bluuebunny/crossref_metadata_2025 huggingface dataset:
Mycosis fungoides and Sézary syndrome tumor cells express epidermal fatty acid‐binding protein, whose expression decreases with loss of epidermotropism
Authors: Takahashi‐Shishido Naomi , Sugaya Makoto , Morimura Soshi , Suga Hiraku , Oka Tomonori , Kamijo Hiroaki , Miyagaki Tomomitsu , Sato Shinichi
Published: February 2021

Fatty acid binding protein (FABP) is a family of transport proteins for fatty acid (FA). Epidermal FABP (E‐FABP) is highly expressed by resident memory T cells (TRM) in the skin. It supports the uptake of exogenous FA for long‐term survival of skin TRM. Mycosis fungoides (MF) is regarded as malignancy of skin TRM. In this study, we investigated E‐FABP expression in psoriasis vulgaris (PV), atopic dermatitis (AD), MF, and Sézary syndrome (SS). E‐FABP mRNA levels in PV were much higher than those in healthy controls. E‐FABP mRNA levels in AD and MF/SS lesional skin were also significantly higher than those of normal skin. By immunohistochemical staining, E‐FABP was positive in MF/SS lesional skin. Interestingly, E‐FABP was stained positive in epidermotropic lymphoid cells in patch, plaque, and erythrodermic lesions of MF/SS, suggesting that a part of tumor cells expressed E‐FABP. In tumorous lesions, however, most dermal tumor cells were negative for E‐FABP. Immunohistochemical staining using patch/plaque lesions and tumorous lesions from the same patients also revealed that E‐FABP expression decreased in tumorous lesions. Our study has suggested that MF/SS tumor cells express E‐FABP, whose expression decreases with loss of epidermotropism.
The effects of resource subsidy duration in a detritus‐based stream ecosystem: A mesocosm experiment
Authors: Sato Takuya , Ueda Rui , Takimoto Gaku
Published: February 2021

Most resource subsidies are temporally variable, dynamically affecting the consumer populations, community structures and ecosystem functions of recipient ecosystems. Temporally variable resource subsidies are characterized by the duration, magnitude, timing and frequency of resource subsidy inputs. These different characteristics may have different mechanisms by which to affect recipient ecosystems.

Few studies have examined the duration of resource subsidy inputs on recipient ecosystems, although there exist previous studies focusing on magnitude, timing and frequency.

We provide the first experimental test of the effects of subsidy duration on a stream ecosystem by using an outdoor mesocosm experiment, in which we directly manipulated the subsidy duration (pulsed vs. prolonged) of terrestrial invertebrate input into the mesocosm.

Given the same overall amount of terrestrial invertebrate subsidy was added, a prolonged subsidy allowed large‐stage fish to effectively monopolize the subsidy over small‐stage fish, which led small‐stage fish to maintain their predation pressure on in‐situ prey, that is, benthic invertebrates. On the other hand, a pulsed subsidy allowed small‐stage fish to increase their feeding rate of the subsidy and to become away from foraging in‐situ prey. Consequently, weaker indirect positive effects on in‐situ benthic prey and leaf break‐down rate were found with the prolonged versus pulsed subsidy. However, these indirect effects varied by the dominant benthic prey species, which differed in edibility for fish. Such predator‐specific vulnerability of benthic prey can be important in mediating trophic cascades in detritus‐based stream food webs.

Phenological events that generate temporal subsidies (e.g. salmon spawning run and arthropod emergence) can be synchronized (pulsed) or desynchronized (prolonged) within and among species, depending on the degree of spatial and temporal environmental heterogeneity. The effects of subsidy duration would thus be important to better understand ecological processes in spatially and temporally coupled ecosystems.
Fast invasives fastly become faster: Invasive plants align largely with the fast side of the plant economics spectrum
Authors: Montesinos Daniel
Published: February 2021

Invasive plants generally align with the fast side of the plant's trait economics spectrum, characterized by fast nutrient acquisition, growth and reproduction. However, there are numerous and notable exceptions, including woody invasives.

The generalization that invasives are fast is driven by the high occurrence of invasive ruderal species colonizing nutrient‐rich disturbed habitats, a consequence of anthropogenic disturbance usually going hand‐in‐hand with biological introductions.

Successful invasive plans have shown a remarkable ability to rapidly adapt to the new regions where they are introduced. These changes predominantly involve increased resource acquisition, growth and reproduction, aligning them even further with the fast side of the plant economics spectrum.

Common garden experiments with invasive model systems provide valuable insights about the speed and direction of adaptive responses to different climates, helping us to predict general plant responses to global change.

Synthesis. Invasive plant species commonly present fast nutrient acquisition, growth and reproduction, but this general pattern is mostly driven by ruderal species. Still, common garden experiments comparing populations from distant world regions show a clear trend for already fast invasive plants to rapidly adapt towards even faster traits in their non‐native regions.
Warming effects on wood decomposition depend on fungal assembly history
Authors: Edman Mattias , Hagos Saba , Carlsson Fredrik
Published: February 2021

Climate warming has the potential to drive changes in fungal community development and dead wood decomposition, but our understanding of this process is obscured by complex interactions between temperature and multiple other factors. A pivotal factor driving decay dynamics is fungal assembly history, yet its response to elevated temperature is poorly understood.

