bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased inward rectifier K+ current of coronary artery smooth muscle cells in spontaneously hypertensive rats; partial compensation of the attenuated endothelium‐dependent relaxation via Ca2+‐activated K+ channels
Authors: Kim Hae Jin , Yin Ming Zhe , Cho Suhan , Kim Sung Eun , Choi Seong Woo , Ye Sang Kyu , Yoo Hae Young , Kim Sung Joon 
Published: August 2019

AbstractEndothelium‐dependent vasorelaxation is partly mediated by small‐conductance (SK3) and intermediate‐conductance Ca2+‐activated K+ channels (SK4) in the endothelium that results in endothelium‐dependent hyperpolarization (EDH). Apart from the electrical propagation through myoendothelial gap junctions, the K+ released from the endothelium facilitates EDH by increasing inward rectifier K+ channel (Kir) conductance in smooth muscle cells. The EDH‐dependent relaxation of coronary artery (CA) and Kir current in smooth muscle cells (CASMCs) of hypertensive animals are poorly understood despite the critical role of coronary flow in the hypertrophic heart. In spontaneously hypertensive (SHR) and control (WKY) rats, we found attenuation of the CA relaxation by activators of SK3 and SK4 (NS309 and 1‐EBIO) in SHR. In isolated CASMCs, whole‐cell patch‐clamp study revealed larger IKir in SHR than WKY, whereas the myocytes of skeletal and cerebral arteries showed smaller IKir in SHR than WKY. While the treatment with IKir inhibitor (0.1 mmol/L Ba2+) alone did not affect the WKY‐CA, the SHR‐CA showed significant contractile response, suggesting relaxing influence of the higher IKir in the CASMCs of SHR. Furthermore, the attenuation of NS309‐induced relaxation of CA by the combined treatment with 0.1 mmol/L Ba2+ was more prominent in SHR than WKY. Our study firstly shows a distinct increase of IKir in the CASMCs of SHR, which could partly compensate for the attenuated relaxation via endothelial SK3 and SK4.
What the Age of Populism Means for Our Liberal Democracy
Authors: Nandy Lisa 
Published: August 2019

AbstractPopulism has leapt from fringe protest to shaping, even dominating, mainstream politics in just a few years. Behind this political and social upheaval is an economic and political settlement that has failed to deliver good jobs, life chances and sustainable communities in many parts of the country, particularly outside urban centres. The failure of mainstream political parties to build a new settlement following the financial crash in 1998 has left a vacuum which now threatens the foundations of liberal, representative democracy. Progressive politicians need to build a new pluralist settlement based on a radical devolution of power that allows decision making to become less remote, more responsive and brings capital under greater democratic control.
Early life famine exposure to the Great Chinese Famine in 1959–1961 and subsequent pregnancy loss: a population‐based study
Authors: Zhang H , Qu X , Wang H , Tang K 
Published: August 2019

ObjectiveTo explore the relation between famine exposure in early life and subsequent pregnancy loss, including stillbirth, and spontaneous abortion in adulthood.DesignA population‐based, partly ecological study.Setting and populationIndividual data of 58 601 females born around the time of the Great Chinese Famine in 1959–1961.MethodsAssociations between the famine exposure in early life and pregnancy loss (stillbirth and spontaneous abortion) in adulthood were analysed using negative binomial regression, with the non‐exposure group as reference, adjusting for region, highest education, monthly income, alcohol consumption, tobacco use, body mass index in 25‐year‐olds and metabolic equivalent. Further analyses were stratified by rural versus urban region.Main outcome measuresContinuous variables of times of stillbirths and spontaneous abortions were used according to the individual self‐reported reproductive history.ResultsNo association was found between famine exposure and spontaneous abortion. In contrast, females experiencing the famine during their prenatal period (incidence rate ratio = 1.15, 95% CI 1.00–1.33) or infant period (incidence rate ratio = 1.27, 95% CI 1.12–1.44) were more likely to report stillbirth in later adult life. Such an association appeared stronger in women living in rural regions.ConclusionsEarly life exposure of famine was associated with an increased risk of stillbirth but not spontaneous abortion in adulthood. The strength of such an association appeared stronger in rural areas. Given the high potential for unmeasured confounding, these associations must be interpreted with caution. Regarding the potential implication that undernutrition in the fetal period is related to reproductive outcome in adulthood, fetal nutritional supply may play an important role in human reproduction.Tweetable abstractExposure to famine in early life was associated with increased pregnancy loss in adulthood.
Using hidden Markov models with raw, triaxial wrist accelerometry data to determine sleep stages
Authors: Trevenen Michelle L. , Turlach Berwin A. , Eastwood Peter R. , Straker Leon M. , Murray Kevin 
Published: August 2019

