bluuebunny/crossref_metadata_2025 huggingface dataset:
Dose–response relationship between Frailty Index and Stroke among middle-aged and elderly Chinese
Authors: Yang Yifang , Ma Yuxia , Yang Tingting , He Xiang , Chen Junbo , Wu Tingting , Nan Jinhan , Feng Juanjuan , Han Lin
Published: June 2023

Background

Stroke has emerged as the leading cause of mortality in China, with the burden of the disease increasing with the aging population. Recent research has established a correlation between frailty and stroke, with the frailty index serving as a comprehensive measure of frailty in elderly populations. This study aimed to explore the dose-response relationship between frailty index and stroke, with the objective of providing a reference for effective stroke identification in middle-aged and elderly individuals, thereby preventing the onset of the disease.

Methods

The data used in this study were derived from the China Health and Retirement Longitudinal Study (CHARLS) database from 2011 to 2018. Proportional hazards model was utilized to investigate the impact of frailty index on stroke risk, while restricted cubic spline analysis was employed to examine the dose-response relationship between frailty index and stroke. Subgroup analysis was used to further understand whether the frailty index has an effect on the occurrence of stroke in different subgroups.

Results

A total of 11328 participants were included in the study, with 401 (3.3%) stroke patients. Frailty and pre-frailty were associated with a high risk of stroke events compared with robust group(HR, 3.89, 95%CI, 2.88-5.26), (HR, 2.09, 95%CI, 1.60-2.75), after adjusting for all covariates. There was a non-linear relationship between frailty index and stroke in the restricted cubic spline regression model. Frailty index was a risk factor of stroke when it exceeded 0.13. Taking the robust as reference, subgroup analysis results showed a significant interaction with the frailty index in all subgroup analyses except for the smoking group.

Conclusion

Pre-frailty and frailty were significantly associated with stroke risk. Frailty index had a nonlinear relationship with stroke occurrence, and frailty index >0.13 was significantly correlated with stroke occurrence. Frailty index is an independent predictor of stroke occurrence.
Construction and Characterisation of a Structured, Tuneable, and Transparent 3D Culture Platform for Soil Bacteria
Authors: Rooney Liam M. , Dupuy Lionel X. , Hoskisson Paul A. , McConnell Gail
Published: June 2023

2.

We have developed a tuneable workflow for the study of soil microbes in an imitative 3D soil environment that is compatible with routine and advanced optical imaging, is chemically customisable, and is reliably refractive index matched based on the metabolic profile of the study organism. We demonstrate our transparent soil pipeline with two representative soil organisms,Bacillus subtilisandStreptomyces coelicolor, and visualise their colonisation behaviours using fluorescence microscopy and mesoscopy. This spatially structured, 3D approach to microbial culture has the potential to further study the behaviour of other difficult-to-culture bacteria in conditions matching their native environment and could be expanded to study microbial interactions, such as interaction, competition, and warfare.

3.

Graphical Abstract

A step-by-step method for creating a tailored 3D culture medium for study of soil microbes.

The complete workflow can be split into three parts: Growth and observation, metabolic profiling to provide a stable refractive index matching solution, and production of the 3D soil environment. The 3D culture scaffold was created by cryomilling Nafion™ resin pellets and size filtration. Chemical processing altered the surface chemistry of Nafion™ particles and facilitated nutrient binding by titration of a defined liquid culture medium. Metabolic profiling determined non-metabolisable sugars and provided an inert refractive index matching substrate, which was added to the final nutrient titration. Inoculation and growth of the test strain allowed for downstream assessment of colonisation behaviours and community dynamicsin situby, for example, optical microscopy.
Collagen prolyl 4-hydroxylases have sequence specificity towards different X-Pro-Gly triplets
Authors: Salo Antti M. , Rappu Pekka , Koski M. Kristian , Karjalainen Emma , Izzi Valerio , Drushinin Kati , Miinalainen Ilkka , Käpylä Jarmo , Heino Jyrki , Myllyharju Johanna
Published: June 2023

Formation of 4-hydroxyproline (4Hyp) in -X-Pro-Gly- collagen sequences is essential for the thermal stability of collagen molecules. 4Hyp formation is catalyzed by collagen prolyl 4-hydroxylases (C- P4H). Here we identify specific roles for the two main C-P4H isoenzymes by 4Hyp analysis of type I and IV collagens. Loss of C-P4H-I mainly affected prolines preceded by an X-position amino acid with a positively charged or a polar uncharged side chain. In contrast, loss of C-P4H-II affected triplets with a negatively charged glutamate or aspartate in the X-position, and their hydroxylation was found to be important as loss of C-P4H-II alone resulted in reduced collagen melting temperature and altered assembly of collagen fibrils and basement membrane. The C-P4H isoenzyme differences in substrate specificity were explained by selective substrate binding to the active site resulting in differences in Km and Vmax values. In conclusion, this study provides a molecular level explanation for the need of multiple C-P4H isoenzymes to generate collagen molecules capable to assemble into intact extracellular matrix structures.
Performance ofOrbicella faveolatalarval cohorts does not align with previously observed thermal tolerance of adult source populations
Authors: Zhang Yingqi , Gantt Shelby E. , Keister Elise F. , Elder Holland , Kolodziej Graham , Aguilar Catalina , Studivan Michael S. , Williams Dana E. , Kemp Dustin W. , Manzello Derek P. , Enochs Ian C. , Kenkel Carly D.
Published: June 2023

