bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of glia in the physiology and pharmacology of glucagon‐like peptide‐1: implications for obesity, diabetes, neurodegeneration and glaucoma
Authors: Cui Qi N. , Stein Lauren M. , Fortin Samantha M. , Hayes Matthew R.
Published: September 2021

The medical applications of glucagon‐like peptide‐1 receptor (GLP‐1R) agonists is evergrowing in scope, highlighting the urgent need for a comprehensive understanding of the mechanisms through which GLP‐1R activation impacts physiology and behaviour. A new area of research aims to elucidate the role GLP‐1R signalling in glia, which play a role in regulating energy balance, glycemic control, neuroinflammation and oxidative stress. Once controversial, existing evidence now suggests that subsets of glia (e.g. microglia, tanycytes and astrocytes) and infiltrating macrophages express GLP‐1Rs. In this review, we discuss the implications of these findings, with particular focus on the effectiveness of both clinically available and novel GLP‐1R agonists for treating metabolic and neurodegenerative diseases, enhancing cognition and combating substance abuse.

LINKED ARTICLES

This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc
Commentary: Getting kids what they need, where they are, when they need it: home‐based services in a continuum of care – a commentary on Boege et al. (2021)
Authors: Simmons Shannon , McClellan Jon
Published: September 2021

In this edition of CAMH, Boege and colleague’s 4‐year follow‐up study supports intensive home‐based treatment as a viable alternative to inpatient hospitalization. Youth receiving home‐based multimodal treatment fared just as well as those who remained hospitalized longer, with higher parental satisfaction. This study contributes to a sparse evidence base regarding longitudinal outcomes of psychiatric inpatient and intensive outpatient treatments for children and adolescents. Although mental illness is prevalent and increasing among youth, existing systems of care are often inadequate to provide flexible, effective, interdisciplinary team‐based treatments, and supports for children and their families. Innovative approaches to providing evidence‐based care and tracking outcomes are needed to strengthen the continuum of care.
The flip side of reactive oxygen species in the tropical disease‐Amoebiasis
Authors: Desure Sakshi , Mallika Arya , Roy Mrinalini , Jyoti Anupam , Kaushik Sanket , Srivastava Vijay Kumar
Published: September 2021

Entamoeba histolytica is the conductive agent of amoebiasis. Upon the parasite's infection, macrophages and neutrophils are activated by interferon γ, IL‐13 and tumour necrosis factor. These immune cells then carry out the amoebicidal activity by releasing nitric oxide synthase and reactive oxygen species (ROS). This review talks about the protective and destructive role of ROS in Eh. E. histolytica has defence strategies against oxidative stress which is a result of excess ROS production. They possess antioxidants for their defence such as L‐Cysteine, flavodiiron proteins, peroxiredoxin and trichostatin A, which contribute to the parasite’s virulence. The ROS are harmful to the host cells as excess ROS production stimulates cell death by mechanisms like apoptosis and necroptosis. NADPH oxidase (NOX) is a key source of ROS in mammalian cells and causes apoptosis of host cells via the protein kinase transduction pathway. This review provides insights into why NOX inhibitors that could be a potent antiparasitic drug, is not effective for in vivo purposes. This paper also gives an insight into a solution that could be a potent source in generating new treatment and vaccines for amoebiasis by targeting parasite development.
Chromones: Privileged scaffold in anticancer drug discovery
Authors: Patil Vaishali M. , Masand Neeraj , Verma Saroj , Masand Vijay
Published: September 2021

In the design and discovery of anticancer drugs, various natural heterocyclic scaffolds have attracted considerable interest as privileged structures. For rational drug design, some of the natural scaffolds such as chromones have exhibited wide acceptability due to their drug‐like properties. Among the approved anticancer drugs, the scaffolds with high selectivity for a small group of closely related targets are of importance. In the development of selective anticancer agents, the natural, as well as synthetic, can generate highly selective compounds toward cancer targets. The present manuscript includes more particularly the development of cancer inhibitors incorporating the chromone scaffold, with a strong emphasis on their molecular interactions in the anticancer mechanism. It also includes the structure‐activity relationship studies and related examples of lead optimization.
Bezafibrate induces hypothyroidism in a patient with resistance to thyroid hormone β due to a G347R variant
Authors: Yamauchi Ichiro , Yamashita Takafumi , Sugawa Taku , Tagami Tetsuya , Hanaoka Ikuko , Usui Takeshi , Hirota Keisho , Hakata Takuro , Ueda Yohei , Fujii Toshihito , Sakane Yoriko , Yasoda Akihiro , Inagaki Nobuya
Published: September 2021

Objective

A unique clinical course was observed in a patient with resistance to thyroid hormone β (RTHβ) caused by a variant of the THRB gene leading to the replacement of glycine with arginine in codon 347 (p.G347R). He presented with the syndrome of inappropriate secretion of thyrotropin (TSH) (free T4 [fT4]: 32.43 pmol/L, TSH: 4.67 mIU/L), but slowly developed progressive hypothyroidism (fT4: 8.37 pmol/L, TSH: 100.90 mIU/L) that resolved after suspending bezafibrate (BZ) treatment (fT4: 32.18 pmol/L, TSH: 7.14 mIU/L). This study clinically and experimentally evaluated this interesting phenomenon.