SummaryAccelerometry is a low‐cost and noninvasive method that has been used to discriminate sleep from wake, however, its utility to detect sleep stages is unclear. We detail the development and comparison of methods which utilise raw, triaxial accelerometry data to classify varying stages of sleep, ranging from sleep/wake detection to discriminating rapid eye movement sleep, stage one sleep, stage two sleep, deep sleep and wake. First‐ and second‐order hidden Markov models (HMMs) with time‐homogeneous and time‐varying transition probability matrices, along with continuous acceleration observations in the form of a Gaussian‐observation HMM and K‐means classified acceleration in a discrete‐observation HMM were explored. In addition, generalised linear mixed models (GLMMs) with binary and multinomial responses and logit link functions were considered as was whether incorporating adjoining acceleration information into the models improved prediction. Model predictions were compared to the reference‐standard in sleep detection (polysomnography) and outcome accuracies were calculated. Consistently, HMMs yielded greater sleep stage detection than GLMMs but there was little difference between first‐ and second‐order HMMs. Varying degrees of difference were observed when comparing Gaussian‐observation HMMs to discrete‐observation HMMs, and time‐varying HMMs yielded greater discrimination than time‐homogeneous HMMs, as did models which considered adjoining acceleration information. These results suggest that wrist‐worn accelerometry data may be able to detect sleep stages but that further investigation is required to optimise classification accuracy.
Paediatric palliative care in practice: Perspectives between acute and long‐term healthcare teams
Authors: Côté Anne‐Josée , Payot Antoine , Gaucher Nathalie 
Published: August 2019

AbstractAimTo explore and compare acute and long‐term care professionals' perspectives about paediatric palliative care.MethodsFocus group interviews were conducted in 2016‐2017 with professionals from acute (Emergency Department, Intensive Care Unit) and long‐term care (Complex Care Service, Palliative Care) teams.ResultsFifty‐eight participants were enrolled. Palliative care definitions were similar throughout groups: to provide active care early in the illness, focusing on the child as a whole and supporting families. Each group perceived a different role in the patient's illness trajectory, reflecting their own culture of care. They demonstrated important differences in their approach to palliative care. Disagreements regarding when or how to discuss goals of care were expressed. Acute care professionals reported discomfort when having to introduce these discussions for the first time, while long‐term care professionals perceived negative judgements about their patients' quality of life by acute care teams during health events. Personalised care, communication with families and continuity of care were thought to be key elements to improve care.ConclusionPaediatric palliative care is well recognised throughout specialties, yet continuity of care is challenged by groups' roles and interventions in a patient's illness. A reflective and mutual clinical approach is needed to improve quality of care and professionals' satisfaction.
Integrative factorization of bidimensionally linked matrices
Authors: Park Jun Young , Lock Eric F. 
Published: August 2019

AbstractAdvances in molecular “omics” technologies have motivated new methodologies for the integration of multiple sources of high‐content biomedical data. However, most statistical methods for integrating multiple data matrices only consider data shared vertically (one cohort on multiple platforms) or horizontally (different cohorts on a single platform). This is limiting for data that take the form of bidimensionally linked matrices (eg, multiple cohorts measured on multiple platforms), which are increasingly common in large‐scale biomedical studies. In this paper, we propose bidimensional integrative factorization (BIDIFAC) for integrative dimension reduction and signal approximation of bidimensionally linked data matrices. Our method factorizes data into (a) globally shared, (b) row‐shared, (c) column‐shared, and (d) single‐matrix structural components, facilitating the investigation of shared and unique patterns of variability. For estimation, we use a penalized objective function that extends the nuclear norm penalization for a single matrix. As an alternative to the complicated rank selection problem, we use results from the random matrix theory to choose tuning parameters. We apply our method to integrate two genomics platforms (messenger RNA and microRNA expression) across two sample cohorts (tumor samples and normal tissue samples) using the breast cancer data from the Cancer Genome Atlas. We provide R code for fitting BIDIFAC, imputing missing values, and generating simulated data.
Evidence for central antispastic effect of botulinum toxin type A
Authors: Matak Ivica 
Published: August 2019