We investigated the combined effect of warming and assembly history on community composition, respiration and decomposition using experimental communities of wood‐decaying fungi on spruce wood. Assembly histories were assigned to microcosms under normal and elevated temperatures in a factorial design.

Both temperature and assembly history influenced wood mass loss and respiration. Temperature was the most important factor, but the effects of warming on decomposition varied greatly with fungal assembly history. Depending on which fungal species colonized first, warming of 5°C increased wood mass loss by 7%–57% after 9 months. The large variation in decomposition response to warming resulted from differential responses in the growth of initial colonizers (pre‐inoculated) and their competitive ability, resulting in different decomposer communities.

Synthesis. Our study demonstrates that temperature and assembly history jointly determine deadwood decomposition and fungal community composition under controlled laboratory conditions. Further investigations are needed to confirm these results under natural conditions. Nevertheless, our findings highlight the importance of considering interactions between priority effects and climate factors to understand forest carbon feedbacks in the context of climate change.
Disturbance of myocardial metabolism participates in autoantibodies against β1‐adrenoceptor‐induced cardiac dysfunction
Authors: Zhao Yuhui , Bai Yan , Li Yang , Dong Yu , Guo Yuhao , Wang Wen , Liu Huirong
Published: February 2021

Cardiac dysfunction is involved in disorders of energy metabolism. High‐titre autoantibodies against the β1‐adrenoceptor (β1‐AAs) have been reported to exist in patients with cardiac dysfunction; however, the mechanism by which β1‐AAs affect cardiac function is unknown. This study aimed to determine whether β1‐AAs disturb myocardium energy metabolism and cause cardiac dysfunction. β1‐AA monoclonal antibodies (β1‐AAmAbs) were successfully pre‐synthesized by hybridoma clones and used in all experiments. β1‐AAmAbs impaired cardiac function and induced a myocardial metabolic disturbance, as evidenced by decreased left ventricular ejection fraction and fractional shortening. In addition, β1‐AAmAbs decreased the adenosine triphosphate level and increased cardiac energy consumption (rate–pressure product). We further showed that the effects of β1‐AAmAbs on heart tissue might involve the mitochondria and metabolic pathways via the β1‐adrenoceptor based on an immunoprecipitation and mass spectrometry. Additionally, we found that β1‐AAmAbs impaired myocardial mitochondrial structure, decreased the membrane potential, and induced insufficient mitophagy. In conclusion, β1‐AAmAb‐induced cardiac dysfunction is partly due to a disturbance in myocardial energy metabolism.
Co‐production of Tet(X) and MCR‐1, two resistance enzymes by a single plasmid
Authors: Xu Yongchang , Liu Lizhang , Zhang Huimin , Feng Youjun
Published: February 2021

Tigecycline and colistin are few of ‘last‐resort’ antibiotic defences used in anti‐infection therapies against carbapenem‐resistant bacterial pathogens. The successive emergence of plasmid‐borne tet(X) tigecycline resistance mechanism and mobile colistin resistance (mcr) determinant, renders them clinically useless. Here, we report that co‐carriage of tet(X6) and mcr‐1 gives co‐resistance to both classes of antibiotics by a single plasmid in Escherichia coli. Tet(X6), the new tigecycline resistance enzyme is functionally defined. Both Tet(X6) and MCR‐1 robustly interfere accumulation of antibiotic‐induced reactive oxygen species (ROS). Unlike that mcr‐1 exerts fitness cost in E. coli, tet(X6) does not. In the tet(X6)‐positive strain that co‐harbors mcr‐1, tigecycline resistance is independently of colistin resistance caused by MCR‐1‐mediated lipid A remodelling, and vice versa. In general consistency with that of MCR‐1, Tet(X6) leads to the failure of tigecycline treatment in the infection model of G. mellonella. Taken together, the co‐production of Tet(X) and MCR‐1 appears as a major clinic/public health concern.
Thresholds of population persistence for the Yangtze finless porpoise: implications for conservation managements
Authors: MEI Zhigang , CHEN Mao , HAN Yi , HAO Yujiang , ZHENG Jinsong , WANG Kexiong , WANG Ding
Published: February 2021

The Yangtze finless porpoise (Neophocaena asiaeorientalis asiaeorientalis), a critically endangered species, is the only cetacean species in the Yangtze River following the functional extinction of baiji (Lipotes vexillifer). To inform conservation actions, two important questions need to be addressed: what is the threshold value of survival rate, and what is the threshold value of population size? We calculate the instantaneous rate of population increase () for the Yangtze finless porpoise for various combinations of the calf and the non‐calf survival rates. We also test the probability of extinction for different minimum carrying capacities for 100 and 500 years using a stable population model. The threshold value of the non‐calf survival rate is never lower than 0.869, but current estimates from field data have been far below this threshold. Our model based on extinction probability and carrying capacity suggests that the threshold for the population size to persist 100 years required 113 animals, and 472 animals are required to persist 500 years. Therefore, we recommend establishing anex situreserve network to guarantee the minimum 100‐year carrying capacity. To ensure the long‐term population viability, we suggest establishing twoin situreserve zones in two lakes and their surrounding reserves to meet a minimum 500‐year carrying capacity. In addition, measures to avoid further habitat fragmentation should be priority.
Early divergence and differential population histories of the Indo‐Pacific humpback dolphin in the Pacific and Indian Oceans
Authors: ZHAO Liyuan , SAKORNWIMON Watchara , LIN Wenzhi , ZHANG Peijun , CHANTRA Rachawadee , DAI Yufei , AIERKEN Reyilamu , WU Fuxing , LI Songhai , KITTIWATTANAWONG Kongkiat , WANG Xianyan
Published: February 2021

