bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using quality improvement strategies to strengthen regional systems for Aboriginal and Torres Strait Islander eye health in the Northern Territory
Authors: Yashadhana Aryati , Morse Anna , Tatipata Shaun , Lim Nicole , Rogers Alison , Lee Ling , Burnett Anthea M. 
Published: January 2020

AbstractProblemIn the Katherine region, Northern Territory, barriers to eye care for Aboriginal and Torres Strait Islander people include unclear eye care referral processes, challenges coordinating patient eye care between various providers, complex socioeconomic determinants and a lengthy outpatient ophthalmology waiting list.DesignMixed methods participatory approach using a regional needs analysis, clinical file audit and stakeholder survey, to develop, implement and monitor quality improvement strategies.SettingCollaboration with Aboriginal Community Controlled Health Services and regional eye care stakeholders in the Katherine region.Key measures for improvementClinical audit data captured frequency and rates of primary eye checks, ophthalmology referrals and spectacle prescriptions. A survey was developed and applied to assess stakeholder perspectives of regional eye care systems.Strategy for changeQuality improvement strategies informed by regional data (clinical audits and survey) included increasing service delivery to match eye care needs, primary eye care training for Aboriginal Community Controlled Health Services staff, updating Aboriginal Community Controlled Health Services primary care templates and forming a regional eye care coalition group.Effects of changePost‐implementation, rates and frequency of recorded optometry examinations, number of spectacles prescribed and rates of annual dilated fundus examinations for patients with diabetes increased. There was a decrease in the number of patients with diabetes who had never had an eye examination. Eye care stakeholders perceived a marked improvement in the effectiveness of the regional eye care system.Lessons learntOur findings highlight the importance of engaging services and stakeholders to ensure a systems approach that is evidence‐informed, contextually appropriate and reflects commitment to improved eye health outcomes.
Establishment of a scalable microfluidic assay for characterization of population‐based neutrophil chemotaxis
Authors: Grigolato Fulvio , Egholm Cecilie , Impellizzieri Daniela , Arosio Paolo , Boyman Onur 
Published: January 2020

AbstractBackgroundRegulation of neutrophil chemotaxis and activation plays crucial roles in immunity, and dysregulated neutrophil responses can lead to pathology as seen in neutrophilic asthma. Neutrophil recruitment is key for initiating immune defense and inflammation, and its modulation is a promising therapeutic target. Microfluidic technology is an attractive tool for characterization of neutrophil migration. Compared to transwell assays, microfluidic approaches could offer several advantages, including precis e control of defined chemokine gradients in space and time, automated quantitative analysis of chemotaxis, and high throughput.MethodsWe established a microfluidic device for fully automated, quantitative assessment of neutrophil chemotaxis. Freshly isolated mouse neutrophils from bone marrow or human neutrophils from peripheral blood were assessed in real time using an epifluorescence microscope for their migration toward the potent chemoattractants C‐X‐C‐motif ligand 2 (CXCL2) and CXCL8, without or with interleukin‐4 (IL‐4) pre‐incubation.ResultsOur microfluidic device allowed the precise and reproducible determination of the optimal CXCL2 and CXCL8 concentrations for mouse and human neutrophil chemotaxis, respectively. Furthermore, our microfluidic assay was able to measure the equilibrium and real‐time dynamic effects of specific modulators of neutrophil chemotaxis. We demonstrated this concept by showing that IL‐4 receptor signaling in mouse and human neutrophils inhibited their migration toward CXCL2 and CXCL8, respectively, and this inhibition was time‐dependent.ConclusionCollectively, our microfluidic device shows several advantages over traditional transwell migration assays and its design is amenable to future integration into multiplexed high‐throughput platforms for screening of molecules that modulate the chemotaxis of different immune cells.
An association of neovascular age‐related macular degeneration with polymorphisms of CFH, ARMS2, HTRA1 and C3 genes in Czech population
Authors: Matušková Veronika , Zeman Tomáš , Ewerlingová Laura , Hlinomazová Zuzana , Souček Jan , Vlková Eva , Goswami Nandu , Balcar Vladimir J. , Šerý Omar 
Published: January 2020