Background and PurposeBotulinum toxin type A (BoNT/A) injections into hyperactive muscles provide effective treatment for spasticity and dystonias, presumably due to its local effects on extrafusal and intrafusal motor fibres. A recent discovery of toxin's retrograde axonal transport to CNS might suggest additional action sites. However, in comparison to cholinergic peripheral terminals, functional consequences of BoNT/A direct central action on abnormally increased muscle tone are presently unknown. To address this question, the central effects of BoNT/A were assessed in experimental local spastic paralysis.Experimental ApproachLocal spastic paralysis was induced by injection of tetanus toxin (1.5 ng) into rat gastrocnemius. Subsequently, BoNT/A (5 U·kg−1) was applied i.m. into the spastic muscle or intraneurally (i.n.) into the sciatic nerve to mimic the action of axonally transported toxin. Functional role of BoNT/A transcytosis in spinal cord was evaluated by lumbar i.t. application of BoNT/A‐neutralizing antitoxin. BoNT/A effects were studied by behavioural motor assessment and cleaved synaptosomal‐associated protein 25 (SNAP‐25) immunohistochemistry.Key ResultsTetanus toxin evoked muscular spasm (sustained rigid hind paw extension and resistance to passive ankle flexion). Subsequent injections of BoNT/A, i.m. or i.n, reduced tetanus toxin‐evoked spastic paralysis. Beneficial effects of i.n. BoNT/A and occurrence of cleaved SNAP‐25 in ventral horn were prevented by i.t. antitoxin.Conclusions and ImplicationsAxonally transported BoNT/A relieves muscle hypertonia induced by tetanus toxin, following the trans‐synaptic movement of BoNT/A in the CNS. These results suggest that such direct, centrally mediated reduction of abnormal muscle tone might contribute to the effectiveness of BoNT/A in spasticity and hyperkinetic movement disorders.
Indoleamine 2,3‐dioxygenase 2 depletion suppresses tumor growth in a mouse model of Lewis lung carcinoma
Authors: Yamasuge Wakana , Yamamoto Yasuko , Fujigaki Hidetsugu , Hoshi Masato , Nakamoto Kentaro , Kunisawa Kazuo , Mouri Akihiro , Nabeshima Toshitaka , Saito Kuniaki 
Published: August 2019

AbstractTryptophan metabolism is important to induce immune tolerance in tumors. To date, 3 types of tryptophan‐metabolizing enzymes have been identified: indoleamine 2,3‐dioxygenase 1 and 2 (IDO1 and IDO2) and tryptophan 2,3‐dioxygenase 2. Numerous studies have focused on IDO1 as its expression is enhanced in various cancers. Recently, IDO2 has been identified as a tryptophan‐metabolizing enzyme that is involved in several immune functions and expressed in cancers such as pancreatic cancer. However, the biological role of IDO2 in the induction of immune tolerance in tumors has not yet been reported. In the present study, we examined the effects of Ido2 depletion on tumor growth in a mouse model of Lewis lung carcinoma by using Ido2‐knockout mice. Ido2‐knockout mice had reduced tumor volumes compared to WT mice. Furthermore, Ido2 depletion altered the tumor microenvironment, such as tryptophan accumulation and kynurenine reduction, leading to enhancement of immune cell invasion. Finally, enzyme‐linked immunospot assay revealed that Ido2 depletion enhanced γ‐interferon secretion in the tumor. In conclusion, Ido2 is an important immune regulator in the tumor microenvironment. Our data indicate that IDO2 is a potential target for cancer treatment and drug development.
Indoor dust acts as an adjuvant to promote sensitization to peanut through the airway
Authors: Smeekens Johanna M. , Immormino Robert M. , Balogh Peter A. , Randell Scott H. , Kulis Michael D. , Moran Timothy P. 
Published: August 2019