Methods

A retrospective cohort analysis of non‐RTHβ patients was performed at Kyoto University Hospital. Data before BZ treatment were compared to the first data after treatment. Using reporter assays of iodothyronine deiodinases (DIO1, DIO2, DIO3) in HEK293T cells, we performed functional analyses of mutant thyroid hormone receptor β with p.G347R (G347R TRβ). Mice with G347R TRβ were generated by hydrodynamic gene delivery.

Results

In non‐RTHβ patients (n = 7), BZ treatment did not change serum free T3 and TSH but significantly increased fT4 (p = .008). BZ administration increased DIO3 reporter activity in the context of G347R TRβ, whereas did not change DIO1 and DIO2 reporter activity. In the livers of mice with G347R TRβ, BZ administration increased reverse T3 content, which corresponded to an increase in Dio3 messenger RNA.

Conclusions

While hypothyroidism associated with BZ treatment did not occur in non‐RTHβ patients, it was observed in a patient with RTHβ due to the p.G347R variant. Liver DIO3 upregulation might involve this hypothyroidism.
Opioid agonist treatment and patient outcomes during the COVID‐19 pandemic in south east Sydney, Australia
Authors: Lintzeris Nicholas , Deacon Rachel M. , Hayes Victoria , Cowan Tracy , Mills Llewellyn , Parvaresh Laila , Harvey Dodds Lucy , Jansen Louisa , Dojcinovic Raelene , Leung Man Cho , Demirkol Apo , Finch Therese , Mammen Kristie
Published: September 2021

Introduction

In early 2020, many services modified their delivery of opioid treatment in response to the COVID‐19 pandemic, to limit viral spread and maintain treatment continuity. We describe the changes to treatment and preliminary analysis of the association with patients' substance use and well‐being.

Methods

A pre‐post comparison of treatment conditions and patient self‐reported outcomes using data extracted from electronic medical records in the 5 months before (December 2019–April 2020) and after (May 2020–September 2020) changes were implemented in three public treatment services in South Eastern Sydney Local Health District.

Results

Data are available for 429/460 (93%) patients. Few (21, 5%) dropped out of treatment. In the ‘post’ period there was significantly more use of depot buprenorphine (12–24%), access to any take‐away doses (TAD; 24–69%), access to ≥6 TAD per week (7–31%), pharmacy dosing (24–52%) and telehealth services. There were significant reductions in average opioid and benzodiazepine use, increases in cannabis use, with limited group changes in social conditions, or quality of life, psychological and physical health. At an individual level, 22% of patients reported increases in their use of either alcohol, opioids, benzodiazepines or stimulants of ≥4 days in the past 4 weeks. Regression analysis indicates increases in substance use were associated with higher levels of supervised dosing.

Discussion and Conclusions

These preliminary findings suggest that the modified model of care continued to provide safe and effective treatment, during the pandemic. Notably, there was no association between more TAD and significant increases in substance use. Limitations are discussed and further evaluation is needed.
A small Rho GTPase OsRacB is required for pollen germination in rice
Authors: Xu Yangfan , Cai Wenguo , Chen Xiaofei , Chen Mingjiao , Liang Wanqi
Published: September 2021

Plant Rho small GTPases (Rop/Rac) are versatile molecular switches regulating many plant developmental processes. Particularly, their important functions in regulating pollen development have been demonstrated in Arabidopsis. A group of conserved Rop/Rac activators RopGEFs were recently reported to regulate rice (Oryza sativa) pollen tube germination, indicating that rice and Arabidopsis may have a conserved Rop/Rac mediated signaling pathway in regulating pollen tube growth. However, the Rop/Rac activated by the rice pollen specific RopGEFs remains to be identified. Here we demonstrated a Rop/Rac gene, OsRacB, co‐expressed with the mature pollen expressed OsRopGEF2/3/6/8. The knockout mutants were normal in anther and pollen development but defective in the pollen grain germination, suggesting a specific and non‐redundant role of OsRacB in the mature pollen. We further demonstrated that OsRacB is directly activated by the pollen specific expressing OsRopGEFs in vitro. Together with the previous study, we establish a RopGEF‐Rop/Rac regulon which plays essential roles in rice pollen grain germination. Our data encourage further identification of the upstream and downstream players of RopGEF‐Rop/Rac signaling in pollen germination and have agricultural implications for breeding robust seed yielding cultivars.
Population stratification in type 2 diabetes mellitus: A systematic review
Authors: Hodgson Sam , Cheema Sukhmani , Rana Zareena , Olaniyan Doyinsola , O’Leary Ellen , Price Hermione , Dambha‐Miller Hajira
Published: September 2021

Aims

There is increasing interest in using stratification in type 2 diabetes to target resources, individualise care and improve outcomes. We aim to systematically review and collate literature that has utilised population stratification methods in the study of adults with type 2 diabetes; and to describe and compare stratification methodologies, population characteristics, variables used to stratify and outcome variables.

Methods

The MEDLINE, EMBASE, CINAHL and Cochrane databases were searched from inception to July 2020. Studies included adults with type 2 diabetes using population stratification methods. The review protocol was registered on PROSPERO (ID: CRD42020206604) and conducted in line with PRISMA guidance. Extracted data included study aims; study setting (primary or secondary care); population characteristics; stratification variables and outcomes; and methodological approach to stratification.

