bluuebunny/crossref_metadata_2025 huggingface dataset:
What does heritability of Alzheimer’s disease represent?
Authors: Baker Emily , Leonenko Ganna , Schmidt Karl Michael , Hill Matthew , Myers Amanda J. , Shoai Maryam , de Rojas Itziar , Tesi Niccoló , Holstege Henne , van der Flier Wiesje M. , Pijnenburg Yolande A.L. , Ruiz Agustin , Hardy John , van der Lee Sven , Escott-Price Valentina
Published: September 2022

INTRODUCTION

Both Alzheimer’s disease (AD) and ageing have a strong genetic component. In each case, many associated variants have been discovered, but how much missing heritability remains to be discovered is debated. Variability in the estimation of SNP-based heritability could explain the differences in reported heritability.

METHODS

We compute heritability in five large independent cohorts (N=7,396, 1,566, 803, 12,528 and 3,963) to determine whether a consensus for the AD heritability estimate can be reached. These cohorts vary by sample size, age of cases and controls and phenotype definition. We compute heritability a) for all SNPs, b) excluding APOE region, c) excluding both APOE and genome-wide association study hit regions, and d) SNPs overlapping a microglia gene-set.

RESULTS

SNP-based heritability of Alzheimer’s disease is between 38 and 66% when age and genetic disease architecture are correctly accounted for. The heritability estimates decrease by 12% [SD=8%] on average when the APOE region is excluded and an additional 1% [SD=3%] when genome-wide significant regions were removed. A microglia gene-set explains 69-84% of our estimates of SNP-based heritability using only 3% of total SNPs in all cohorts.

CONCLUSION

The heritability of neurodegenerative disorders cannot be represented as a single number, because it is dependent on the ages of cases and controls. Genome-wide association studies pick up a large proportion of total AD heritability when age and genetic architecture are correctly accounted for. Around 13% of SNP-based heritability can be explained by known genetic loci and the remaining heritability likely resides around microglial related genes.

Author Summary

Estimates of heritability in Alzheimer’s disease, the proportion of phenotypic variance explained by genetics, are very varied across different studies, therefore, the amount of ‘missing’ heritability not yet captured by current genome-wide association studies is debated. We investigate this in five independent cohorts, provide estimates based on these cohorts and detail necessary suggestions to accurately calculate heritability in age-related disorders. We also confirm the importance of microglia relevant genetic markers in Alzheimer’s disease. This manuscript provides suggestions for other researchers computing heritability in late-onset disorders and the microglia gene-set used in this study will be published alongside this manuscript and made available to other researchers. The correct assessment of disease heritability will aid in better understanding the amount of ‘missing heritability’ in Alzheimer’s disease.
Phagocytosis underpins the biotrophic lifestyle of intracellular parasites in the class Phytomyxea (Rhizaria)
Authors: Garvetto Andrea , Murúa Pedro , Kirchmair Martin , Salvenmoser Willibald , Hittorf Michaela , Ciaghi Stefan , Harikrishnan Srilakshmy L. , Gachon Claire M.M. , Burns John A. , Neuhauser Sigrid
Published: September 2022

Phagocytosis is a complex multi-gene trait of eukaryotes and allegedly one of the very defining features of this group. Although well documented for free-living unicellular eukaryotes and in specific cellular types of animals, data on phagocytosis in intracellular biotrophic parasites are scant. Indeed, the definition of intracellular biotrophy as complete reliance of a parasite on a living host, with which it constantly negotiates for the exchange of nutrients, is at odd with the consumption of particulate matter suggested by phagocytosis. Phytomyxea are intracellular biotrophic parasites infecting a broad group of hosts, ranging from plants to stramenopiles. They belong to the clade Rhizaria, where phagotrophy (i.e., phagocytosis as main mode to acquire nutrients) is the main mode of nutrition. The exact mode of nutrition of the biotrophic phytomyxea, including the agriculturally impactful phytomyxid Plasmodiophora brassicae, is still unresolved; despite investigations and the availability of molecular data. For other Phytomyxea, observations are patchy and molecular data altogether lacking. Here, using available genomic and transcriptomic data for Phytomyxea and the de novo sequenced transcriptome of the brown algae parasite Maullinia ectocarpii, we investigate the likelihood that the genetic machinery underpinning phagotrophy is conserved within the clade. We further document intracellular phagocytosis in P. brassicae and M. ectocarpii by transmission electron microscopy and fluorescent in situ hybridization. Our investigations confirm that molecular signatures underpinning phagocytosis exist in Phytomyxea and hint at a smaller subset of genes used for intracellular phagocytosis, which is similar between the two parasites. Microscopic evidence confirms the existence of intracellular phagocytosis, which seems to coexist with the manipulation of host physiology typical of biotrophic interactions. In both phytomyxid parasites investigated intracellular phagocytosis has adapted to the intracellular environment and seemingly targets specific organelles. Our findings shed light on the feeding behaviour of Phytomyxea, providing new molecular data for the class; and suggest a paramount and previously unrecognised role for phagocytosis in biotrophic interactions between host and parasite.
Evolved bacterial resistance to the chemotherapy gemcitabine modulates its efficacy
Authors: Sayin Serkan , Rosener Brittany , Li Carmen G , Ho Bao , Ponomarova Olga , Ward Doyle V , Walhout Albertha JM , Mitchell Amir
Published: September 2022

