bluuebunny/crossref_metadata_2025 huggingface dataset:
Viscoelastic characteristics of the canine cranial cruciate ligament complex at slow strain rates
Authors: Readioff Rosti , Geraghty Brendan , Elsheikh Ahmed , Comerford Eithne
Published: September 2020

Ligaments including the cruciate ligaments support and transfer loads between bones applied to the knee joint organ. The functions of these ligaments can get compromised due to changes to their viscoelastic material properties. Currently there are discrepancies in the literature on the viscoelastic characteristics of knee ligaments which are thought to be due to tissue variability and different testing protocols.

The aim of this study was to characterise the viscoelastic properties of healthy cranial cruciate ligaments (CCLs), from the canine knee (stifle) joint, with a focus on the toe region of the stress-strain properties where any alterations in the extracellular matrix which would affect viscoelastic properties would be seen.

Six paired CCLs, from skeletally mature and disease-free Staffordshire bull terrier stifle joints were retrieved as a femur-CCL-tibia complex and mechanically tested under uniaxial cyclic loading up to 10 N at three strain rates, namely 0.1, 1 and 10 %/min, to assess the viscoelastic property of strain rate dependency. The effect of strain history was also investigated by subjecting contralateral CCLs to an ascending (0.1, 1 and 10 %/min) or descending (10, 1 and 0.1 %/min) strain rate protocol.

The differences between strain rates were not statistically significant. However, hysteresis and recovery of ligament lengths showed some dependency on strain rate. Only hysteresis was affected by the test protocol and lower strain rates resulted in higher hysteresis and lower recovery. These findings could be explained by the slow process of uncrimping of collagen fibres and the contribution of proteoglycans in the ligament extracellular matrix to intra-fibrillar gliding, which results in more tissue elongations and higher energy dissipation. This study further expands our understanding of canine CCL behaviour, providing data for material models of femur-CCL-tibia complexes, and demonstrating the challenges for engineering complex biomaterials such as knee joint ligaments.
Association between COMT gene Val158Met heterozygote polymorphism and enhanced brain predicting processes
Authors: Bonetti L. , Sedghi N.A. , Bruzzone S.E.P. , Haumann N.T. , Paunio T. , Kantojärvi K. , Kliuchko M. , Vuust P. , Brattico E.
Published: September 2020

Predicting events in the ever-changing environment is a fundamental survival function intrinsic to the physiology of sensory systems, whose efficiency varies among the population. Even though it is established that a major source of such variations is genetic heritage, there are no studies tracking down auditory predicting processes to genetic mutations. Thus, we examined the neurophysiological responses to deviant stimuli recorded with magnetoencephalography (MEG) in 108 healthy participants carrying different variants of the Val158Met single-nucleotide polymorphism (SNP) within the catechol-O-methyltransferase (COMT) gene, which is responsible for the majority of catecholamines degradation in the prefrontal cortex. Our results showed significant amplitude enhancement of neural responses localized within inferior frontal gyrus, superior and middle temporal cortices to deviant auditory stimuli in heterozygote genotype carriers (Val/Met) vs homozygote (Val/Val and Met/Met) carriers. Integrating neurophysiology and genetics, this study provided new and broader insights into the brain mechanisms underlying optimal deviant detection.
Predictive Maps in Rats and Humans for Spatial Navigation
Authors: de Cothi William , Nyberg Nils , Griesbauer Eva-Maria , Ghanamé Carole , Zisch Fiona , Lefort Julie M. , Fletcher Lydia , Newton Coco , Renaudineau Sophie , Bendor Daniel , Grieves Roddy , Duvelle Éléonore , Barry Caswell , Spiers Hugo J.
Published: September 2020

Much of our understanding of navigation comes from the study of individual species, often with specific tasks tailored to those species. Here, we provide a novel experimental and analytic framework, integrating across humans, rats and simulated reinforcement learning (RL) agents to interrogate the dynamics of behaviour during spatial navigation. We developed a novel open-field navigation task (ʻTartarus Maze’) requiring dynamic adaptation (shortcuts and detours) to frequently changing obstructions in the path to a hidden goal. Humans and rats were remarkably similar in their trajectories. Both species showed the greatest similarity to RL agents utilising a ʻsuccessor representation’, which creates a predictive map. Humans also displayed trajectory features similar to model-based RL agents, which implemented an optimal tree-search planning procedure. Our results help refine models seeking to explain mammalian navigation in dynamic environments, and highlight the utility of modelling the behaviour of different species to uncover the shared mechanisms that support behaviour.
Image-based patch selection for deep learning to improve automated Gleason grading in histopathological slides
Authors: Speier William , Li Jiayun , Li Wenyuan , Sarma Karthik , Arnold Corey
Published: September 2020