Results

Across 348 included studies, there were a total of 10,776,009 participants with a mean age of 61.0 years (SD 5.94). 6.7% of studies used data‐driven methods and the rest employed expert‐driven approaches using pre‐defined stratification criteria. The commonest variable used to stratify populations was HbA1c (n = 57, 16.4%); few studies stratified using clinically important non‐traditional variables such as health behaviours and beliefs.

Conclusions

Most studies performing population stratification in type 2 diabetes used expert‐driven approaches with the aim of predicting outcomes in glycaemic control, mortality and cardiovascular complications. We identified relatively few studies using data‐driven approaches, which offer opportunities generate hypotheses beyond current expert knowledge. We describe important research gaps including stratification with regard to disease remission.
Hydrogen sulphide in liver glucose/lipid metabolism and non‐alcoholic fatty liver disease
Authors: Mateus Inês , Prip‐Buus Carina
Published: September 2021

Background

For a long time, hydrogen sulphide (H2S) was considered only as a toxic gas, inhibiting mitochondrial respiration at the level of cytochrome c oxidase, and an environmental pollutant. Nowadays, H2S is recognized as the third mammalian gasotransmitter, playing an important role in inflammation, septic shock, ischaemia reperfusion events, cardiovascular disease and more recently in liver physiology and chronic liver diseases such as non‐alcoholic fatty liver disease (NAFLD).

Methods

This narrative review is based on literature search using PubMed.

Results

From a bioenergetic perspective, H2S is a very unique molecule, serving as a mitochondrial poison at high concentrations or as an inorganic mitochondrial substrate at low concentrations. By using transgenic animal models to specifically modulate liver H2S biosynthesis or exogenous compounds that release H2S, several studies demonstrated that H2S is a key player in liver glucose and lipid metabolism. Liver H2S content and biosynthesis were also altered in NAFLD animal models with the in vivo administration of H2S‐releasing molecules preventing the further escalation into non‐alcoholic‐steatohepatitis. Liver steady‐state levels of H2S, and hence its cell signalling properties, are controlled by a tight balance between its biosynthesis, mainly through the transsulphuration pathway, and its mitochondrial oxidation via the sulphide oxidizing unit. However, studies investigating mitochondrial H2S oxidation in liver dysfunction still remain scarce.

Conclusions

Since H2S emerges as a key regulator of liver metabolism and metabolic flexibility, further understanding the physiological relevance of mitochondrial H2S oxidation in liver energy homeostasis and its potential implication in chronic liver diseases are of great interest.
A global perspective on the functional responses of stream communities to flow intermittence
Authors: Crabot Julie , Mondy Cedric P. , Usseglio‐Polatera Philippe , Fritz Ken M. , Wood Paul J. , Greenwood Michelle J. , Bogan Michael T. , Meyer Elisabeth I. , Datry Thibault
Published: September 2021

The current erosion of biodiversity is a major concern that threatens the ecological integrity of ecosystems and the ecosystem services they provide. Due to global change, an increasing proportion of river networks are drying and changes from perennial to non‐perennial flow regimes represent dramatic ecological shifts with potentially irreversible alterations of community and ecosystem dynamics. However, there is minimal understanding of how biological communities respond functionally to drying. Here, we highlight the taxonomic and functional responses of aquatic macroinvertebrate communities to flow intermittence across river networks from three continents, to test predictions from underlying trait‐based conceptual theory. We found a significant breakpoint in the relationship between taxonomic and functional richness, indicating higher functional redundancy at sites with flow intermittence higher than 28%. Multiple strands of evidence, including patterns of alpha and beta diversity and functional group membership, indicated that functional redundancy did not compensate for biodiversity loss associated with increasing intermittence, contrary to received wisdom. A specific set of functional trait modalities, including small body size, short life span and high fecundity, were selected with increasing flow intermittence. These results demonstrate the functional responses of river communities to drying and suggest that on‐going biodiversity reduction due to global change in drying river networks is threatening their functional integrity. These results indicate that such patterns might be common in these ecosystems, even where drying is considered a predictable disturbance. This highlights the need for the conservation of natural drying regimes of intermittent rivers to secure their ecological integrity.
Integration of presence‐only data from several sources: a case study on dolphins' spatial distribution
Authors: Martino Sara , Pace Daniela Silvia , Moro Stefano , Casoli Edoardo , Ventura Daniele , Frachea Alessandro , Silvestri Margherita , Arcangeli Antonella , Giacomini Giancarlo , Ardizzone Giandomenico , Jona Lasinio Giovanna
Published: September 2021