Drug metabolism by the microbiome can influence anti-cancer treatment success. We previously suggested that chemotherapies with antimicrobial activity can select for adaptations in bacterial drug metabolism that can inadvertently influence the host’s chemoresistance. We demonstrated that evolved resistance against fluoropyrimidine chemotherapy lowered its efficacy in worms feeding on drug-evolved bacteria (Rosener et al., 2020). Here we examine a model system that captures local interactions that can occur in the tumor microenvironment. Gammaproteobacteria colonizing pancreatic tumors can degrade the nucleoside-analog chemotherapy gemcitabine and, in doing so, can increase the tumor’s chemoresistance. Using a genetic screen inEscherichia coli, we mapped all loss-of-function mutations conferring gemcitabine resistance. Surprisingly, we found that one third of resistance mutations increase or decrease bacterial drug breakdown and therefore can either lower or raise the gemcitabine load in the local environment. Experiments in threeE. colistrains revealed that evolved adaptation converged to inactivation of the nucleoside permease NupC, an adaptation that increased the drug burden on co-cultured cancer cells. The two studies provide complementary insights on the potential impact of microbiome adaptation to chemotherapy by showing that bacteria-drug interactions transpire locally and systemically and can influence chemoresistance in the host.
The DEPDC1 protein LET-99 is required for cortical stability and antagonizes branched actin formation to promote robust cytokinesis
Authors: Price Kari L. , Lamb Helen , Alvarado Jocelyn V. , Rose Lesilee S.
Published: September 2022

During cytokinesis, signals from the central spindle stimulate the accumulation of active RhoA-GTPase and thus contractile ring components at the equator, while the astral microtubules inhibit such components at the polar cortex. The DEPDC1 family protein LET-99 is required for furrow ingression in the absence of the central spindle signal, and for timely onset of furrowing even in the presence of the central spindle signal. Here we show that LET-99 works downstream or independently of RhoA-GTP and antagonizes branched F-actin and the Rac protein CED-10 to promote furrow initiation. This interaction with CED-10 is separable from LET-99’s function in spindle positioning. We also characterize a new role for LET-99 in regulating cortical stability, where LET-99 acts in parallel with the actomyosin scaffolding protein anillin, but LET-99 does not antagonize CED-10 in this case. We propose that LET-99 acts in a pathway that inhibits the Rac CED-10 to promote the proper balance of branched versus linear F-actin for cytokinesis, and that LET-99 also regulates another factor that contributes to cortical stability.
Rapid Evolution of Glycan Recognition Receptors Reveals an Axis of Host-Microbe Conflicts at Carbohydrate-Protein Interfaces
Authors: Hilbert Zoë A. , Young Hannah J. , Schwiesow Mara , Elde Nels C.
Published: September 2022

Detection of microbial pathogens is a primary function of many mammalian immune proteins. This can be accomplished through the recognition of diverse microbial-produced macromolecules including proteins, nucleic acids and carbohydrates. Many pathogens subvert host defenses by rapidly changing these structures to avoid detection, placing strong selective pressures on host immune proteins that repeatedly adapt to remain effective. Signatures of rapid evolution have been identified in numerous host immunity proteins involved in the detection of pathogenic protein substrates, but whether the same signals can be observed in host proteins engaged in interactions with other pathogen-derived molecules has received much less attention. This focus on protein-protein interfaces has largely obscured the study of fungi as contributors to host-pathogen evolutionary conflicts, despite their importance as a formidable class of vertebrate pathogens. Here, we provide evidence that many mammalian immune receptors involved in the detection of microbial glycans have been subject to recurrent positive selection. Notably, we find that rapidly evolving sites in these genes primarily cluster in key functional domains involved in carbohydrate recognition. Further, we identified convergent patterns of substitution in distinct primate populations at a site in the Melanin Lectin gene that has been associated with increased risk of invasive fungal disease. Our results also highlight the power of evolutionary analyses to reveal uncharacterized interfaces of host-pathogen conflict by identifying genes, such as CLEC12A, with strong signals of positive selection across multiple mammalian lineages. These results suggest that the realm of interfaces shaped by host-microbe conflicts extends beyond the world of host-viral protein-protein interactions and into the world of microbial glycans and fungi.
Peptide-PAINT using a transfected-docker enables live- and fixed-cell super-resolution imaging
Authors: Maity Barun Kumar , Nall Duncan , Lee Yongjae , Selvin Paul R
Published: September 2022

Point accumulation for imaging in nanoscale topography (PAINT) is a single-molecule technique for super-resolution microscopy, achieving ∼5-25 nanometer resolution. Here we show that by transfecting the protein-of-interest with a docker-coil, rather than by adding the docker externally—as is the norm when using DNA tethers or antibodies as dockers—we can achieve similar localization, ∼10 nm. However, using a transfected docker has several experimental advances and simplifications. Most importantly, it allows Peptide-PAINT to be applied to transfected live cells, including surface proteins in mammalian cells and neurons under physiological conditions. The enhance resolution of Peptide-PAINT is also shown for organelles in fixed cells to unravel structural details including ≈40-nm and ≈60-nm axial repeats in vimentin filaments in the cytoplasm, and fiber shapes of sub-100-nm histone-rich regions in the nucleus.
Atg1 modulates mitochondrial dynamics to promote germline stem cell maintenance inDrosophila
Authors: Ayachit Minal S. , Shravage Bhupendra V.
Published: September 2022