The currently recognized Indo‐Pacific humpback dolphin occurs in estuaries and surrounding shallow waters from the South China Sea to the Asian coast of the Indian Ocean. However, a recent study suggested that the humpback dolphin from the Bay of Bengal may represent a distinct phylogenetic species. In this study, we sequenced 915‐bp mtDNA segments from five geographic populations in both Chinese and Thai waters; together with previously published sequences, these data revealed that the ancestral Indo‐Pacific humpback dolphin might have split during the transition from the Oligocene to Miocene (23.45 Mya, 95% HPD: 16.65–26.55 Mya), and then dispersed along the Pacific and Indian Ocean coasts of Asia. Genetic differentiation was detected between most of the examined populations, except for only a few pairwise populations in the northern South China Sea. Genetic differentiation/distance between the humpback dolphins from the northern and southern South China Sea met the sub‐species threshold value proposed for marine mammals, whereas that between the humpback dolphins in the Pacific and the Indian Ocean was above the species threshold. Bayesian inference of historic gene flow indicated low but constant northward gene flow along the Indian Ocean coast; however, there was a recent abrupt increase in gene flow in the Pacific region, likely due to the shortening coastline at the low stand of sea level. Our results revealed that the current taxonomic classification of Indo‐Pacific humpback dolphins may not reflect their phylogeography.
Pairwise linkage disequilibrium estimation for polyploids
Authors: Gerard David
Published: February 2021

Many tasks in statistical genetics involve pairwise estimation of linkage disequilibrium (LD). The study of LD in diploids is mature. However, in polyploids, the field lacks a comprehensive characterization of LD. Polyploids also exhibit greater levels of genotype uncertainty than diploids, yet no methods currently exist to estimate LD in polyploids in the presence of such genotype uncertainty. Furthermore, most LD estimation methods do not quantify the level of uncertainty in their LD estimates. Our study contains three major contributions. (i) We characterize haplotypic and composite measures of LD in polyploids. These composite measures of LD turn out to be functions of common statistical measures of association. (ii) We derive procedures to estimate haplotypic and composite LD in polyploids in the presence of genotype uncertainty. We do this by estimating LD directly from genotype likelihoods, which may be obtained from many genotyping platforms. (iii) We derive standard errors of all LD estimators that we discuss. We validate our methods on both real and simulated data. Our methods are implemented in the R package ldsep, available on the Comprehensive R Archive Network https://cran.r‐project.org/package=ldsep.
A potential third‐order role of the host endoplasmic reticulum as a contact site in interkingdom microbial endosymbiosis and viral infection
Authors: Almeida Celso
Published: February 2021

The normal functioning of eukaryotic cells depends on the compartmentalization of metabolic processes within specific organelles. Interactions among organelles, such as those between the endoplasmic reticulum (ER) – considered the largest single structure in eukaryotic cells – and other organelles at membrane contact sites (MCSs) have also been suggested to trigger synergisms, including intracellular immune responses against pathogens. In addition to the ER‐endogenous functions and ER‐organelle MCSs, we present the perspective of a third‐order role of the ER as a host contact site for endosymbiotic microbial non‐pathogens and pathogens, from endosymbiont bacteria to parasitic protists and viruses. Although understudied, ER‐endosymbiont interactions have been observed in a range of eukaryotic hosts, including protists, plants, algae, and metazoans. Host ER interactions with endosymbionts could be an ER function built from ancient, conserved mechanisms selected for communicating with mutualistic endosymbionts in specific life cycle stages, and they may be exploited by pathogens and parasites. The host ER‐‘guest’ interactome and traits in endosymbiotic biology are briefly discussed. The acknowledgment and understanding of these possible mechanisms might reveal novel evolutionary perspectives, uncover the causes of unexplained cellular disorders and suggest new pharmacological targets.
Discovery of a macromolecular complex mediating the hunger suppressive actions of cocaine: Structural and functional properties
Authors: Casanovas Mireia , Jiménez‐Rosés Mireia , Cordomí Arnau , Lillo Alejandro , Vega‐Quiroga Ignacio , Izquierdo Joan , Medrano Mireia , Gysling Katia , Pardo Leonardo , Navarro Gemma , Franco Rafael
Published: February 2021