Presence‐only data are typical occurrence information used in species distribution modelling. Data may be originated from different sources, and their integration is a challenging exercise in spatial ecology as detection biases are rarely fully considered. We propose a new protocol for presence‐only data fusion, where information sources include social media platforms, to investigate several possible solutions to reduce uncertainty in the modelling outputs. As a case study, we use spatial data on two dolphin species with different ecological characteristics and distribution, collected in central Tyrrhenian through traditional research campaigns and derived from a careful selection of social media images and videos. We built a spatial log‐Gaussian cox process that incorporates different detection functions and thinning for each data source. To finalize the model in a Bayesian framework, we specified priors for all model parameters. We used slightly informative priors to avoid identifiability issues when estimating both the animal intensity and the observation process. We compared different types of detection function and accessibility explanations. We showed how the detection function's variation affects ecological findings on two species representatives for different habitats and with different spatial distribution. Our findings allow for a sound understanding of the species distribution in the study area, confirming the proposed approach's appropriateness. Besides, the straightforward implementation in the R software, and the provision of examples' code with simulated data, consistently facilitate broader applicability of the method and allow for further validations. The proposed approach is widely functional and can be considered with different species and ecological contexts.
Micro‐climate correlations and conserved sexual dimorphism of cuticular hydrocarbons in European populations of the jewel wasp Nasonia vitripennis
Authors: Buellesbach Jan , Diao Wenwen , Schmitt Thomas , Beukeboom Leo W.
Published: September 2021

1. Protection against desiccation and chemical communication are two fundamental functions of cuticular hydrocarbons (CHCs) in insects. In the parasitoid jewel wasp Nasonia vitripennis (Walker), characterised by a cosmopolitan distribution through largely different environments, CHCs function as universally recognised female sex pheromones. However, CHC uniformity as basis for sexual recognition may conflict with the desiccation protection function, expected to display considerable flexibility through adaptation to different environmental conditions.

2. We compared male and female CHC profiles of N. vitripennis across a wide latitudinal gradient in Europe and correlated their CHC variation with climatic factors associated with desiccation. Additionally, we tested male mate discrimination behaviour between populations to detect potential variations in female sexual attractiveness.

3. Results did not conform to the general expectation that longer, straight‐chain CHCs occur in higher proportions in warmer and drier climates. Instead, unexpected environmental correlations of intermediate chain‐length CHCs (C31) were found exclusively in females, potentially reflecting the different life histories of the sexes in N. vitripennis.

4. Furthermore, we found no indication of population‐specific male mate preference, confirming the stability of female sexual attractiveness, likely conveyed through their CHC profiles. C31 mono‐ and C33 di‐methyl‐branched alkanes were consistently and most strongly associated with sexual dimorphism, suggesting their potential role in encoding the female‐specific sexual signalling function.

5. Our study sheds light on how both adaptive flexibility and conserved sexual attractiveness can potentially be integrated and encoded in CHC profiles of N. vitripennis females across a wide distribution range in Europe.
Cereal straw incorporation and ryegrass cover crops: The path to equilibrium in soil carbon storage is short
Authors: Jensen Johannes L. , Eriksen Jørgen , Thomsen Ingrid K. , Munkholm Lars J. , Christensen Bent T.
Published: September 2021

Reduced use of fossil energy by removing cereal straw for bioenergy potentially threatens soil organic carbon (SOC) storage. Straw incorporation plays a key role for SOC storage in cereal‐based cropping systems, but the use of cover crops (CCs) may compensate for straw removal. However, assessing the SOC sequestration potential of management changes requires field experiments with long continued treatments and frequent soil sampling. Based on a field experiment initiated in 1981 on a sandy loam soil at Askov Experimental Station (Denmark), we examined the effect of annual additions of spring barley straw (0, 4, 8 and 12 Mg ha−1) and undersown ryegrass CC on SOC storage in the 0‐ to 20‐cm layer. The effect of straw incorporation and CC on SOC was additive. At steady‐state conditions, the SOC stock based on equivalent soil mass (SOC stockFM) increased 3.9, 6.7 and 9.3 Mg C ha−1 after annual incorporation of 4, 8 and 12 Mg straw ha−1, respectively. The ryegrass CC increased SOC stockFM by 3.3 Mg C ha−1 and thus almost compensated for removal of 4 Mg straw ha−1. An asymptotic regression model best described the temporal changes in SOC and showed that the effect of straw incorporation and ryegrass CC on SOC sequestration peaks after 10–15 years when a new equilibrium between input and output of C is reached. Clearly, reliable assessments of SOC sequestration potentials following changes in management require field experiments with frequent soil sampling until reaching steady‐state conditions.

Highlights

SOC sequestration potentials of straw incorporation and CCs were assessed.

The crucial issue of sequestration duration of experimental treatments is often neglected.

The effect of straw and CC peaked after 10–15 years when a new equilibrium in SOC was reached.

Reliable assessments require frequent soil sampling until reaching steady‐state conditions.
Predicting atrial fibrillation after cryptogenic stroke via a clinical risk score—a prospective observational study
Authors: Kneihsl Markus , Bisping Egbert , Scherr Daniel , Mangge Harald , Fandler‐Höfler Simon , Colonna Isabella , Haidegger Melanie , Eppinger Sebastian , Hofer Edith , Fazekas Franz , Enzinger Christian , Gattringer Thomas
Published: September 2021

Background and purpose

Atrial fibrillation (AF) often remains undiagnosed in cryptogenic stroke (CS), mostly because of limited availability of cardiac long‐term rhythm monitoring. There is an unmet need for a pre‐selection of CS patients benefitting from such work‐up. A clinical risk score was therefore developed for the prediction of AF after CS and its performance was evaluated over 1 year of follow‐up.