AbstractBackgroundThere is growing evidence that environmental peanut exposure through non‐oral routes, including the skin and respiratory tract, can result in peanut sensitization. Environmental adjuvants in indoor dust can promote sensitization to inhaled antigens, but whether they contribute to peanut allergy development is unclear.ObjectiveWe investigated whether indoor dust promotes airway sensitization to peanut and peanut allergy development in mice.MethodsFemale and male C57BL/6J mice were exposed via the airways to peanut, indoor dust extract, or both for 2 weeks. Mice were then challenged with peanut and assessed for anaphylaxis. Peanut‐specific immunoglobulins, peanut uptake by lung conventional dendritic cells (cDCs), lung innate cytokines, and T cell differentiation in lung‐draining lymph nodes were quantified. Innate cytokine production by primary human bronchial epithelial cells exposed to indoor dust was also determined.ResultsInhalational exposure to low levels of peanut in combination with indoor dust, but neither alone, resulted in production of peanut‐specific IgE and development of anaphylaxis upon peanut challenge. Indoor dust triggered production of innate cytokines in murine lungs and in primary human bronchial epithelial cells. Additionally, inhaled indoor dust stimulated maturation and migration of peanut‐laden lung type 1 cDCs to draining lymph nodes. Inhalational exposure to peanut and indoor dust induced peanut‐specific T helper 2 cell differentiation and accumulation of T follicular helper cells in draining lymph nodes, which were associated with increased B cell numbers and peanut‐specific immunoglobulin production.Conclusions & clinical relevanceIndoor dust promotes airway sensitization to peanut and development of peanut allergy in mice. Our findings suggest that environmental adjuvants in indoor dust may be determinants of peanut allergy development in children.
Tumor necrosis factor receptor 2: A potential target for antidepressant drug development
Authors: Seymour Natasha , Gibbons Andrew , Dean Brian 
Published: August 2019

AbstractA large body of work implicates cytokines and their related pathways in the pathophysiologies of mood disorders. Much of the data on the role of cytokines in major depression and bipolar disorder suggest that pathways regulated by tumor necrosis factor (TNF)‐α make a significant contribution to their pathophysiologies. In the present review, we contrast the well‐established role of TNF‐related pathways acting to mediate classic pro‐inflammatory cytokine activity with growing evidence that such pathways have more diverse functions in the human central nervous system. Here, it will be argued that changes in levels of the TNF receptor type 2 in mood disorders would be consistent with a neuroprotective role for the receptor against the pathophysiologies of mood disorders. This hypothesis is of significance when considering how interventions that act to modulate TNF‐regulated pathways can be used to treat the symptoms of mood disorders.
Relationships Between Allopurinol Dose, Oxypurinol Concentration and Urate‐Lowering Response—In Search of a Minimum Effective Oxypurinol Concentration
Authors: Stamp Lisa K. , Chapman Peter T. , Barclay Murray , Horne Anne , Frampton Christopher , Merriman Tony R. , Wright Daniel F. B. , Drake Jill , Dalbeth Nicola 
Published: August 2019