Cocaine not only increases brain dopamine levels but also activates the sigma1 receptor (σ1R) that in turn regulates orexigenic receptor function. Identification of interactions involving dopamine D1 (D1R), ghrelin (GHS‐R1a), and σ1 receptors have been addressed by biophysical techniques and a complementation approach using interfering peptides. The effect of cocaine on receptor functionality was assayed by measuring second messenger, cAMP and Ca2+, levels. The effect of acute or chronic cocaine administration on receptor complex expression was assayed by in situ proximity ligation assay. In silico procedures were used for molecular model building. σ1R KO mice were used for confirming involvement of this receptor. Upon identification of protomer interaction and receptor functionality, a unique structural model for the macromolecular complex formed by σ1R, D1R, and GHS‐R1a is proposed. The functionality of the complex, able to couple to both Gs and Gq proteins, is affected by cocaine binding to the σ1R, as confirmed using samples from σ1R−/− mice. The expression of the macromolecular complex was differentially affected upon acute and chronic cocaine administration to rats. The constructed 3D model is consistent with biochemical, biophysical, and available structural data. The σ1R, D1R, and GHS‐R1a complex constitutes a functional unit that is altered upon cocaine binding to the σ1R. Remarkably, the heteromer can simultaneously couple to two G proteins, thus allowing dopamine to signal via Ca2+ and ghrelin via cAMP. The anorexic action of cocaine is mediated by such complex whose expression is higher after acute than after chronic administration regimens.
Who would be targeted by increasing the legal age of sale of cigarettes from 18 to 21? A cross‐sectional study exploring the number and characteristics of smokers in England
Authors: Beard Emma , Brown Jamie , Jackson Sarah E. , West Robert , Anderson Will , Arnott Deborah , Shahab Lion
Published: February 2021

Aims

To establish the number of smokers in England who would be targeted by increasing the age of sale of cigarettes from 18 to 21 years and to assess the smoking and socio‐demographic profile of those smokers.

Design and setting

Nationally representative cross‐sectional survey of adults in England conducted between January 2009 and July 2019.

Participants

A total of 219 720 adults.

Measurements

All participants reported their current smoking status and socio‐demographic characteristics (i.e. age, gender, home ownership, social grade and ethnicity). Smokers reported motivation to quit, urges to smoke and the Heaviness of Smoking Index (HIS). Weighted prevalence statistics were calculated. Multinomial regression and logistic regression were used to assess differences in smoking characteristics among smokers and socio‐demographic characteristics relative to non‐smokers.

Findings

The prevalence of smoking between January 2009 and July 2019 was highest among those aged 21–30. In 2019, 15.6% [95% confidence interval (CI) = 12.8–18.8%] of 18–20‐year‐olds reported smoking, which is estimated to represent 364 000 individuals in England. Relative to smokers aged 18–20, older smokers (aged 21+) had a higher motivation to quit smoking [odds ratios (ORs) = 1.40–1.45 range] and higher nicotine dependency as measured by urges to smoke (ORs = 1.06–1.24 range) and HSI (ORs = 1.05–2.85 range). Compared with non‐smokers aged 18–20, smokers in this age group had lower odds of being female (OR = 0.89) and higher odds of being of white ethnicity (OR = 2.78) and from social grades C1–E (lower social grades) compared with AB (higher social grades) (OR = 1.19–1.83 range).

Conclusion

Increasing the age of sale of cigarettes to 21 years in England would currently target approximately 364 000 lower dependent smokers from more disadvantaged backgrounds aged 18–20, who have less motivation to quit.
Content analysis of cannabis vaping videos on YouTube
Authors: Lim Carmen C. W. , Leung Janni , Chung Jack Yiu Chak , Sun Tianze , Gartner Coral , Connor Jason , Hall Wayne , Chiu Vivian , Tisdale Calvert , Stjepanović Daniel , Chan Gary
Published: February 2021

Background and Aims

There has been an increase in the potency of cannabis during the last two decades and adoption of a novel method of administration—vaping. YouTube, a social media platform, has become a popular source to access cannabis‐related information. This study aimed to identify cannabis vaping YouTube videos from 2016 to 2020 and examine the themes and metrics.

Design

Cross‐sectional sample of 200 YouTube videos.

Setting

YouTube, an on‐line video sharing platform.

Measurements

Videos related to cannabis vaping were identified using the search terms: ‘vaping cannabis’, ‘vaping weed’, ‘vaping marijuana’ and ‘vaping THC’ [tetrahydrocannabinol]. Videos were independently coded by two researchers. The number of views, likes, dislikes and comments were also collected. Robust regression was used to analyse the relationship between identified video themes and video metrics.

Findings

Six themes were identified: ‘advertisement’, ‘product review’, ‘celebratory’, ‘reflective’, ‘how‐to’ and ‘warning’. The ‘how‐to’ and ‘celebratory’ videos received the highest number of views and likes. The most popular video was viewed more than 4 000 000 times. Many videos portrayed risky behaviour (e.g. vaping a whole THC cartridge in a single setting). Fifty‐two percent of these videos had no age access restrictions. The robust regression model also found that engagement metric was positively associated with ‘reflective’ videos and negatively associated with ‘advertisement’ videos.

Conclusions

A large number of videos on cannabis vaping are available on‐line without age‐restriction. Videos that portrayed risky behaviour appear to be prevalent.
Modelling the number of avoidable new cancer cases in France attributable to alcohol consumption by following official recommendations: a simulation study
Authors: Ren Yan , Chase Earl , d'Almeida Tania , Allègre Julien , Latino‐Martel Paule , Deschamps Valérie , Arwidson Pierre , Etilé Fabrice , Hercberg Serge , Touvier Mathilde , Julia Chantal
Published: February 2021

Aims

To predict the effects of perfect adherence to the French alcohol consumption guidelines, a maximum of 10 standard alcoholic drinks per week with no more than two standard alcoholic drinks per day, during a 36‐year period (2014–50).