Methods

Our proposed risk score ranges from 0 to 16 points and comprises variables known to be associated with occult AF in CS patients including age, N‐terminal pro‐brain natriuretic peptide, electrocardiographic and echocardiographic features (supraventricular premature beats, atrial runs, atrial enlargement, left ventricular ejection fraction) and brain imaging markers (multi‐territory/prior cortical infarction). All CS patients admitted to our Stroke Unit between March 2018 and August 2019 were prospectively followed for AF detection over 1 year after discharge.

Results

During the 1‐year follow‐up, 24 (16%) out of 150 CS patients with AF (detected via electrocardiogram controls, n = 18; loop recorder monitoring, n = 6) were diagnosed. Our predefined AF Risk Score (cutoff ≥4 points; highest Youden's index) had a sensitivity of 92% and a specificity of 67% for 1‐year prediction of AF. Notably, only two CS patients with <4 score points were diagnosed with AF later on (negative predictive value 98%).

Conclusions

A clinical risk score for 1‐year prediction of AF in CS with high sensitivity, reasonable specificity and excellent negative predictive value is presented. Generalizability of our score needs to be tested in external cohorts with continuous cardiac rhythm monitoring.
Alterations of brain structural MRI are associated with outcome of surgical treatment in trigeminal neuralgia
Authors: Albano Luigi , Agosta Federica , Basaia Silvia , Castellano Antonella , Messina Roberta , Parisi Veronica , Barzaghi Lina Raffaella , Falini Andrea , Mortini Pietro , Filippi Massimo
Published: September 2021

Background and purpose

To assess magnetic resonance imaging (MRI) alterations occurring in patients with trigeminal neuralgia (TN) and to explore the predictive ability of MRI for initial surgical outcome and long‐term pain relief/recurrence after Gamma Knife radiosurgery (GKS).

Methods

Thirty patients with idiopathic or classic TN, who underwent GKS and were followed for at least 24 months, were retrospectively included. Pre‐treatment structural MRI and pre‐ and serial, postoperative clinical features were investigated. Fifteen age‐ and sex‐matched healthy controls were also enrolled. Cortical thickness and gray matter (GM) volumes were assessed in TN patients relative to controls, as well as between patient subgroups according to treatment outcomes (initial responders/non‐responders, patients with pain recurrence/long‐lasting pain relief at the last follow‐up). Clinical and MRI predictors of treatment outcomes were explored.

Results

Cortical thinning of temporal, prefrontal, cingulate, somatosensory and occipital areas bilaterally was found in TN patients relative to controls. No cortical thickness and GM volume differences were observed when TN initial responders and non‐responders were compared. Patients who experienced TN recurrence after initial pain relief were characterized by thicker parahippocampal and temporal cortices bilaterally and greater volume of right amygdala and hippocampus compared to patients with long‐lasting pain relief. In TN patients, disease duration and baseline cortical thinning of right parahippocampal, left fusiform and middle temporal cortices were associated with poor outcome after GKS at the last follow‐up (R2=0.57, p<0.001).

Conclusion

The study provides novel insights into structural brain alterations of TN patients, which might contribute to disease development and pain maintenance.
Stakeholder participation in the development of International Public Sector Accounting Standard 42, Social Benefits
Authors: De Wolf Anschi , Christiaens Johan
Published: September 2021

This study aims to contribute to the understanding of stakeholder participation within the International Public Sector Accounting Standards Board's (IPSASB) due process. This study examines IPSASB's input legitimacy by analysing who the respondents are in exposure draft (ED) 63, Social Benefits, and to what extent they support the ED; however, the emphasis lies on the quality of the IPSASB's due process through the legitimacy theory, more precisely procedural legitimacy, by investigating to what extent the respondents’ input was considered and integrated into the final International Public Sector Accounting Standards. Most respondents originate from Europe and Oceania and consist of professional associations and public sector entities. There are indications that some respondents’ input was integrated; however, results indicate a clear flaw in the lack of transparency regarding how respondents’ input is analysed, which makes the decision‐making process seem arbitrary and subjective and could potentially have a negative effect on the IPSASB's legitimacy.
An alternative hypothesis for the evolution of sexual segregation in endotherms
Authors: Magory Cohen Tali , Kiat Yosef , Sharon Haggai , Levin Eran
Published: September 2021

Aim

Patterns of separation among males and females, known as sexual segregation, are traditionally correlated with elevation or latitude in animals. Alternatively, in humans, spatial and behavioural segregation is driven by inherent sex‐based differences in thermal preference, although the cause and adaptive value of these differences remain unclear. Here, we explore whether, similar to humans, ambient temperature can explain patterns of separation among males and females in endotherms.

Location

Israel.

Time period

1981–2018.

Major taxa studied

Migratory sexually dimorphic birds (13 species) and bats (18 species).

Methods

We calculated the proportion of males and females at each sampling site for each bird or bat species. We used general linear mixed models (GLMMs) to quantify the variance explained by elevation, latitude, body size and ambient temperature and corrected for phylogeny, site and year. We used model averaging over the best models by comparing the corrected Akaike information criterion.

Results

We found a correlation between geographical separation and temperature that accounted for variance in the data that was not explained by elevation and latitude. We showed that temperature was negatively correlated with the proportion of males in bats and birds, whereas body size explained this response only in birds.

