bluuebunny/crossref_metadata_2025 huggingface dataset:
MECP2pedia: A Comprehensive Transcriptome Portal for MECP2 Disease Research
Authors: Trostle Alexander J. , Li Lucian , Kim Seon-Young , Wang Jiasheng , Al-Ouran Rami , Yalamanchili Hari Krishna , Liu Zhandong , Wan Ying-Wooi
Published: November 2021

Mutations in MeCP2 result in a crippling neurological disease, but we lack a lucid picture of MeCP2s molecular role. Focusing on individual transcriptomic studies yields inconsistent differentially expressed genes. We have aggregated and homogeneously processed modern public MeCP2 transcriptome data, which we present in a web portal. With this big data, we discovered a commonly perturbed core set of genes that transcends the limitations of any individual study. We then found distinct consistently up and downregulated subsets within these genes. We observe enrichment for this mouse core in other species MeCP2 models and see overlap between this core and ASD models. Analysis of signal to noise finds that many studies lack enough biological replicates. By integrating and examining transcriptomic data at scale, we have generated a valuable resource and insight on MeCP2 function.
Natural selection shapes the population dynamics of birds and mammals
Authors: Witting Lars
Published: November 2021

With eco-evolutionary processes explaining a wide range of ecological dynamics, I analyse for natural selection effects in the population dynamics of birds and mammals. By fitting single-species age-structured population dynamic models to 3,369 and 483 timeseries of 900 and 208 species of birds and mammals, I estimate that selection-based models are 780 (se:1.3) to 150,000 (se:2) times more probable than models with no selection. AIC model-selection includes natural selection in 79% to 92% of the accepted models, explaining 80% of the population dynamics variance, with median selection regulation being 1.2 (se:0.11) times stronger than density regulation. The estimated dynamics is damped to stable cyclic with median population periods around seven and eight generations for stable cycles. The estimated cycles follow from selected life history changes that solve several population cycle enigmas, highlighting the population dynamic implications of a natural selection that predicts also the life histories and abundancies of animals.
A predictive framework for sustainable youth skills development
Authors: Telukdarie Arnesh , Munsamy Megashnee , Mohlala Popopo Jonas , Monnapula Lesego Lydia , Viswanathan Radhakrishnan
Published: November 2021

Purpose

The purpose of this research is to investigate sustainable strategies for skills development that is specific to the youth of South Africa. International and South African data are statistically analysed and quantified to provide inputs for the systems dynamics (SD)-based predictive skills model. The skills model simulates the impact of barriers and drivers on youth skills development towards identification of focus areas for improvement.

Design/methodology/approach

The research adopts a mixed-methods approach. The study begins with an explorative literature study on skills development, with the findings applied in developing (1) South African specific research instruments for small, medium and micro enterprises (SMMEs) and skills programme grant recipients and (2) a conceptual framework of the SD predictive skills model. The responses to the South African specific instruments are analysed via confirmatory factor analysis (CFA), which quantifies the input coefficients to the system dynamics model. To quantify the global inputs for the SD model, an in-depth literature review of the global skills development initiatives is conducted. The SD model output on skills, for the South African inputs, is comparatively evaluated against global inputs.

Findings

The paper details the results of the literature analysis, instrument analyses, CFA and SD model. The instrument results rank experience, skills and interactions with experts and work-based learning as most important. South African and global learners identify networking as the primary medium for identifying training and employment opportunities. South African and global learners also identify qualifications and work-based experience as key to finding employment. The quantified results of the SA and global analysis are used as inputs in the SD model to deliver a forecasting tool. The SD model finds that the global data provide for better development of the skills base than the South African inputs. The key focus areas identified for improvement in South Africa include networking, work-based experience and a reduction in administrative requirements.

Originality/value

The research's originality resides in the ability to predict the impact of drivers and barriers on skills development. This research sought to transform qualitative global and South African inputs into a consolidated, predictive systems-based model. The SD model can be adopted as an indicator of drivers and barriers focused towards the optimisation of skills development.
Temperature sensitivity of Antarctic soil‐humic substance degradation by cold‐adapted bacteria
Authors: Kim Dockyu , Park Ha Ju , Kim Mincheol , Lee Seulah , Hong Soon Gyu , Kim Eungbin , Lee Hyoungseok
Published: November 2021

Heteropolymer humic substances (HS) are the largest constituents of soil organic matter and are key components that affect plant and microbial growth in maritime Antarctic tundra. We investigated HS decomposition in Antarctic tundra soils from distinct sites by incubating samples at 5°C or 8°C (within a natural soil thawing temperature range of −3.8°C to 9.6°C) for 90 days (average Antarctic summer period). This continuous 3‐month artificial incubation maintained a higher total soil temperature than that in natural conditions. The long‐term warming effects rapidly decreased HS content during the initial incubation, with no significant difference between 5°C and 8°C. In the presence of Antarctic tundra soil heterogeneity, the relative abundance of Proteobacteria (one of the major bacterial phyla in cold soil environments) increased during HS decomposition, which was more significant at 8°C than at 5°C. Contrasting this, the relative abundance of Actinobacteria (another major group) did not exhibit any significant variation. This microcosm study indicates that higher temperatures or prolonged thawing periods affect the relative abundance of cold‐adapted bacterial communities, thereby promoting the rate of microbial HS decomposition. The resulting increase in HS‐derived small metabolites will possibly accelerate warming‐induced changes in the Antarctic tundra ecosystem.
Lithic cyanobacterial communities in the polyextreme Sahara Desert: implications for the search for the limits of life
Authors: Mehda Smail , Muñoz‐Martín M. Ángeles , Oustani Mabrouka , Hamdi‐Aïssa Baelhadj , Perona Elvira , Mateo Pilar
Published: November 2021