AbstractPurposeWe investigated associations between neovascular age‐related macular degeneration (AMD) and rs10490924 polymorphism of ARMS2 gene (age‐related maculopathy susceptibility 2), rs1061170 polymorphism of gene for complement factor H (CFH), rs2230199 polymorphism of gene for complement component C3 and rs11200638 polymorphism of gene for serine protease high‐temperature requirement A1 (HTRA1) in the Czech population.MethodsWe analysed samples of DNA from 307 patients diagnosed with neovascular form of late AMD (average age: 73.7 ± 7.7 years) and 191 control subjects, recruited from patients awaiting cataract surgery (average age, 73.6 ± 8.7 years).ResultsHTRA1, CFH and ARMS2 genes polymorphisms were found to be related to neovascular AMD in the Czech population. All analysed polymorphisms were statistically significantly associated with neovascular AMD, with stronger associations in females than in males. In whole group, CC genotype of CFH gene polymorphism, TT genotype of ARMS2 gene polymorphism and AA genotype of HTRA1 gene polymorphism showed the greatest risk for neovascular AMD with odds ratios equal to 8.43, 10.07, 9.83, respectively (p < 0.0001). Only CG polymorphism of C3 gene showed statistically significant risk for neovascular AMD. In addition, we observed an association between waist circumference and neovascular AMD in both sexes, which further suggests the significance of excessive abdominal fat as a risk factor of AMD. We found a statistically significant association between polymorphisms in HTRA1, CFH and ARMS2 genes and neovascular AMS in the Czech population. The association was stronger in females than in males.ConclusionWe demonstrated a relationship between neovascular AMD and genes for HTRA1, CFH, ARMS2 and C3 in Czech population. To our knowledge, the relationship between these polymorphisms and neovascular AMD in Czech population has never been investigated before.
Perfecting a high hypoxanthine phosphoribosyltransferase activity–uricase KO mice to test the effects of purine‐ and non‐purine‐type xanthine dehydrogenase (XDH) inhibitors
Authors: Hosoya Takuji , Uchida Shunya , Shibata Shigeru , Tomioka Naoko H. , Hosoyamada Makoto 
Published: January 2020

Background and PurposePurine metabolism in mice and human differ in terms of uricase (Uox) activity as well as hypoxanthine phosphoribosyltransferase (HPRT) activity. The aim of this study was the establishment of high HPRT activity–Uox knockout (KO) mice as a novel hyperuricaemic model. Then to investigate the effects of purine‐type xanthine dehydrogenase (XDH) inhibitor, allopurinol, and non‐purine‐type XDH inhibitor, topiroxostat, on purine metabolism.Experimental ApproachA novel hyperuricaemic mouse model was established by mating B6‐ChrXCMSM mice with uricase KO mice. The pharmacological effects of allopurinol and topiroxostat were explored by evaluating urate, hypoxanthine, xanthine and creatinine in the plasma and urine of these model mice. Furthermore, we analysed the effect of both drugs on erythrocyte hypoxanthine phosphoribosyltransferase activity.Key ResultsPlasma urate level and urinary urate/creatinine ratio significantly decreased after administration of allopurinol 30 mg·kg−1 or topiroxostat 1 mg·kg−1 for 7 days. The urate‐lowering effect was equivalent for allopurinol and topiroxostat. However, the urinary hypoxanthine/creatinine ratio and xanthine/creatinine ratio after treatment with topiroxostat were significantly lower than for allopurinol. In addition, the urinary oxypurine/creatinine ratio was significantly lowered after treatment with topiroxostat, but allopurinol elicited no such effect. Furthermore, allopurinol inhibited mouse erythrocyte hypoxanthine phosphoribosyltransferase, while topiroxostat did not.Conclusions and ImplicationsHigh hypoxanthine phosphoribosyltransferase activity– uricase KO mice were established as a novel hyperuricaemic animal model. In addition, topiroxostat, a non‐purine‐type xanthine dehydrogenase inhibitor, elicited a potent plasma urate‐lowering effect. However, unlike allopurinol, topiroxostat did not perturb the salvage pathway, resulting in lowered total oxypurine excretion.
HWL‐088, a new potent free fatty acid receptor 1 (FFAR1) agonist, improves glucolipid metabolism and acts additively with metformin in ob/ob diabetic mice
Authors: Chen Yueming , Ren Qiang , Zhou Zongtao , Deng Liming , Hu Lijun , Zhang Luyong , Li Zheng 
Published: January 2020

