bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of molecule GRP94 favors tumor progression in lung adenocarcinoma by interaction with regulatory T cells
Authors: Duan Xiao‐Feng , Xin Ya‐Wei
Published: January 2020

Background

Endoplasmic reticulum stress exists within a tumor. Glucose‐regulated protein 94 (GRP94) is a stress‐induced chaperone protein involved in tumor development and progression. Its role in myeloma, colon cancer, and other tumors has been confirmed, but its role in lung cancer is unclear. This study aimed to determine the role of GRP94 in lung cancer progression and prognostic prediction.

Methods

Immunohistochemical staining of GRP94 in human lung adenocarcinoma (AD) and corresponding normal tissue was performed, and its relationship with FOXP3+ regulatory T‐cell (Treg) infiltration analyzed. We investigated the role of GRP94 in the behavior of lung AD cells by inhibiting GRP94 expression in A549 cells. Western blotting was used to detect the TGF‐β/SMAD2 signaling molecules and explore the possible molecular mechanism of GRP94.

Results

GRP94 mRNA (encoded by HSP90B1) and protein levels were upregulated and elevated, respectively, in lung AD compared to normal lung tissues. High GRP94 expression was associated with an advanced disease stage and poor survival. There was a positive correlation between GRP94 expression and FOXP3+ Treg infiltration into lung AD tissues. Our results confirm that GRP94 knockdown inhibits cell proliferation and promotes cell apoptosis by increasing caspase‐7 and CHOP levels in lung AD cells. TGF‐β and SMAD2 protein levels were decreased after GRP94 depletion.

Conclusions

Our study revealed that that GRP94 expression in lung AD favors tumor progression and predicts poor prognosis. The oncogenic role of GRP94 may involve inducing Treg infiltration by promoting the TGF‐β signaling pathway.

Key points

GRP94 protein levels were elevated in lung AD tissues compared to normal lung tissues. The high expression of GRP94 in lung AD favors tumor progression and predicts poor prognosis.

The oncogenic role of the molecule GRP94 may involve the stimulation of Treg infiltration via promotion of the TGF‐β signaling pathway.
Constructing and analysing time‐aggregated networks: The role of bootstrapping, permutation and simulation
Authors: Bonnell Tyler R. , Vilette Chloé
Published: January 2020

Animal social networks are often used to describe dynamic social systems, where individual behaviour generates network‐level structures that subsequently influence individual‐level behaviour. This interdependence between individual behaviour and group structuring is of central concern for questions concerning the evolution and development of social systems and collective animal behaviour more generally.

Various statistical methods exist for estimating network changes through time. One approach, time‐aggregated networks, takes repeated snapshots of interactions within windows of time to generate a time series of networks. However, there remain many analytical hurdles when implementing the time‐aggregated approach. To ameliorate this, we introduce an r package netTS that focuses on three analytical steps for analysing time‐aggregated networks: choosing appropriate time scale using bootstrapping, comparing patterns to relevant null models using permutation and finally building and interpreting statistical models using simulated data. We use simulated data to first highlight these steps, then use observed grooming data from a group of vervet monkeys as an applied example.

Our results suggest that the use of bootstrapping and permutation can accurately extract known patterns from simulated data. Using this approach with vervet data suggests that there is consistent social structuring, differing from what would be expected due to chance, and that some individuals are contributing to this structure more than others (i.e. keystone individuals).

We demonstrate that bootstrapping, permutation and simulation can aid in constructing and interpreting time‐aggregated networks. We suggest that the use of time‐aggregated networks to quantify patterns of network change can be a useful tool alongside process‐based approaches that seek mechanistic descriptions. Ultimately, by looking at both patterns and processes, dynamic networks can be used to better understand how individual behaviour generates social structures, and in turn how individual behaviour can be influenced by social structures, ultimately leading to a better understanding of the evolution of social behaviour.
Genetic structure and admixture in sheep from terminal breeds in the United States
Authors: Davenport K. M. , Hiemke C. , McKay S. D. , Thorne J. W. , Lewis R. M. , Taylor T. , Murdoch B. M.
Published: January 2020