The hyperarid Sahara Desert presents extreme and persistent dry conditions with a limited number of hours during which the moisture availability, temperature and light allow phototrophic growth. Some cyanobacteria can live in these hostile conditions by seeking refuge under (hypolithic) or inside (endolithic) rocks, by colonizing porous spaces (cryptoendoliths) or fissures in stones (chasmoendoliths).Chroococcidiopsisspp. have been reported as the dominant or even the only phototrophs in these hot desert lithic communities. However, the results of this study reveal the high diversity of and variability in cyanobacteria among the sampled habitats in the Sahara Desert. The chasmoendolithic samples presented high coccoid cyanobacteria abundances, although the dominant cyanobacteria were distinct among different locations. A high predominance of a newly described cyanobacterium,Pseudoacaryochloris sahariense, was found in hard, compact, and more opaque stones with cryptoendolithic colonization. On the other hand, the hypolithic samples were dominated by filamentous, non‐heterocystous cyanobacteria. Thermophysiological bioassays confirmed desiccation and extreme temperature tolerance as drivers in the cyanobacterial community composition of these lithic niches. The results of the present study provide key factors for understanding life strategies under polyextreme environmental conditions. The isolated strains, especially the newly described cyanobacteriumP. sahariense, might represent suitable microorganisms in astrobiology studies aimed at investigating the limits of life.
Controlling pathogenic risks of water treatment biotechnologies at the source by genetic editing means
Authors: Wu Jie , Liu Dong‐Feng , Li Hui‐Hui , Min Di , Liu Jia‐Qi , Xu Peng , Li Wen‐Wei , Yu Han‐Qing , Zhu Yong‐Guan
Published: November 2021

Antimicrobial‐resistant pathogens in the environment and wastewater treatment systems, many of which are also important pollutant degraders and are difficult to control by traditional disinfection approaches, have become an unprecedented treat to ecological security and human health. Here, we propose the adoption of genetic editing techniques as a highly targeted, efficient and simple tool to control the risks of environmental pathogens at the source. An ‘all‐in‐one’ plasmid system was constructed in Aeromonas hydrophila to accurately identify and selectively inactivate multiple key virulence factor genes and antibiotic resistance genes via base editing, enabling significantly suppressed bacterial virulence and resistance without impairing their normal phenotype and pollutant‐degradation functions. Its safe application for bioaugmented treatment of synthetic textile wastewater was also demonstrated. This genetic‐editing technique may offer a promising solution to control the health risks of environmental microorganisms via targeted gene inactivation, thereby facilitating safer application of water treatment biotechnologies.
Predicting the Divestment of Prior Acquisitions
Authors: Amiri Sina , King David R. , DeMarie Samuel , Brown James R.
Published: November 2021

We evaluate whether, in addition to seeking higher stock performance from acquisitions, firm managers also seek predictable stock performance. Building on prior research, we argue that higher volatility in a firm's stock performance following an acquisition is associated with divestment of a prior acquisition. Survival analysis of a longitudinal, panel dataset of 738 matched US acquisitions with 9,973 firm‐year observations shows that higher volatility in an acquiring firm's stock performance, following an acquisition, significantly predicts divestment of a prior acquisition. This effect is independent and stronger than the effect of the mean stock performance of an acquiring firm following an acquisition. We also find moderating effects for acquisition relatedness and acquiring firm stock performance after an acquisition. When an acquired unit is related to the parent firm's operations, it will be more likely to be divested if subsequent stock performance displays higher volatility. Still, higher overall stock performance makes a parent firm less likely to divest an acquired unit, suggesting that larger mean returns override concerns about higher stock performance volatility during corporate restructuring.
A More Miserable Life than Living in the Jungle: A Japanese ‘Comfort Woman’ Story
Authors: Tsukamoto Sachiyo
Published: November 2021

This article analyses the recollection of a Japanese ‘comfort women’ survivor published in 1975. By applying the analytical concept of gender and trauma, this study draws on the ‘politics of integrity’ theorised by Aurora Levins Morales (1998) as well as the theory of ‘coherence of the self’ proposed by Charlotte Linde (1993). The social, political and psychological analysis of her life story reveals the complexity of the politics of integrity in telling a story of trauma. It concludes how strongly her silent voice of trauma required societal acknowledgement of her sense of self to regain human integrity and dignity.
There is no association between combined oral hormonal contraceptives and depression: a Swedish register‐based cohort study
Authors: Lundin C , Wikman A , Lampa E , Bixo M , Gemzell‐Danielsson K , Wikman P , Ljung R , Sundström Poromaa I
Published: November 2021

Objective

To investigate whether users of hormonal contraceptives (HCs) are at increased risk of depression compared with non‐users.

Design

Register‐based cohort study.

Setting

Sweden.

Sample

Women aged 15–25 years between 2010 and 2017 with no prior antidepressant treatment, psychiatric diagnose or contraindication for HCs (n = 739 585).