Background and PurposeThe free fatty acid receptor 1 (FFAR1) plays an important role in glucose‐stimulated insulin secretion making it an attractive anti‐diabetic target. This study characterizes the pharmacological profile of HWL‐088 (2‐(2‐fluoro‐4‐((2′‐methyl‐[1,1′‐ biphenyl]‐3‐yl)methoxy)phenoxy)acetic acid), a novel highly potent FFAR1 agonist in vitro and in vivo. Moreover, we investigated the long‐term effects of HWL‐088 alone and in combination with metformin in diabetic mice.Experimental ApproachIn vitro effects of HWL‐088 on FFAR1 and PPARα/γ/δ were studied in cell‐based assays. Glucose‐dependent insulinotropic effects were evaluated in MIN6 cell line and in rats. Long‐term effects on glucose and lipid metabolism were investigated in ob/ob mice.Key ResultsHWL‐088 is a highly potent FFAR1 agonist (EC50 = 18.9 nM) with moderate PPARδ activity (EC50 = 570.9 nM) and promotes glucose‐dependent insulin secretion in vitro and in vivo. Long‐term administration of HWL‐088 exhibited better glucose control and plasma lipid profiles than those of another FFAR1 agonist, TAK‐875, and synergistic improvements were observed when combined with metformin. Moreover, HWL‐088 and combination therapy improved β‐cell function by up‐regulation of pancreas duodenum homeobox‐1, reduced fat accumulation in adipose tissue and alleviated fatty liver in ob/ob mice. The effect of HWL‐088 involves a reduction in hepatic lipogenesis and oxidative stress, increased lipoprotein lipolysis, glucose uptake, mitochondrial function and fatty acid β‐oxidation.Conclusion and ImplicationsThese data indicate that long‐term treatment with HWL‐088, a highly potent FFAR1 agonist, improves glucose and lipid metabolism and may be useful for the treatment of diabetes mellitus by mono‐therapy or combination with metformin.
Novel insights into dendritic cells in the pathogenesis of systemic sclerosis
Authors: Carvalheiro T , Zimmermann M , Radstake T R D J , Marut W 
Published: January 2020

SummarySystemic sclerosis (SSc) is a severe autoimmune fibrotic disease characterized by fibrosis, vasculopathy, and immune dysregulation. Dendritic cells (DCs) are the most potent antigen-presenting cells, specialized in pathogen sensing, with high capacity to shape the immune responses. The most recent technological advances have allowed the discovery of new DC subsets with potential implications in inflammatory conditions. Alterations of DC distribution in circulation and affected tissue as well as impaired DC function have been described in SSc patients, pointing towards a crucial role of these cells in SSc pathogenesis. In particular, recent studies have shown the importance of plasmacytoid DCs either by their high capacity to produce type I interferon or other inflammatory mediators implicated in SSc pathology, such as chemokine C-X-C motif ligand 4 (CXCL4). In-vivo models of SSc have been vital to clarify the implications of DCs in this disease, especially DCs depletion and specific gene knock-down studies. This review provides these new insights into the contribution of the different DCs subsets in the pathogenesis of SSc, as well as to the novel developments on DCs in in-vivo models of SSc and the potential use of DCs and their mediators as therapeutic targets.
Hearing outcome after myringoplasty in Sweden: A nationwide registry‐based cohort study
Authors: Berglund Malin , Olaison Sara , Bonnard Åsa , Fransson Mattias , Hultcrantz Malou , Florentzson Rut , Dahlin Christer , Eriksson Per Olof , Westman Eva 
Published: January 2020

