic DED can include a cycle of inflammation involving both innate and adaptive immune responses. Recently, in vitro/in vivo models have been used to obtain a better understanding of DED‐related inflammatory processes at molecular/cellular levels although they do not truly reproduce the complex and chronic hallmarks of human DED. In clinical DED research, advanced techniques such as impression cytology, conjunctival biopsy, in vivo confocal microscopy and multiplex tear analyses have allowed an improved assessment of inflammation in DED patients. This was supported by the identification of reliable inflammatory markers including matrix metalloproteinase‐9, human leucocyte antigen‐DR or intercellular adhesion molecule‐1 in tears and impression cytology samples. One of the current therapeutic strategies focuses on breaking the inflammatory cycle perpetuating the ocular surface disease, and preclinical/clinical research has led to the development of promising anti‐inflammatory compounds. For instance, cyclosporine, already approved in the United States, has recently been authorized in Europe to treat DED associated with severe keratitis. In addition, other agents such as corticosteroids, doxycycline and essential fatty acids, through their anti‐inflammatory properties, show encouraging results. We now have a clearer understanding of the inflammatory processes involved in DED, and there is hope that the still emerging preclinical/clinical findings will be translated into new and highly effective therapies for patients in the near future.
Observer variability identifying attention deficit/hyperactivity disorder in 10‐year‐old children born extremely preterm
Authors: Leviton Alan , Hunter Scott J. , Scott Megan N. , Hooper Stephen R. , Joseph Robert M. , O'Shea Thomas Michael , Allred Elizabeth N. , Kuban Karl 
Published: April 2017

AbstractAimA DSM‐5 diagnosis of attention deficit/hyperactive disorder (ADHD) requires that symptoms be present in two settings. We wanted to see how teachers and parents compare on their assessments.MethodsWe evaluated how well Child Symptom Inventory‐4 (CSI‐4) reports from 871 parents and 634 teachers of 10‐year‐old children born before the 28th week of gestation provided information about indicators of school dysfunction.ResultsKappa values for parent and teacher agreement of any ADHD were at best fair to poor (<0.41). Nevertheless, ADHD identified by each alone provided a moderate amount of information about such indicators of school dysfunction as grade repetition. Only occasionally did agreement provide more information than provided by only one reporter. Mother's social class and intelligence level did not discriminate between parents who did and did not agree with the teacher.ConclusionADHD identified by a single observer can provide appreciable information about a range of the child's functions needed for success in school and, therefore, should not be discounted when another observer does not consider the child to have ADHD symptoms.
Design, synthesis, and evaluation of novel Akt1 inhibitors based on an indole scaffold
Authors: Yang Dezhi , Tong Dongdong , Zhang Qian , Wang Yongtao , Sun Jing , Zhang Fenghe , Zhao Guisen 
Published: April 2017

A new series of potential Akt1 inhibitors with indole scaffold were designed and synthesized. The antiproliferative activity against PC‐3 cell line and enzyme inhibitory activity against Akt1 were evaluated. Among them, some compounds showed much more potent antiproliferative activity and stronger Akt1 inhibitory activity compared to the positive control of GSK690693. In particular, compound 19b exhibited the most potent inhibitory activity against Akt1 with inhibition rate of 70.3% at a concentration of 10 nm. Furthermore, compound 19b could dose dependently reduce the phosphorylation of the downstream GSK3β protein in the PC‐3 cell line and displayed fivefold higher antiproliferative activity against PC‐3 cell line with IC50 value of 3.1 ± 0.1 μm than positive control (15.5 ± 0.4 μm). Herein, compound 19b may serve as a promising lead for further optimization and development of novel Akt1 inhibitors based on an indole scaffold.
The anti‐Trichomonas vaginalis phloroglucinol derivative isoaustrobrasilol B modulates extracellular nucleotide hydrolysis
Authors: Menezes Camila Braz , Rigo Graziela Vargas , Bridi Henrique , Trentin Danielle da Silva , Macedo Alexandre José , von Poser Gilsane Lino , Tasca Tiana 
Published: April 2017