Mitochondrial dynamics (fusion and fission) are necessary for stem cell maintenance and differentiation. However, the relationship between mitophagy, mitochondrial dynamics and stem cell exhaustion is not clearly understood. Here we report the multifaceted role of Atg1 in mitophagy, mitochondrial dynamics and stem cell maintenance in female germline stem cells (GSCs) inDrosophila. We found that depletion ofAtg1in GSCs leads to impaired autophagy (mitophagy) as measured by reduced formation of autophagosomes, increased accumulation of p62/Ref (2)P and accumulation of damaged mitochondria. Disrupting Atg1 function led to mitochondrial fusion in developing cysts. The fusion was a result of an increase in Marf levels in both GSCs and cysts, and the fusion phenotype could be rescued by overexpression ofDrp1or by depletingMarfvia RNAi in Atg1-depleted cyst cells. Interestingly, double knockdown of bothAtg1:Marfaffected ovariole size and the number of vitellogenic oocytes. WhileAtg1:Marfknockdown led to decrease in germ cell number. Strikingly,Atg1:Marfdouble knockdown leads to a dramatic loss of GSCs, GCs and a total loss of vitellogenic stages, suggesting a block in oogenesis. Overall, our results demonstrate that Drp1, Marf and Atg1 function together to influence female GSC maintenance and their differentiation into cysts.

Research Highlights

Atg1, in addition to its role in mitophagy, influences mitochondrial dynamics during oogenesis through modulation of Marf.

Atg1 and Marf promote Germline stem cell maintenance in Drosophila.
Comparison of machine learning predictions of subjective poverty in rural China
Authors: Maruejols Lucie , Wang Hanjie , Zhao Qiran , Bai Yunli , Zhang Linxiu
Published: September 2022

Purpose

Despite rising incomes and reduction of extreme poverty, the feeling of being poor remains widespread. Support programs can improve well-being, but they first require identifying who are the households that judge their income is insufficient to meet their basic needs, and what factors are associated with subjective poverty.

Design/methodology/approach

Households report the income level they judge is sufficient to make ends meet. Then, they are classified as being subjectively poor if their own monetary income is inferior to the level they indicated. Second, the study compares the performance of three machine learning algorithms, the random forest, support vector machines and least absolute shrinkage and selection operator (LASSO) regression, applied to a set of socioeconomic variables to predict subjective poverty status.

Findings

The random forest generates 85.29% of correct predictions using a range of income and non-income predictors, closely followed by the other two techniques. For the middle-income group, the LASSO regression outperforms random forest. Subjective poverty is mostly associated with monetary income for low-income households. However, a combination of low income, low endowment (land, consumption assets) and unusual large expenditure (medical, gifts) constitutes the key predictors of feeling poor for the middle-income households.

Practical implications

To reduce the feeling of poverty, policy intervention should continue to focus on increasing incomes. However, improvements in nonincome domains such as health expenditure, education and family demographics can also relieve the feeling of income inadequacy. Methodologically, better performance of either algorithm depends on the data at hand.

Originality/value

For the first time, the authors show that prediction techniques are reliable to identify subjective poverty prevalence, with example from rural China. The analysis offers specific attention to the modest-income households, who may feel poor but not be identified as such by objective poverty lines, and is relevant when policy-makers seek to address the “next step” after ending extreme poverty. Prediction performance and mechanisms for three machine learning algorithms are compared.
Corruption in NREGA: a theoretical analysis
Authors: Sanyal Tilak
Published: September 2022

Purpose

Niehaus and Sukhtankar (2013a, 2013b) find that in response to an increase in the public wage rate in National Rural Employment Guarantee Act (NREGA), underpayment of wage and embezzlement rates increase monotonically. This paper aims to investigate theoretically whether the empirical finding of Niehaus and Sukhtankar (2013b) is valid in the long run. The author also verify whether their observation extends to the situation where multiple types of corruption coexist.

Design/methodology/approach

The author builds a theoretical model comprising of three individuals – a government official, a landlord and a representative worker. First, the author defines a no-corruption equilibrium where the official honestly reports the employment period to the government. In a two-stage game, the landlord announces the private wage rate in stage one, followed by the worker deciding on the allocation of time between private and public works and leisure. Then the author considers a single type of corruption where the official embezzles a part of public money by over-reporting the employment period. The landlord-worker game remains the same as before. Finally, the author considers multiple types of corruption where alongside embezzlement, the official takes a bribe from the worker for employing her. Here also, the author considers a two-stage game where in stage one, the official and landlord simultaneously determine embezzlement and bribe rates and the private wage rate, respectively. In stage two, the worker decides on the allocation of time. In both types of corruption, the probability of detection increases with the corruption rate.

Findings

In the case of a single type of corruption, the embezzlement rate behaves nonmonotonically in response to an increase in the public wage rate. A similar kind of result is obtained with multiple types of corruption as well.