Methods

Women with a prescription of HC were identified via the Swedish Prescribed Drug Register (SPDR). Relative risks (RRs) for first depression diagnosis in current HC‐users compared with non‐users were modelled by Poisson regression. Adjustments included age, medical indication for HC‐use and parental history of mental disorders, among others.

Main outcome measures

Depression, captured by a redeemed prescription of antidepressant treatment, or a first depression diagnosis in the SPDR and the National Patient Register.

Results

Compared with non‐users, women on combined oral contraceptives (COCs) and oral progestogen‐only products had lower or no increased risk of depression, relative risk (RR) 0.89 (95% CI 0.87–0.91) and 1.03 (95% CI 0.99–1.06) after adjustments, respectively. Age‐stratified analyses demonstrated that COC use in adolescents conferred no increase in risk (RR 0.96, 95% CI 0.93–0.98), whereas use of progestogen‐only pills (RR 1.13, 95% CI 1.07–1.19), contraceptive patch/vaginal ring (RR 1.43, 95% CI 1.30–1.58), implant (RR 1.38, 95% CI 1.30–1.45) or a levonorgestrel intrauterine device (RR 1.59, 95% CI 1.46–1.73) were associated with increased risks.

Conclusions

This study did not find any association between use of COCs, which is the dominating HC in first time users, and depression. Non‐oral products were associated with increased risks. Residual confounding must be addressed in the interpretation of the results.

Tweetable abstract

There is no association between combined hormonal contraceptives and depression.
Humoral response to BNT162b2 mRNA COVID‐19 vaccine in peritoneal and hemodialysis patients: A comparative study
Authors: Duarte Rui , Roldão Marisa , Figueiredo Cátia , Luz Ivan , Ferrer Francisco , Gonçalves Hernâni , Sofia Flora , Lopes Karina
Published: November 2021

Introduction

Maintenance dialysis patients (MDP) are at higher risk of exposure with increased mortality from COVID‐19 with generalized immunization becoming the cornerstone in prevention. This study aims to compare humoral response between hemodialysis (HD) and peritoneal dialysis (PD) patients.

Materials and Methods

Observational prospective study following HD and PD programs from a Portuguese Center receiving BNT162b2 vaccine. Specific anti‐Spike IgG quantification to compare both for absolute value and non‐responders (NR) between modalities and against risk factors.

Results

Of 67 MDP, 42 were HD and 25 PD patients. PD developed higher antibody titers after both first (median 5.44 vs. 0.99 AU/ml, p < 0.01) and second dose (median 170.43 vs. 65.81 AU/ml; p < 0.01). HD associated with NR after the first dose (p < 0.01).

Conclusion

This study demonstrated improved humoral immunogenicity with BNT162b2 in PD compared to HD patients. These differences are attributed to comorbidity burden and age differences, rather than dialysis modality.
12‐year review of MRI‐detected breast cancers. How often was a diagnosis of malignancy established using targeted ultrasound and standard 14‐gauge core biopsy?
Authors: Price Jeremy
Published: November 2021

Introduction

This retrospective study aimed to determine the percentage of MRI‐detected breast cancers diagnosed using targeted ultrasound and standard 14‐gauge (14g) biopsy in the setting of an Australian breast MRI service. This is of clinical relevance because malignancies not identifiable on mammography or by ultrasound may then require more invasive, technically demanding and costly MRI‐guided interventional procedures, usually by large‐core vacuum‐assisted biopsy (VAB) or hook‐wire localisation with open surgical biopsy.

Methods

On review of the 12‐year period 2006–2018, we identified 67 new breast cancer events in 64 women where the diagnosis was made on the basis of the MRI scan findings either alone (n = 60) or in combination with a concurrent mammogram (n = 7), with no recorded clinical abnormality. The percentage in which malignancy was confirmed on histopathology using targeted ultrasound in combination with 14g biopsy was determined versus other biopsy methods, for both invasive cancer and in situ disease.

Results

Ultrasound‐guided 14g biopsy was successful in establishing the presence of malignancy in 42/46 (91%) of events with a final diagnosis of invasive cancer, with 2 more proven by MRI‐guided interventional procedures (1 VAB and 1 hook‐wire) and 1 by open surgical biopsy. In the final case, a 5 mm focus on MRI with no sonographic correlate at the initial presentation was only identified and biopsied by ultrasound at 12‐month follow‐up.

For events with a final diagnosis of DCIS/pLCIS (pleomorphic LCIS, n = 2), US‐guided 14g biopsy was successful in 10/21 (48%), while 4/7 events with corresponding mammographic microcalcifications were proven by x‐ray stereotactic interventions. A further 5 events had MRI‐guided interventions (3 VAB and 2 hook‐wires) and 1 an open surgical biopsy to confirm malignancy. In the final case (a woman with a 30 × 20 mm focal area of non‐mass enhancement with corresponding microcalcifications consistent with DCIS), a pathologic diagnosis was not made until the patient presented 5 years later with invasive disease. There were also 3 instances of upgrades to invasion on final surgical pathology, one from pLCIS to microinvasion and 2 others from DCIS to IDC. Among the DCIS/pLCIS events, semi‐random 14g core biopsy (sampling at the expected location of the MRI abnormality without a specific sonographic correlate) proved to be successful in 3 women.