Trichomonas vaginalis causes trichomoniasis, a neglected sexually transmitted disease. Due to severe health consequences and treatment failure, new therapeutic alternatives are crucial. Phloroglucinols from southern Brazilian Hypericum species demonstrated anti‐T. vaginalis and anti‐Leishmania amazonensis activities. The modulation of biochemical pathways involved in the control of inflammatory response by ectonucleotidases, NTPDase, and ecto‐5′‐nucleotidase represents new targets for combating protozoa. This study investigated the activity of phloroglucinol derivatives of Hypericum species from southern Brazil against T. vaginalis as well as its ability on modulating parasite ectonucleotidases and, consequently, immune parameters through ATP and adenosine effects. Phloroglucinol derivatives screening revealed activity for isoaustrobrasilol B (IC50 38 μm) with no hemolytic activity. Although the most active compound induced cytotoxicity against a mammalian cell lineage, the in vivo model evidenced absence of toxicity. Isoaustrobrasilol B significantly inhibited NTPDase and ecto‐5′‐nucleotidase activities, and the immune modulation attributed to extracellular nucleotide accumulation was evaluated. The production of ROS and IL‐6 by T. vaginalis‐stimulated neutrophils was not affected by the treatment. Conversely, IL‐8 levels were significantly enhanced. The associative mechanism of trophozoites death and ectonucleotidases modulation by isoaustrobrasilol B may increase the susceptibility of T. vaginalis to host innate immune cell like neutrophils consequently, contributing to parasite clearance.
High fractional exhaled nitric oxide and sputum eosinophils are associated with an increased risk of future virus‐induced exacerbations: A prospective cohort study
Authors: Bjerregaard A. , Laing I. A. , Backer V. , Sverrild A. , Khoo S.‐K. , Chidlow G. , Sikazwe C. , Smith D. W. , Le Souëf P. , Porsbjerg C. 
Published: April 2017

SummaryBackgroundThe major trigger of asthma exacerbations is infection with a respiratory virus, most commonly rhinovirus. Type 2 inflammation is known to be associated with an increased risk of exacerbations in general. Whether type 2 inflammation at baseline increases the risk of future virus‐induced exacerbations is unknown.ObjectiveTo assess whether type 2 inflammation is associated with an increased risk of virus‐induced exacerbations of asthma.MethodsStable asthmatics had spirometry, skin prick test, measurement of FeNO and sputum induced for differential cell counts. Patients were followed up for 18 months, during which they were assessed at the research unit when they had symptoms of an exacerbation. Nasal swabs collected at these assessments underwent viral detection by PCR.ResultsA total of 81 asthma patients were recruited, of which 22 (27%) experienced an exacerbation during the follow‐up period. Of these, 15 (68%) had a respiratory virus detected at exacerbation. Sputum eosinophils >1% at baseline increased the risk of having a subsequent virus‐induced exacerbation (HR 7.6 95% CI: 1.6‐35.2, P=.010) as did having FeNO >25 ppb (HR 3.4 95% CI: 1.1‐10.4, P=.033).Conclusion and Clinical RelevanceEstablished type 2 inflammation during stable disease is a risk factor for virus‐induced exacerbations in a real‐life setting. Measures of type 2 inflammation, such as sputum eosinophils and FeNO, could be included in the risk assessment of patients with asthma in future studies.
PGAP3‐related hyperphosphatasia with mental retardation syndrome: Report of 10 new patients and a homozygous founder mutation
Authors: Abdel‐Hamid M.S. , Issa M.Y. , Otaify G.A. , Abdel‐Ghafar S.F. , Elbendary H.M. , Zaki M.S. 
Published: April 2017

BackgroundHyperphosphatasia with mental retardation syndrome (HPMRS) is caused by recessive mutations in genes involved in the glycosylphosphatidylinsitol pathway, including PGAP3.Materials and MethodsWe describe 10 patients from 8 Egyptian families presenting with developmental delay, severe intellectual disability, distinct facial dysmorphism and increased alkaline phosphatase. Sanger sequencing of PGAP3 was performed.ResultsEight patients had cleft palate, 4 had postnatal microcephaly and 5 had seizures. Neuro‐imaging findings showed thin corpus callosum in 9 patients, mild ventriculomegaly in 3 patients and variable degrees of cerebellar vermis hypoplasia in 4 patients, a finding not previously reported in patients with HPMRS. Additional manifestations included double row teeth, hypogenitalism and congenital heart disease. Biallelic loss of function mutations in the PGAP3 gene were detected in all patients. Nine patients were homozygous for the c.402dupC (p.M135Hfs*28) mutation strongly suggesting a founder effect. On the other hand, 1 patient had a novel mutation, c.817_820delGACT (p.D273Sfs*37).ConclusionThis is the largest series of patients with HPMRS from same ethnic group. Our results reinforce the distinct clinical and facial features of PGAP3‐related HPMRS which are the clue for targeted genetic testing. Moreover, we present additional unreported clinical and neuro‐imaging findings and a novel mutation thus expanding the phenotypic and mutational spectrum of this rare disorder.
Ecosystem‐Based Fisheries Management for Social–Ecological Systems: Renewing the Focus in the United States with Next Generation Fishery Ecosystem Plans
Authors: Marshall Kristin N. , Levin Phillip S. , Essington Timothy E. , Koehn Laura E. , Anderson Lee G. , Bundy Alida , Carothers Courtney , Coleman Felicia , Gerber Leah R. , Grabowski Jonathan H. , Houde Edward , Jensen Olaf P. , Möllmann Christian , Rose Kenneth , Sanchirico James N. , Smith Anthony D.M. 
Published: April 2017