Orbicella faveolata, commonly known as the mountainous star coral, is a dominant reef-building species in the Caribbean, but populations have suffered sharp declines since the 1980s due to repeated bleaching and disease-driven mortality. Prior research has shown that inshore adultO. faveolatapopulations in the Florida Keys are able to maintain high coral cover and recover from bleaching faster than their offshore counterparts. However, whether this origin-specific variation in thermal resistance is heritable remains unclear. To address this knowledge gap, we produced purebred and hybrid larval crosses fromO. faveolatagametes collected at two distinct reefs in the Upper Florida Keys, a nearshore site (Cheeca Rocks, CR) and an offshore site (Horseshoe Reef, HR), in two different years (2019, 2021). We then subjected these aposymbiotic larvae to severe (36 °C) and moderate (32 °C) heat challenges to quantify their thermal tolerance. Contrary to our expectation based on patterns of adult thermal tolerance, HR purebred larvae survived better and exhibited gene expression profiles that were less driven by stress response under elevated temperature compared to purebred CR and hybrid larvae. One potential explanation could be compromised reproductive output of CR adult colonies due to repeated summer bleaching events in 2018 and 2019, as gametes originating from CR in 2019 contained less storage lipids than those from HR. These findings provide an important counter-example to the current selective breeding paradigm, that more tolerant parents will yield more tolerant offspring, and highlight the importance of adopting a holistic approach when evaluating larval quality for conservation and restoration purposes.
Reconstructing the evolutionary history of human, simian, and prosimian immunodeficiency viruses
Authors: Ghafari Mahan , Simmonds Peter , Katzourakis Aris
Published: June 2023

While paleovirological evidence supports the idea that the ancestors of modern simian (SIV) and prosimian (pSIV) immunodeficiency viruses have been evolving in nonhuman primates for millions of years, standard molecular clock methods calibrated using contemporary sequences significantly underestimate their times of origin. This discrepancy is attributed to the time-dependent nature of evolutionary rate estimates whereby the rate of virus evolution varies with respect to the time window of its measurement. While biogeographical calibrations may provide better estimates across intermediate timescales, there is currently no unifying framework that can allow inference of lentiviral ages across all relevant timescales. Here we showed that by correcting for such time-dependent rate effects using the recently developed Prisoner-of-War evolutionary model, we can successfully reconstruct the evolutionary history of human, simian, and prosimian immunodeficiency viruses across vastly different timescales and allowed estimates of the age of lineages that gave rise to HIV-1 and HIV-2. The model also predicted that the most recent common ancestor of SIV and pSIV lived around 21 million years ago, suggesting that the most likely explanation for the origins of primate lentiviruses is a terrestrial transfer of lentiviruses between African and Malagasy primates during the last episode of colonisation of Madagascar. Infections have entered via a land bridge in a group of mammals or through a nonprimate vector or transfer mediated by an aerial vector species. We also found that the most recent common ancestor of SIVs lived nearly a million years ago and that some SIV lineages codiverged with their hosts for several hundreds of thousands of years. The predicted long evolutionary timescales of SIVs and potential for close virus/host co-adaptation is consistent with their reduced or minimal pathogenicity in their native hosts, contrasting with the very recent evolutionary origins of highly pathogenic HIV strains in humans.
Inter individual variability in neuronal expression of heat shock protein genes predicts stress survival inCaenorhabditis elegans
Authors: Todtenhaupt Pia , Murdoch Sharlene , Vallejos Catalina A. , Casanueva Olivia , Chauve Laetitia
Published: June 2023

Despite being isogenic and grown under controlled conditions,C. eleganspopulations exhibit widespread inter-individual variability in many traits, making it an ideal model organism to investigate non-genetic influences on phenotypic diversity. Our particular interest is to study the consequences of inter-individual variability in genes encoding heat shock proteins, which are expressed at low levels under non-stimulated conditions. To robustly quantify inter-individual gene expression, we developed a novel pipeline that combines a highly efficient cDNA extraction method with a high-throughput qPCR nanofluidics technology with a bespoke computational analysis. We validated our approach by benchmarking againstin vivoreporters. We also screened among hundreds of stress inducible genes, and identified a regulon formed by transcripts belonging to the inducible heat shock protein family. We demonstrate, using a bipartitein vivofluorescent reporter, that the inter-individual variability in the stress regulon stems mostly from anterior neurons. Our studies demonstrate for the first time that, under physiological and unstimulated conditions, the variable expression of neural stress responses has cross-tissue consequences for fitness at the individual worm level, suggesting an adaptive role under variable environmental conditions.
The human Dicer helicase domain mediates ATP hydrolysis and RNA rearrangement
Authors: Ciechanowska Kinga , Szczepanska Agnieszka , Szpotkowski Kamil , Wojcik Klaudia , Urbanowicz Anna , Kurzynska-Kokorniak Anna
Published: June 2023