AbstractObjectivesTo present hearing results after successful primary myringoplasty surgeries registered in the Swedish Quality Registry for Myringoplasty and to evaluate the chance of hearing improvement and the risk of hearing loss.DesignA retrospective nationwide cohort study based on prospectively collected registry data between 2002 and 2012.SettingsRegistry data from secondary and tertiary hospitals performing myringoplasty.ParticipantsPatients with healed tympanic membrane after primary myringoplasty surgery performed from 2002 to 2012 in Sweden.Main outcome measuresPostoperative hearing results, hearing gain and air‐bone gap (ABG).ResultsIn 2226 myringoplasties, air conduction audiograms were recorded, and the average preoperative pure tone average (PTA4) of the group was 28.5 dB, which improved postoperatively to 19.6 dB with an average of 8.8 dB improvement. Bone conduction was measured for 1476 procedures. Closure of the ABG to 10 dB or less was achieved in 51% of the ears and to less than 20 dB in 89% of the ears. Sixty‐one percent of patients with preoperatively deteriorated hearing experienced improved hearing, but 3% of all patients experienced deteriorated hearing. After the surgery, 93% of the patients were satisfied.ConclusionsHearing results after successful myringoplasty surgery are often favourable, but although the tympanic membrane is healed, hearing improvement is not guaranteed, and hearing deterioration can also occur.
Relationship between hypoglycaemia, body mass index and quality of life among patients with type 1 diabetes: Observations from the DEPICT clinical trial programme
Authors: Gordon Jason , Beresford‐Hulme Lee , Bennett Hayley , Tank Amarjeet , Edmonds Christopher , McEwan Phil 
Published: January 2020

AbstractAimsTo demonstrate the relationships between hypoglycaemia, body mass index (BMI) and quality of life, and to examine the impact of dapagliflozin on patient‐reported treatment satisfaction in patients with type 1 diabetes mellitus (T1DM), using data from the DEPICT (Dapagliflozin Evaluation in Patients With Inadequately Controlled Type 1 Diabetes) clinical trial programme.MethodsA two‐stage modelling approach, using a linear regression framework, was adopted to evaluate the relationship between hypoglycaemia, BMI and quality of life. Hypoglycaemia fear score (HFS) was modelled as a function of hypoglycaemic events (non‐severe documented symptomatic and severe) and, subsequently, quality of life (as measured by the EQ‐5D questionnaire) was modelled as a function of HFS and BMI. A linked evidence approach correlated the relationship between treatment, hypoglycaemic events and glycated haemoglobin (HbA1c), to the relationships captured within the regression models. The proportion of patients achieving increased patient‐reported treatment satisfaction, as measured by the Diabetes Treatment Satisfaction Questionnaire (DTSQ) total score, was compared between study arms.ResultsIncident severe hypoglycaemia was associated with significantly higher HFS (coefficient estimate [CE] 14.62, P=0.004). The frequency of symptomatic hypoglycaemic events was associated with a significantly higher HFS (log transposed, CE 1.32, P=0.026). Higher HFS and higher BMI were both independently associated with a significantly lower EQ‐5D score (HFS: CE –0.0024, P<0.001; BMI: CE ‐0.0026, P=0.016). Significantly higher proportions of dapagliflozin‐treated patients achieved ≥3‐point increases in DTSQ total score compared to patients in the placebo group.ConclusionThe results of this study demonstrated that increases in hypoglycaemia and BMI were associated with reduced quality of life in people with T1DM. Dapagliflozin‐treated patients achieved a reduction in HbA1c whilst avoiding an increase in hypoglycaemic events. The results also showed that treatment with dapagliflozin was associated with an improvement in treatment satisfaction.
Assessing seasonal demographic covariation to understand environmental‐change impacts on a hibernating mammal
Authors: Paniw Maria , Childs Dylan Z. , Armitage Kenneth B. , Blumstein Daniel T. , Martin Julien G. A. , Oli Madan K. , Ozgul Arpat 
Published: January 2020

AbstractNatural populations are exposed to seasonal variation in environmental factors that simultaneously affect several demographic rates (survival, development and reproduction). The resulting covariation in these rates determines population dynamics, but accounting for its numerous biotic and abiotic drivers is a significant challenge. Here, we use a factor‐analytic approach to capture partially unobserved drivers of seasonal population dynamics. We use 40 years of individual‐based demography from yellow‐bellied marmots (Marmota flaviventer) to fit and project population models that account for seasonal demographic covariation using a latent variable. We show that this latent variable, by producing positive covariation among winter demographic rates, depicts a measure of environmental quality. Simultaneously, negative responses of winter survival and reproductive‐status change to declining environmental quality result in a higher risk of population quasi‐extinction, regardless of summer demography where recruitment takes place. We demonstrate how complex environmental processes can be summarized to understand population persistence in seasonal environments.
Neural hierarchical models of ecological populations
Authors: Joseph Maxwell B. 
Published: January 2020