Automated Gleason grading can be a valuable tool for physicians when assessing risk and planning treatment for prostate cancer patients. Semantic segmentation provides pixel-wise Gleason predictions across an entire slide, which can be more informative than classification of pre-selected homogeneous regions. Deep learning methods can automatically learn visual semantics to accomplish this task, but training models on whole slides is impractical due to large image sizes and scarcity of fully annotated data. Patch-based methods can alleviate these problems, and have been shown to produce significant results in histopathology segmentation. However, the irregular contours of biopsies on slides makes performance highly dependent on patch selection. In the traditional grid-based strategy, many patches lie on biopsy boundaries, reducing segmentation accuracy due to a reduction in contextual information. In this paper, we propose an automatic patch selection process based on image features. This algorithm segments the biopsy and aligns patches based on the tissue contour to maximize the amount of contextual information in each patch. This method was used to generate patches for a fully convolutional network to segment high grade, low grade, and benign tissue from a set of 59 histopathological slides, and results were compared against manual physician labels. We show that using our image-based patch selection algorithm results in a significant improvement in segmentation accuracy over the traditional grid-based approach. Our results suggest that informed patch selection can be a valuable addition to an automated histopathological analysis pipeline.
The vitamin A ester retinyl propionate has a unique metabolic profile and higher retinoid-related bioactivity over retinol and retinyl palmitate in human skin models
Authors: Bjerke Donald L. , Li Rui , Price Jason M. , Dobson Roy L.M. , Rodrigues MyriamRubecca , Tey ChingSiang , Vires Laura , Adams Rachel L. , Sherrill Joseph D. , Styczynski Peter B. , Goncalves Kirsty , Maltman Victoria , Przyborski Stefan , Oblong John E.
Published: September 2020

Human skin is exposed daily to environmental stressors, which cause acute damage and inflammation. Over time this leads to morphological and visual appearance changes associated with premature aging. Topical vitamin A derivatives such as retinol (ROL), retinyl palmitate (RPalm), and retinyl propionate (RP) have been used to reverse these changes and improve the appearance of skin. This study investigated a stoichiometric comparison of these retinoids usingin vitroandex vivoskin models. Skin biopsies were treated topically to compare skin penetration and metabolism. Treated keratinocytes were evaluated for transcriptomics profiling and hyaluronic acid (HA) synthesis and treated 3D epidermal skin equivalents were stained for epidermal thickness, Ki67, and filaggrin. A retinoic acid receptor-alpha (RARα) reporter cell line was used to compare retinoid activation levels. Results fromex vivoskin found that RP and ROL have higher penetration levels compared to RPalm. RP is metabolized primarily into ROL in the viable epidermis and dermis whereas ROL is esterified into RPalm and metabolized into the inactive retinoid 14-hydroxy-4,14-retro-retinol (14-HRR). RP treatment yielded higher RARα activation and HA synthesis levels than ROL whereas RPalm had a null effect. In keratinocytes, RP and ROL stimulated similar gene expression patterns and pathway theme profiles. In conclusion, RP and ROL show a similar response directionality whereas RPalm response was inconsistent. Additionally, RP has a consistently higher magnitude of response compared with ROL or RPalm.
Fine tuning of Piezo1 Expression and Activity Ensures Efficient Myoblast Fusion during Skeletal Myogenesis
Authors: Ortuste Quiroga Huascar Pedro , Ganassi Massimo , Yokoyama Shingo , Nakamura Kodai , Yamashita Tomohiro , Raimbach Daniel , Hagiwara Arisa , Harrington Oscar , Breach-Teji Jodie , Asakura Atsushi , Suzuki Yoshiro , Tominaga Makoto , Zammit Peter S. , Goto Katsumasa
Published: September 2020

Mechanical stimuli such as stretch and resistance training are essential to regulate growth and function of skeletal muscle. However, the molecular mechanisms involved in sensing mechanical stress during muscle formation remain unclear. Here, we investigate the role of the mechano-sensitive ion channel Piezo1 during myogenic progression. Direct manipulation of Piezo1 in muscle stem cells alters their myogenic progression. Indeed,Piezo1knockdown suppresses myoblast fusion leading to smaller myotubes. Such event is accompanied by significant downregulation of the fusogenic proteinMyomaker. In parallel, whilePiezo1knockdown also lowers Ca2+influx in response to stretch, Piezo1 activation increases Ca2+influx in response to stretch and enhances myoblasts fusion. We believe these findings may help understand molecular defects present in some muscle diseases. Altogether our study shows that Piezo1 is essential for terminal muscle differentiation acting on myoblast fusion, suggesting that Piezo1 deregulation may have implications in muscle aging and degenerative diseases including muscular dystrophies.
Testing multiple drivers of the temperature‐size rule with nonlinear temperature increase
Authors: Tabi Andrea , Garnier Aurélie , Pennekamp Frank
Published: September 2020

The temperature‐size rule (TSR) describes the inverse relationship between organism size and environmental temperature in uni‐ and multicellular species. Despite the TSR being widespread, the mechanisms for shrinking body size with warming remain elusive.

Here, we experimentally test three hypotheses (differential development and growth [DDG], maintain aerobic scope and regulate oxygen supply [MASROS] and the supply–demand [SD] hypothesis) potentially explaining the TSR using the aquatic protist Colpidium striatum in three gradually changing and one constant temperature environment crossed with three different nutrient levels.

We find that the constant and slowly warming environments show similar responses in terms of population dynamics, whereas populations with linear and fast warming quickly decline and show a stronger temperature‐size response.

Our analyses suggest that acclimation may have played a role in observing these differences among treatments. The SD hypothesis is most parsimonious with the data, however, neither the DDG nor the MASROS hypothesis can be firmly dismissed. We conclude that the TSR is driven by multiple ecological and acclimatory responses, hence multicausal.