Vertebrates have one Dicer ortholog that generates both microRNAs (miRNAs) and small interfering RNAs (siRNAs), in contrast to the multiple Dicer-like proteins found in flies and plants. Here, we focus on the functions of the human Dicer (hDicer) helicase domain. The helicase domain of hDicer is known to recognize pre-miRNA substrates through interactions with their apical loop regions. Besides interacting with canonical substrates, the hDicer helicase domain has also been suggested to bind many different cellular RNAs; however, a comprehensive study of the biochemical activities and substrate specificity of the hDicer helicase domain towards different nucleic acids has yet to be undertaken. Here, we conduct such an analysis and reveal that full-length hDicer, through its helicase domain, hydrolyzes ATP. We also show that the hDicer helicase domain binds single-but not double-stranded RNAs and DNAs and that a structural rearrangement of the substrate accompanies the binding of single-stranded RNAs. This RNA rearrangement activity is ATP-independent. Our findings open new avenues for future studies aimed at defining the cellular activities of hDicer that may be associated with these newly described biochemical properties.
Cryo-electron microscopy of cytoskeletal ‘fibril’ involved inSpiroplasmaswimming
Authors: Sasajima Yuya , Kato Takayuki , Miyata Tomoko , Kiyama Hana , Kawamoto Akihiro , Makino Fumiaki , Namba Keiichi , Miyata Makoto
Published: June 2023

Spiroplasma, parasitic or commensal bacteria, can swim by switching the handedness of its helical cell body. A helical cell body is formed by an internal ribbon of MreB, an actin superfamily, andSpiroplasma-specific fibril proteins. Here we have solved the structure of the fibril filament by single-particle cryo-electron microscopy at 3.6 Å resolution and built its atomic structure. The structure is composed of repeated rings and cylinders. The N-terminal cylinder of the fibril protein shows a structure similar to that of S-adenosylhomocysteine nucleosidase, while the C-terminal ring does not show similarity to other proteins. The filament is nonpolar and flexible, possessing a helical pitch of 700 nm, consistent with cell helicity. Cryo-electron tomography revealed aligned several MreB filaments in the center of the ribbon, flanked by membrane-binding fibril filaments through electrostatic interactions. This study discusses the evolution and roles of the fibril filament.
Mn2+-Induced Structural Flexibility Enhances the Entire Catalytic Cycle and the Cleavage of Mismatches in Prokaryotic Argonaute Proteins
Authors: Zheng Lirong , Zan Bing , Yang Yu , Zhou Bingxin , Wu Banghao , Feng Yan , Liu Qian , Hong Liang
Published: June 2023

Prokaryotic Argonaute (pAgo) proteins, a class of DNA/RNA-guided programmable endonucleases, have been extensively utilized in nucleic acid biosensors. The specific binding and cleavage of nucleic acids by pAgo proteins, which are crucial processes for their applications, are dependent on the presence of Mn2+bound in the pockets, as verified through X-ray crystallography. However, a comprehensive understanding of how dissociated Mn2+in the solvent affects the catalytic cycle, and its underlying regulatory role in this structure-function relationship, remains underdetermined. By combining experimental and computational methods, this study reveals that unbound Mn2+in solution enhances the flexibility of diverse pAgo proteins. This increase in flexibility through decreasing the number of hydrogen bonds, induced by Mn2+, leads to higher affinity for substrates, thus facilitating cleavage. More importantly, Mn2+-induced structural flexibility increases the mismatch tolerance between guide-target pairs by increasing the conformational states, thereby enhancing the cleavage of mismatches. Further simulations indicated that the enhanced flexibility in linkers triggers conformational changes in the PAZ domain for recognizing various lengths of nucleic acids. Additionally, Mn2+-induced dynamic alterations of the protein cause a conformational shift in the N domain and catalytic sites towards their functional form, resulting in a decreased energy penalty for target release and cleavage. These findings demonstrate that the dynamic conformations of pAgo proteins, resulting from the presence of the unbound Mn2+in solution, significantly promote the catalytic cycle of endonucleases and the tolerance of cleavage to mismatches. This flexibility enhancement mechanism serves as a general strategy employed by Ago proteins from diverse prokaryotes to accomplish their catalytic functions and provide useful information for Ago-based precise molecular diagnostics.
Acoustically evoked K-complexes together with sleep spindles boost verbal declarative memory consolidation in healthy adults
Authors: Leach Sven , Krugliakova Elena , Sousouri Georgia , Snipes Sophia , Scorucak Jelena , Schuehle Selina , Mueller Manuel , Ferster Maria Laura , Da Poian Giulia , Karlen Walter , Huber Reto
Published: June 2023

Over the past decade, phase-targeted auditory stimulation (PTAS), a neuromodulation approach which presents auditory stimuli locked to the ongoing phase of slow waves during sleep, has shown potential to enhance specific aspects of sleep functions. However, the complexity of PTAS responses complicates the establishment of causality between specific electroencephalographic events and observed benefits. Here, we used down-PTAS during sleep to specifically evoke the early, K-complex (KC)-like response following PTAS without leading to a sustained increase in slow-wave activity throughout the stimulation window. Over the course of two nights, one with down-PTAS, the other without, high-density electroencephalography (hd-EEG) was recorded from 14 young healthy adults. The early response exhibited striking similarities to evoked KCs and was associated with improved verbal memory consolidation via stimulus-evoked spindle events nested into the up-phase of ongoing 1~Hz waves in a central region. These findings suggest that the early, KC-like response is sufficient to boost memory, potentially by orchestrating aspects of the hippocampal-neocortical dialogue.
Insights into the precipitation kinetics of CaCO3 particles in the presence of polystyrene sulfonate using in situ small-angle X-ray scattering
Authors: Gibaud A. , Younas D. , Matthews L. , Narayanan T. , Longkaew K. , Hageberg I. U. , Chushkin Y. , Breiby D. W. , Chattopadhyay B.
Published: June 2023