Design

This simulation study is an adaption of the Sheffield Alcohol Policy Model. The dose–response relationship between alcohol consumption and alcohol‐attributable cancer risks was defined by cancer site‐specific risk functions, each modelled as a continuous risk. These estimates were used to compute the potential impact fraction (PIF) associated with alcohol consumption by cancer site.

Setting

The French general adult population during a 36‐year period (2014–50).

Participants

For the baseline scenario, the current distribution of consumption levels, the counterfactual scenario and perfect adherence to the French alcohol consumption guidelines, we generated for each gender and age group 1000 randomly distributed alcohol consumption values from calibrated group‐specific gamma distribution.

Measurements

The predicted number of new cancer cases among men and women in France between 2015 and 2050 that could have been prevented by following the French government's alcohol consumption guidelines.

Findings

The simulation predicted that perfect adherence to the French government's alcohol consumption guidelines would prevent, on average, an estimated 15 952 cancer cases per year after the PIF reached its full effect, which would have represented 4.5% of new cancer cases in 2015. The number of averted cancer cases over the study period were highest for oral cavity, oropharynx and hypopharynx cancer (respectively, 118 462, 95% CI = 113 803–123 022 and 11 167, 95% CI = 10 149–12 229] for men and women; liver and intrahepatic bile ducts cancer (123 447, 95% CI = 112 581–133 404 and 2825, 95% CI = 2208,4095); colorectal cancer (89 859, 95% CI = 84 651–95 355 and 12 847, 95% CI = 11 545–14 245); and female breast cancer (61 649, 95% CI = 56 330–67 452).

Conclusion

This simulation study of the French general population predicted that perfect adherence to the French government's alcohol consumption guidelines (no more than 10 standard alcoholic drinks per week and two per day) would prevent almost 16 000 cancer cases per year.
Random Utility Models, Wine and Experts
Authors: Villas‐Boas Sofia B. , Bonnet Céline , Hilger James
Published: February 2021

We empirically investigate the welfare effects of providing product quality information to consumers in the form of expert opinion scores in a setting of asymmetric information. Identification of the effects of the provision of information comes from a field experiment in the retail wine market. We use a monthly‐product‐store panel scanner data set, collected before and during the field experiment, which involves treating a random subset of wine products by displaying expert scores in one store and comparing sales in similar non‐treated stores. Using a structural random utility model of demand, we show that, on average, consumers significantly value one score point increase due to the treatment by about 0.5 to 0.7 cents. As a consequence, for a bottle featuring an average score of 83, consumers would be willing to pay additionally between twenty and sixty cents more due to the treatment. Using counterfactual scenarios, we find that adding expert opinion shelf labels increases consumer surplus. In addition, allowing for strategic price reactions by retailers would lead to an overall significant welfare improvement given that (a) consumers significantly value the score information albeit facing higher prices, and (b) the profits increase with the market power of firms.
A population‐based combination strategy to improve the cervical cancer screening coverage rate in Bamako, Mali
Authors: Téguété Ibrahima , Tounkara Fatoumata K. , Diawara Broulaye , Traoré Sidy , Koné Diakaridia , Bagayogo Aliou , Sissoko Abdoulaye , Traoré Cheick B.
Published: February 2021

Introduction

Cervical cancer screening coverage rate is <5% in Sub‐Saharan Africa and <2% in French‐ speaking African countries. In 2016, we implemented strategies to improve cervical cancer screening in Bamako, the “Weekend70 program”. The present study objectives are to determine the effect of this program on women’s participation in cervical cancer screening in Bamako, and to estimate the cervical cancer screening coverage rate in Bamako.

Material and methods

From 1 January 2016 to 31 July 2020, we conducted an operational research by developing several strategies to improve the cervical cancer screening coverage rate among adolescents and women ≥15 years old in Bamako, Mali. The strategies consisted of awareness‐raising activities, strengthening of screening practices in healthcare facilities and cost‐free cervical cancer screening during the weekend. Descriptive statistics were presented. The cervical cancer coverage rate was calculated by dividing the number of women screened by the total number of women ≥20 years old, based on Mali demographic data.

Results

The total number of women screened was 289 924. Residents from Bamako represented 91.9% (266 436/289 924) vs 8.1% (23 488/289 924) who lived outside Bamako. The mean age was 33.2 (± 11.5) years old. Around 46.1% of participants attending the cervical cancer screening were between 30 and 49 years old (World Health Organization prioritized target age for cervical cancer screening). Women ≥60 years old represented <5%. Cervical cancer screening participation increased significantly, from <800 women screened per week before the implementation of the program to a peak of 4100 women screened per week during the “Weekend70 program”. Overall, the cervical cancer screening coverage rates at the end of the study among women ≥20 years old was 47.3%, and 56.9% in the WHO target population.