Selection for performance in diverse production settings has resulted in variation across sheep breeds worldwide. Although sheep are an important species to the United States, the current genetic relationship among many terminal sire breeds is not well characterized. Suffolk, Hampshire, Shropshire and Oxford (terminal) and Rambouillet (dual purpose) sheep (n = 248) sampled from different flocks were genotyped using the Applied Biosystems Axiom Ovine Genotyping Array (50K), and additional Shropshire sheep (n = 26) using the Illumina Ovine SNP50 BeadChip. Relationships were investigated by calculating observed heterozygosity, inbreeding coefficients, eigenvalues, pairwise Wright’s FST estimates and an identity by state matrix. The mean observed heterozygosity for each breed ranged from 0.30 to 0.35 and was consistent with data reported in other US and Australian sheep. Suffolk from two different regions of the United States (Midwest and West) clustered separately in eigenvalue plots and the rectangular cladogram. Further, divergence was detected between Suffolk from different regions with Wright’s FST estimate. Shropshire animals showed the greatest divergence from other terminal breeds in this study. Admixture between breeds was examined using admixture, and based on cross‐validation estimates, the best fit number of populations (clusters) was K = 6. The greatest admixture was observed within Hampshire, Suffolk, and Shropshire breeds. When plotting eigenvalues, US terminal breeds clustered separately in comparison with sheep from other locations of the world. Understanding the genetic relationships between terminal sire breeds in sheep will inform us about the potential applicability of markers derived in one breed to other breeds based on relatedness.
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

Problem

In 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.

Design

Mixed methods participatory approach using a regional needs analysis, clinical file audit and stakeholder survey, to develop, implement and monitor quality improvement strategies.

Setting

Collaboration with Aboriginal Community Controlled Health Services and regional eye care stakeholders in the Katherine region.

Key measures for improvement

Clinical 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 change

Quality 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 change

Post‐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 learnt

Our 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

Background

Regulation 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.

Methods

We 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.

Results

Our 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.

Conclusion

Collectively, 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

Purpose

We 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.

Methods

We 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).

Results

HTRA1, 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.

Conclusion

We 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 Purpose

Purine 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 Approach

A 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 Results

Plasma 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 Implications

High 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 Purpose

The 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 Approach

In 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 Results

HWL‐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 Implications

These 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

Systemic 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

Objectives

To 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.

Design

A retrospective nationwide cohort study based on prospectively collected registry data between 2002 and 2012.

Settings

Registry data from secondary and tertiary hospitals performing myringoplasty.

Participants

Patients with healed tympanic membrane after primary myringoplasty surgery performed from 2002 to 2012 in Sweden.

Main outcome measures

Postoperative hearing results, hearing gain and air‐bone gap (ABG).

Results

In 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.

Conclusions

Hearing 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.
Endoscopic submucosal dissection using a traction method for gastric tube cancer
Authors: Oguri Noriaki , Ikeya Takashi , Shiratori Yasutoshi
Published: January 2020

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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

Aims

To 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.

Methods

A 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.

Results

Incident 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.

Conclusion

The 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

Natural 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

Neural 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

Background

The 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.

Objectives

Measure 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 design

Ex vivo cadaveric study.

Methods

McIIIs 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.

Results

The 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 limitations

The number of specimens available for study was restricted.

Conclusions

Osteoclasts 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.
Hypoxia‐inducible factors in metabolic reprogramming during sepsis
Authors: Vanderhaeghen Tineke , Vandewalle Jolien , Libert Claude
Published: January 2020

Sepsis is a highly heterogeneous syndrome that is caused by an imbalanced host response to infection. Despite huge investments, sepsis remains a contemporary threat with significant burden on health systems. Vascular dysfunction and elevated oxygen consumption by highly metabolically active immune cells result in tissue hypoxia during inflammation. The transcription factor hypoxia‐inducible factor‐1a (HIF1α), and its family members, plays an important role in cellular metabolism and adaptation to cellular stress caused by hypoxia. In this review, we discuss the role of HIF in sepsis. We show possible mechanisms by which the inflammatory response activated during sepsis affects the HIF pathway. The activated HIF pathway in turn changes the metabolism of both innate and adaptive immune cells. As HIF expression in leukocytes of septic patients can be directly linked with mortality, we discuss multiple ways of interfering with the HIF signaling pathway.
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

Finnish 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.
The osprey‐like reversible outer toe: a conspicuous trait in the overlooked morphology of the Grey‐headed and Lesser Fish Eagles
Authors: Londei Tiziano
Published: January 2020

The ability to rotate the fourth toe to accompany the first toe in opposition of the second and third toes is well known for the Osprey Pandion haliaetus, as an adaptation to have a stronger grip in catching and carry fish. The presence of a similar ability in the Grey‐headed Fish Eagle Haliaeetus ichthyaetus and Lesser Fish Eagle Haliaeetus humilis, not shared with other piscivorous eagles, has largely been overlooked. Based on the growing number of photographs of these birds on the internet, the still scarce literature on their ecology and phylogeny, and personal field observation, I draw attention to this and other traits of their morphology, speculating on their origin and adaptive value.
A new procedure, free from human assessment, that automatically grades some facial skin signs in men from selfie pictures. Application to changes induced by a severe aerial chronic urban pollution
Authors: Zhang Y. , Jiang R. , Kezele I. , Flament F. , Elmozino E. , Zhang J. , Ye C. , Amar D. , Coquide J. , Dwivedi S. , Sarda‐Dutilh L. , Arcin V. , Aarabi P.
Published: January 2020

