bluuebunny/crossref_metadata_2025 huggingface dataset:
Host genetic background is a barrier to broadly effective vaccine protection: Relevance to BCG andMycobacterium tuberculosisInfection
Authors: Lai Rocky , Gong Diana , Williams Travis , Ogunsola Abiola F. , Cavallo Kelly , Arlehamn Cecilia S. Lindestam , Acolatse Sarah , Beamer Gillian L. , Ferris Martin T. , Sassetti Christopher M. , Lauffenburger Douglas A. , Behar Samuel M.
Published: September 2022

The heterogeneity of immune responses observed in humans is difficult to model in standard inbred laboratory mice. To capture the diversity inherent in mice and better understand how host variation affects BCG-induced immunity againstMycobacterium tuberculosis, 24 unique Collaborative Cross (CC) recombinant inbred mouse strains and the C57BL/6 reference strain were vaccinated with or without BCG, and then challenged with low-dose aerosolized virulentM. tuberculosis. In contrast to standard lab strains, BCG protected only half of the CC strains tested. Furthermore, BCG efficacy is dissociable from inherent susceptibility to TB. As these strains differed primarily in the genes and alleles they inherited from the CC founder strains, we conclude that the host genetic background has a major influence on whether BCG confers protection againstM. tuberculosisinfection and indicates that host genetics should be considered as an important barrier to vaccine-mediated protection. Importantly, we wished to identify the components of the immune response stimulated by BCG, which were subsequently recalled after Mtb infection and associated with protection. The T cell immune response following BCG vaccination and Mtb challenge was extensively characterized. Although considerable diversity was observed, BCG vaccination had little impact on the composition of T cells recruited and maintained in the lung after infection. Instead, the variability was largely shaped by the genetic background. We developed models to detect vaccine-induced differences, which identified immune signatures associated with BCG-elicited protection against TB. Importantly, even when categorized as susceptible vs. resistant, and protected vs. unprotected, many of the protected CC strains had unique flavors of immunity, indicating multiple paths to protection. Thus, CC mice can be used to define correlates of protection and to identify vaccine strategies that protect a larger fraction of genetically diverse individuals instead of optimizing protection for a single genotype.
Eliminating Genes for a Two Component System Increases PHB Productivity in Cupriavidus basilensis 4G11 Under PHB Suppressing, Non-Stress Conditions
Authors: Sander Kyle , Abel Anthony J. , Friedline Skyler , Sharpless William , Skerker Jeffrey , Deutschbauer Adam , Clark Douglas S. , Arkin Adam P.
Published: September 2022

Species of bacteria from the genus Cupriavidus are known, in part, for their ability to produce high amounts of poly-hydroxybutyrate (PHB) making them attractive candidate bioplastic producers. The native production of PHB occurs during periods of metabolic stress, and the process regulating the initiation of PHB accumulation in these organisms is not fully understood. Screening an RB-TnSeq transposon library of Cupriavidus basilensis 4G11 allowed us to identify two genes of an apparent, uncharacterized two component system which, when omitted from the genome, are capable of increased PHB productivity in balanced, non-stress growth conditions. We observe average increases in PHB productivity of 56% and 41% relative to the wildtype parent strain, upon deleting each of two genes individually from the genome. The increased PHB phenotype disappears, however, in nitrogen-free unbalanced growth conditions suggesting the phenotype is specific to fast-growing, replete, non-stress growth. Bioproduction modeling suggests this phenotype could be due to a decreased reliance on metabolic stress induced by nitrogen limitation to initiate PHB production in the mutant strains. Such strains may allow for the use of single stage, continuous bioreactor systems, which are far simpler than PHB bioproduction schemes used previously. Bioproductivity modeling suggests that omitting this regulation in the cells may increase PHB productivity up to 24% relative to the wildtype organism when using single stage continuous systems. This work furthermore expands our understanding of the regulation of PHB accumulation in Cupriavidus, in particular the initiation of this process upon transition into unbalanced growth regimes.
Host immunological responses facilitate development of SARS-CoV-2 mutations in patients receiving monoclonal antibody treatments
Authors: Gupta Akshita , Konnova Angelina , Smet Mathias , Berkell Matilda , Savoldi Alessia , Morra Matteo , Van averbeke Vincent , De Winter Fien , Peserico Denise , Danese Elisa , Hotterbeekx An , Righi Elda ,   mAb ORCHESTRA working group, De Nardo Pasquale , Tacconelli Evelina , Kumar Surbhi Malhotra , Singh Samir Kumar
Published: September 2022