Conclusion

In an impoverished context, a multi‐component strategy significantly increases cervical cancer screening participation.
A high gas transfer efficiency microfluidic oxygenator for extracorporeal respiratory assist applications in critical care medicine
Authors: Gimbel Alla A. , Hsiao James C. , Kim Ernest S. , Lewis Diana J. , Risoleo Thomas F. , Urban Joseph N. , Borenstein Jeffrey T.
Published: February 2021

Advances in microfluidics technologies have spurred the development of a new generation of microfluidic respiratory assist devices, constructed using microfabrication techniques capable of producing microchannel dimensions similar to those found in human capillaries and gas transfer films in the same thickness range as the alveolar membrane. These devices have been tested in laboratory settings and in some cases in extracorporeal animal experiments, yet none have been advanced to human clinical studies. A major challenge in the development of microfluidic oxygenators is the difficulty in scaling the technology toward high blood flows necessary to support adult humans; such scaling efforts are often limited by the complexity of the fabrication process and the manner in which blood is distributed in a three‐dimensional network of microchannels. Conceptually, a central advantage of microfluidic oxygenators over existing hollow‐fiber membrane‐based configurations is the potential for shallower channels and thinner gas transfer membranes, features that reduce oxygen diffusion distances, to result in a higher gas transfer efficiency defined as the ratio of the volume of oxygen transferred to the blood per unit time to the active surface area of the gas transfer membrane. If this ratio is not significantly higher than values reported for hollow fiber membrane oxygenators (HFMO), then the expected advantage of the microfluidic approach would not be realized in practice, potentially due to challenges encountered in blood distribution strategies when scaling microfluidic designs to higher flow rates. Here, we report on scaling of a microfluidic oxygenator design from 4 to 92 mL/min blood flow, within an order of magnitude of the flow rate required for neonatal applications. This scaled device is shown to have a gas transfer efficiency higher than any other reported system in the literature, including other microfluidic prototypes and commercial HFMO cartridges. While the high oxygen transfer efficiency is a promising advance toward clinical scaling of a microfluidic architecture, it is accompanied by an excessive blood pressure drop in the circuit, arising from a combination of shallow gas transfer channels and equally shallow distribution manifolds. Therefore, next‐generation microfluidic oxygenators will require novel design and fabrication strategies to minimize pressure drops while maintaining very high oxygen transfer efficiencies.
EMBRACE: An EM‐based bias reduction approach through Copas‐model estimation for quantifying the evidence of selective publishing in network meta‐analysis
Authors: Marks‐Anglin Arielle , Luo Chongliang , Piao Jin , Gibbons Mary Beth Connolly , Schmid Christopher H. , Ning Jing , Chen Yong
Published: February 2021

Systematic reviews and meta‐analyses synthesize results from well‐conducted studies to optimize healthcare decision‐making. Network meta‐analysis (NMA) is particularly useful for improving precision, drawing new comparisons, and ranking multiple interventions. However, recommendations can be misled if published results are a selective sample of what has been collected by trialists, particularly when publication status is related to the significance of the findings. Unfortunately, the missing‐not‐at‐random nature of this problem and the numerous parameters involved in modeling NMAs pose unique computational challenges to quantifying and correcting for publication bias, such that sensitivity analysis is used in practice. Motivated by this important methodological gap, we developed a novel and stable expectation‐maximization (EM) algorithm to correct for publication bias in the network setting. We validate the method through simulation studies and show that it achieves substantial bias reduction in small to moderately sized NMAs. We also calibrate the method against a Bayesian analysis of a published NMA on antiplatlet therapies for maintaining vascular patency.
Ruxolitinib‐combined doxorubicin‐etoposide‐methylprednisolone regimen as a salvage therapy for refractory/relapsed haemophagocytic lymphohistiocytosis: a single‐arm, multicentre, phase 2 trial
Authors: Wang Jingshi , Zhang Rui , Wu Xiaoyan , Li Fei , Yang Haixia , Liu Ligen , Guo Haixia , Zhang Xuejun , Mai Huirong , Li Hui , Wang Zhao
Published: February 2021

We performed a multicentre, non‐randomised trial (NCT03533790) to investigate the efficacy of ruxolitinib combined with the doxorubicin‐etoposide‐methylprednisolone (Ru‐DEP) regimen as a salvage therapy for refractory/relapsed haemophagocytic lymphohistiocytosis (HLH). All patients failing to achieve a complete or partial response 2 weeks after initial HLH‐94/HLH‐04 regimen or relapsed after remission were enrolled in the study between June 2018 and June 2019. The efficacy was evaluated 2 weeks after initiating Ru‐DEP salvage therapy. Fifty‐four eligible patients with refractory/relapsed (R/R) HLH were enrolled. One case could not be evaluated for efficacy. Excluding 12 patients who had previously received the DEP regimen, the overall response rate was 32 of 41 (78·0%) patients, with eight of 41 (19·5%) achieving complete response and 24 of 41 (58·5%) attaining a partial response. Of the R/R HLH patients who had previously received the DEP regimen, 7 of 12 (58·3%) achieved a partial response. Ferritin and soluble CD25 concentrations were significantly lower (P < 0·05), while the platelet count increased significantly (P = 0·034), and triglycerides decreased significantly (P = 0·002) compared with those before treatment. The Ru‐DEP regimen may be a safe and effective salvage therapy, remaining effective in refractory/relapsed HLH following DEP treatment, especially in macrophage activation syndrome. In addition, the regimen can be considered for patients with contraindications to glucocorticoid, especially those with gastrointestinal bleeding.
Seed dispersal effectiveness by oilbirds (Steatornis caripensis) in the Southern Andes of Colombia
Authors: Cárdenas Sasha , Echeverry‐Galvis María Ángela , Stevenson Pablo R.
Published: February 2021