Objective

These were two folds: at first, to develop an automatic grading system specifically dedicated to some facial signs of men, similar to the one previously validated on women of different ethnic ancestry and second, to assess its potential in detecting and grading the possible impacts of a severe aerial urban pollution on some facial signs of Chinese men.

Methods

In both studies, selfie images were obtained from differently aged men. Nine facial signs were automatically graded through a specific A.I‐based algorithm and clinically assessed by a panel of experts and dermatologists. Selfie pictures were taken from individual smartphones of variable optical properties. The first study, designed for developing an automatic grading system, involved three comparable cohorts of men from three different regional ancestries (African, Asian, Caucasian, 110 each) the selfie images of which were acquired under four different lighting conditions. As a second use case study, the facial signs of two cohorts of Chinese men (101 and 100, each), differently aged, regularly exposed to very different aerial urban pollution conditions (UP) were analysed by the same algorithm, selfies being taken under only one lighting condition.

Results

The new automatic grading system of facial signs suits well to men, showing comparable results than that the one dedicated to women and provides data in close agreement with experts’ assessments.

In both cases (expert’s or automatic methodology), the accuracy of the scores appeared ethnic‐dependent.

The applied case confirmed previous results obtained clinically, that is, that many facial signs were found of an increased severity among men exposed to a severe urban pollution, as compared to those living in a less polluted city.

In both studies, statistical agreements between the automatic grading system and expert’s assessments were reached. In some facial signs, the automatic grading system seems offering a slightly better accuracy than the assessments made by the experts.

Conclusion

Apart from some minor limitations, this A.I‐based automatic grading system, free from human intervention, performed as well as the one previously developed in women, in close agreement with expert’s assessments. In epidemiological studies, this system offers an easy, fast, affordable and confidential approach in the detection and quantification of male facial signs.
The effects of climate change on human health in Africa, a dermatologic perspective: a report from the International Society of Dermatology Climate Change Committee
Authors: Coates Sarah J. , Enbiale Wendemagegn , Davis Mark D. P. , Andersen Louise K.
Published: January 2020

Throughout much of the African continent, healthcare systems are already strained in their efforts to meet the needs of a growing population using limited resources. Climate change threatens to undermine many of the public health gains that have been made in this region in the last several decades via multiple mechanisms, including malnutrition secondary to drought‐induced food insecurity, mass human displacement from newly uninhabitable areas, exacerbation of environmentally sensitive chronic diseases, and enhanced viability of pathogenic microbes and their vectors. We reviewed the literature describing the various direct and indirect effects of climate change on diseases with cutaneous manifestations in Africa. We included non‐communicable diseases such as malignancies (non‐melanoma skin cancers), inflammatory dermatoses (i.e. photosensitive dermatoses, atopic dermatitis), and trauma (skin injury), as well as communicable diseases and neglected tropical diseases. Physicians should be aware of the ways in which climate change threatens human health in low‐ and middle‐income countries in general, and particularly in countries throughout Africa, the world's lowest‐income and second most populous continent.
Limits of Social Capital for Refugee Integration: The Case of Gay Iranian Male Refugees' Integration in Canada
Authors: Karimi Aryan
Published: January 2020

Each year thousands of refugees, including racialized LGBT refugees, are resettled in Canada. Currently, economic independence is the foremost policy goal in integrating Canada's refugees. This policy often relies on social capital as a non‐economic solution to integration. I draw on 35 multi‐sequential interviews with 19 gay Iranian men to connect the empirical and theoretical debates around refugee integration and argue that over‐reliance on refugees' deployment of social capital for integration has grave shortcomings for their senses of belonging. I suggest that examining racialized LGBT refugees' integration strategies best reveals communitarian social capital's flaws at the conjunction of sexuality, gender, race, and class. I draw on Bourdieu's writings on social capital to highlight internal group differences, social inequalities, and the vital convertibility between financial, social, and cultural capital in building transferrable resources for refugee integration. I conclude by urging policy‐oriented studies of social capital.
Holocene matters: Landscape history accounts for current species richness of vascular plants in forests and grasslands of eastern Central Europe
Authors: Divíšek Jan , Hájek Michal , Jamrichová Eva , Petr Libor , Večeřa Martin , Tichý Lubomír , Willner Wolfgang , Horsák Michal
Published: January 2020

Aim

Current species‐richness patterns are sometimes interpreted as a legacy of landscape history, but historical processes shaping the distribution of species during the Holocene are frequently omitted in biodiversity models. Here, we test their importance in modelling current species richness of vascular plants in forest and grassland vegetation.