A free Plain Language Summary can be found within the Supporting Information of this article.
The importance of individual‐to‐society feedbacks in animal ecology and evolution
Authors: Cantor Maurício , Maldonado‐Chaparro Adriana A. , Beck Kristina B. , Brandl Hanja B. , Carter Gerald G. , He Peng , Hillemann Friederike , Klarevas‐Irby James A. , Ogino Mina , Papageorgiou Danai , Prox Lea , Farine Damien R.
Published: September 2020

The social decisions that individuals make—who to interact with and how frequently—give rise to social structure. The resulting social structure then determines how individuals interact with their surroundings—resources and risks, pathogens and predators, competitors and cooperators.

However, despite intensive research on (a) how individuals make social decisions and (b) how social structure shapes social processes (e.g. cooperation, competition and conflict), there are still few studies linking these two perspectives. These perspectives represent two halves of a feedback loop: individual behaviour scales up to define the social environment, and this environment, in turn, feeds back by shaping the selective agents that drive individual behaviour.

We first review well‐established research areas that have captured both elements of this feedback loop—host–pathogen dynamics and cultural transmission. We then highlight areas where social structure is well studied but the two perspectives remain largely disconnected. Finally, we synthesise existing research on 14 distinct research topics to identify new prospects where the interplay between social structure and social processes are likely to be important but remain largely unexplored.

Our review shows that the inherent links between individuals’ traits, their social decisions, social structure and social evolution, warrant more consideration. By mapping the existing and missing connections among many research areas, our review highlights where explicitly considering social structure and the individual‐to‐society feedbacks can reveal new dimensions to old questions in ecology and evolution.
Decoupling the effects of food and density on life‐history plasticity of wild animals using field experiments: Insights from the steward who sits in the shadow of its tail, the North American red squirrel
Authors: Dantzer Ben , McAdam Andrew G. , Humphries Murray M. , Lane Jeffrey E. , Boutin Stan
Published: September 2020

Long‐term studies of wild animals provide the opportunity to investigate how phenotypic plasticity is used to cope with environmental fluctuations and how the relationships between phenotypes and fitness can be dependent upon the ecological context.

Many previous studies have only investigated life‐history plasticity in response to changes in temperature, yet wild animals often experience multiple environmental fluctuations simultaneously. This requires field experiments to decouple which ecological factor induces plasticity in fitness‐relevant traits to better understand their population‐level responses to those environmental fluctuations.

For the past 32 years, we have conducted a long‐term integrative study of individually marked North American red squirrelsTamiasciurus hudsonicusErxleben in the Yukon, Canada. We have used multi‐year field experiments to examine the physiological and life‐history responses of individual red squirrels to fluctuations in food abundance and conspecific density.

Our long‐term observational study and field experiments show that squirrels can anticipate increases in food availability and density, thereby decoupling the usual pattern where animals respond to, rather than anticipate, an ecological change.

As in many other study systems, ecological factors that can induce plasticity (such as food and density) covary. However, our field experiments that manipulate food availability and social cues of density (frequency of territorial vocalizations) indicate that increases in social (acoustic) cues of density in the absence of additional food can induce similar life‐history plasticity, as does experimental food supplementation.

Changes in the levels of metabolic hormones (glucocorticoids) in response to variation in food and density are one mechanism that seems to induce this adaptive life‐history plasticity.

Although we have not yet investigated the energetic response of squirrels to elevated density or its association with life‐history plasticity, energetics research in red squirrels has overturned several standard pillars of knowledge in physiological ecology.

We show how a tractable model species combined with integrative studies can reveal how animals cope with resource fluctuations through life‐history plasticity.
Why we should care about movements: Using spatially explicit integrated population models to assess habitat source–sink dynamics
Authors: Paquet Matthieu , Arlt Debora , Knape Jonas , Low Matthew , Forslund Pär , Pärt Tomas
Published: September 2020

Assessing the source–sink status of populations and habitats is of major importance for understanding population dynamics and for the management of natural populations. Sources produce a net surplus of individuals (per capita contribution to the metapopulation > 1) and will be the main contributors for self‐sustaining populations, whereas sinks produce a deficit (contribution < 1). However, making these types of assessments is generally hindered by the problem of separating mortality from permanent emigration, especially when survival probabilities as well as moved distances are habitat‐specific.

To address this long‐standing issue, we propose a spatial multi‐event integrated population model (IPM) that incorporates habitat‐specific dispersal distances of individuals. Using information about local movements, this IPM adjusts survival estimates for emigration outside the study area.

Analysing 24 years of data on a farmland passerine (the northern wheatear Oenanthe oenanthe), we assessed habitat‐specific contributions, and hence the source–sink status and temporal variation of two key breeding habitats, while accounting for habitat‐ and sex‐specific local dispersal distances of juveniles and adults. We then examined the sensitivity of the source–sink analysis by comparing results with and without accounting for these local movements.

Estimates of first‐year survival, and consequently habitat‐specific contributions, were higher when local movement data were included. The consequences from including movement data were sex specific, with contribution shifting from sink to likely source in one habitat for males, and previously noted habitat differences for females disappearing.