The formation of calcium carbonate (CaCO3) nanoparticles (NPs) in the presence of polystyrene sulfonate (PSS) as an additive was examined by time-resolved small-angle X-ray scattering (SAXS) in a flow system that mimics experimental conditions used at home facilities where the precipitation can be achieved in a beaker. The experiments were carried out at low concentrations to remain in the dilute regime. A model-independent analysis was performed using the Porod invariant which defines the scale factor, leaving only the distribution of radii as the adjustable parameter. The presence of the PSS additive strongly retards the precipitation of CaCO3 NPs. The formation of NPs reaches a state of equilibrium after a few minutes. Here, it is shown that the concentration of precursors at a fixed PSS concentration plays a key role in determining the size of the NPs obtained. A full analysis of the SAXS patterns was carried out using the Hurd–Flower model to account for the weaker intensity decay than the classical Porod behaviour. The temporal evolution of the particle radii was determined. Wide-angle X-ray scattering experiments carried out simultaneously show that the particles formed have the structure of vaterite with growth consistent with the evolution of the Porod invariant.
The structure of magnesium stearate trihydrate determined from a micrometre-sized single crystal using a microfocused synchrotron X-ray beam
Authors: Herzberg Mikkel , Rekis Toms , Støttrup Larsen Anders , Gonzalez Ana , Rantanen Jukka , Østergaard Madsen Anders
Published: June 2023

Crystalline magnesium stearate has been extensively used as an additive in pharmaceutical and other industries for decades. However, the lack of suitably large crystals has hindered the determination of the crystal structure and thereby a more fundamental understanding of the structure–functionality relationship. Presented here is the structure of magnesium stearate trihydrate as determined from X-ray diffraction data of a micrometre-sized single crystal measured at a fourth-generation synchrotron facility. Despite the small size of the single crystals and the weak diffraction, it was possible to determine the positions of the non-hydrogen atoms reliably. Periodic dispersion-corrected density functional theory calculations were used to obtain the positions of the hydrogen atoms playing an important role in the overall organization of the structure via a hydrogen-bond network.
(Re)Investigating the pathways between instructional leadership, collective teacher efficacy, and teacher commitment: a multilevel analysis
Authors: Thien Lei Mee , Darmawan Igusti Ngurah , Adams Donnie
Published: June 2023

Purpose

This study aims to investigate the direct and indirect relationships among principal instructional leadership, collective teacher efficacy, and teacher commitment using multilevel analysis.

Design/methodology/approach

This study employed quantitative cross-sectional research design. Data were collected from 1,328 teachers selected from 71 Malaysian primary schools.

Findings

The direct relationship between instructional leadership and teacher commitment was significant at the school level. Similarly, instructional leadership exhibits a significant direct effect on collective teacher efficacy. Collective teacher efficacy also has a significant direct effect on teacher commitment. The results also indicate a significant indirect effect at school level between instructional leadership and teacher commitment through collective teacher efficacy.

Research limitations/implications

The multilevel analysis among instructional leadership, collective teacher efficacy, and teacher commitment warrant further investigations with larger sample sizes at both group and individual levels.

Originality/value

This study supplements previous findings by contributing more rigorous empirical evidence using multilevel analysis. The findings extend current knowledge in the principal instructional leadership literature in the context of a Southeast Asian country.
The more perceived training effectiveness, the greater the risk of voluntary separation: testing a turnover intent model among police officers in Taiwan
Authors: Lin Wen-Yu , Lai Yung-Lien , Luo Fei , Kuo Shih-ya , Chang Kwang-Ming
Published: June 2023

Purpose

Building on Lambert’s (2001) work on turnover intent in law enforcement, this study examines how organizational characteristics and job attitudes along with job satisfaction, and organizational commitment affect turnover intent among Taiwanese police officers.

Design/methodology/approach

Data were collected from the New Taipei City Police Department (NTCPD) in the summer of 2012 via stratified random sampling (N = 1,035). Structural equation modeling was employed to examine factors affecting turnover intent.

Findings

Job satisfaction and organizational commitment reduced the risk of turnover, while job stressors and training effectiveness directly increased the risk. Worthy of note, officers with a Central Police University degree and who were married had a lower risk of turnover.

Originality/value

This study applies Lambert’s (2001) turnover intent model in law enforcement agencies developed in the West to a non-western policing setting. The use of SEM assures the robustness of the findings. Some noteworthy contrasts in findings from Western and non-Western settings are presented.
Limiting scaring activities reduces economic costs associated with foraging barnacle geese: Results from an individual‐based model
Authors: de Jager Monique , Buitendijk Nelleke H. , Baveco Johannes M. , van Els Paul , Nolet Bart A.
Published: June 2023

With increasing numbers of large grazing birds on agricultural grassland, conflict with farmers is rising. One management approach to alleviate conflict allows foraging on dedicated agricultural land (accommodation areas) and nature reserves, combined with scaring on remaining agricultural land. Here, we examine the cost‐effectiveness of these measures by studying the influence on barnacle goose distribution and associated economic damage.