Conclusion

Ultrasound‐guided 14g core biopsy established a malignant diagnosis in 91% of invasive cancers and in 48% of DCIS/pLCIS cases. This relatively non‐invasive, technically easy to perform and low‐cost biopsy procedure can be used immediately when targeted ultrasound shows a correlate for a suspicious MRI scan finding. Careful imaging‐pathologic correlation is required after 14g biopsy, and a discordant result will usually prompt recourse to an MRI‐guided VAB or hook‐wire localisation.
A chromosomal level genome sequence for Quasipaa spinosa (Dicroglossidae) reveals chromosomal evolution and population diversity
Authors: Hu Xiaoxiao , Jiang Zeyuan , Ming Yao , Jian Jianbo , Jiang Sanjie , Zhang Dandan , Zhang Jiayong , Zheng Shanjian , Fang Xiaodong , Yang Yulan , Zheng Rongquan
Published: November 2021

Quasipaa spinosa is an Asian commercial Dicroglossidae species noted for its spiny chest found in adult males. Here, we report the first chromosomal level Q. spinosa genome employing PacBio long read sequencing and high‐resolution chromosome conformation capture (Hi‐C) technology. The total length of the final assembled genome was 2,839,292,578 bp, with contig N50 of 3.79 Mb and scaffold N50 of 327.44 Mb. Approximately 99.30% of the length of the assembled genome sequences were anchored to 13 chromosomes with the assistance of Hi‐C reads. A total of 26,173 protein‐coding genes were predicted, and 95.98% of the genes were functionally annotated. The annotated genes covered a total of 92.10% of the complete vertebrate core gene set according to the BUSCO pipeline evaluation. Approximately 41 million years ago, Q. spinosa began to diverge from its dicroglossid sister taxon Nanorana parkeri. The Q. spinosa genome revealed obvious chromosomal fissions compared with Xenopus tropicalis, which probably represented a specific chromosome evolutionary history within frogs. Population analysis showed that Chinese Q. spinosa could be divided into eastern and western genetic clusters, with the western population showing higher diversity than the eastern population. The effective population size of Q. spinosa showed a continuously decreasing trend from one million years ago to 10,000 years ago. In summary, this study sheds light on Q. spinosa evolution and population differentiation, providing a valuable genomic resource for further biological and genetic studies on this species, and other closely related frog taxa.
Occurrence and phylogenetic analysis of Pseudanabaena sp. producing 2‐methylisoborneol in drinking water source of South Korea
Authors: Lee Jung Eun , Yu Mi Na , Yu Soonju , Byeon Myeongseop
Published: November 2021

We investigated the abundance of Pseudanabaena species and the concentration of the monoterpene 2‐methylisoborneol (2‐MIB) from July to October at three sampling sites in South Korea. To identify the main cause of 2‐MIB occurrence in drinking water source, we characterized and performed a phylogenetic analysis of the 2‐MIB synthase gene. Pseudanabaena was the dominant cyanobacterium (68%–100%) among the samples. At all three sampling sites, a strong positive correlation was detected between 2‐MIB concentrations and Pseudanabaena cell numbers. A phylogenetic analysis of 222 MIB sequences isolated from the water samples showed that all of the clones were affiliated with the Pseudanabaena MIB synthase gene, demonstrating that the 2‐MIB in the Han River drinking water source was produced by Pseudanabaena sp. Using a clone of the 2‐MIB gene, network‐based analysis and unweighted pair group method with arithmetic mean analysis were used to examine temporal and spatial variation in the 2‐MIB concentration and Pseudanabaena abundance. The network analysis showed greater temporal than spatial similarity among the 2‐MIB gene clones. Together, our results demonstrate that Pseudanabaena was the main producer of 2‐MIB. These findings provide important information for odour management in drinking water source.
Belief in the myth of an American Indian/Alaska Native biological vulnerability to alcohol problems among reservation‐dwelling participants with a substance use problem
Authors: Gonzalez Vivian M. , Skewes Monica C.
Published: November 2021

Background

Belief in the myth of an American Indian/Alaska Native (AIAN)–specific biological vulnerability (BV) to alcohol problems is associated with worse alcohol outcomes among AIAN college students who drink, despite also being associated with greater attempts to reduce drinking. This study examined the association of belief in a BV with alcohol use among reservation‐dwelling AI adults with a substance use problem.

Methods

Participants (n = 141) who drank alcohol in the past 90 days were selected from a larger AI sample who self‐identified as having a substance use problem. Moderated‐mediation analyses examined whether belief in a BV was positively associated with alcohol‐ and substance use‐related consequences and whether self‐efficacy and craving mediated the association of belief in a BV with alcohol use.

Results

Among participants who reported using alcohol but not hard drugs (e.g., methamphetamine, opioids), greater belief in a BV was associated with more drinking days, which in turn was associated with greater alcohol‐related consequences. Among participants who used alcohol only, belief in a BV was also significantly associated with greater craving, and in turn with more drinking days. Among individuals who used both alcohol and hard drugs, greater belief in a BV was associated with fewer drinking days, but was not significantly associated with substance use‐related consequences. No association was found between belief in a BV and self‐efficacy to avoid alcohol or drug use.