Assessing the source–sink status of habitats is extremely challenging. We show that our spatial IPM accounting for local movements can reduce biases in estimates of the contribution by different habitats, and thus reduce the overestimation of the occurrence of sink habitats. This approach allows combining all available data on demographic rates and movements, which will allow better assessment of source–sink dynamics and better informed conservation interventions.
The last moves: The effect of hunting and culling on the risk of disease spread from a population of reindeer
Authors: Mysterud Atle , Rauset Geir Rune , Van Moorter Bram , Andersen Roy , Strand Olav , Rivrud Inger Maren
Published: September 2020

Hunting and culling are frequently used to combat infectious wildlife diseases. The aim is to markedly lower population density in order to limit disease transmission or to eradicate the host. Massive host culling can yield a trade‐off when combating wildlife disease; it follows that intrusive actions may have unintended behavioural side effects, leading to the geographic spread of disease. The manner in which such excessive hunting and culling of hosts can affect the movement and dispersion of cervids has not been studied.

In this study, we quantified the behaviour (daily movements and habitat use) and dispersion of GPS‐marked reindeer (n = 24) before and during the eradication of an entire population (>2,000 reindeer) infected with chronic wasting disease (CWD) in Norway. We compared behaviour and dispersion during 10 ordinary hunting seasons (2007–2016), an extended hunting season (2017) and marksmen culling (2017/2018).

Seasonality had a major impact on movements. Reindeer movements during the early hunting season (20 August–20 September) did not increase the overall movements compared to that in the pre‐hunt season (20 July–19 August), while extended hunting into October (as in 2017) and marksmen culling from November to February markedly increased daytime movements relative to that normally observed in this time of the year. Towards the end of the eradication, the remaining reindeer sought refuge at restricted high‐elevation areas with limited forage production. Reindeer used novel areas towards the perimeter of the range, but active herding during culling stopped one herd from leaving the CWD zone.

Synthesis and applications. With emerging wildlife diseases, host culling is becoming a more frequently used tool for managers in Europe. Our study highlights the potential trade‐off between combating disease transmission within a population and the risk of geographic spread. Such insight is important to design mitigation measures, such as perimeter fencing or herding, to avoid the risk of the geographic spread of disease in cases of severe and economically important wildlife diseases.
Do Voters Follow? The Effect of Party Cues on Public Opinion During a Process of Policy Change
Authors: Nordø Åsta Dyrnes
Published: September 2020

A large body of literature has demonstrated how citizens use party endorsements when shaping their policy opinions. However, recent studies question the centrality of party cues in shaping public opinion. This study advances the literature with a four‐wave panel survey design that measures citizens’ policy opinions before, during and after a controversial policy proposal to ban street begging was made by the Norwegian government in 2014. Two main findings inform previous work. First, voters are modestly affected by party cues as the proposition turns salient. Second, when a party shifts their policy position on a highly salient issue, voters do not automatically shift their opinions accordingly. Thus, the magnitude and direction of opinion change in the electorate indicate that party cue effects are modest and that instead of polarizing patterns across time parallel publics moving in the same direction independent of party cues are detected. These findings demonstrate that under some conditions, voters’ opinion formation is less dependent on partisan elites than much of the previous work indicates.
Military crisis responses to COVID‐19
Authors: Kalkman Jori Pascal
Published: September 2020

Countries across the globe have mobilized their armed forces in response to the COVID‐19 pandemic. Current contributions of armed forces have resulted from an urgent need for additional personnel and resources, and were facilitated by a framing of the crisis in terms of war. These deployments were in the interest of armed forces and enabled them to improve their operational readiness, boost their societal standing and support societies with their expertise. Even though armed forces may provide crucial aid in times of need, it is important that civilian crisis organizations are not undermined, civilian control and civil rights are guaranteed, and the effects on other military operations are considered and discussed. This Forum contribution offers some reflections and recommendations.
Incidence of postpartum hypertension within 2 years of a pregnancy complicated by pre‐eclampsia: a systematic review and meta‐analysis
Authors: Giorgione V , Ridder A , Kalafat E , Khalil A , Thilaganathan B
Published: September 2020

Background

Women with a history of hypertensive disorders of pregnancy (HDP) are at increased long‐term risk of cardiovascular disease. However, there has been increasing evidence on the same risks in the months following birth.

Objectives

This review aims to estimate the incidence of hypertension in the first 2 years after HDP.

Search strategy

MEDLINE, Embase and Cochrane databases were systematically searched in October 2019.

Selection criteria

Observational studies comparing hypertension rate following HDP and normotensive pregnancies up to 2 years.

Data collection and analysis

A meta‐analysis to calculate the odds ratio (OR) with a 95% confidence interval (CI) and a sub‐group analysis excluding women with chronic hypertension were performed.

Main results

Hypertension was diagnosed within the first 2 years following pregnancy in 468/1646 (28.4%) and 584/6395 (9.1%) of the HDP and control groups, respectively (OR 6.28; 95% CI 4.18–9.43; I2 = 56%). The risk of hypertension in HDP group was significantly higher in the first 6 months following delivery (OR 18.33; 95% CI 1.35–249.48; I2 = 84%) than at 6–12 months (OR 4.36; 95% CI 2.81–6.76; I2 = 56%) or between 1–2 years postpartum (OR 7.24; 95% CI 4.44–11.80; I2 = 9%). A sub‐group analysis demonstrated a similar increase in the risk of developing postpartum hypertension after HDP (OR 5.75; 95% CI 3.92–8.44; I2 = 49%) and pre‐eclampsia (OR 6.83; 95% CI 4.25–10.96; I2 = 53%).