AbstractResource managers and policy makers have long recognized the importance of considering fisheries in the context of ecosystems; yet, movement towards widespread Ecosystem‐based Fisheries Management (EBFM) has been slow. A conceptual reframing of fisheries management is occurring globally, which envisions fisheries as systems with interacting biophysical and human subsystems. This broader view, along with a process for decision making, can facilitate implementation of EBFM. A pathway to achieve these broadened objectives of EBFM in the United States is a Fishery Ecosystem Plan (FEP). The first generation of FEPs was conceived in the late 1990s as voluntary guidance documents that Regional Fishery Management Councils could adopt to develop and guide their ecosystem‐based fisheries management decisions, but few of these FEPs took concrete steps to implement EBFM. Here, we emphasize the need for a new generation of FEPs that provide practical mechanisms for putting EBFM into practice in the United States. We argue that next‐generation FEPs can balance environmental, economic, and social objectives—the triple bottom line—to improve long‐term planning for fishery systems.
Antibiotic stewardship: The need to reduce antibiotics in acne treatment
Authors: Gollnick Harald P. M. , Buer Jan , Beissert Stefan , Sunderkätter Cord 
Published: April 2017

SummaryExcessive or uncritical worldwide use of antibiotics in medicine has accelerated the selection and spread of resistant bacteria. In some areas many antibiotics have become ineffective for infections which had previously been well susceptible to antibacterial agents. Dermato‐venereologists have used oral and topical antibiotics routinely to treat acne vulgaris, although acne is neither an infectious disease nor triggered exclusively by Propionibacterium. It is rather a complex chronic inflammatory skin disorder based on multiple pathogenic factors including follicular hyperkeratinization, increased sebum production, bacterial proliferation and inflammation. Consequently, effective treatment should target multiple pathogenic factors instead of primarily Propionibacterium acnes. Therefore, topical retinoids and benzoyl peroxide have been defined as the standard first‐line drugs. Monotherapy with local antibiotics should be avoided altogether. Systemic antibiotics of the tetracycline group still have their indication in certain stages of acne, but their efficacy may be based rather on anti‐inflammatory than antibiotic actions. Health authorities are urging all healthcare providers to limit antibiotic use. The risk‐benefit ratio must be carefully observed between the need for antibiotic treatment in the individual patient and the public interest in preserving the effectiveness of antibiotics. Here we summarize the current concept of acne vulgaris and its consequences for the use of antibiotics.
The golf ball method for rapid assessment of grassland structure
Authors: Schultz Nick , Keatley Marie , Antos Mark , Wong Nathan , Moxham Claire , Farmilo Brad , Morgan John W. 
Published: April 2017

SummaryA key task for native grassland managers is to assess when biomass reduction is necessary to maintain plant and animal diversity. This requires managers to monitor grassland structure. Parks Victoria and La Trobe University developed a method for rapid assessment of grassland structure using golf balls. Baker‐Gabb et al. (Ecological Management & Restoration, 17, 2016, p235) provide an example of where the method has been used to manage grassland structure to favour an endangered bird, the Plains‐wanderer (Pedionomus torquatus). In this study, we provide further critical analysis of the method using three data sets collected across different parts of Victoria that relate golf ball scores to various habitat attributes. We demonstrate how the golf ball score provides a good surrogate for key aspects of grassland structure. We show that the method does not provide a reliable surrogate for above‐ground biomass or vegetation cover, although we discuss how biomass and cover are not particularly good indicators of grassland structure. We argue that elements of grassland structure may be better correlated with desired conservation outcomes (e.g. plant species diversity or the presence of a particular species) than biomass or cover alone. We discuss examples of how the golf ball method has been used, and how it can be improved. The method will be particularly useful where a link can be demonstrated between golf ball scores and desired conservation outcomes, such as in the case of the Plains‐wanderer.
Symbiodinium mitigate the combined effects of hypoxia and acidification on a noncalcifying cnidarian
Authors: Klein Shannon G. , Pitt Kylie A. , Nitschke Matthew R. , Goyen Samantha , Welsh David T. , Suggett David J. , Carroll Anthony R. 
Published: April 2017