We present an individual/agent‐based model of barnacle geese (Branta leucopsis) foraging on grasslands in Friesland, the Netherlands. The model is parameterized using field observations and GPS‐tracks and allows simulation of management scenarios, differing in scaring probability and accommodation area size, with different potential management costs.

Our model shows that, while yield loss decreases with higher scaring probabilities, costs of damage appraisal increase because geese graze on more fields. With small accommodation areas, achieving high scaring probabilities takes more effort and could result in goose population decline. Total management costs are lowest without scaring activity.

Synthesis and applications. Considering costs of active scaring and the need to maintain the barnacle goose population in a favourable conservation status, our model suggests that the most cost‐effective scenario is to prevent disturbance of geese. A high scaring probability could be beneficial if applied in small areas, for example around sensitive crops or airfields. Scaring in large areas could result in costs outweighing benefits and a declining barnacle goose population.
Attention Focus and Attention Framework: A Configuration Perspective of Attention to Innovation
Authors: Cai Jing , Canales J. Ignacio
Published: June 2023

The current understanding of the unique contribution of single factors to attention may underestimate the complexity involved in attention allocation. This study aims to design an attention framework and examine the interdependencies between organisational and contextual factors that affect firm attention to exploitation, exploration, and ambidexterity. Drawing on a longitudinal study from 2008 to 2021, we use a configurational approach and identify seven distinct attention configurations as a result of different factor interdependencies, shedding light on how stability in attention configurations produces consistent attention focus. We also identify four change pathways that illustrate how configurations could be modified in response to radical environmental changes. Our study contributes to the attention‐based view by stressing the importance of two alignments that explain a firm's high performance: between attention and contextual factors; between attention and organisational factors. Methodologically, the novelty of the configurational approach is its ability to capture configuration stability in normal external conditions and trace sudden changes in attention focus and configuration paths under extreme external conditions. This study also enhances exploitation and exploration research on managing attention configuration pathways in terms of path flexibility, path emergence, and path deterioration.
The probiotic chestnut‐based dairy matrix: Influence on the metabolomic formation and the nutritional quality
Authors: Yilmaz‐Ersan Lutfiye , Ozcan Tulay , Akpinar‐Bayizit Arzu , Usta‐Gorgun Buse , Keser Gokce , Ciniviz Melike , Demiray‐Teymuroglu Merve
Published: June 2023

The aim of this study was to characterise the impact of mixed probiotic strains and fortification with chestnut beverage (CB) on metabolomic formation in a plant‐based dairy matrix. Bacterial growth, nutritional composition and metabolomics were investigated during the period of 21‐day storage. The amino acid score (AAS), essential amino acid index (EAAI), nutritional index (NI) and biological value (BV) of the samples were determined to characterise their nutritional quality. The fortification with CB increased the nutritional quality of samples due to high EAAI, AAS, NI and BV. Using HPLC‐DAD, GC–MS and HS‐GC/MS‐based instrumental techniques, 48 metabolomics were identified.
Retail Investor Trading Intentions: New Evidence from Australia*
Authors: Tsiaplias Sarantis , Zeng Qi , Lim Guay C.
Published: June 2023

Using a quarterly survey of 23,000 Australian retail equity investors, we study the relationship between beliefs about risk and returns and stock market intentions regarding holding, buying and selling. We provide evidence that investor intentions regarding buying or selling are primarily characterised by risk and return expectations, but sensitivity to their beliefs about risk and returns is greater for the intention to sell than to buy. In contrast, demographic factors such as gender, income and age play a key role in the decision to hold rather than trade. The results have significant ramifications for stock market participation and trading intensity in Australia.
Evaluation of the genetic viability of metapopulation scenarios for the Iberian lynx
Authors: Pacín C. , Garrote G. , Godoy J. A.
Published: June 2023

The Iberian lynx has shown a favourable demographic trajectory in the last decade as a result of the conservation measures adopted which are still ongoing. However, the viability of the species is still compromised by genetic factors. Here, we used the GESP software that predicts the effective population size (Ne) and inbreeding accumulation (∆f) over time in metapopulations, to find realistic scenarios that guarantee the genetic viability of this species. We proposed as genetic targets that Ne of the metapopulation (NeMeta) should exceed 500 in 20 generations (long term), whereas ∆f of the subpopulations (∆fx) should not exceed 0.05 in five generations (short term). The current Iberian lynx metapopulation configuration, with the expected subpopulations sizes at carrying capacity (5 subpops.; Ne1 = 100, Ne2,3,4,5 = 25), does not reach the long‐term goal, with a NeMeta ~ 150 in 20 generations. The results indicate that the long‐term genetic viability of the metapopulation requires an increase in the subpopulation size of 50–200%, the creation of at least 8 new subpopulations, and migration rates close to 0.1 between neighbouring subpopulations, comprising 2165 effective individuals (ca. 1100 breeding females). In addition, a minimum migration rate of 0.05 into the smallest subpopulations of Ne = 25 (i.e. 1.25 migrants/generation) is needed to avoid excessive inbreeding accumulation (short‐term goal). Larger subpopulations are preferable to several smaller subpopulations with the same number of effective individuals, even when the latter are well connected. Although these requirements seem challenging to achieve in the short‐medium term, the study provides key information for informed decision making by environmental managers and policymakers. The conclusions drawn here apply to other carnivores in need of conservation.
The implementation and public health impacts of cannabis legalization in Canada: a systematic review
Authors: Hall Wayne , Stjepanović Daniel , Dawson Danielle , Leung Janni
Published: June 2023

Aims

We provide a narrative summary of research on changes in cannabis arrests, cannabis products and prices, cannabis use and cannabis‐related harm since legalization.