Conclusions

Among individuals who use only alcohol, belief in a BV may contribute to more drinking days and greater alcohol‐related consequences through its association with greater craving. This study provides further evidence of the potential harm of internalizing the belief that being AIAN contributes to the risk for alcohol problems, a notion that lacks scientific evidence despite decades of research. The findings highlight the importance of combating societal myths regarding AIAN peoples and the internalization of these stereotypes.
Factors associated with caregiver distress among home care clients in New Zealand: Evidence based on data from interRAI Home Care assessment
Authors: Abey‐Nesbit Rebecca , Van Doren Shauni , Ahn SangNam , Iheme Linda , Peel Nancye M. , Declercq Anja , Hirdes John , Allore Heather , Jamieson Hamish A.
Published: November 2021

Objective

To identify factors associated with caregiver distress among home care clients in New Zealand.

Methods

The cohort consisted of 105,978 community‐dwelling people aged 65 years or older requiring home care services in New Zealand who had at least one informal caregiver. Bivariate and multivariable logistic regression analyses were used to identify factors associated with caregiver distress.

Results

Variables associated with risk of caregiver distress included Depression Rating Scale score, aggressive behaviour symptoms, primary informal caregiver relationship to patient, Cognitive Performance Scale score, Changes in Health, End‐stage disease, and Signs and Symptoms Scale score, informal care time, secondary informal caregiver relationship to care recipient, activities of daily living hierarchy scale score and any hospitalisation.

Conclusions

The study has identified important characteristics that are associated with caregiver stress. These results suggest that caregiver distress can be relieved by promoting protective factors and aiming to reduce risk factors among home care clients in New Zealand.
Isolation of nanobodies with potential to reduce patients' IgE binding to Bet v 1
Authors: Zettl Ines , Ivanova Tatiana , Strobl Maria R. , Weichwald Christina , Goryainova Oksana , Khan Evgenia , Rutovskaya Marina V. , Focke‐Tejkl Margarete , Drescher Anja , Bohle Barbara , Flicker Sabine , Tillib Sergei V.
Published: November 2021

Background

Recent studies showed that a single injection of human monoclonal allergen‐specific IgG antibodies significantly reduced allergic symptoms in birch pollen‐allergic patients. Since the production of full monoclonal antibodies in sufficient amounts is laborious and expensive, we sought to investigate if smaller recombinant allergen‐specific antibody fragments, that is, nanobodies, have similar protective potential. For this purpose, nanobodies specific for Bet v 1, the major birch pollen allergen, were generated to evaluate their efficacy to inhibit IgE‐mediated responses.

Methods

A cDNA‐VHH library was constructed from a camel immunized with Bet v 1 and screened for Bet v 1 binders encoding sequences by phage display. Selected nanobodies were expressed, purified, and analyzed in regards of epitope‐specificity and affinity to Bet v 1. Furthermore, cross‐reactivity to Bet v 1‐homologues from alder, hazel and apple, and their usefulness to inhibit IgE binding and allergen‐induced basophil activation were investigated.

Results

We isolated three nanobodies that recognize Bet v 1 with high affinity and cross‐react with Aln g 1 (alder) and Cor a 1 (hazel). Their epitopes were mapped to the alpha‐helix at the C‐terminus of Bet v 1. All nanobodies inhibited allergic patients' polyclonal IgE binding to Bet v 1, Aln g 1, and Cor a 1 and partially suppressed Bet v 1‐induced basophil activation.

Conclusion

We identified high‐affinity Bet v 1‐specific nanobodies that recognize an important IgE epitope and reduce allergen‐induced basophil activation revealing the first proof that allergen‐specific nanobodies are useful tools for future treatment of pollen allergy.
Opioid use is associated with increased out‐of‐hospital cardiac arrest risk among 40 000‐cases across two countries
Authors: Eroglu Talip E. , Barcella Carlo A. , Blom Marieke T. , Souverein Patrick C. , Mohr Grimur H. , Torp‐Pedersen Christian , Folke Fredrik , Wissenberg Mads , de Boer Anthonius , Gislason Gunnar H. , Tan Hanno L. ,   for the ESCAPE‐NET Investigators
Published: November 2021

Aims

Opioid use has substantially increased in the last decade and is associated with overdose mortality, but also with increased mortality from cardiovascular causes. This finding may partly reflect an association between opioids and out‐of‐hospital cardiac arrest (OHCA). Therefore, we aimed to investigate OHCA‐risk of opioids in the community.

Methods

We conducted 2 population‐based case–control studies separately in the Netherlands (2009–2018) and Denmark (2001–2015). Cases were individuals who experienced OHCA of presumed cardiac cause. Each case was matched with up to 5 non‐OHCA‐controls according to age, sex and OHCA‐date. Conditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs).

Results

We included 5473 OHCA‐cases matched with 21 866 non‐OHCA‐controls in the Netherlands, and 35 017 OHCA‐cases matched with 175 085 non‐OHCA‐controls in Denmark. We found that use of opioids (the Netherlands: cases: 5.4%, controls: 1.8%; Denmark: cases: 11.9%, controls: 4.4%) was associated with increased OHCA‐risk in both regions (the Netherlands: OR 2.1 [95% CI 1.8–2.5]; Denmark: OR 1.8 [95% CI 1.5–2.1]). The association was observed in both sexes, and in individuals with cardiovascular disease (the Netherlands: OR 1.8 [95% CI 1.5–2.1]; Denmark: OR 1.6 [95% CI 1.5–1.7]) or without (the Netherlands: OR 3.4 [95% CI: 2.4–4.8], Pinteraction < .0001; Denmark: OR 2.3 [95% CI: 2.0–2.5], Pinteraction < .0001).