Location

Western Carpathians and adjacent regions.

Taxon

Vascular plants.

Methods

Numbers of all species and of habitat specialists were extracted from plot records of forest and grassland vegetation. For each plot, environmental and historical data were derived from thematic maps. Historical data related to the persistence of (a) temperate taxa during the Late Glacial and Early Holocene, (b) open‐landscape taxa during the Middle Holocene and (c) taiga taxa during the Late Holocene were based on 112 fossil pollen profiles. Boosted regression trees were used to model spatial patterns in species richness.

Results

Historical variables always appeared among the best predictors of current species richness. In light forests, species richness highly mirrored both the Late Glacial (12.5% contribution) and Middle‐Holocene (8.6%) landscape history. The latter factor became an important predictor also for species richness of steppe grasslands (8.3%) along with temperature seasonality (11.9%). Species richness of dark coniferous forests was best predicted by the Late‐Holocene occurrence of taiga forests (14.8%), which had an even stronger effect on the richness of habitat specialists (20.5%).

Main conclusions

Landscape changes since the Last Glacial Maximum are important predictors of current plant species richness. The historical effects were found to be habitat specific and, because they may interact with recent environmental conditions and anthropogenic pressures, they often show a nonlinear relationship with species richness. We provide one possible direction of incorporating past landscape changes to the models of species richness.
Circulating adiposity‐related microRNAs as predictors of the response to a low‐fat diet in subjects with obesity
Authors: Assmann Taís Silveira , Riezu‐Boj José I. , Milagro Fermín I. , Martínez J. Alfredo
Published: January 2020

Recent studies have revealed the critical role of several microRNAs (miRNAs) in energy homeostasis and metabolic processes and suggest that circulating miRNAs can be used as early predictors of weight loss in the design of precision nutrition. Thus, the aim of this study was to investigate circulating adiposity‐related miRNAs as biomarkers of the response to two specific weight loss dietary treatments. The expression of 86 miRNAs was investigated in plasma of 78 subjects with obesity randomized to two different diets [moderately high‐protein diet (n = 38) and low‐fat diet (n = 40)] and in 25 eutrophic controls (BMI ≤ 25 kg/m2). Bioinformatic analyses were performed to explore the target genes and biological pathways regulated by the dysregulated miRNAs. As results, 26 miRNAs were found differently expressed in eutrophic and volunteers with obesity. Moreover, 7 miRNAs (miR‐130a‐3p, miR‐142‐5p, miR‐144‐5p, miR‐15a‐5p, miR‐22‐3p, miR‐221‐3p and miR‐29c‐3p) were differentially expressed between responders and non‐responders to a low‐fat diet. Furthermore, after adjustment for basal glucose levels, 1‐SD increase in miR‐22‐3p expression was associated with reduction in the risk of non‐response to low‐fat diet [OR = 0.181, 95% CI (0.084‐0.947), P = .043]. Bioinformatic analyses evidenced that these 7 miRNAs regulate the expression of genes participating in important metabolic pathways. Conclusively, 7 circulating miRNAs related to adiposity could be used for predicting the response to a low‐fat diet intervention prescribed to lose weight.
Marine trophic niche use and life history diversity among Arctic charrSalvelinus alpinusin southwestern Greenland
Authors: Davidsen Jan G. , Power Michael , Knudsen Rune , Sjursen Aslak D. , Kjærstad Gaute , Rønning Lars , Arnekleiv Jo V.
Published: January 2020