Conclusions

The augmented risk of hypertension after HDP is highest in the early postpartum period, suggesting that diagnosis and targeted interventions to improve maternal cardiovascular health may need to be commenced in the immediate postpartum period.

Tweetable abstract

The risk of hypertension within 2 years of birth is six‐fold higher in women who experienced pre‐eclampsia.
Improved physicochemical stability of emulsions enriched in lutein by a combination of chlorogenic acid–whey protein isolate–dextran and vitamin E
Authors: Wang Hao , Yan Yong , Feng Xiangru , Wu Zijian , Guo Yatu , Li Heyu , Zhu Qiaomei
Published: September 2020

Lutein, as a bioactive substance, has the ability to decrease the risk of some chronic diseases, but the poor water solubility, chemical instability, and low bioaccessibility limit its wide application in foods. In this study, an emulsion‐based delivery system stabilized by chlorogenic acid (CA)–whey protein isolate (WPI)–dextran (DEX) ternary conjugates was prepared and vitamin E (VE) was added to increase the chemical stability of lutein. Molecular weight and conformational information of ternary conjugates were obtained by sodium dodecyl sulphate‐polyacrylamide gel electrophoresis, fluorescence spectroscopy, and Fourier transform infrared spectroscopy. o‐Phthalaldehyde results suggested that the extent of glycation was 16.4% and 19.5% for (CA–WPI)–DEX and WPI–DEX conjugates, respectively. The physicochemical stability of lutein‐enriched emulsions was evaluated under different environmental stresses and long‐term storage. The obtained results showed that compared with emulsions stabilized by WPI alone or binary conjugates, ternary conjugates imparted emulsions high stability under different environmental stress conditions (ionic strength, freeze–thaw, and heat) and long‐term storage (within 3 weeks). VE can effectively decrease the degradation rate of lutein without changing the physical stability of emulsions. Additionally, the lutein‐enriched emulsions prepared by ternary conjugates and VE exhibited a relatively high bioaccessibility.

Practical Application

The ternary conjugates constructed in this paper has excellent physicochemical characteristics to stabilize emulsion, and can increase the water solubility of functional factors and reduce their degradation rate. Additionally, this conjugate was prepared by food‐grade materials. Therefore, it can be used as emulsion‐based delivery systems in food industrials.
elfgen: A New Instream Flow Framework for Rapid Generation and Optimization of Flow–Ecology Relations
Authors: Kleiner Joseph , Passero Elaina , Burgholzer Robert , Rapp Jennifer , Scott Durelle
Published: September 2020

Effective water resource management requires practical, data‐driven determination of instream flow needs. Newly developed, high‐resolution flow models and aquatic species databases provide enormous opportunity, but the volume of data can prove challenging to manage without automated tools. The objective of this study was to develop a framework of analytical methods and best practices to reduce costs of entry into flow–ecology analysis by integrating widely available hydrologic and ecological datasets. Ecological limit functions (ELFs) describing the relation between maximum species richness and stream size characteristics (streamflow or drainage area) were developed. Species richness is expected to increase with streamflow through a watershed up to a point where it either plateaus or transitions to a decreasing trend in larger streams. Our results show that identifying the location of this "breakpoint" is critical for producing optimal ELF model fit. We found that richness breakpoints can be estimated using automated low‐supervision methods, with high‐supervision providing negligible improvement in detection accuracy. Model fit (and predictive capability) was found to be superior in smaller hydrologic units. The ELF model ("elfgen" R package available on GitHub: https://github.com/HARPgroup/elfgen) can be used to generate ELFs using built‐in datasets for the conterminous United States, or applied anywhere else streamflow and biodiversity data inputs are available.
MicroRNA‐200b is a potential biomarker of the expression of PD‐L1 in patients with lung cancer
Authors: Katakura Seigo , Kobayashi Nobuaki , Hashimoto Hisashi , Kamimaki Chisato , Tanaka Katsushi , Kubo Sousuke , Nakashima Kentaro , Teranishi Shuhei , Manabe Saki , Watanabe Keisuke , Horita Nobuyuki , Hara Yu , Yamamoto Masaki , Kudo Makoto , Piao Hongmei , Kaneko Takeshi
Published: September 2020

Background

Advanced non‐small cell lung cancer (NSCLC) has a high mortality rate and poor prognosis. However, outcomes have gradually improved after the introduction of novel immunotherapies, including immune checkpoint inhibitors (ICIs). Although programmed death‐ligand 1 (PD‐L1) expression in tumor tissues is a known biomarker for guiding ICI treatment of NSCLC, challenges such as difficulty of liquid biopsy and heterogeneous results during treatment persist. This study evaluated the potential of miR200b as a surrogate biomarker for PD‐L1 expression.

Methods

We used the human lung cancer cell lines H226, H460, H520, A549, and H1975. miR200b expression in blood and bronchoscopy specimens of NSCLC patients was evaluated using reverse‐transcription‐quantitative PCR. Using flow cytometry, PD‐L1 expression in vitro, as well as in tumor tissues, was evaluated after transfection with a mimic miR200b or siRNA.