Conclusion

Use of opioids is associated with increased OHCA‐risk in both sexes, independently of concomitant cardiovascular disease. These findings should be considered when evaluating the harms and benefits of treatment with opioids.
Application of a physiologically based pharmacokinetic model of rivaroxaban to prospective simulations of drug–drug–disease interactions with protein kinase inhibitors in cancer‐associated venous thromboembolism
Authors: Cheong Eleanor Jing Yi , Ng Daniel Zhi Wei , Chin Sheng Yuan , Wang Ziteng , Chan Eric Chun Yong
Published: November 2021

Aims

Rivaroxaban is a viable anticoagulant for the management of cancer‐associated venous thromboembolism (CA‐VTE). A previously verified physiologically‐based pharmacokinetic (PBPK) model of rivaroxaban established how its multiple pathways of elimination via both CYP3A4/2J2‐mediated hepatic metabolism and organic anion transporter 3 (OAT3)/P‐glycoprotein‐mediated renal secretion predisposes rivaroxaban to drug–drug–disease interactions (DDDIs) with clinically relevant protein kinase inhibitors (PKIs). We proposed the application of PBPK modelling to prospectively interrogate clinically significant DDIs between rivaroxaban and PKIs (erlotinib and nilotinib) for dose adjustments in CA‐VTE.

Methods

The inhibitory potencies of the PKIs on CYP3A4/2J2‐mediated metabolism of rivaroxaban were characterized. Using prototypical OAT3 inhibitor ketoconazole, in vitro OAT3 inhibition assays were optimized to ascertain the in vivo relevance of derived transport inhibitory constants (Ki). Untested DDDIs between rivaroxaban and erlotinib or nilotinib were simulated.

Results

Mechanism‐based inactivation (MBI) of CYP3A4‐mediated rivaroxaban metabolism by both PKIs and MBI of CYP2J2 by erlotinib were established. The importance of substrate specificity and nonspecific binding to derive OAT3‐inhibitory Ki values of ketoconazole and nilotinib for the accurate prediction of interactions was illustrated. When simulated rivaroxaban exposure variations with concomitant erlotinib and nilotinib therapy were evaluated using published dose–exposure equivalence metrics and bleeding risk analyses, dose reductions from 20 to 15 and 10 mg in normal and mild renal dysfunction, respectively, were warranted.

Conclusion

We established a PBPK‐DDDI model to prospectively evaluate clinically relevant interactions between rivaroxaban and PKIs for the safe and efficacious management of CA‐VTE.
Variable Selection in Regression-Based Estimation of Dynamic Treatment Regimes
Authors: Bian Zeyu , Moodie Erica E. M. , Shortreed Susan M. , Bhatnagar Sahir
Published: November 2021

Dynamic treatment regimes (DTRs) consist of a sequence of decision rules, one per stage of intervention, that aim to recommend effective treatments for individual patients according to patient information history. DTRs can be estimated from models which include interactions between treatment and a (typically small) number of covariates which are often chosen a priori. However, with increasingly large and complex data being collected, it can be difficult to know which prognostic factors might be relevant in the treatment rule. Therefore, a more data-driven approach to select these covariates might improve the estimated decision rules and simplify models to make them easier to interpret. We propose a variable selection method for DTR estimation using penalized dynamic weighted least squares. Our method has the strong heredity property, that is, an interaction term can be included in the model only if the corresponding main terms have also been selected. We show our method has both the double robustness property and the oracle property theoretically; and the newly proposed method compares favorably with other variable selection approaches in numerical studies. We further illustrate the proposed method on data from the Sequenced Treatment Alternatives to Relieve Depression study.
Endogenous catch per unit effort and congestion externalities between vessels in a search‐matching model: Evidence from the French Guiana shrimp fishery
Authors: Sanz Nicolas , Diop Bassirou
Published: November 2021

This paper aims at explaining the recent rise in profits in the French Guiana shrimp fishery (FGSF) despite the overall fall in activity observed between 1990 and 2009. We develop a stochastic search‐matching version of the usual Cobb–Douglas bioeconomic fishery model. In this version catch per unit effort becomes endogenous, decreasing in the ratio of empty vessels to escaped fish, which we call “anthropic pressure” and which is determined by standard profit maximization. We first estimate the stochastic harvest function, which exhibits nearly constant returns to scale. We then show that a decrease in equilibrium anthropic pressure and congestion between vessels may be more than compensated by the consecutive rise in catch per unit effort. This leads to a fall in average harvesting costs and thus, to a rise in profits. In addition, we identify the condition under which a search‐matching fishery, working under open access, could reach a maximum economic yield equilibrium, which corresponds to a very particular case. Finally, the model makes it possible to evaluate the actual catch per unit effort and explain how the FGSF changed over the period considered with the help of the open access and maximum economic yield frameworks.
Demand for insurance with nonadditive probabilistic beliefs
Authors: Wang Jianli , Su Yingrong , Li Jingyuan , Yick Ho Yin
Published: November 2021

This work examines optimal demand for insurance coverage when the insured has nonadditive subjective probability beliefs about loss uncertainty. By showing the equivalent conditions of Jensen's inequality under the Choquet expected utility framework, we not only provide the threshold on the insurance premium for Mossin's theorem to hold but also explore the joint effect of both risk aversion and uncertainty aversion on optimal insurance demand.
Inflation, innovation, and growth: A survey
Authors: Chu Angus C.
Published: November 2021