Methods

We systematically searched for research on the impacts of cannabis legalization in Canada in PubMed, Embase, Statistics Canada and government websites and Google Scholar, published between 2006 and 2021.

Results

Cannabis legalization in Canada has been followed by substantial reductions in cannabis‐related arrests and cannabis prices. It has also increased adults’ access to a diverse range of cannabis products, including edibles and extracts. The prevalence of cannabis use among young adults has increased, but there have been no marked increases or decreases in use among high school students or changes in the prevalence of daily or near‐daily use. Legalization has been associated with increased adult hospital attendances for psychiatric distress and vomiting, unintentional ingestion of edible cannabis products by children and hospitalizations for cannabis use disorders in adults. There is conflicting evidence on whether cannabis‐impaired driving has increased since legalization. There is suggestive evidence that presentations to emergency departments with psychoses and cannabis use disorders may have increased since legalization.

Conclusions

Legalization of cannabis in Canada appears to have reduced cannabis arrests and increased access to a variety of more potent cannabis products at lower prices. Since 2019, recent cannabis use in Canada has modestly increased among adults but not among adolescents. There is evidence of increased acute adverse effects of cannabis among adults and children.
Significant association of mutations close to LCORL gene with growth performance in Zhedong white geese (Anser cygnoides)
Authors: Yang Yunzhou , Wang Cui , Li Guangquan , Wang Xianze , Qiu Songyin , Liu Yi , Wang Huiying , He Daqian
Published: June 2023

This study aimed to investigate the role of the LCORL gene in regulating the growth performance of Zhedong white (ZDW) geese, belonging to the swan geese (Anser cygnoides), and identify possible selective signatures in diverse goose breeds. Single nucleotide polymorphisms around LCORL were genotyped, and their associations with body‐size‐related (BSR) traits were estimated. The results showed that the genotyped loci upstream of LCORL were significantly related to the body weight and breast width of ZDW geese aged 10 weeks (p < 0.05). A genome scan comparing expected heterozygosity among different breeds identified a ~150 kb long genomic region with extremely low heterozygosity downstream of LCORL among swan geese. Further, significant associations of variants within the low heterozygosity region among ZDW geese with BSR traits, including body weight, body length and breast width (p < 0.05) were also detected. Overall, mutations adjacent to LCORL were related to the growth performance of swan geese, and the significant effects of variants in a low‐heterozygosity region on BSR traits provided valuable insights into the molecular mechanism of artificial selection reshaping body stature in swan geese.
Opioid analgesic effects on subjective well‐being in the operating theatre*
Authors: Eikemo M. , Meier I. M. , Løseth G. E. , Trøstheim M. , Ørstavik N. , Jensen E. N. , Garland E. L. , Berna C. , Ernst G. , Leknes S.
Published: June 2023

Exposure to opioid analgesics due to surgery increases the risk of new persistent opioid use. A mechanistic hypothesis for opioids' abuse liability rests on the belief that, in addition to pain relief, acute opioid treatment improves well‐being (e.g. via euphoria) and relieves anxiety. However, opioids do not consistently improve mood in laboratory studies of healthy non‐opioid users. This observational study determined how two commonly used opioid analgesics affected patients' subjective well‐being in standard clinical practice. Day surgery patients rated how good and how anxious they felt before and after an open‐label infusion of remifentanil (n = 159) or oxycodone (n = 110) in the operating theatre before general anaesthesia. One minute after drug injection, patients reported feeling intoxicated (> 6/10 points). Anxiety was reduced after opioids, but this anxiolytic effect was modest (remifentanil Cohen's d = 0.21; oxycodone d = 0.31). There was moderate to strong evidence against a concurrent improvement in well‐being (Bayes factors > 6). After remifentanil, ratings of ‘feeling good’ were significantly reduced from pre‐drug ratings (d = 0.28). After oxycodone, one in three participants felt better than pre‐drug. Exploratory ordered logistic regressions revealed a link between previous opioid exposure and opioid effects on well‐being, as only 14 of the 80 opioid‐naïve patients reported feeling better after opioid injection. The odds of improved well‐being ratings after opioids were higher in patients with previous opioid exposure and highest in patients with > 2 weeks previous opioid use (adjusted OR = 4.4). These data suggest that opioid‐induced improvement of well‐being is infrequent in opioid‐naïve patients. We speculate that peri‐operative exposure could increase risk of persistent use by rendering subsequent positive opioid effects on well‐being more likely.
On Interquantile Smoothness of Censored Quantile Regression with Induced Smoothing
Authors: Cai Zexi , Sit Tony
Published: June 2023