Oilbirds are specialized frugivores that disperse seeds; however, no study has evaluated their seed dispersal effectiveness (SDE). We estimated SDE for nine plant species and tested if high‐altitude plants are more effectively dispersed than lowland species and if there are high SDE scores in non‐breeding periods of oilbirds. The quantity factor was estimated from seed rain data in the main cave of Cueva de Los Guacharos National Park (Colombia). The quality component considered germination chance, the probability that seeds reach suitable habitats (using data from GPS devices on three birds) and the probability of establishment in different habitats (literature review). Our model showed that the habitat with more seedrain was the cave (41%), followed by dense forest and mosaics of crops and forests (both ca. 20%). Seed germination was evidenced in 7 of the species, and the other two indicated viability (using tetrazolium tests). The most dispersed species corresponded to palms (Prestoea acuminata and Geonoma undata), but, in terms of biomass, P. acuminata and Dacryodes olivifera (Burseraceae) were the top species. D. olivifera, G. undata, and P. acuminata showed the highest SDE values. No relationship was found between the probability of arrival to suitable habitats and the altitudinal level of the species, but the oilbirds were more effective dispersing seeds in non‐breeding periods. Despite a large amount of seeds dropped at the caves, oilbirds disperse seed to suitable habitats, move seeds long distances, and disperse large seeds. As some of these ecosystem services are unique, oilbird's conservation seems imperative.

Abstract in Spanish is available with online material.
W2476 represses TXNIP transcription via dephosphorylation of FOXO1 at Ser319
Authors: Zhong Li , Liu Qing , Liu Qiaofeng , Zhang Shikai , Cao Yongbing , Yang Dehua , Wang Ming‐Wei
Published: February 2021

Thioredoxin‐interacting protein (TXNIP) overexpression is implicated in the pathogenesis of type 2 diabetes. Previous studies have shown that a small molecule compound (W2476) was able to improve β‐cell dysfunction and exert therapeutic effects in diabetic mice via repression of TXNIP signaling pathway. The impact of W2476 on TXNIP transcription was thus investigated using the chromatin immunoprecipitation method. It was found that W2476 promotes competitive binding of forkhead box O1 transcription factor (FOXO1) to the carbohydrate response element (ChoRE) sequence associated with ChoRE‐binding protein (ChREBP)/Mlx interacting protein‐like(Mlx) complexes. This interaction hinders the attachment of histone acetyltransferase p300 and reduces histone H4 acetylation on the TXNIP promoter, leading to decreasing TXNIP transcription.
Health professionals' views and experiences of discussing weight with children and their families: A systematic review of qualitative research
Authors: Abdin Shanara , Heath Gemma , Welch Richard K.
Published: February 2021

Background

Healthcare professionals are ideally placed to discuss weight management with children and families to treat and prevent childhood obesity. The aim of this review was to collect and synthesize primary research evidence relating to health professional's views and experiences of discussing weight with children and their families.

Methods

Systematic searches were conducted using the following databases: MEDLINE (OVID), Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE (OVID), PsycINFO (OVID) and Healthcare Management Information Consortium (HMIC). Twenty‐six full text qualitative studies published in English Language journals since inception to October 2019 were included. Papers were quality assessed and synthesized using an inductive thematic analysis approach.

Results

Data analysis generated five themes: sensitivity of the issue, family–professional relationships, whole systems approach, professional competency and sociocultural context.

Conclusion

Supporting behaviour change through discussion of healthy weight with children and families is an important part of the health professional's role. Tailored information for professionals, including resources and training, facilitates them to confidently talk to children and families about weight prioritized within interventions. The success of such interventions requires commitment from a range of professionals to ensure healthy weight is tackled through a whole system approach.
The impact of a needs‐based model of care on accessibility and quality of care within children's mental health services: A qualitative investigation of the UK i‐THRIVE Programme
Authors: Farr Joanna , Moore Anna , Bruffell Hilary , Hayes Jacqueline , Rae John P. , Cooper Mick
Published: February 2021

Background

The i‐THRIVE Programme is a needs‐based model of care, based on the THRIVE Framework, that is being implemented across the United Kingdom with the aim of improving outcomes for children and young people's mental health and wellbeing. This study aimed to investigate the impact that this programme has on accessibility and quality of care, as viewed by key stakeholders.

Methods

Interviews with professionals and service users were conducted during the implementation of the THRIVE Framework in four sites of one mental health and community service provider.

Results

Three themes are identified: ‘impact of needs‐based groupings on referral’, ‘impact of collaborative and interagency approach’ and ‘impact of i‐THRIVE on clinical practice’. Findings suggest that accessibility was seen to be promoted through the integration of a needs‐based approach, flexible re‐referral, signposting and information sharing, the use of goal‐orientated interventions and collaboration over risk and treatment endings. Shared decision making was perceived to improve the experience of care for young people, as was interagency working. Goal‐focused interventions and upfront discussion of treatment endings were seen to help clinicians manage expectations and discharge but could also compromise effectiveness and engagement. Obstacles to impact were resistance to interagency working and a shortage of resources across the system.