AbstractNeural networks are increasingly being used in science to infer hidden dynamics of natural systems from noisy observations, a task typically handled by hierarchical models in ecology. This article describes a class of hierarchical models parameterised by neural networks – neural hierarchical models. The derivation of such models analogises the relationship between regression and neural networks. A case study is developed for a neural dynamic occupancy model of North American bird populations, trained on millions of detection/non‐detection time series for hundreds of species, providing insights into colonisation and extinction at a continental scale. Flexible models are increasingly needed that scale to large data and represent ecological processes. Neural hierarchical models satisfy this need, providing a bridge between deep learning and ecological modelling that combines the function representation power of neural networks with the inferential capacity of hierarchical models.
Abundant osteoclasts in the subchondral bone of the juvenile Thoroughbred metacarpus suggest an important role in joint maturation
Authors: Gilday Rebecca , Richard Hélène , Beauchamp Guy , Fogarty Ursula , Laverty Sheila 
Published: January 2020

AbstractBackgroundThe administration of bisphosphonate medications, which target osteoclastic‐bone remodelling, to juvenile and adult racehorses is a matter of debate owing to concerns that these molecules remain bound to the bone‐mineralised matrix and may interfere with subsequent bone growth, adaptation to exercise and healing of bone microdamage in equine athletes. Osteoclasts participate in endochondral ossification, subchondral bone remodelling and bone repair. There is a knowledge gap on the role of equine osteoclast biology in the growth and maturation of joint surfaces and this information is important to inform judicious bisphosphonate use.ObjectivesMeasure and compare the osteoclast density in the subchondral bone of Thoroughbred (TB) distal third metacarpi (McIII) at different sites, varying depths from the articular surface and with age (0‐84 months).Study designEx vivo cadaveric study.MethodsMcIIIs from foals, yearlings and adults were collected, fixed in formaldehyde and stored at 4°C. Sections were cut from the lateral hemi‐metacarpus, stained and scored for cartilage degeneration. Osteoclasts were counted on immunohistochemically (Cathepsin K) stained sections. Osteoclast density was compared in regions of interest (ROIs—the sagittal ridge, axial and abaxial condyle) and also at two depths (0‐3 mm and 3‐6 mm) into the subchondral bone below the osteochondral junction.ResultsThe osteoclast density was consistently highest in the subchondral cortical bone plate (0‐3 mm) when compared with the deeper trabecular bone in all age groups. Furthermore, the osteoclast density was significantly higher in juvenile Thoroughbreds (foals and yearlings) within both sites in the subchondral bone when compared with adults.Main limitationsThe number of specimens available for study was restricted.ConclusionsOsteoclasts are important in normal McIII epiphyseal and articular surface maturation and have a propensity to localise at the osteochondral junction and subchondral cortical bone plate zone in juvenile Thoroughbreds.
Effects of nitrogen application rate on productivity, nutritive value and winter tolerance of timothy and meadow fescue cultivars
Authors: Termonen Maarit , Korhonen Panu , Kykkänen Sanna , Kärkönen Anna , Toivakka Minna , Kauppila Raimo , Virkajärvi Perttu 
Published: January 2020

AbstractFinnish N fertilizer application regulations for forage grasses are based on field experiments mainly conducted in the 1960–1970s with cultivars and management practices typical of the time. In order to update the yield response function of N, to make it better suited to current grassland farming, field experiments were conducted at two sites in 2015–2017 with two cultivars of timothy (Phleum pratense L.) and one of meadow fescue (Festuca pratensis Huds.). Dry matter (DM) yield, nutritive value and N balance were evaluated, with N application levels 0, 150, 200, 250, 300, 350, 400 and 450 kg N ha−1 year−1. The grasses were harvested three times per season. The data indicate that the DM yield response was significantly stronger, and N was used more efficiently for DM production than earlier without compromising the nutritive value, especially during the first two years. The third harvest produced on average 23% of the annual yield, utilizing N efficiently. N application rates below 350 kg N ha−1 year−1 did not cause substantial overwintering losses or lodging. The data indicate that with changing climate and improved cultivars and management practices, there is a need to modify the rates and timing of N application. The results suggest that N application levels could be increased by at least 50 kg N ha−1 year−1 from the current maximum accepted rate (250 kg N ha−1 year−1) without too high NO3‐ or CP concentrations in feed, or too high N balance that indicates increasing risk of N leaching.