In this survey, we provide a selective review of the literature on inflation, innovation, and economic growth. The relationship between economic growth and inflation is a fundamental question in economics. Most studies in this literature explore this relationship in capital‐based growth models. This survey reviews a recent branch of this literature on inflation and innovation‐driven growth. Specifically, we use a canonical monetary Schumpeterian growth model to demonstrate the effects of inflation on innovation and the macroeconomy via different channels. We find that the cash‐in‐advance constraints on consumption and R&D investment have drastically different implications on the macroeconomic effects of inflation.
Inflammation, ageing and diseases of the lung: Potential therapeutic strategies from shared biological pathways
Authors: Faniyi Aduragbemi A. , Hughes Michael J. , Scott Aaron , Belchamber Kylie B. R. , Sapey Elizabeth
Published: November 2021

Lung diseases disproportionately affect elderly individuals. The lungs form a unique environment: a highly elastic organ with gaseous exchange requiring the closest proximity of inhaled air containing harmful agents and the circulating blood. The lungs are highly susceptible to senescence, with age and ‘inflammageing’ creating a pro‐inflammatory environment with a reduced capacity to deal with challenges. While lung diseases may have disparate causes, the burden of ageing and inflammation provides a common process that can exacerbate seemingly unrelated pathologies. However, these shared pathways may also provide a common route to treatment, with increased interest in drugs that target ageing processes across respiratory diseases. In this review, we will examine the evidence for the increased burden of lung disease in older adults, the structural and functional changes seen with advancing age and assess what our expanding knowledge of inflammation and ageing pathways could mean for the treatment of lung disease.

LINKED ARTICLES

This article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc
Strategies towards safer opioid analgesics—A review of old and upcoming targets
Authors: Varga Balazs R. , Streicher John M. , Majumdar Susruta
Published: November 2021

Opioids continue to be of use for the treatment of pain. Most clinically used analgesics target the μ opioid receptor whose activation results in adverse effects like respiratory depression, addiction and abuse liability. Various approaches have been used by the field to separate receptor‐mediated analgesic actions from adverse effects. These include biased agonism, opioids targeting multiple receptors, allosteric modulators, heteromers and splice variants of the μ receptor. This review will focus on the current status of the field and some upcoming targets of interest that may lead to a safer next generation of analgesics.

LINKED ARTICLES

This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc
Tectonostratigraphic framework in the eastern Korean continental margin, East Sea: Implication for evolution of the Hupo Basin
Authors: Park Yongjoon , Kang Nyeonkeon , Yi Boyeon , Lee Gwangsoo , Yoo Donggeun
Published: November 2021

Integrating seismic interpretation facilitates the discernment of tectonostratigraphic evolution in the eastern Korean continental margin, East Sea. The sedimentary succession of this margin is divided into three major seismic units based on distinct unconformities. These unconformities and their associated seismic characteristics indicate that the eastern Korean continental margin has experienced four evolutionary stages through extensional and subsequent two‐phase tectonic inversions. Early Miocene back‐arc opening of the East Sea triggered the extension of NNW–SSE and N–S trending rifts, resulting in non‐marine to deep‐marine deposition of typical rift‐related linked sedimentological systems in the eastern Korean continental margin. In the early Late Miocene, changes in plate motion and the subduction mode of the Japanese island (NW–SE compression) caused the positive inversion of extensional fault‐bounded half‐grabens in the eastern Korean continental margin, and the Hupo Basin was likely created by the regional flexural response. During this depositional period, hemipelagic sedimentation accompanied by episodic gravity‐controlled slope failures was predominant in the deep‐water environment. The subsidence of the Hupo Basin was enhanced by crustal shortening (E–W compression) that was induced by subduction initiation at the western margin of the Ulleung Basin during the late Early Pliocene (ca. 3.8 Ma). At that time, sedimentary environment gradually became shallower with time and coarse‐grained terrigenous input into the Hupo Basin began so that shallow‐ to deep‐marine sedimentation occurred. In the Quaternary period, the uplift of the Hupo Bank and coeval subsidence of the Hupo Basin were maintained by continued compressive neotectonics. The shallow‐ to deep‐marine deposition continued, but greater quantities of coarse‐grained terrestrial sediment were transported into the Hupo Basin due to combined effects on tectonics and eustasy. Based on the tectonostratigraphic reconstruction developed in this study, we propose that the Hupo Basin is likely a Late Miocene–Quaternary compression‐related basin induced by crustal or thrust loading.
Decreased expression of T‐cell‐associated immune markers predicts poor prognosis in patients with follicular lymphoma
Authors: Rai Shinya , Inoue Hiroaki , Sakai Kazuko , Hanamoto Hitoshi , Matsuda Mitsuhiro , Maeda Yasuhiro , Haeno Takahiro , Watatani Yosaku , Kumode Takahiro , Serizawa Kentaro , Taniguchi Yasuhiro , Hirase Chikara , Espinoza J. Luis , Morita Yasuyoshi , Tanaka Hirokazu , Ashida Takashi , Tatsumi Yoichi , Nishio Kazuto , Matsumura Itaru
Published: November 2021