The aims of this study were to determine factors that predict serum urate (SU) lowering response to allopurinol and the conversion of allopurinol to oxypurinol, and to determine a minimum therapeutic oxypurinol concentration. Data from 129 participants in a 24‐month open, randomized, controlled, parallel‐group, comparative clinical trial were analyzed. Allopurinol dose, SU, and plasma oxypurinol concentrations were available at multiple time points. The slope for the association between allopurinol dose and SU was calculated as a measure of sensitivity to allopurinol. The slope for the association between allopurinol dose and oxypurinol was calculated as a measure of allopurinol metabolism. Receiver operating characteristic (ROC) curves were used to identify a minimum oxypurinol concentration predictive of SU < 6 mg/dL. There was a wide range of SU concentrations for each allopurinol dose. The relationship between sensitivity to allopurinol and allopurinol metabolism for each 100 mg allopurinol dose increase varied between individuals. Body mass index (P = 0.023), creatinine clearance (CrCL; P = 0.037), ABCG2 Q141K (P = 0.019), and SU (P = 0.004) were associated with sensitivity to allopurinol. The minimum oxypurinol concentration for achieving the urate target was found to be about 104 μmol/L, but predictive accuracy was poor (ROC curve area under the curve (AUC) 0.65). The minimum therapeutic oxypurinol concentration was found to increase with decreasing renal function. Although there is a positive relationship between change in oxypurinol and change in SU concentration, a minimum therapeutic oxypurinol is dependent on CrCL and cannot reliably predict SU target. Other variables, including ABCG2 Q141K genotype, impact on sensitivity to allopurinol (ACTRN12611000845932).
Profile and costs associated with the use of osteosynthesis materials in victims of traffic accidents
Authors: Aires Carolina Chaves Gama , Vasconcelos Belmiro Cavalcanti Do Egito , Da Silva Igor Chaves Gama 
Published: August 2019

AbstractBackground/AimsFacial trauma arising from traffic accidents is one of the most prevalent injuries in urban trauma centers. The aim of this study was to evaluate the frequency, types, and costs associated with osteosynthesis material used in facial fractures of traffic accident victims seen at the Hospital da Restauração, Recife/PE, Brazil, from January to December 2014.Materials and methodsData were collected from the medical records of hospitalized patients submitted to surgery under general anesthesia for the treatment of facial fractures during the period. The data were analyzed descriptively by calculating absolute frequencies, percentages, and means. Statistical analysis was performed using SPSS v.21.0.ResultsAmong the patients, 73.1% were victims of motorcycle accidents that led to higher costs as they were the most prevalent injuries. Mandibular fractures were the most prevalent injury (53.5%). A total of 477 osteosynthesis materials were used, of which 76.51% were a 2.0‐mm plate system, 15.51% were a 1.5‐mm plate system, 3.14% were a 2.4‐mm plate system, 3.77% titanium meshes, 0.83% lag screws, and 0.2% steel wires. The use of these materials for the treatment of facial fractures resulted in a cost of US $51.285,00 for the Brazilian public health system.ConclusionThe increase in the number of traffic accidents implies significant numbers of victims with facial fractures, as well as considerable costs associated with the use of osteosynthesis materials for public health services.
Forest complexity drives dung beetle assemblages along an edge‐interior gradient in the southwest Amazon rainforest
Authors: Bitencourt Bruna S. , Dimas Tiffany M. , Da Silva Pedro G. , Morato Elder F. 
Published: August 2019

1. The habitat heterogeneity hypothesis predicts that heterogeneous habitats may provide more niches and diverse ways of exploiting environmental resources, thereby allowing more species to coexist, persist and diversify.2. We aimed to investigate how an edge‐interior gradient related to forest complexity influences species composition, abundance and richness of dung beetles in the western Amazon rainforest. We expected dung beetle abundance and richness to increase along the forest edge‐interior gradient, in accordance with the habitat heterogeneity hypothesis. We also expected strong changes in species composition driven by species turnover in the forest interior and nestedness along the forest edges. We sampled dung beetles using baited pitfall traps across an edge‐interior gradient. We also assessed the variation in forest features along the edge‐interior gradient to identify changes in forest complexity.3. Both species richness and abundance of dung beetles increased along the forest edge‐interior, following the gradient of forest complexity. The Sorensen dissimilarity of dung beetle assemblages was higher among sampling units placed near the forest edge, although neither turnover, nor nestedness was different between the extremes of the forest edge‐interior gradient. There was a clear compositional change along the edge‐interior gradient mostly driven by species turnover. Individual indicator value analysis revealed that species were strongly associated with the forest interior conditions.4. The simplification of the Amazon rainforest near clearings causes compositional changes in dung beetle assemblages. These changes are characterised by species‐poor and low‐abundance assemblages and may impair dung beetle ecological functions and therefore forest recovery.