Results

miR200b expression negatively correlated with PD‐L1 expression in all cell lines. The induction or knockdown of miR200b also altered PD‐L1 expression in vitro. The patient group with a PD‐L1 tumor proportion score ≥ 50% had significantly lower miR200b expression in the bronchoscopy specimens (P = 0.025) and serum‐derived exosomes (P = 0.022) than that with PD‐L1 tumor proportion score < 50%.

Conclusions

miR200b can regulate PD‐L1 expression in lung cancer cells, and miR200b expression in clinical specimens negatively correlated with PD‐L1 expression. Thus, miR200b may be a useful surrogate biomarker for PD‐L1 expression in lung cancer patients.

Key points

Significant findings of the study

High PD‐L1 expression was linked to low miR200b expression, whereas low PD‐L1 expression was linked to high miR200b expression in human lung cancer patients. Thus, miR200b overexpression or silencing can control PD‐L1 expression in cancer cells.

What this study adds

We demonstrated the potential of miR200b as a surrogate biomarker for PD‐L1 expression in lung cancer patients.
Evaluating tooth strontium and barium as indicators of weaning age in Pacific walruses
Authors: Clark Casey T. , Horstmann Lara , Misarti Nicole
Published: September 2020

Lactation length and weaning age provide important information about maternal investment, which can reflect the health and nutritional status of the mother, as well as broader reproductive strategies in mammals. Calcium‐normalized strontium (Sr) and barium (Ba) concentrations in the growth layers of mammalian teeth differ for nursing animals and those consuming non‐milk foods, thus can be used to estimate age‐at‐weaning. To date, this approach has been used only for terrestrial animals, and almost exclusively for primates.

The goal of this study was to determine whether Sr and Ba concentrations in the cementum of Pacific walrus Odobenus rosmarus divergens teeth can be used to estimate weaning age. Teeth from 107 walruses were analysed using laser ablation inductively coupled plasma mass spectrometry, and calcium‐normalized 88Sr and 137Ba concentrations were quantified.

For most walruses, both Sr and Ba concentrations exhibited rapid changes in early life. Ba concentrations matched closely with expected patterns in the published literature, rapidly declining from high to low concentrations (typically from ~10 ppm to ~5 ppm). In contrast, Sr exhibited a pattern opposite to that presented in studies of terrestrial mammals, appearing nearly identical to Ba (typically declining from ~400 ppm to ~200 ppm). To explain these findings, we present conceptual models of the factors generating weaning signals in Sr and Ba for terrestrial mammals, as well as a new, hypothetical model for walruses. Both a visual and mathematical approach to weaning age estimation indicated a median weaning age of walruses at the end of the second year of life (in the second dark layer of the tooth cementum), with many walruses estimated to have weaned in their third year of life, and a smaller group weaning in their fourth or fifth year. This is later than expected, given a published estimate of walrus weaning at 18–24 months.

These results do not conclusively support the use of tooth Sr and Ba for estimating weaning age in walruses, and further research is warranted to better understand the drivers of the observed patterns of Ba and Sr accumulation in walrus teeth.
A Distinct Neurophenotype of Fearful Face Processing in Alcohol Use Disorder With and Without Comorbid Anxiety
Authors: MacIlvane Nicole , Fede Samantha J. , Pearson Emma E. , Diazgranados Nancy , Momenan Reza
Published: September 2020

Background

Individuals with alcohol use disorder (AUD) can present with comorbid anxiety symptoms and often have deficits in emotional processing. Previous research suggests brain response is altered during facial affect recognition tasks, especially in limbic areas, due to either AUD or anxiety symptomology; however, the impact of both AUD and clinically significant anxiety symptoms during these tasks has not yet been examined.

Methods

In this study, we investigated neural activation differences during an emotional face‐matching task. Participants (N = 232) underwent fMRI scanning, as part of a larger study. Three groups were investigated: individuals with diagnosed AUD and elevated anxiety traits (AUD + ANX, n = 90), individuals with diagnosed AUD but non‐clinically significant levels of anxiety (AUD‐ANX, n = 39), and healthy controls (HC, n = 103).

Results

Our results illustrate distinct neurophenotypes of AUD, where individuals with comorbid anxiety symptomology have blunted emotional face processing while those with singular AUD are hyperresponsive.

Conclusions

This suggests AUD with anxiety symptomology may have a unique neurobiological underpinning, and treatment and intervention should be tailored to individual constellations of symptoms.
The Effects of a Brief Motivational Intervention for Alcohol Use through Stages of Change among Nontreatment Seeking Injured Patients
Authors: Field Craig A. , Richards Dylan K. , Castro Yessenia , Alonso Cabriales José , Wagler Amy , von Sternberg Kirk
Published: September 2020

Background

Little is known about the mechanisms of change underlying brief interventions and the patient characteristics that may affect them. The present study tested whether the stages of change mediate the effects of a BMI with and without a telephone booster relative to brief advice (i.e., multiple mediation). Further, the present study tested whether the effects of the BMI conditions on the stages of change were contingent on patients’ alcohol use severity (i.e., moderated mediation).

Methods

The present study is a secondary analysis using data from injured adult patients at 3 trauma centers who were screened for inclusion in the study and randomly assigned to brief advice (n = 200), BMI (n = 203), or BMI with a telephone booster (n = 193) (Field et al., 2014). Participants completed a baseline assessment and 3‐, 6‐, and 12‐month follow‐up assessments that included self‐report measures of the stages of change, alcohol use, and alcohol‐related problems, as well as other variables of interest.