Life history strategies and potential marine niche use of Arctic charrSalvelinus alpinus(n= 237, 84–652 mm, total body length,LT) were determined during the ice‐free season (2012) at three different watercourses in south‐western Greenland. All Arctic charr were collected from freshwater habitats. Based on stable isotopes of δ34S, the Arctic charr were categorized as either marine‐ or freshwater‐dependent feeders. The use of time‐integrated trophic tracers (stable isotopes of δ13C, δ15N, δ34S) suggested that several trophic groups of Arctic charr operate alongside within each fjord system. The groups suggested were one group that specialized in the marine habitat, in addition to two freshwater resident morphs (small‐sized resident and/or large‐growing cannibalistic individuals). Stomach contents consisted entirely of freshwater and terrestrial prey (i.e., insects), indicating that marine‐dependent feeders also fed in freshwater habitats after return from their marine migration. Growth and maturity patterns further supported variable life history strategies within each watercourse. The life history strategy patterns and marine trophic niche use were consistent across the watercourses along several hundred kilometres of coastline. This study represents the first ecological baseline for partially anadromous populations of Greenland Arctic charr.
Anemia and iron deficiency in compensated and decompensated cirrhosis: Prevalence and impact on clinical outcomes
Authors: Paternostro Rafael , Kapzan Lea , Mandorfer Mattias , Schwarzer Remy , Benedikt Schaefer , Viveiros André , Bauer David , Ferlitsch Monika , Zoller Heinz , Trauner Michael , Ferlitsch Arnulf
Published: January 2020

Background and Aim

Iron deficiency anemia (IDA)is the leading cause of anemia worldwide. Data on prevalence and clinical impact of anemia in cirrhosis are scarce. Aim was to report on the following:(i) prevalence of anemia and IDA in cirrhosis and (ii) its possible impact on clinical outcomes.

Methods

Consecutive cirrhotic patients from a prospective registry study were included. Anemia was defined as hemoglobin concentration ≤ 12 g/dL. IDA was defined as Hb ≤ 12 g/dL + transferrin‐saturation < 20%. Follow up for hepatic decompensation and mortality started with study inclusion and terminated in December 2017. A retrospective validation cohort of 1244 patients was used to validate our findings.

Results

Two hundred forty‐two patients with compensated (n = 53 [21.9%]) and decompensated (n = 189 [78.1%]) cirrhosis were included. Anemia was present in 128 patients (52.9%); of those, 63 (49.2%) had IDA. Prevalence of anemia increased with Child–Pugh Score (CPS; A: 26.5%, B: 59.2%, C: 69%; P < 0.001) and with decompensated cirrhosis(62.4% vs 18.8%, P < 0.001). Within anemic patients, a higher proportion of patients in CPS A/B vs C (73% vs 35%; P = 0.025) and in compensated cirrhosis (80% vs 46.6%; P = 0.043) were found with IDA. Model for End‐Stage Liver Disease (MELD) scores were significantly lower in patients with IDA (14.4 vs 17.9 non‐ID‐anemia; P = 0.005). Similar results were found in the validation cohort: median MELD (16[8–28]non‐IDA vs 12 [7–23] IDA; P < 0.001) and within anemic patients IDA was more common in patients with MELD <15 (58%) versus >15 (24%, P < 0.001).

Anemia was associated with a significant risk for hepatic decompensation and/or mortality both in the validation (aSHR: 1.65, P = 0.008) and in the derivation cohort (aSHR: 2.11, P < 0.001) and an independent risk factor for hepatic decompensation and/or mortality in compensated patients (aHR: 4.91, P = 0.004).

Conclusion

Anemia is highly prevalent in cirrhosis. In compensated cirrhosis, CPS A/B, and low MELD, IDA seems to be the most likely reason for anemia. Furthermore, anemia is associated with a significant risk for hepatic decompensation or mortality during long‐term follow up.
Risk Factors for Postpartum Depression: An Umbrella Review
Authors: Hutchens Bridget F. , Kearney Joan
Published: January 2020

Introduction

A deeper understanding of risk factors for postpartum depression (PPD) is essential to better target prevention and screening. An umbrella review was conducted to summarize and synthesize previously published systematic reviews and meta‐analyses.

Methods

Eight databases were searched in October of 2016, including PubMed, CINAHL, MEDLINE, PsycINFO, Embase, SCOPUS, PsycEXTRA, and Cochrane. Studies were included if they were reviews examining one or more risk factors for PPD and published between 1996 and 2016. The final sample included 21 articles, which varied in numerous ways, including the scope of risk factors explored and statistical methods.

Results

Because of methodological variations between reviews, standardized statistical aggregation was not possible. From this body of literature, 25 statistically significant risk factors emerged with 2 additional risk factors presenting inconclusive findings. The most common risk factors identified were high life stress, lack of social support, current or past abuse, prenatal depression, and marital or partner dissatisfaction. The 2 strongest risk factors for PPD were prenatal depression and current abuse.

Discussion

Because untreated PPD leaves women and their children vulnerable to numerous negative short‐term and long‐term outcomes, a better understanding of PPD risk factors serves to improve maternal and child outcomes by allowing health care providers to better anticipate the needs of affected women.