Originality/value

First, to the best of the author’s knowledge, no paper prior to this has theoretically modeled corruption in NREGA. Also, the observations of Niehaus and Sukhtankar (2013a, 2013b) is neither valid in the long run nor extend to multiple corruptions.
Development of the cybercrime awareness scale (CAS): a validity and reliability study in a Turkish sample
Authors: Arpaci Ibrahim , Ateş Ersin
Published: September 2022

Purpose

Cybercrimes increase day by day in parallel to cyber-attacks and cyber-threats. Due to such an increase, required cybersecurity precautions against all kinds of cyber-attacks and cyber-threats should be taken by both organizations and individuals. This study aims to develop a reliable and valid measurement tool to measure cybercrime awareness levels of individuals.

Design/methodology/approach

In this study, a scale named as Cybercrime Awareness Scale (CAS) has been developed and psychometric properties of the scale have been tested by two separate studies.

Findings

The first study included a total of 500 respondents (294 female and 206 male). In the first study, factor structure of the proposed scale has been determined through an exploratory factor analysis. The results revealed a three-factor structure (i.e. information systems crimes, personal data crimes, and privacy and security). Cronbach's alpha reliability coefficients for the subdimensions were 0.95, 0.92, and 0.90, respectively. The sample of the second study consisted of 494 respondents (281 female and 213 male). The confirmatory-factor-analysis results revealed that three-factor structure is valid and optimal model. Further, the proposed scale demonstrated moderate concurrent validity results in relation to the Digital Data Security Awareness Scale.

Originality/value

Findings indicated that the CAS is a valid and reliable measurement tool to measure individuals' cybercrime awareness level. This study makes a novel contribution to the existing cybersecurity literature by providing the CAS, which is developed by following rigorous methodological standards.

Peer review

The peer review history for this article is available at:https://publons.com/publon/10.1108/OIR-01-2022-0023/
Empirical evidence of attribute framing: the case of unsophisticated IPO investors
Authors: Rapp Albert
Published: September 2022

Purpose

The purpose of this paper is to investigate the empirical relevance of attribute framing in the financial marketplace.

Design/methodology/approach

Incorporating a sample of German initial public offerings (IPOs) from 2010 to 2019, the author uses quantitative methods, including regression models and tests for the equality of means, to analyze whether unsophisticated investors are susceptible to attribute framing and whether this susceptibility reflects irrational behavior.

Findings

Unsophisticated investors, who are typically retail investors, are susceptible to attribute framing. They are likely to subscribe to IPOs whose attribute “market valuation” is framed in a positive way, that is, IPOs with low offer prices. As low-priced IPOs are overvalued and underperform in the secondary market relative to high-priced IPOs, the susceptibility to attribute framing reflects irrational behavior. The findings are robust to controlling for sentiment.

Research limitations/implications

Since this paper includes a relatively small sample from a single stock market, future research might employ alternative approaches.

Social implications

When issuers and underwriters are able to exploit retail investors through attribute framing, the participation of these investors in the financial marketplace may finally decrease. Therefore, the financial literacy of retail investors needs to be improved.

Originality/value

This paper is the first to provide empirical evidence of attribute framing in a financial markets context. While most previous research on IPO offer prices focuses on US stocks, this paper is the first to incorporate German stocks.
Comprehensive analysis of mitogenome of native Henan pig breeds with 58 worldwide pig breeds
Authors: Zhang Menghao , Zhang Chen , Hu Panyang , Shi Lidan , Ju Mingming , Zhang Ben , Li Xinjian , Han Xuelei , Wang Kejun , Li Xiuling , Qiao Ruimin
Published: September 2022

Mitochondria follow non‐Mendelian maternal inheritance, and thus can be used to compare genetic diversity and infer the expansion and migration between animal populations. Based on the mitochondrial DNA sequences of 58 pig breeds from Asia, Europe, Oceania, and America, we observed a distinct division of Eurasian pig species into two main Haplogroups (A and B), with the exception of the Berkshire and Yorkshire breeds. Oceanian pigs were much more similar to European and American pigs in Haplogroup A. Additionally, native Chinese pigs exhibited the most abundant genetic polymorphisms and occupied the centre of Haplogroup B. Miyazaki (Japan) and Siberia (Russia) are two distant and disconnected regions; however, most pigs from these regions were clustered into a subcluster, while native pigs from Korea clustered into a second subcluster. This study is the first to report that pigs from Thailand and Vietnam had haplotypes similar to those of Henan, where the earliest evidence of domestic pigs was found from the Yellow River Basin of North China. Local Henan pig breeds are related to many Asian breeds while still having their own mutation identity, such as g.314 delins T>AC/AT/C of the 12S rRNA gene in Yuxi. Some pigs from Palawan, Itbayat, and Batan Islands of the Philippines and Lanyu Island of China were distinct from other Asian pigs and clustered together into Haplogroup C. These findings show that the complexity of domestication of worldwide pig breeds and mitochondria could reflect genetic communication between pig breeds due to geographical proximity and human activities.
Alcohol exposure prior to pregnancy—does hazardous consumption affect placenta‐ and inflammatory‐mediated pregnancy outcomes? A Swedish population‐based cohort study
Authors: Asp Joline , Bergman Lina , Lager Susanne , Axelsson Ove , Wikström Anna‐Karin , Hesselman Susanne
Published: September 2022

Introduction

Alcohol consumption during pregnancy is related to severe birth complications such as low birthweight, preterm birth and birth defects. During the last decade, the Alcohol Use Disorders Identification Test (AUDIT) has been used as a screening tool in Swedish maternal healthcare units to identify hazardous, pre‐pregnancy alcohol use. However, evaluation of the screening with AUDIT, as well as adverse maternal or neonatal outcomes, has not been assessed at a national level.