AbstractAnthropogenic nutrient inputs enhance microbial respiration within many coastal ecosystems, driving concurrent hypoxia and acidification. During photosynthesis, Symbiodinium spp., the microalgal endosymbionts of cnidarians and other marine phyla, produce O2 and assimilate CO2 and thus potentially mitigate the exposure of the host to these stresses. However, such a role for Symbiodinium remains untested for noncalcifying cnidarians. We therefore contrasted the fitness of symbiotic and aposymbiotic polyps of a model host jellyfish (Cassiopea sp.) under reduced O2 (~2.09 mg/L) and pH (~ 7.63) scenarios in a full‐factorial experiment. Host fitness was characterized as asexual reproduction and their ability to regulate internal pH and Symbiodinium performance characterized by maximum photochemical efficiency, chla content and cell density. Acidification alone resulted in 58% more asexual reproduction of symbiotic polyps than aposymbiotic polyps (and enhanced Symbiodinium cell density) suggesting Cassiopea sp. fitness was enhanced by CO2‐stimulated Symbiodinium photosynthetic activity. Indeed, greater CO2 drawdown (elevated pH) was observed within host tissues of symbiotic polyps under acidification regardless of O2 conditions. Hypoxia alone produced 22% fewer polyps than ambient conditions regardless of acidification and symbiont status, suggesting Symbiodinium photosynthetic activity did not mitigate its effects. Combined hypoxia and acidification, however, produced similar numbers of symbiotic polyps compared with aposymbiotic kept under ambient conditions, demonstrating that the presence of Symbiodinium was key for mitigating the combined effects of hypoxia and acidification on asexual reproduction. We hypothesize that this mitigation occurred because of reduced photorespiration under elevated CO2 conditions where increased net O2 production ameliorates oxygen debt. We show that Symbiodinium play an important role in facilitating enhanced fitness of Cassiopea sp. polyps, and perhaps also other noncalcifying cnidarian hosts, to the ubiquitous effects of ocean acidification. Importantly we highlight that symbiotic, noncalcifying cnidarians may be particularly advantaged in productive coastal waters that are subject to simultaneous hypoxia and acidification.
Biocompatibility and mineralized nodule formation of Neo MTA Plus and an experimental tricalcium silicate cement containing tantalum oxide
Authors: Tanomaru‐Filho M. , Andrade A. S. , Rodrigues E. M. , Viola K. S. , Faria G. , Camilleri J. , Guerreiro‐Tanomaru J. M. 
Published: April 2017

AbstractAimTo evaluate the biocompatibility and mineralized nodule formation of an experimental tricalcium silicate cement with tantalum oxide (TSC/Ta2O5) as radiopacifier, NeoMTAPlus (Avalon Biomed Inc., Bradenton,FL,USA) andMTA(Angelus, Londrina,PR, Brazil) on human osteoblast‐like cells (Saos‐2).MethodologyBiocompatibility was evaluated by 3‐(4,5‐dimethyl‐thiazoyl)‐2,5‐diphenyl‐tetrazolium bromide (MTT) and neutral red (NR) assays, after exposure of Saos‐2 to cement extracts at 1 : 1, 1 : 2, 1 : 4 and 1 : 8 dilutions for 24 h. Bioactivity was evaluated by alkaline phosphatase (ALP) activity, and calcium deposits were detected with alizarin red staining (ARS). Statistical analysis was performed with analysis of variance and Bonferroni or Tukey post‐test (α = 0.05).ResultsTheMTTassay revealed lower cytotoxicity forNEOandMTA(P < 0.05), and higher forTSC/Ta2O5at 1 : 1 and 1 : 2 dilutions when compared to serum‐free medium – control (P > 0.05). At 1 : 4 dilution, theTSC/Ta2O5cytotoxicity was similar to the control (P > 0.05). At 1 : 8 dilution, cell viability was significantly greater than the control (P < 0.05). Saos‐2 cell viability performed using theNRassay at all dilutions revealed no cytotoxic effect ofMTA,NEOandTSC/Ta2O5.ALPactivity at 1 and 3 days was similar to the control (P > 0.05).TSC/Ta2O5had significantly greaterALPactivity at 7 days when compared with the control (P < 0.05). All materials induced the production of mineralized nodules, andNEOproduced significantly more mineralized nodules thanMTAandTSC/Ta2O5(P < 0.05).ConclusionsNeoMTAPlus andTSC/Ta2O5were biocompatible and inducedALPactivity in Saos‐2 cells. Both materials induced mineralized nodule formation by Saos‐2 with NeoMTAPlus producing significantly more.
Preparation and properties of an oxide fiber‐reinforced silica matrix composite
Authors: Gao Yingqian , Zhang Lifu , Chen Jian , Wang Xiangwei , Cheng Haifeng 
Published: April 2017