Conclusions

i‐THRIVE is a promising approach with the potential to facilitate the accessibility and quality of mental health care. However, a tension exists between enhancing accessibility and quality of care, which points towards the importance of outcome and satisfaction monitoring. Obstacles to impact point to the importance of a whole‐system approach supported by sufficient resources across the locality.
Guidance on the clinical understanding and use of long‐acting injectable antipsychotics in Schizophrenia: Hong Kong Consensus Statements
Authors: Wong Michael Ming Cheuk , Chung Albert Kar Kin , Yeung Timothy Ming Hong , Wong David Tai Wai , Lee Che Kin , Lai Eric , Chan Gloria Fong Yeung , Mak Gregory Kai Lok , Wong Jessica Oi Yin , Ng Roger Man Kin , Mak Ki Yan
Published: February 2021

Aims

There is increasing evidence showing the importance of long‐acting injectable antipsychotics in the management of schizophrenia, especially in terms of improving patient medication compliance. A panel of experienced clinicians in Hong Kong mapped out a set of consensus statements with an aim to facilitate the understanding and use of long‐acting injectable antipsychotics among local physicians.

Methods

Eight discussion areas regarding long‐acting injectable antipsychotics were selected by the chairman of the consensus group. A series of meetings were held for the panelists to discuss the published literature and their clinical experience, followed by the drafting of consensus statements. At the final meeting, each consensus statement was voted on anonymously by all members based on its practicability of recommendation in Hong Kong.

Results

A total of 12 consensus statements on the rational use of long‐acting injectable antipsychotics were established and accepted by the consensus group.

Conclusion

The consensus statements aim to provide practical guidance for Hong Kong physicians on the use of long‐acting injectable antipsychotics in schizophrenia patients. These statements may also serve as a reference for doctors in other parts of the Asia–Pacific region.
Rear‐edge populations are important for understanding climate change risk and adaptation potential of threatened species
Authors: Habibzadeh Nader , Ghoddousi Arash , Bleyhl Benjamin , Kuemmerle Tobias
Published: February 2021

Climate change disproportionately threatens alpine species, by reducing available habitat and by isolating their populations. These pressures are particularly relevant for rear‐edge populations, which typically occupy more marginal habitat compared to populations at the core of species' ranges. We studied Caucasian grouse Lyrurus mlokosiewiczi in the Caucasus ecoregion, a global biodiversity hotspot where this species is endemic, to understand potential climate change impacts on the species. Specifically, we assessed how climate change impacts rear‐edge populations and how important these populations are for understanding range shifts and adaptive capacity under climate change. We used maximum entropy modeling to assess changes in the distribution of climatically suitable habitat under present and 2070 climate conditions for the representative concentration pathways 8.5 (RCP8.5). Our results revealed that ignoring rear‐edge populations leads to a significant underestimation of the future range (by about 14,700 km2). Rear‐edge populations were better adapted to warmer climates compared to core populations, and ignoring them, therefore, also underestimates adaptive capacity. Preventing the loss of rear‐edge populations should, therefore, be a priority for conservation planning in the face of climate change. Because the Caucasian grouse is associated with alpine mountain tops, conservation should focus on establishing connectivity between rear‐edge and core populations (e.g., via transboundary corridors or assisted colonizations). Our study reveals how species distribution modeling can highlight the importance of rear‐edge populations for mitigating climate change impacts on species of conservation concern.
Associations between attainment of incentivized primary care indicators and incident sight‐threatening diabetic retinopathy in England: A population‐based historical cohort study
Authors: McKay Ailsa J. , Gunn Laura H. , Nugawela Manjula D. , Sathish Thirunavukkarasu , Majeed Azeem , P. Vamos Eszter , Molina German , Sivaprasad Sobha
Published: February 2021

Aim

To examine the impact of attainment of primary care diabetes clinical indicators on progression to sight‐threatening diabetic retinopathy (STDR) among those with mild non‐proliferative diabetic retinopathy (NPDR).

Materials and Methods

An historical cohort study of 18,978 adults (43.63% female) diagnosed with type 2 diabetes before 1 April 2010 and mild NPDR before 1 April 2011 was conducted. The data were obtained from the UK Clinical Practice Research Datalink during 2010‐2017, provided by 330 primary care practices in England. Exposures included attainment of the Quality and Outcomes Framework HbA1c (≤59 mmol/mol [≤7.5%]), blood pressure (≤140/80 mmHg) and cholesterol (≤5 mmol/L) indicators in the financial year 2010‐2011, as well as the number of National Diabetes Audit processes completed in 2010‐2011. The outcome was time to incident STDR. Nearest neighbour propensity score matching was undertaken, and univariable and multivariable Cox proportional hazards models were then fitted using the matched samples. Concordance statistics were calculated for each model.

Results

A total of 1037 (5.5%) STDR diagnoses were observed over a mean follow‐up of 3.6 (SD 2.0) years. HbA1c, blood pressure and cholesterol indicator attainment were associated with lower rates of STDR (adjusted hazard ratios [95% CI] 0.64 [0.55‐0.74; p < .001], 0.83 [0.72‐0.94; p = .005] and 0.80 [0.66‐0.96; p = .015], respectively).

Conclusions

Our findings provide support for meeting appropriate indicators for the management of type 2 diabetes in primary care to bring a range of benefits, including improved health outcomes—such as a reduction in the risk of STDR—for people with type 2 diabetes.