Material and methods

This was a population‐based cohort study of 530 458 births from 2013 to 2018 using demographic, reproductive and maternal health data from the Swedish Pregnancy Register. Self‐reported alcohol consumption in the year before pregnancy, measured as AUDIT scores, was categorized into moderate (6–13 points) and high‐risk (14–40 points) consumption, with low‐risk (0–5 points) consumption as the reference group. Associations with pregnancy‐ and birth outcomes were explored with logistic regressions using generalized estimating equation models, adjusting for maternal and socioeconomic characteristics. Estimates are presented as adjusted odds ratios (aORs) with 95% confidence intervals (CIs).

Results

High‐risk and moderate pre‐pregnancy alcohol consumption was associated with preeclampsia, preterm birth and birth of an infant small for gestational age (SGA), but these associations were nonsignificant after adjustments. Prior moderate‐risk (aOR 1.29, 95% CI 1.17–1.42) and high‐risk consumption (aOR 1.62, 95% CI 1.17–2.25) increased the likelihood of intrapartum and neonatal infections.

Conclusions

Apart from identifying hazardous alcohol consumption prior to pregnancy and the offer of counseling, screening with the AUDIT in early pregnancy indicates a high risk of inflammatory‐/placenta‐mediated pregnancy and birth outcomes. For most outcomes, AUDIT was not an independent contributor when adjusting for confounding factors. Hazardous alcohol use prior to pregnancy was independently linked to intrapartum and neonatal infections; conditions associated with morbidity and long‐term sequalae. These associations may be explained by alcohol‐induced changes in the maternal or fetal immune system in early pregnancy or persistent alcohol intake during pregnancy, or may depend on unidentified confounding factors.
Interventions to enhance eudaemonic psychological well‐being: A meta‐analytic review with Ryff's Scales of Psychological Well‐being
Authors: van Dierendonck Dirk , Lam Hodar
Published: September 2022

This meta‐analysis enhances our insight into the effectiveness of interventions aimed at improving eudaemonic well‐being. The focal outcome of these interventions is Ryff's Scales of Psychological Well‐being. We summarized experimental studies and concluded whether a specific intervention approach improves individual positive functioning by assessing the six dimensions of psychological well‐being and the composite score of well‐being. Our study confirmed that eudaemonic well‐being can be improved. The strongest influence is seen in integral programs that link directly to Ryff's conceptual model. Breaking down to dimensional scores, existing interventions had the strongest influence on Environmental Mastery, Personal Growth, and Self‐Acceptance. The weakest influence was on Autonomy and Positive Relations with Others. Overall, our result is an important contribution to the well‐being literature in that it shows, more convincing than previous meta‐analyses due to its exclusive and comprehensive focus on Ryff's model, that psychological eudaemonic well‐being can be enhanced by targeted intervention programs.
Association of maternal psychological distress with children with overweight/obesity in Ethiopia
Authors: Biadgilign Sibhatu , Mgutshini Tennyson , Deribew Amare , Gelaye Bizu , Memiah Peter
Published: September 2022

Background

Poor maternal mental health is a major risk factor for adverse offspring health outcomes, including overweight/obesity status. Maternal mental distress is highly prevalent and associated with parenting practices influencing child weight. To date, there is little information documented in Ethiopia on maternal mental distress and children with overweight/obesity status. This study examined the association between maternal mental distress and children with overweight/obesity among mother–child dyads in Addis Ababa, Ethiopia.

Methods

An observational population‐based cross‐sectional study was conducted among mother–child dyads in representative samples in Addis Ababa, Ethiopia. Maternal mental distress was measured using the Self‐Reporting Questionnaire (SRQ)‐20. Child/adolescent overweight/obesity was defined as more than 1 SD above the median World Health Organization (WHO) growth reference. Multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Results

The prevalence of maternal mental distress and children with overweight/obesity was estimated to be 10.1% and 28.8%, respectively. After adjusting for confounders, including maternal education, maternal occupation, average monthly household income, maternal body mass index (BMI) and the number of household members/family size, maternal psychological distress was not associated with offspring overweight/obesity status (adjusted OR [aOR] = 0.54; 95% CI: 0.25, 1.14).