The role of host immunity in emergence of evasive SARS-CoV-2 Spike mutations under therapeutic monoclonal antibody (mAb) pressure remains to be explored. Here, we show that patients treated with various anti-SARS-CoV-2 mAb regimens develop evasive Spike mutations with remarkable speed and high specificity to the targeted mAb-binding sites. Mutations develop more frequently in immunocompromised patients and strongly correlate not only with the neutralizing capacity of the therapeutic mAbs, but also with an anti-inflammatory and healing-promoting host milieu. Machine-learning models based on soluble host-derived biomarkers identified patients at high risk of developing escape mutations against therapeutic mAbs with high accuracy. While our data demonstrate that host-driven immune and non-immune responses are essential for development of mutant SARS-CoV-2, these data could also support point-of-care decision making in reducing the risk of mAb treatment failure and improving mitigation strategies for possible dissemination of escape SARS-CoV-2 mutants.
The Long Noncoding RNA Playrr Regulates Pitx2 Dosage and Protects Against Cardiac Arrhythmias
Authors: Chen Frances L. , Oxford Eva M. , Chou Shao-Pei , Li Na , Leach John P. , Perry Sienna K. , Sanketi Bhargav D. , Cong Christina , Kupiec-Weglinski Sophie A. , Dubowitz Rebecca , Daugherity Erin , Martin James F. , Danko Charles G. , Kurpios Natasza A.
Published: September 2022

Rationale

The most significantly associated atrial fibrillation (AF) risk loci in humans map to a noncoding gene desert upstream of the evolutionarily conserved left-right (LR) transcription factor Pitx2, a master regulator of LR asymmetric organ development. Pitx2 dosage is fundamentally linked to the development of sinus node dysfunction (SND) and AF, the most common cardiac arrhythmia affecting adults, but the mechanistic basis for this remains obscure. We identified a conserved long noncoding RNA (lncRNA), Playrr, which is exclusively transcribed on the embryo’s right side, opposite to Pitx2 on the left, that participates in mutually antagonistic transcriptional regulation with Pitx2.

Objective

The objective of this study was to investigate a role of Playrr in regulating Pitx2 transcription and protecting against the development of cardiac rhythm disturbances.

Methods and Results

Playrr expression in the developing heart was analyzed with RNA in situ hybridization. Playrr was expressed asymmetrically (on the right) to Pitx2 (on the left) in developing mouse embryos, including in mouse embryonic sinoatrial node cells. We utilized CRISPR/Cas9 genome editing in mice to target Playrr, generating mice lacking Playrr RNA transcript (PlayrrEx1sj allele). Using qRT-PCR we detected upregulation of the cardiac isoform, Pitx2c, during visceral organ morphogenesis in PlayrrEx1sj mutant embryos. Surface ECG (AliveCor®) and 24-hour telemetry ECG detected bradycardia and irregular interbeat (R-R) intervals suggestive of SND in PlayrrEx1sj mutant adults. Programmed stimulation of PlayrrEx1sj mutant adults resulted in pacing-induced AF. Within the right atrium of PlayrrEx1sj mutant hearts, Masson’s trichrome stain revealed increased collagen deposition indicative of fibrosis, and immunofluorescence demonstrated mis-localization of Connexin 43 in atrial cardiomyocytes. These findings suggested an altered atrial substrate in PlayrrEx1sj adult mice. Finally, transcriptomic analysis by chromatin run-on and sequencing (ChRO-seq) in atria of PlayrrEx1sj mutant mice compared to wild type controls revealed differential expression of genes involved in cell-cell adhesion and motility, fibrosis, and dysregulation of the key cardiac genes Tbx5 and Hcn1.

Conclusions

Adult mice lacking functional Playrr lncRNA transcript have baseline bradyarrhythmia and increased susceptibility to AF. These cardiac phenotypes are similar to those observed in Pitx2 heterozygous mice. Interactions between Pitx2 and Playrr may provide a genetic mechanism for modulating Pitx2 dosage and susceptibility to SND and AF.
Dispersal provides trophic-level dependent insurance against a heatwave in freshwater ecosystems
Authors: Vad Csaba F. , Hanny-Endrédi Anett , Kratina Pavel , Abonyi András , Mironova Ekaterina , Murray David S. , Samchyshyna Larysa , Tsakalakis Ioannis , Smeti Evangelia , Spatharis Sofie , Tan Hanrong , Preiler Christian , Petrusek Adam , Bengtsson Mia M. , Ptacnik Robert
Published: September 2022