Results

The results demonstrated significant and consistent mediation at p < 0.05 wherein BMI with a telephone booster increased action at 3‐month follow‐up leading to reduced likelihood of at‐risk drinking, less alcohol use, and fewer alcohol problems at both 6‐ and 12‐month follow‐up. However, moderated mediation analyses suggested that the effects of the BMI conditions on the stages of change were not contingent on patients’ alcohol use severity.

Conclusions

This study contributes to the understanding of stages of change as potential mechanisms of change in BMI. Directions for future research are discussed.
Social trust and the speed of corporate leverage adjustment: evidence from around the globe
Authors: Huang Peng , Lu Yue , Faff Robert
Published: September 2020

We examine the relation between social trust and the speed of leverage adjustment (SOA) around the world. Using a large international sample (65 countries, 1996–2016), we find that social trust has a positive effect on SOA. In the cross section, we find that the positive effect of social trust on the SOA is more pronounced for: (i) over‐levered firms; (ii) firms with higher information asymmetry; (iii) firms with lower ease of financing; and (iv) firms located in countries with weaker governance quality. Overall, we highlight the role of social trust in shaping corporate capital structure.
Transitions in frequency of hookah smoking among youth and adults: findings from waves 1 and 2 of the Population Assessment of Tobacco and Health (PATH) study, 2013–15
Authors: Soneji Samir , Knutzen Kristin E. , Gravely Shannon , Elton‐Marshall Tara , Sargent James , Lambert Elizabeth , Hilmi Nahla , Sharma Eva , Jackson Kia J. , Wang Baoguang , Robinson Joelle , Driezen Pete , Bover Manderski Michelle , Bansal‐Travers Maansi , Hyland Andrew , Travers Mark , Yang Duck‐Hye , Dang Rui , Fong Geoffrey T.
Published: September 2020

Background and Aims

The prevalence of hookah smoking has increased in the United States since at least 2010, especially among youth and young adults. This study assessed self‐reported reasons for hookah smoking cessation and transition to or maintenance of high‐frequency hookah smoking among current hookah smokers.

Design

Separately analyzed data from the Population Assessment of Tobacco and Health (PATH) study, a longitudinal cohort study. Frequency of and reasons for hookah smoking were ascertained at wave 1 (2013–14); frequency of hookah smoking and past‐year cessation were ascertained at wave 2 (2014–15). Weighted multivariable logistic and ordinal logistic regression models were fitted to predict hookah smoking cessation and frequency of hookah smoking at wave 2, respectively, accounting for demographic and behavioral risk factors, reasons for hookah smoking and frequency of hookah smoking at wave 1.

Setting

United States.

Participants

A total of 693 youth and 4400 adult past‐year hookah smokers.

Measurements

Self‐reported tobacco‐use patterns and associated health behaviors were measured via audio computer‐assisted self‐interviews (ACASI).

Findings

At wave 1, 5.9% of youth and 7.5% of adults were past‐year hookah smokers. Among all age groups, the leading reasons for hookah smoking were enjoyment of socializing while smoking, the availability of appealing flavors and believing that it was less harmful than cigarette smoking. The odds of cessation were lower for adults who liked hookah flavors [adjusted odds ratio (aOR) = 0.40; 95% confidence interval (CI) = 0.26–0.62] compared with adults who did not like hookah flavors. The odds of transitioning to, or maintaining, monthly or more frequent hookah smoking at wave 2, compared with cessation or less than monthly smoking, were higher for adults who liked hookah flavors [adjusted proportional odds ratio (aPOR) = 2.10; 95% CI = 1.48–2.99 and enjoyed socializing while smoking hookah (aPOR = 1.82; 95% CI =1.13–2.94) compared with adults who did not like hookah flavors or socializing.

Conclusion

The availability of appealing flavors, affordability and socialization while smoking hookah in the United States are associated with reduced likelihood of cessation and increased likelihood of high‐frequency hookah smoking.
A genome‐wide association study revealed five SNPs affecting 8‐month weight in sheep
Authors: Pasandideh M. , Gholizadeh M. , Rahimi‐Mianji G.
Published: September 2020

Lamb weight at 8 months of age is an important trait in the sheep industry in terms of the onset of puberty around this age; however, knowledge of its effective genetic factors is limited. Therefore, a GWAS using the 50K SNP‐Chip was performed on 96 Baluchi sheep to identify the genomic regions associated with 8‐month weight. The results of the present study revealed five SNPs on chromosomes 4, 14 and 16 at 5% chromosome‐wide significance level, jointly accounting for 0.95% of total genetic variance. Four genes – MTPN, HYDIN, LRGUK and ZFP90 – were found in 50 kb intervals around the significant SNPs, of which MTPN is involved in regulation of skeletal muscle growth. Our results may provide a new vision to identify the genomic regions affecting growth traits in sheep.
Environmental Externalities from Agriculture: Evidence from Water Quality in the United States
Authors: Paudel Jayash , Crago Christine L.
Published: September 2020