Conclusions

There is no evidence of an association between maternal psychological distress and children with overweight/obesity. This lack of association might be attributable to our cross‐sectional study design. Future epidemiologic studies, particularly those using prospectively collected data, are warranted to examine better the effects of maternal psychological distress on offspring body weight.
The role of epigenetics in multi‐generational transmission of asthma: An NIAID workshop report‐based narrative review
Authors: Wheatley Lisa M. , Holloway John W. , Svanes Cecilie , Sears Malcolm R. , Breton Carrie , Fedulov Alexey V. , Nilsson Eric , Vercelli Donata , Zhang Hongmei , Togias Alkis , Arshad Syed Hasan
Published: September 2022

There is mounting evidence that environmental exposures can result in effects on health that can be transmitted across generations, without the need for a direct exposure to the original factor, for example, the effect of grandparental smoking on grandchildren. Hence, an individual's health should be investigated with the knowledge of cross‐generational influences. Epigenetic factors are molecular factors or processes that regulate genome activity and may impact cross‐generational effects. Epigenetic transgenerational inheritance has been demonstrated in plants and animals, but the presence and extent of this process in humans are currently being investigated. Experimental data in animals support transmission of asthma risk across generations from a single exposure to the deleterious factor and suggest that the nature of this transmission is in part due to changes in DNA methylation, the most studied epigenetic process. The association of father's prepuberty exposure with offspring risk of asthma and lung function deficit may also be mediated by epigenetic processes. Multi‐generational birth cohorts are ideal to investigate the presence and impact of transfer of disease susceptibility across generations and underlying mechanisms. However, multi‐generational studies require recruitment and assessment of participants over several decades. Investigation of adult multi‐generation cohorts is less resource intensive but run the risk of recall bias. Statistical analysis is challenging given varying degrees of longitudinal and hierarchical data but path analyses, structural equation modelling and multilevel modelling can be employed, and directed networks addressing longitudinal effects deserve exploration as an effort to study causal pathways.
Sam50 exerts neuroprotection by maintaining the mitochondrial structure during experimental cerebral ischemia/reperfusion injury in rats
Authors: Yin Xulong , Wang Jiahe , Yang Siyuan , Li Haiying , Shen Haitao , Wang Hui , Li Xiang , Chen Gang
Published: September 2022

Aim

To investigate the role of Sam50, a barrel protein on the surface of the mitochondrial outer membrane, in cerebral ischemia–reperfusion (I/R) injury and its underlying mechanisms.

Methods

A middle cerebral artery occlusion/reperfusion (MCAO/R) model in adult male Sprague–Dawley rats was established in vivo, and cultured neurons were exposed to oxygen–glucose deprivation/reoxygenation (OGD/R) to simulate I/R injury in vitro. Lentiviral vector encoding Sam50 or Sam50 shRNA was constructed and administered to rats by intracerebroventricular injection to overexpress and knockdown Sam50, respectively.

Results

First, after MCAO/R induction, the mitochondrial structure was damaged, and Sam50 protein levels were increased responsively both in vivo and in vitro. Then, it was found that Sam50 overexpression could reduce infarction size, inhibit neuronal cell death, improve neurobehavioral disability, protect mitochondrial structure integrity, and ameliorate mitochondrial dysfunction, which was induced by I/R injury both in vivo and in vitro. However, Sam50 downregulation showed the opposite results and aggravated I/R injury by inducing neuronal cell death, neurobehavioral disability, and mitochondrial dysfunction. Moreover, we found that the interaction between Sam50 and Mic19 was broken off after OGD/R, showing that the Sam50–Mic19–Mic60 axis was breakage in neurons, which would be a reason for mitochondrial structure and function abnormalities induced by I/R injury.

Conclusion

Sam50 played a vital role in the protection of neurons and mitochondria in cerebral I/R injury, which could be a novel target for mitochondrial protection and ameliorating I/R injury.
Superficial low‐grade fibromyxoid sarcoma
Authors: Ronen Shira , Ko Jennifer S. , Rubin Brian P. , Kilpatrick Scott E. , Wang Wei‐Lien , Lazar Alexander J. , Goldblum John R. , Billings Steven D.
Published: September 2022

Background

Low‐grade fibromyxoid sarcoma (LGFMS) typically involves deep soft tissue (beneath the fascia) of the proximal extremities and trunk. Long‐term follow‐up has shown a high rate of local recurrence, metastasis, and death. To the best of our knowledge, there is only one previous large series focusing on superficial LGFMS suggesting superficial tumors are disproportionately more common in children and may have a better prognosis. Our study's primary goals are to confirm these findings and increase general awareness that LGFMS may arise in superficial soft tissue.

Methods

We retrieved our cases of superficial LGFMS diagnosed between 2008 and 2020. Available slides were reviewed, and clinical data and follow‐up information were obtained.

Results

The patients included nine males and 14 females with a median age of 29 years; eight (35%) were children (<18 years) and five (22%) were young adults (18–30 years). The majority involved the lower extremities (65%). The tumors were primarily centered in the subcutis (91%) and dermis (9%). Microscopically, they had typical features of LGFMS with alternating fibrous and myxoid zones composed of bland, slightly hyperchromatic spindled cells. All were positive for MUC4 by immunohistochemistry and/or FUS rearrangement by FISH. Follow‐up on 14 cases ranged from 11 to 148 months (median 61 months) with no evidence of recurrences or distant metastases.