AbstractOxide (Nextel™ 440) fiber‐reinforced silica composites, with the density and porosity of 1.97 g/cm3 and 21.8%, were prepared through sol‐gel. Their average flexure strength, elastic modulus, shear strength, and fracture toughness at room temperature were 119.7 MPa, 25.6 GPa, 10.8 MPa, and 4.0 MPa·m1/2, respectively. The composites showed typical toughened fracture behavior, and distinct pullout fibers were observed at the fracture surface. Their mechanical properties were performant up to 1000°C, with the maximum flexural strength of 132.2 MPa at 900°C. Moreover, the composites showed good thermal stability, even after thermal aging and thermal shock at elevated temperatures.
Understanding the role of the gut ecosystem in diabetes mellitus
Authors: Aw Wanping , Fukuda Shinji 
Published: April 2017

AbstractDiabetes mellitus is a type of metabolic disorder whereby patients are unable to regulate glycemia. It is currently a worldwide public health issue, and is a burden to society because of its disabling and common complications. Diabetes is multifactorial, and also induces the onset of other diseases. In the present report, we review the labyrinth encompassing the gut microbiota and gut microbiota‐derived metabolites in type 1 diabetes and type 2 diabetes pathogenesis. There have been exceptional improvements in deoxyribonucleic acid sequencing and mass spectrometry technologies throughout these past years, and these have allowed the comprehensive collection of information on our unique gut ecosystem. We would like to advocate incorporating metagenome and metabolome information for a comprehensive perspective of the complex interrelationships between the gut environment, host metabolism and diabetes pathogenesis. We hope that with this improved understanding we would be able to provide exciting novel therapeutic approaches to engineer an ideal gut ecosystem for optimal health.
Subcutaneous injection of hydrogen gas is a novel effective treatment for type 2 diabetes
Authors: Zhang Xiaolong , Liu Jiaming , Jin Keke , Xu Haifeng , Wang Chuang , Zhang Zhuang , Kong Mimi , Zhang Zhengzheng , Wang Qingyi , Wang Fangyan 
Published: April 2017

AbstractAims/IntroductionIn previous studies, hydrogen gas (H2) administration has clearly shown effectiveness in inhibiting diabetes. Here, we evaluated whether subcutaneous injection of H2 shows enhanced efficacy against type 2 diabetes mellitus induced in mice by a high‐fat diet and low‐dose streptozotocin treatment.Material and MethodsH2 was injected subcutaneously at a dose of 1 mL/mouse/week for 4 weeks. Type 2 diabetes mellitus‐associated parameters were then evaluated to determine the effectiveness of subcutaneous H2 administration.ResultsThe bodyweight of H2‐treated mice did not change over the course of the experiment. Compared with the untreated control animals, glucose, insulin, low‐density lipoprotein and triglyceride levels in the serum were significantly lower in treated mice, whereas high‐density lipoprotein cholesterol in the serum was significantly higher. Glucose tolerance and insulin sensitivity were both improved in H2‐treated mice. Diabetic nephropathy analysis showed significant reductions in urine volume, urinary total protein and β2‐microglobulin, kidney/bodyweight ratio, and kidney fibrosis associated with subcutaneous injection of H2.ConclusionsSubcutaneous injection of H2 significantly improves type 2 diabetes mellitus and diabetic nephropathy‐related outcomes in a mouse model, supporting further consideration of subcutaneous injection as a novel and effective route of clinical H2 administration.