Climate change-related heatwaves are major recent threats to biodiversity and ecosystem functioning. However, our current understanding of the mechanisms governing community resilience (resistance and recovery) to extreme temperature events is still rudimentary. The spatial insurance hypothesis postulates that diverse regional species pools can buffer ecosystem functioning against local disturbances through immigration of better adapted taxa. However, experimental evidence for such predictions from multi-trophic communities and pulse-type disturbances, like heatwaves, are largely missing. We performed an experimental mesocosm study with alpine lake plankton to test whether a dispersal event from natural lakes prior to a simulated heatwave could increase resistance and recovery of local communities. As the buffering effect of dispersal may differ among trophic groups, we independently manipulated dispersal of organisms from lower (microorganisms) and higher (zooplankton) trophic levels. The experimental heatwave suppressed total community biomass by having a strong negative effect on zooplankton biomass, probably due to a heat-induced increase in metabolic costs that in turn caused mortality. Heating thus resulted in weaker top-down control and a subsequent shift to bottom-heavy food webs. While zooplankton dispersal did not alleviate the negative heatwave effects on zooplankton biomass, dispersal of microorganism enhanced biomass recovery at the level of phytoplankton, thereby providing evidence for spatial insurance. The different response of trophic groups may be related to the timing of dispersal, which happened under strongly monopolized resource conditions by zooplankton, creating limited opportunity for competitors to establish. At the same time, the heatwave released phytoplankton from grazing pressure and increased nutrient recycling, which may have facilitated the establishment of new phytoplankton taxa. Our findings clearly show that even a short heatwave can strongly alter energy flow in aquatic ecosystems. Although dispersal can enhance community resilience, the strength of its buffering effects depends on the trophic level.
ShIVA – A user-friendly and interactive interface giving biologists control over their single-cell RNA-seq data
Authors: Aussel Rudy , Asif Muhammad , Chenag Sabrina , Jaeger Sébastien , Milpied Pierre , Spinelli Lionel
Published: September 2022

Single-cell technologies have revolutionised biological research and applications. As they continue to evolve with multi-omics and spatial resolution, analysing single-cell datasets is becoming increasingly complex. For biologists lacking expert data analysis resources, the problem is even more crucial, even for the simplest single-cell transcriptomics datasets.

We propose ShIVA, an interface for the analysis of single-cell RNA-seq and CITE-seq data specifically dedicated to biologists. Intuitive, iterative and documented by video tutorials, ShIVA allows biologists to follow a robust and reproducible analysis process, mostly based on the Seurat v4 R package, to fully explore and quantify their dataset, to produce useful figures and tables and to export their work to allow more complex analyses performed by experts.
Tubulin engineering by semisynthesis reveals that polyglutamylation directs detyrosination
Authors: Ebberink Eduard , Fernandes Simon , Hatzopoulos Georgios , Agashe Ninad , Guidotti Nora , Reichart Timothy M. , Reymond Luc , Velluz Marie-Claire , Schneider Fabian , Pourroy Cédric , Janke Carsten , Gönczy Pierre , Fierz Beat , Aumeier Charlotte
Published: September 2022

Microtubules, a critical component of the cytoskeleton, carry combinations of post-translational modifications (PTMs), which are critical for the regulation of key cellular processes. Long-lived microtubules, in neurons particularly, exhibit both detyrosination of α-tubulin as well as polyglutamylation. Dysregulation of these PTMs results in disease, including developmental defects and neurodegeneration. Despite their importance, the mechanisms governing the emergence of such PTM patterns are not well understood, mostly because tools to dissect the function and regulation of tubulin PTMs have been lacking. Here, we report a chemical method to produce fully functional tubulin carrying precisely defined PTMs within its C-terminal tail. Using a sortase- and intein-mediated tandem transamidation strategy, we ligate synthetic α-tubulin tails, which are site-specifically glutamylated to specific extents, to recombinant human tubulin heterodimers. Using microtubules reconstituted with such designer tubulins, we show that polyglutamylation of α-tubulin promotes its detyrosination by enhancing the activity of the tubulin tyrosine carboxypeptidase vasohibin/SVBP in a manner dependent on the length of polyglutamyl chains. Moreover, modulating polyglutamylation levels in cells results in corresponding changes in detyrosination. Together, using synthetic chemistry to produce tubulins carrying defined PTMs, we can directly link the detyrosination cycle to polyglutamylation, connecting two key regulatory systems that control tubulin function.
Rethinking recruitment ethically through the lens of corporate social responsibility (CSR)
Authors: Benuyenah Vic
Published: September 2022

Purpose

Traditional recruitment practices tend to be rigorous, but some of its elements can be improved. The length of applications, missing or unstated salary details and lack of anonymity in some emerging countries' recruitment processes mean that recruitment standards remain questionable and unethical. This paper presents a conceptual discourse on how current recruitment activities can be improved in light of progress made with global Internet infrastructure and CSR standards.