Conclusions

Compared to conventional deep‐seated counterparts, superficial LGFMS is more likely to occur in the extremities of children and young adults and may have a better clinical outcome. Further studies with longer follow‐up will likely help support these findings.
Differentiating typical Tako‐tsubo syndrome from extensive anterior STEMI: Look behind the anterior wall
Authors: Berti Marco , Pernigo Matteo , Dinatolo Elisabetta , Cozza Fabiana , Cuccia Claudio
Published: September 2022

Background

Tako‐tsubo syndrome (TTS) in its most typical form shares common features with anterior ST‐segment elevation myocardial infarction (AMI) during acute presentation. Differential diagnosis between the two conditions is often challenging especially if ST‐segment elevation is associated with extensive apical akinesis.

Methods

We sought to systematically analyze ECG and echocardiographic parameters including LV longitudinal strain and two new indexes: the inferior‐apex ratio (IAR) and the inferior‐lateral‐apex ratio (ILAR), to assess if ventricular involvement may be different in TTS and AMI.

Results

A retrospective cohort study was conducted with two groups: patients with TTS (n = 22) and patients with extensive anterior STEMI (n = 22). Lack of ST elevation in V1 was associated with TTS with sensitivity and specificity of 86%, positive and negative predictive value of 86%. Longitudinal strain in mid inferior and mid inferior‐lateral segments were more compromised in TTS: −4.3 ± 6.4% and −5.4 ± 5.4% in TTS versus −10.2 ± 5.5% and −9.9 ± 4.9% in AMI, respectively (p < .01 for all). By multivariate analysis, both longitudinal strain values, inferior‐apical ratio (IAR) < 1 and inferior‐lateral‐apical ratio (ILAR) < 1 were independently associated with diagnosis of TTS during acute phase.

Conclusions

Our results suggest that impaired contractility extending beyond apex to mid inferior and inferior‐lateral walls can be easily assessed by IAR and ILAR, and these indexes facilitate non‐invasive differentiation of TTS from extensive anterior STEMI.
Dataset for reporting of gastrointestinal stromal tumours: recommendations from the International Collaboration on Cancer Reporting (ICCR)
Authors: Hornick Jason L , Webster Fleur , Dei Tos Angelo Paolo , Hemmings Chris , Miettinen Markku , Oda Yoshinao , Raut Chandrajit P , Rubin Brian P , Von Mehren Margaret , Wardelmann Eva , Fletcher Christopher D M
Published: September 2022

Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumours of the gastrointestinal tract and are among the most frequent sarcomas. Accurate diagnosis, classification, and reporting are critical for prognostication and patient management, including selection of appropriate targeted therapy. Here we report on international consensus‐based datasets for the pathology reporting of biopsy and resection specimens of GIST. The datasets were produced under the auspices of the International Collaboration on Cancer Reporting (ICCR), a global alliance of major international pathology and cancer organizations. An international expert panel consisting of pathologists, a surgical oncologist, and a medical oncologist produced a set of core and noncore data items for biopsy and resection specimens based on a critical review and discussion of current evidence. All professionals involved were subspecialized soft tissue tumour experts and affiliated with tertiary referral centres. Commentary was provided for each data item to explain its clinical relevance and the rationale for selection as a core or noncore element. Following international public consultation, the datasets, which include synoptic reporting guides, were finalized and ratified, and published on the ICCR website. These first international datasets for GIST are intended to promote high‐quality, standardised pathology reporting. Their widespread adoption will improve consistency of reporting, facilitate multidisciplinary communication, and enhance comparability of data, all of which will ultimately help to improve the management of patients with GIST. All the ICCR datasets, including these on GIST, are freely available worldwide on the ICCR website (www.iccr‐cancer.org/datasets).
The role of audit styles in financial statement comparability: South African evidence
Authors: Smith Christelle
Published: September 2022

This study investigates the role of audit styles at different levels on financial statement comparability in South Africa, a setting where firms report under International Financial Reporting Standards (IFRS), the institutional environment is strong and the audit environment is dominated by the Big 4 audit firms. An output‐based comparability measure is used to consider the association between audit styles at a firm level, audit office level and individual auditor level and financial statement comparability. Evidence of audit style effects on financial statement comparability is found at the three different levels—the audit firm, the audit office and the individual auditor. The study further finds some evidence that audit office style dominates audit firm style and individual auditor style dominates audit office style. This finding suggests that even in countries where internal (within the audit firm) and external (country regulations) control mechanisms are strong, the audit style of the individual auditor is present and associated with increased financial statement comparability. Using a setting where firms report under IFRS further suggests that in a principles‐based environment, despite strong internal controls and in‐house working rules by audit firms, individual auditors continue to have some level of autonomy in the interpretation and application of the accounting principles and in‐house working rules.
Challenges around quantifying uncertainty in a holistic approach to hard‐to‐heal wound management: Health economic perspective
Authors: Veličković Vladica , Janković Dina
Published: September 2022

Treatment of hard‐to‐heal wounds involves a holistic approach for choosing between available treatment options. However, evidence for informing these choices is sparse, introducing uncertainty into decisions about the optimum treatment pathways that reflect the vast heterogeneity in this patient population. This paper discusses the existing clinical and health economic literature in order to provide insight into sources of uncertainty in the evaluation of the holistic approach to management of the hard‐to‐heal wounds, and how this uncertainty can be appropriately reflected in research. We identified three key sources of uncertainty in the evaluation of chronic wound treatments, namely heterogeneity in aetiology and patient populations, heterogeneity in treatment pathways, and challenges around capturing all relevant outcomes. Reflecting these complexities requires sophisticated modelling of treatment sequencing and long‐term outcomes. The paper discusses how the scope specification, scenario analyses, and sensitivity analyses can be used to fully characterise analytical uncertainty.
Pericarditis following left atrial ablation
Authors: Aksu Tolga , Mutluer Ferit O. , Tanboga Halil I. , Gupta Dhiraj
Published: September 2022

Introduction

We aimed to evaluate the incidence of acute pericarditis following cardioneuroablation (CNA) and to compare this with patients undergoing left atrial (LA) radiofrequency ablation for atrial fibrillation (AF).