Quantile regression has emerged as a useful and effective tool in modeling survival data, especially for cases where noises demonstrate heterogeneity. Despite recent advancements, non-smooth components involved in censored quantile regression estimators may often yield numerically unstable results, which, in turn, lead to potentially self-contradicting conclusions. We propose an estimating equation-based approach to obtain consistent estimators of the regression coefficients of interest via the induced smoothing technique to circumvent the difficulty. Our proposed estimator can be shown to be asymptotically equivalent to its original unsmoothed version, whose consistency and asymptotic normality can be readily established. Extensions to handle functional covariate data and recurrent event data are also discussed. To alleviate the heavy computational burden of bootstrap-based variance estimation, we also propose an efficient resampling procedure that reduces the computational time considerably. Our numerical studies demonstrate that our proposed estimator provides substantially smoother model parameter estimates across different quantile levels and can achieve better statistical efficiency compared to a plain estimator under various finite-sample settings. The proposed method is also illustrated via four survival datasets, including the HMO (health maintenance organizations) HIV (human immunodeficiency virus) data, the primary biliary cirrhosis (PBC) data, and so forth.
Therapeutic role of mesenchymal stem cell‐derived extracellular vesicles in neuroinflammation and cognitive dysfunctions induced by binge‐like ethanol treatment in adolescent mice
Authors: Mellado Susana , Cuesta Carlos M. , Montagud Sandra , Rodríguez‐Arias Marta , Moreno‐Manzano Victoria , Guerri Consuelo , Pascual María
Published: June 2023

Background

Extracellular vesicles (EVs) are heterogeneous membrane vesicles secreted by cells in extracellular spaces that play an important role in intercellular communication under both normal and pathological conditions. Mesenchymal stem cells (MSC) are anti‐inflammatory and immunoregulatory cells capable of secreting EVs, which are considered promising molecules for treating immune, inflammatory, and degenerative diseases. Our previous studies demonstrate that, by activating innate immune receptors TLR4 (Toll‐like receptor 4), binge‐like ethanol exposure in adolescence causes neuroinflammation and neural damage.

Aims

To evaluate whether the intravenous administration of MSC‐derived EVs is capable of reducing neuroinflammation, myelin and synaptic alterations, and the cognitive dysfunction induced by binge‐like ethanol treatment in adolescent mice.

Materials & Methods

MSC–derived EVs obtained from adipose tissue were administered in the tail vein (50 microg/dose, one weekly dose) to female WT adolescent mice treated intermittently with ethanol (3.0 g/kg) during two weeks.

Results

MSC‐derived EVs from adipose tissue ameliorate ethanol‐induced up‐regulation of inflammatory genes (e.g., COX‐2, iNOS, MIP‐1α, NF‐κB, CX3CL1, and MCP‐1) in the prefrontal cortex of adolescent mice. Notably, MSC‐derived EVs also restore the myelin and synaptic derangements, and the memory and learning impairments, induced by ethanol treatment. Using cortical astroglial cells in culture, our results further confirm that MSC‐derived EVs decrease inflammatory genes in ethanol‐treated astroglial cells. This, in turn, confirms in vivo findings.

Conclusion

Taken together, these results provide the first evidence for the therapeutic potential of the MSC‐derived EVs in the neuroimmune response and cognitive dysfunction induced by binge alcohol drinking in adolescence.
Functional analysis of two SLC9A6 frameshift variants in lymphoblastoid cells from patients with Christianson syndrome
Authors: He Hailan , Zhang Huiwen , Chen Hui , He Fang , Yin Fei , Stauber Tobias , Zou Xiaomin , Peng Jing
Published: June 2023

Background

Christianson syndrome (CS) is caused by mutations in SLC9A6 and is characterized by global developmental delay, epilepsy, hyperkinesis, ataxia, microcephaly, and behavioral disorder. However, the molecular mechanism by which these SLC9A6 mutations cause CS in humans is not entirely understood, and there is no objective method to determine the pathogenicity of single SLC9A6 variants.

Methods

Trio‐based whole exome sequencing (WES) was carried out on two individuals with suspicion of CS. qRT‐PCR, western blot analysis, filipin staining, lysosomal enzymatic assays, and electron microscopy examination, using EBV‐LCLs established from the two patients, were performed.

Results

Trio‐based WES identified a hemizygous SLC9A6 c.1560dupT, p.T521Yfs*23 variant in proband 1 and a hemizygous SLC9A6 c.608delA, p.H203Lfs*10 variant in proband 2. Both children exhibited typical phenotypes associated with CS. Expression analysis in EBV‐LCLs derived from the two patients showed a significant decrease in mRNA levels and no detectable normal NHE6 protein. EBV‐LCLs showed a statistically significant increase in unesterified cholesterol in patient 1, but only non‐significant increase in patient 2 when stained with filipin. Activities of lysosomal enzymes (β‐hexosaminidase A, β‐hexosaminidase A + B, β‐galactosidase, galactocerebrosidase, arylsulfatase A) of EBV‐LCLs did not significantly differ between the two patients and six controls. Importantly, by electron microscopy we detected an accumulation of lamellated membrane structures, deformed mitochondria, and lipid droplets in the patients' EBV‐LCLs.

Conclusions

The SLC9A6 p.T521Yfs*23 and p.H203Lfs*10 variants in our patients result in loss of NHE6. Alterations of mitochondria and lipid metabolism may play a role in the pathogenesis of CS. Moreover, the combination of filipin staining with electron microscopy examination of patient lymphoblastoid cells can serve as a useful complementary diagnostic method for CS.
Baseline determinants of remission of type 2 diabetes in response to short‐term insulin‐based therapy: The pivotal role of beta‐cell function
Authors: Retnakaran Ravi , Pu Jiajie , Emery Alexandra , Kramer Caroline K. , Zinman Bernard
Published: June 2023

Aim

To identify baseline determinants of diabetes remission in response to short‐term insulin‐based therapy.