Main conclusions

Our findings suggest that females are found in higher ambient temperatures. We term this differential sex‐related thermal preference (DSTP) and propose that it is a broad phenomenon common in many endotherms, acting as a significant force shaping dispersal, sociality and behaviour of animals, and should be explored from this wide perspective.
R&D internationalization and innovation performance of Chinese enterprises: The mediating role of returnees and foreign professionals
Authors: Si Yuefang , Zhang Yi , Teng Tangwei
Published: September 2021

In the innovation‐driven economy of the 21st century, the emerging global innovation landscape is one of geographically concentrated centers of excellence in developed markets, which are embedded in a global network carrying, collaborating and sharing knowledge. Without top‐level innovation resources in the home country, how do emerging market multinational enterprises (EMMNEs) learn to innovate on global markets? This paper takes Chinese enterprises operating in the ICT industry from Shanghai Zhangjiang as example, to explore whether EMMNEs can promote their innovation performances via R&D internationalization to acquire external knowledge and technology resources abroad, by the establishment of international technology alliances, cross‐border mergers and acquisitions along with greenfield investment in overseas research institutions, in relation to their hiring returnees and foreign professionals. The empirical results reveal that R&D internationalization is positively related to enterprises’ innovation performance, and that the relationship is fully mediated by returnees, with the effect also being partially mediated by foreign professionals. Our research unpacks the different mediating effects of returnees and foreign professionals on the gains of sourcing external knowledge, providing some implications for enterprises’ innovation practices.
Does immune checkpoint inhibitor exhibit limited efficacy against non‐viral hepatocellular carcinoma?: A review of clinical trials
Authors: Eso Yuji , Taura Kojiro , Seno Hiroshi
Published: September 2021

Immunotherapy with immune checkpoint inhibitors has been shown to be beneficial for cancers originating from various organs. In May 2020, combination therapy with anti‐programmed death‐ligand 1 antibody atezolizumab and anti‐vascular endothelial growth factor (VEGF) antibody bevacizumab was approved as a novel first‐line systemic therapy for hepatocellular carcinoma (HCC). The number of patients with HCC not caused by hepatitis virus infection (non‐viral HCC), including non‐alcoholic steatohepatitis (NASH)‐related HCC, has been increasing in recent years. Recently, Pfister and colleagues reported that immune checkpoint inhibitors may exhibit limited efficacy against NASH‐related HCC, based on basic research and clinical data. This review will discuss the mechanism of impaired tumor immune surveillance in NASH and analyze the results of previously published clinical trials of immune checkpoint inhibitors to investigate whether patients with non‐viral HCC are less likely to benefit from immunotherapy with immune checkpoint inhibitors. Furthermore, we also discuss the possibility of enhancing the therapeutic effect of immune checkpoint inhibitors for NASH‐related HCC by combining anti‐VEGF agents.
Diffusion bonding of Ti‐coated Cf‐SiCf/SiBCN composites to Nb using Ag–Pd interlayer
Authors: Lin Jincheng , Zhang Xunye , Wang Wei , Yu Di , Jia Dechang , Lin Tiesong , Lin Panpan , He Peng
Published: September 2021

The Ti‐coated Cf‐SiCf/SiBCN ceramic was diffusion‐bonded to Nb using an Ag–Pd interlayer. At a ceramic/Ag–Pd interface, it is found that Ti first reacted with C and Pd to form a TiCx/Ti(Pd) double‐layer structure, and then Ti(Pd) completely converted into TiCx with the increase of holding time or temperature. Meanwhile, the infiltration of Pd along TiCx grain boundary reacted with Si to form brittle Pd2Si compound. By contrary, only a simple NbPd3 layer was formed at the Nb/Ag–Pd interface during the whole process. A maximum shear strength of 16 ± 3 MPa is obtained for the joint prepared at 900°C for 30 min. The plastic deformation of the Ag–Pd interlayer and pullout of fibers inside ceramic contributed to the superior performance. Nevertheless, as the holding time and temperature reached 90 min and 950°C, the high chemical affinity of the Pd–Si system and enhanced atomic diffusion led to the massive formation of Pd2Si, which increased the joint brittleness and degraded the ceramic performance.
Porous silicon nitride–based drug delivery carrier
Authors: Hičák Michal , Medvecký Ľubomír , Hnatko Miroslav , Stulajterová Radoslava , Giretová Mária , Tatarková Monika , Lenčéš Zoltán , Šajgalík Pavol
Published: September 2021

Tetracalcium phosphate/monetite biocement was modified with the addition of 30 wt% highly porous silicon nitride/α‐tricalcium phosphate (α‐TCP) microgranules. The volume ratio of Si3N4 and α‐TCP in microgranules was 1:1 and showed good in vitro simulated body fluid bioactivity with precipitation of hydroxyapatite particles. The intention of addition of microgranules to the biocement was to have a carrier of drug, which can be released into the body in due time. Granules prepared by the freeze granulation of starting mixture of silicon nitride and calcium phosphate and subsequent sintering at 1100°C have a suitable pore structure for the foreseen use. The pore volume was almost 1000 mm3/g with the open porosity of 77 vol%. This porosity and the biocompatible composition of silicon nitride–based granules gave a chance to fabricate a suitable composite cement for dexamethasone (DMZ) drug release into the human body. An accelerated release of dexamethasone from composite cement was observed and the full amount of DMZ was released from the composite biocement after 10 days. The presented results are a good base to adjust the total drug release time by the mixing of an appropriate amount of drug infiltrated ceramic granules with the tetracalcium phosphate/monetite cement.
Exposure to quadrivalent influenza vaccine during pregnancy: Results from a global pregnancy registry
Authors: Ledlie Shaleesa , Gandhi‐Banga Sonja , Shrestha Anju , Mallett Moore Tamala , Khromava Alena
Published: September 2021