Methods and Results

This is a single‐center prospective study. During the study period, CNA for vasovagal syncope was performed in 42 patients, pulmonary vein isolation (PVI) for paroxysmal AF in 46 patients, and posterior wall isolation (PWI) in addition to PVI for persistent AF in 22 patients. Pericarditis was reported by 18 (16.4%) patients overall: 1 (2.4%) patient in CNA group, 8 (17.4%) patients in PVI group, and 9 (40.9%) patients in PWI (p < .001). On univariable logistic regression analysis, CNA was associated with a lower risk of pericarditis (odds ratio 0.11, 95% confidence interval [CI] 0.01–0.97), while ablation of PWI plus PVI was associated with a higher risk of pericarditis compared with PVI (odds ratio 3.29, 95% CI 1.05–10.3).

Conclusion

This study shows that pericarditis is extremely uncommon following CNA and is significantly less frequent than following AF ablation. This difference is likely related to the much lower amount of LA ablation necessary in this group.
The effect of breastfeeding support provided by video call on postpartum anxiety, breastfeeding self‐efficacy, and newborn outcomes: A randomized controlled study
Authors: Akyıldız Deniz , Bay Betül
Published: September 2022

Aim

To examine the effects of breastfeeding support given by video call on anxiety, breastfeeding self‐efficacy, and newborn outcomes.

Methods

We conducted a randomized controlled experimental trial with 72 women and their babies. Participants were randomly assigned to the intervention (video call) group (VCG: standard care + video call) and control group (CG: standard care). The primary outcomes of this study were the mean postpartum maternal anxiety level and the mean breastfeeding self‐efficacy level. The secondary outcome was neonatal outcomes. This study followed the CONSORT (Consolidated Standards of Reporting Trials) checklist.

Results

Women in VCG had lower anxiety levels than the CG at postpartum 2 weeks (mean difference [MD] 25.42, p = .000) and 1 month (MD 47.72, p = .000). The breastfeeding self‐efficacy level of women in the VCG was higher than the CG at postpartum 2 weeks (MD 13.18, p = .007) and 1 month (MD 10.1, p = .001). The newborns in VCG had higher weight gain and daily breastfeeding frequency than the CG at the postpartum second week (MD 9.64, p = .001, MD 2.88, p = .000; respectively) and 1 month (MD 47.16, p = .000, MD 2.98, p = .000; respectively). There were lower rates of challenges of breastfeeding, hyperbilirubinemia, and feeding with formula in VCG than CG at the postpartum second week (p = .043, p = .043, p = .039; respectively).

Conclusions

Breastfeeding support via video calling has positive effects on maternal anxiety, breastfeeding self‐efficacy, and newborn health. Postpartum caregivers may benefit from video calling for breastfeeding support.
Sini powder with paroxetine ameliorates major depressive disorder by modulating circadian rhythm: A randomized, double‐blind, placebo‐controlled trial
Authors: He Xu , Zhang Ruihuan , Li Zhe , Yao Zhen , Xie Xiaoxia , Bai Ruoxue , Li Lan , Zhang Xu , Zhang Sha , Shen Yan , Li Shaowei , Hui Zhenliang , Liu Rongrong , Chen Jun
Published: September 2022

Circadian rhythm disorder is a significant risk factor for mental diseases, and the recovery of circadian rhythm function has gradually become a signal of effective antidepressant therapy. Sini powder (SNP) is a classical, traditional Chinese formula for depression treatment. However, few clinical reports have been recorded. This randomized, double‐blinded, controlled trial (ChiCTR1900022700) aimed to explore the efficacy of SNP on depression via regulating circadian rhythm. In total, 36 patients with major depressive disorder (MDD) were enrolled for 4‐weeks medication and 6‐weeks follow‐up. HAMD‐24 score and circadian rhythm index, including dim light melatonin onset (DLMO) and phase angle difference (PAD), were included in the assessment. DLMO and PAD were statistically significant in the SNP group after 4 weeks of treatment (p < .05) and with greater improvement in DLMO (p = .03). In addition, DLMO and the HAMD‐24 score showed a positive correlation (p < .05); the HAMD‐24 score degree decreased significantly over time (p < .001). Similarly, interaction effects were shown significantly between group and time (p = .049). The duration of SNP supplementation was relatively short, and the sample size was relatively small. SNP granules combined with paroxetine tablets have definite efficacy in improving the circadian rhythms of MDD patients, reflecting the therapeutic advantages of traditional Chinese medicine as antidepressants.
A paediatric bronchoscopist's ‘Field of Dreams’: Will the flexible cryoprobe hit a home run?
Authors: Vicencio Alfin
Published: September 2022

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