Methods

In this study, adult patients with type 2 diabetes (T2D) of less than 7 years duration were randomized to 8 weeks of treatment with (a) insulin glargine, (b) glargine + thrice‐daily lispro, or (c) glargine + twice‐daily exenatide, followed by 12 weeks of washout that enabled assessment of remission (defined as HbA1c < 6.5% after ≥ 3 months without glucose‐lowering therapy). At baseline, 8 weeks and washout, beta‐cell function was assessed with four measures: Insulin Secretion‐Sensitivity Index‐2 (ISSI‐2), insulinogenic index/Homeostatic Model Assessment for Insulin Resistance (HOMA‐IR), ΔC‐peptide0‐120/Δglucose0‐120 × Matsuda and Δinsulin secretion rate (ISR)0‐120/Δgluc0‐120 × Matsuda.

Results

Diabetes remission was achieved in 31 of 90 participants (34.4%). Compared with their peers, those who went on to remission had lower HbA1c (P < .001) and better beta‐cell function at baseline (all four measures P ≤ .01). The non‐remission and remission groups did not otherwise differ in baseline insulin sensitivity/resistance (Matsuda, HOMA‐IR), body mass index, duration of diabetes, pretrial diabetes medications or allocated insulin‐based therapy during the trial. On logistic regression analyses, each baseline measure of beta‐cell function emerged as a significant predictor of remission (log ISSI‐2: adjusted OR 4.41 [95% CI: 1.71‐11.34]; log insulinogenic index/HOMA‐IR: 2.21 [1.26‐3.89]; log ΔC‐peptide0‐120/Δglucose0‐120 × Matsuda: 1.62 [1.00‐2.64]; log ΔISR0‐120/Δgluc0‐120 × Matsuda: 1.87 [1.09‐3.23]). Similarly, higher baseline ISSI‐2 tertile predicted longer time to glycaemic relapse after cessation of the insulin‐based therapy (log‐rank P = .029).

Conclusion

Beta‐cell function is the dominant baseline pathophysiological determinant of the likelihood of achieving remission of diabetes in response to short‐term insulin‐based therapy.
Brain transcriptome of gobies inhabiting natural CO2 seeps reveal acclimation strategies to long‐term acidification
Authors: Suresh Sneha , Mirasole Alice , Ravasi Timothy , Vizzini Salvatrice , Schunter Celia
Published: June 2023

Ocean acidification (OA) is known to affect the physiology, survival, behaviour and fitness of various fish species with repercussions at the population, community and ecosystem levels. Some fish species, however, seem to acclimate rapidly to OA conditions and even thrive in acidified environments. The molecular mechanisms that enable species to successfully inhabit high CO2 environments have not been fully elucidated especially in wild fish populations. Here, we used the natural CO2 seep in Vulcano Island, Italy to study the effects of elevated CO2 exposure on the brain transcriptome of the anemone goby, a species with high population density in the CO2 seep and investigate their potential for acclimation. Compared to fish from environments with ambient CO2, gobies living in the CO2 seep showed differences in the expression of transcripts involved in ion transport and pH homeostasis, cellular stress, immune response, circadian rhythm and metabolism. We also found evidence of potential adaptive mechanisms to restore the functioning of GABAergic pathways, whose activity can be affected by exposure to elevated CO2 levels. Our findings indicate that gobies living in the CO2 seep may be capable of mitigating CO2‐induced oxidative stress and maintaining physiological pH while meeting the consequent increased energetic costs. The conspicuous difference in the expression of core circadian rhythm transcripts could provide an adaptive advantage by increasing the flexibility of physiological processes in elevated CO2 conditions thereby facilitating acclimation. Our results show potential molecular processes of acclimation to elevated CO2 in gobies enabling them to thrive in the acidified waters of Vulcano Island.
Dilemma between yield and quality: Multigenerational effect of elevated CO2 and nitrogen supply on wheat cultivars
Authors: Wang Xizi , Yang Xin , Li Shenglan , Li Xiangnan , Liang Kehao , Liu Fulai
Published: June 2023

Studying the long‐term effect of elevated atmospheric CO2 concentration (e[CO2]) on wheat (Triticum aestivum L.) over multiple generations has received increasing attention. Here, five wheat cultivars were grown under ambient CO2 concentration (a[CO2], 400 ppm) and e[CO2] (800 ppm), respectively, for three consecutive generations (G1 to G3) under two nitrogen (N) levels (1N and 2N). Compared to plants grown under a[CO2], e[CO2] increased shoot biomass and grain yield (GY) over three generations and the enhancement was greater in G3 than in G1. However, plant N concentration was lowered by e[CO2] and the reduction was not mitigated by higher N supply. The carbon (C) concentration significantly increased in leaf and stem but decreased in grain, indicating an inhibited C translocation to grain under e[CO2]. Most importantly, these negative impacts were exacerbated in G3. Concentrations of mineral nutrients in grain were significantly lowered by e[CO2] with larger reduction in G3 than in G1 in some micronutrients such as Zn, Cu and Fe. These findings suggest that long‐term exposure to e[CO2] sustained the positive effects on plant growth and production but aggravated the reduction of grain quality over multiple generations. Among the five cultivars, 325Jimai showed the greatest increase in shoot biomass and GY, and a greater sink capacity compared with the other cultivars, indicating its potential for future breeding strategies.