Background

The Fluzone® Quadrivalent (IIV4, Sanofi Pasteur) Pregnancy Registry was created to monitor vaccine safety during pregnancy (clinicaltrials.gov, NCT01945424). Here, we describe maternal, pregnancy, obstetrical and neonatal outcomes after vaccine exposure in pregnant women between August 2013 and September 2019.

Methods

All women exposed to IIV4 during their pregnancy were eligible for inclusion. Outcomes were prospective (reported following vaccine exposure but before knowledge of pregnancy outcome ascertained through prenatal tests) or retrospective (prenatal tests were undertaken before the exposure was reported).

Results

Among 239 IIV4 vaccine exposure reports received, there were 105 prospective and 10 retrospective reports of maternal adverse events (AEs). The most frequent prospectively reported maternal AEs were medication errors (expired product [n = 8, 3.8%]; extra dose [n = 7, 3.3%]) and injection site pain (n = 7, 3.3%). Among 62 prospectively reported pregnancy and obstetrical events with available follow‐up information, seven AEs were reported, four (6.4%) of which were spontaneous abortions. A further seven AEs were reported among the 29 retrospective pregnancy and obstetrical events with available follow‐up information. Among neonatal outcomes (15 prospective; 28 retrospective), >85% were reported as full‐term births. One premature birth was reported prospectively. Four other neonatal AEs were reported, all retrospectively: two cases of talipes (club foot), one central nervous system anomaly and one atrial septal defect. All infants with available information had normal APGAR scores at 5 minutes.

Conclusions

The frequency of AEs following exposure to IIV4 during pregnancy did not indicate new safety concerns.
Nearly stoichiometric BN fiber with high crystallinity achieved by boron trichloride assisted curing process
Authors: Du Yiang , Wang Bing , Meng Fanxiu , Li Wei , Wang Yingde
Published: September 2021

Given the superior thermal stability and microwave transparency features, continuous BN fibers have displayed great potential to fulfill the increasing demand for high‐temperature structural and functional materials. The performance of BN ceramic fiber depends heavily upon its composition and microstructure. Herein, nearly stoichiometric BN fibers with high crystallinity were achieved through a facile boron trichloride (BCl3) assisted curing process. The fibers achieved a boron/nitrogen element ratio of 0.996:1 with increasing the degree of curing. After subsequent heat treatment, the fibers had uniform elemental distribution and h‐BN crystal structure. Compared with pure NH3 curing, the BN fibers cured with BCl3 demonstrated higher crystallinity (92.35%) and consistent orientation (79.8%). The existing state changes of elements revealed BCl3 assisted curing process could evenly disperse B atoms into the precursor fibers to fill the vacancies caused by nitrogen enrichment. These insights improve our understanding of preceramic fibers treatment for exploiting high‐performance BN ceramic fibers.
Sperm numbers on the perivitelline layers of blue tit eggs are repeatable within a clutch, but independent of the occurrence of extra‐pair paternity
Authors: Santema Peter , Teltscher Kim , Kempenaers Bart
Published: September 2021

In many socially monogamous bird species, females produce offspring sired by males other than their social partner. A large body of research has aimed to elucidate the evolutionary causes and consequences of such extra‐pair paternity, but relatively little is known about the underlying behaviour. The number of sperm on the egg's perivitelline layers (PVL) is related to recent copulation activity and may thus give some insight into the female's mating behaviour. We used a simple technique that allowed us to remove embryonic cells from the blastoderm for DNA extraction whilst keeping the PVL intact for sperm counts. Using 243 eggs from 99 blue tits Cyanistes caeruleus, we show that PVL sperm numbers were repeatable within clutches (r = 0.40 [95% CI: 0.25–0.53]). However, neither overall sperm numbers nor changes in sperm numbers across the laying sequence differed between clutches that contained extra‐pair sired eggs and those that did not. Our results, therefore, provide no evidence that females with and without extra‐pair young differ in their copulation activity.
Role of the Chicamocha River Canyon on the phylogeography of humid montane forest birds in Colombia
Authors: Arbeláez‐Cortés Enrique , Trujillo‐Arias Natalia
Published: September 2021