Agricultural fertilizer use is widely acknowledged to be a leading cause of water pollution. Yet, no national estimates exist on the effect of fertilizer application on concentrations of agricultural pollutants in US watersheds. This paper employs a watershed‐level panel data on nitrogen and phosphorus pollution readings to examine the impact of fertilizer use on US water quality over a fifty‐five‐year time period from 1951 to 2005. Findings show that a 10% increase in the use of nitrogen and phosphorus fertilizers leads to a 1.52% increase in the concentration of nitrogen and a 1.37% increase in the concentration of phosphorus across watersheds. Results also indicate that there exists heterogeneity in nutrient pollution elasticity estimates across eighteen US water resource regions, ranging from 0.082 to 0.733 in the case of nitrogen and from 0.036 to 0.475 in the case of phosphorus. Combining our results with prior hydrology‐based studies, we find that a 100% increase in the use of nitrogen fertilizers in the Lower Mississippi water resource region expands the size of the hypoxic zone in the Gulf of Mexico by roughly 3,389 square miles, equivalent to about two‐fifths of the estimated size of the dead zone in the Gulf of Mexico.
Patterns of oxycodone controlled release use in older people with cancer following public subsidy of oxycodone/naloxone formulations: An Australian population‐based study
Authors: Daniels Benjamin , Luckett Tim , Holliday Simon , Liauw Winston , Lovell Melanie , Phillips Jane , Rowett Debra , John Toby Newton , Tervonen Hanna , Pearson Sallie‐Anne
Published: September 2020

Aim

Public subsidy of the oxycodone/naloxone controlled release (CR) combination in December 2011 expanded the overall market for oxycodone CR in the general public in Australia; we evaluate its impact in people with cancer.

Methods

We used Repatriation Pharmaceutical Benefits dispensing data linked with the NSW Cancer Registry for Department of Veterans’ Affairs (DVA) healthcare card holders 65 years and older residing in NSW between 2004 and 2013 to identify clients with cancer and their opioid dispensings. We used interrupted time series analysis to model changes in monthly rates of oxycodone CR tablets dispensed and initiations. We performed a retrospective cohort study to examine changes in client characteristics and opioid utilization over time by comparing clients initiating oxycodone CR before and after subsidy.

Results

The rate of oxycodone CR tablets dispensed/month increased by 20% from December 2011, due to uptake of the oxycodone/naloxone CR combination; monthly initiations increased immediately by 17%. Initiations of buprenorphine, fentanyl, and morphine declined from December 2011. DVA healthcare card holders were significantly more likely to initiate the 5 mg oxycodone CR formulation; more likely to use immediate release oxycodone in the 90 days following initiation; and less likely to use a weak opioid in the 90 days preceding oxycodone CR initiation following December 2011 than they were prior to that time.

Conclusions

The public subsidy of the oxycodone/naloxone CR formulation expanded the overall oxycodone CR market for DVA healthcare card holders with cancer. Our findings highlight the need for updated guidelines around risk management for opioid treatment in patients with cancer.
Cutaneous manifestations of viral outbreaks
Authors: Bothra Atul , Maheswari Anshu , Singh Mehak , Pawar Manoj , Jodhani Kirti
Published: September 2020

As the world tries to grapple with the COVID‐19 pandemic, dermatologists are left in a lurch as there is a lacuna in dermatologic literature as well as training regarding the cutaneous manifestations of varied viral agents capable of causing epidemics/pandemics or the potential to be bio‐weaponised. Such outbreaks have the potential to become a pandemic given this age of globalisation. The quote by George Santayana stands true ‘Those who cannot remember the past are condemned to repeat it’. Thus, this article lends a perspective to the recent viral outbreaks and is aimed at summarising these agents and their clinical features to serve as a quick reference for dermatologists.
Evaluation of the efficacy of cysteamine cream compared to hydroquinone in the treatment of melasma: A randomised, double‐blinded trial
Authors: Nguyen Jennifer , Remyn Laura , Chung In Young , Honigman Anthony , Gourani‐Tehrani Shima , Wutami Ilycia , Wong Celestine , Paul Eldho , Rodrigues Michelle
Published: September 2020

Background/Objective

Melasma is a commonly acquired disorder of hyperpigmentation that often poses a therapeutic challenge for dermatologists. Recently, cysteamine cream has shown promising results compared to placebo. This study aims to determine the efficacy of cysteamine cream compared to hydroquinone cream in the treatment of melasma.

Methods

A randomised, double‐blinded, single‐centre trial was conducted in Victoria, Australia. 20 recruited participants were given either cysteamine cream or hydroquinone cream for 16 weeks. The primary outcome measure was a change in the modified Melasma Area and Severity Index (mMASI). Quality of life at baseline and week 16 as well as standard digital photography at each follow‐up visit was assessed as secondary outcome measures.

Results

At week 16, 14 participants completed the study with 5 participants in the cysteamine group and 9 patients in the hydroquinone group. In the intention to treat analysis, there was a 1.52 ± 0.69 (21.3%) reduction in mMASI for the cysteamine group and a 2.96 ± 1.15 (32%) reduction in the hydroquinone group. The difference between groups was not statistically significant (P = 0.3). Hydroquinone cream was generally better tolerated that cysteamine cream.

Conclusion

Our study suggests that topical cysteamine may have comparable efficacy to topical hydroquinone. Cysteamine thus provides a possible alternative to patients and clinicians who wish to avoid or rotate off topical hydroquinone. While side effects were more common for participants using cysteamine compared with hydroquinone, these were mild and reversible. Larger studies comparing cysteamine and hydroquinone are required to support these findings.