We previously examined the utility of rituximab‐bendamustine (RB) in patients with follicular lymphoma (FL) exhibiting less than optimal responses to 2 cycles of the R‐CHOP chemotherapy regimen. The aim of this study was to identify molecular biomarkers that can predict prognosis in RB‐treated patients in the context of the prospective cohort. We first analyzed the mutational status of 410 genes in diagnostic tumor specimens by target capture and Sanger sequencing. CREBBP, KMT2D, MEF2B, BCL2, EZH2, and CARD11 were recurrently mutated as reported before, however none was predictive for progression‐free survival (PFS) in the RB‐treated patients (n = 34). A gene expression analysis by nCounter including 800 genes associated with carcinogenesis and/or the immune response showed that expression levels of CD8+ T‐cell markers and half of the genes regulating Th1 and Th2 responses were significantly lower in progression of disease within the 24‐mo (POD24) group (n = 8) than in the no POD24 group (n = 31). Collectively, we selected 10 genes (TBX21, CXCR3, CCR4, CD8A, CD8B, GZMM, FLT3LG, CD3E, EOMES, GZMK), and generated an immune infiltration score (IIS) for predicting PFS using principal component analysis, which dichotomized the RB‐treated patients into immune IIShigh (n = 19) and IISlow (n = 20) groups. The 3‐y PFS rate was significantly lower in the IISlow group than in the IIShigh group (50.0% [95% CI: 27.1‐69.2%] vs. 84.2% [95% CI: 58.7‐94.6%], P = .0237). Furthermore, the IIS was correlates with absolute lymphocyte counts at diagnosis (r = 0.460, P = .00355). These results suggest that the T‐cell‐associated immune markers could be useful to predict prognosis in RB‐treated FL patients. (UMIN:000 013 795, jRCT:051 180 181)
Socio‐demographic and familial factors associated with hospital admissions and repeat admission for dental caries in early childhood: A population‐based study
Authors: Chen Rebecca , Schneuer Francisco J , Irving Michelle J , Chow Clara K , Kumar Harleen , Tsai Carrie , Sohn Woosung , Spallek Heiko , Bell Jane , Nassar Natasha
Published: November 2021

Objectives

Dental caries remains a complex childhood condition often requiring preventable hospital admissions. There are limited population‐based epidemiological studies that use large and linked data sets to quantify the clinical, socio‐demographic and familial risk factors related to hospital admissions for dental caries. The aim of this study was to describe and quantify the rates, socio‐demographic, clinical characteristics and familial factors including repeat admissions associated with young children admitted to hospital for dental caries.

Methods

This cohort study (n = 33,438) used longitudinally linked hospital admission data among all children aged <six years in NSW, Australia. Socio‐demographic and admission characteristics of children and those with one versus two or more admissions for dental caries were compared. Familial risk factors were analysed for a restricted cohort of families with two or more children (n = 18,174) using multivariable logistic regression to assess the familial factors associated with multiple hospital admissions for dental caries adjusting for other socio‐demographic characteristics.

Results

There were 33,438 children aged <six years who had 34,446 hospital admissions for dental caries between 2001 and 2014. The annual rate of 4.3 per 1000 children remained unchanged over the period. Most admissions required general anaesthesia (96%), and 8.4% of children had repeat admissions. Children living in disadvantaged or in regional and rural areas attending public hospitals were more likely to have dental extractions during the admission. Children from the same family had a 2.7‐fold increased odds of admission if the first child admitted was less than three years of age (adjusted odd ratio 2.69; 95% CI: 2.36–3.07), a 1.5 fold increase for socioeconomic disadvantage (aOR 1.45; 1.19 – 1.77) and a 1.9 fold increase of admission if the family had 4 or more children (aOR1.88; 1.47 – 2.42).

Conclusions

Findings highlight socio‐demographic inequities associated with hospital admission for dental caries. The provision of targeted dental care programs for ‘at‐risk’ families should address these inequalities and presents an opportunity to reduce dental caries related hospitalizations.
Child care institutions in India: Caregivers' solutions to challenges in childcare
Authors: Wanglar Evergreat
Published: November 2021

For effective childcare, identifying challenges and exploring the solutions to those challenges is critical. This study explores the different challenges of childcare in child care institutions and its solutions from caregivers' perspectives. The researcher uses a basic interpretive design approach and selects 39 respondents by purposive sampling, and uses semi‐structured interviews. The findings indicate need for separate institutions for different categories of children and trained and professional caregivers, balancing gender engagement, the necessity for establishing separate institutional care for differently able children, need for effective implementation of foster care and sponsorship and need to work with families for effective children's restoration.
Line Art Colorization Based on Explicit Region Segmentation
Authors: Cao Ruizhi , Mo Haoran , Gao Chengying
Published: November 2021

Automatic line art colorization plays an important role in anime and comic industry. While existing methods for line art colorization are able to generate plausible colorized results, they tend to suffer from the color bleeding issue. We introduce an explicit segmentation fusion mechanism to aid colorization frameworks in avoiding color bleeding artifacts. This mechanism is able to provide region segmentation information for the colorization process explicitly so that the colorization model can learn to avoid assigning the same color across regions with different semantics or inconsistent colors inside an individual region. The proposed mechanism is designed in a plug‐and‐play manner, so it can be applied to a diversity of line art colorization frameworks with various kinds of user guidances. We evaluate this mechanism in tag‐based and reference‐based line art colorization tasks by incorporating it into the state‐of‐the‐art models. Comparisons with these existing models corroborate the effectiveness of our method which largely alleviates the color bleeding artifacts. The code is available athttps://github.com/Ricardo-L-C/ColorizationWithRegion.