Neotropical humid montane forest (HMF) is divided by landform discontinuities which could limit gene flow among populations. The northern Andes is a complex montane system and an excellent region to compare the role of discontinuities dividing HMFs on the phylogeography of bird species. We study phylogeographic patterns of seven HMF bird species in the western slope of the eastern Cordillera to test whether the phylogeographic structure coincides with the presence of two landform discontinuities. We sequenced and analyzed a mitochondrial DNA locus from individuals collected in localities on both sides of the xeric ecosystems of the Chicamocha River Canyon and on both sides of the depression below 2000 m a.s.l. that separates the mountain range of Serranía de los Yariguies from the rest of the eastern Cordillera. Despite the low sample size for some species in particular localities, our results show that the major phylogeographic structure within most species (i.e. Adelomyia melanogenys, Henicorhina leucophrys, Basileuterus tristriatus, and Mionectes olivaceus) is located between both sides of the canyon. However, there is no phylogeographic structure in Doryfera ludovicae, Premnoplex brunnescens, and Arremon brunneinucha, despite some degree of genetic structure in the last two. Our results support a role of the Chicamocha River Canyon as a barrier diminishing, or precluding, gene flow. Evidence of gene flow between populations separated by the landform discontinuity between Serranía de los Yariguies and the rest of the eastern Cordillera indicates that it is not a barrier for most of the species, but could be a barrier to A. melanogenys that exhibits a different phylogeographic pattern. For this hummingbird, the haplotype of the Serranía de los Yariguies is related to haplotypes in other HMFs far away from the study region. Altitudinal changes of the HMF due to paleoclimatic changes are considered to explain the phylogeographic patterns of the species.
Effect of total dissolved gas supersaturation on the survival of common carp (Cyprinus carpio) and silver carp (Hypophthalmichthys molitrix)
Authors: Deng Yuxuan , Feng Cuixia , Yin Qingjie , Liu Xiaoqing , Shi Haoran , Yang Yao , Wu Yufeng
Published: September 2021

Flood discharge results in total dissolved gas (TDG) supersaturation downstream of a dam during the flood period. Fish suffer death from gas bubble disease (GBD) caused by TDG supersaturation. Nonetheless, current studies mainly attach importance to the survival of benthic fish affected by TDG supersaturation in the Yangtze River in China. Few studies have attempted to investigate the survival of pelagic fish influenced by TDG supersaturated water and compare the tolerance characteristics to TDG supersaturation between benthic and pelagic fish. To identify the survival of fish species that inhabit the various water layers affected by TDG supersaturation, silver carp (Hypophthalmichthys molitrix) (pelagic fish) and common carp (Cyprinus carpio) (benthic fish) were chosen to conduct an acute exposure experiment of four different TDG supersaturation levels (125%, 130%, 135% and 140%). The findings illustrated that the two fish species both exhibited evident aberrant behaviours of maladjustment in TDG supersaturated water. Obvious GBD symptoms were also found in the test fish. The survival probability of silver carp and common carp decreased with increasing levels of TDG supersaturation. The median survival time (ST50) values of the silver carp exposed to four levels of TDG supersaturated water (125%, 130%, 135% and 140%) were 26.84, 7.96, 5.56 and 3.62 h, respectively, whereas the ST50 values of common carp were 53.50, 26.00, 16.50 and 11.70 h, respectively. When compared with common carp, silver carp had a weaker tolerance to TDG‐supersaturated water and were vulnerable to GBD. It shows that levels above 125% are not safe for common carp survival. In terms of the tolerance threshold value, silver carp merits further investigation because it showed lower tolerance to TDG than did common carp.
All‐cause hepatocellular carcinoma survival in the era of direct‐acting antiviral therapy
Authors: Lockart Ian , Hajarizadeh Behzad , Buckley Niamh , Davison Scott , Prakoso Emilia , Levy Miriam T , George Jacob , Dore Gregory J , Danta Mark
Published: September 2021

Background and Aim

Hepatitis C virus (HCV) cure with direct‐acting antiviral (DAA) therapy improves survival in patients with HCV‐related hepatocellular carcinoma (HCC). We hypothesized that HCV‐HCC survival has increased in the DAA era, more than other aetiologies of HCC. We aimed to evaluate survival following HCC diagnosis in the pre‐DAA and DAA eras, across each aetiology of HCC.

Methods

Patients with HCC at three tertiary referral hospitals were included retrospectively (January 2008 to December 2019). Patients were categorized as HCV‐HCC, hepatitis B virus (HBV)‐HCC, or non‐viral HCC. For each aetiology, the risk of death following incident HCC among patients diagnosed in the DAA era (2015–2019) was compared with patients diagnosed in the pre‐DAA era (2008–2014).

Results

Among 1161 patients, there were 422 (36%) patients with HCV‐HCC, 227 (20%) with HBV‐HCC, and 512 (44%) with non‐viral HCC. In adjusted analysis, the risk of death was lower in patients with HCV‐HCC diagnosed in 2015–2019, compared with patients diagnosed in 2008–2014 (adjusted hazard ratio [aHR]: 0.68; 95% confidence interval [CI]: 0.52–0.89; P = 0.005). In contrast, there was no difference in the risk of death between time periods for patients with HBV‐HCC (HR: 0.91; 95% CI: 0.64–1.29; P = 0.602) or non‐viral HCC on adjusted analysis (aHR: 0.92; 95% CI: 0.74–1.15; P = 0.476). Although patients with HBV‐HCC had better survival compared with patients with HCV‐HCC in 2008–2014 (aHR: 0.74; 95% CI: 0.55–0.98; P = 0.037), this difference disappeared in 2015–2019 (aHR: 1.26; 95% CI: 0.90–1.77; P = 0.175).

Conclusions

Hepatitis C virus‐related HCC survival has increased in the DAA era, whereas adjusted survival remained stable for HBV‐HCC and non‐viral HCC.