Design/methodology/approach

This is primarily a conceptual paper intended to discuss unethical recruitment practices. The author used selected studies and case studies to present the case for improvements in the field of recruitment.

Findings

Compared with easy apply options popularised through recruitment websites, organisations continue to favour traditionally lengthy and complicated applications. The incidence of unstated salary, lack of anonymity and poor communication from some recruiters imply that more has to be done in these areas of CSR.

Research limitations/implications

As with most conceptual papers, this study lacks adequate empirical support. The claims and propositions made are largely based on a scanty number of current research and industry observations.

Practical implications

This study will have potential application in scenarios where recruiters are seeking to improve their practice; however, the recommendations may not be applicable to all organisations.

Social implications

The understanding of ethical values and their application to recruitment will vary from culture to culture.

Originality/value

The paper offers a clear path to debating recruitment ethics and improvements in current practices. No known studies have specifically targeted this area of ethical recruitment.
Handle with care! Service contract termination as a service delivery task
Authors: Wetzel Hauke , Haenel Christina , Hess Alexandra Claudia
Published: September 2022

Purpose

Profitability considerations lead service providers to terminate service contracts with low-value customers. However, customers targeted by service contract terminations often take revenge through negative word-of-mouth (NWOM). Presently, it is unclear how service contract termination initiatives prevent this harmful side effect. The purpose of this study is to compare the effectiveness of common service contract termination initiatives for reducing NWOM of customers whose service contracts are being cancelled. The study results provide guidance for minimizing the downside of service contract termination.

Design/methodology/approach

This study distinguishes between service contract termination initiatives common in practice (preannouncement, explanation, financial compensation, apology and support in finding an alternative provider). Drawing on a multi-industry survey of 245 customers who have experienced service contract terminations in real life, the authors estimate regression models to link perceived service contract termination initiatives to NWOM.

Findings

All else equal, only preannouncement and support in finding an alternative are effective to reduce NWOM. This study also shows that the right choice of service contract termination initiatives depends on the context of the termination. Making a preannouncement, offering an explanation and providing support in finding an alternative are more effective in reducing NWOM when these actions are aligned with the contextual factors of relationship duration and competitive intensity.

Research limitations/implications

This study shows that service contract termination needs to address several aspects of the service termination experience. The key implication for future research is that it matters in terms of NWOM how service contract terminations are performed.

Practical implications

This research identifies the service contract termination initiatives that are most effective to reduce NWOM after service contract termination in general and under consideration of the moderating roles of relationship duration and competitive intensity.

Originality/value

While most related studies have considered customer responses to the cancellation of other customers’ contracts, this study contributes to the scarce literature on the undesirable customer responses (such as NWOM) to the termination of their own contract. To the best of the authors’ knowledge, it is the first study in this emerging stream of research that accounts for the effects of process- and outcome-oriented contract termination initiatives on NWOM. To the best of the authors’ knowledge, it is also the first study to account for moderators of the effect of contract termination initiatives on NWOM, namely, relationship duration and competitive intensity.
The determinants of Muslim millennials’ visiting intention towards halal tourist attraction
Authors: Juliana Juliana , W. Mahri A. Jajang , Salsabilla Azkiya Rahmah , Muhammad Mumuh , Nusannas Iman Sidik
Published: September 2022

Purpose

This study aims to investigate the relationship between destination image (DI), travel motivation, religiosity, Islamic attributes of destination and the Muslim millennial’s visiting intention to halal tourist attraction.

Design/methodology/approach

Using quantitative method, this study analyses responses to a questionnaire distributed to 200 respondents living in various province in Indonesia. To prove the hypothesis, the data collected are analysed using partial least square-structural equation modelling (PLS-SEM).

Findings

This study shows that there is significant relationship positively between travel motivation, religiosity, Islamic attributes of destination and Muslim millennials’ visiting intention to Lombok as halal tourist attraction. However, the DI shows insignificant impact on Muslim millennials’ visiting intention. The results confirm that travel motivation, religiosity and Islamic attributes of destination are highly important in encouraging the intention of Muslim millennials to visit halal tourist attraction.

Research limitations/implications

This study, however, has limitations. Firstly, the observation of this study is only aimed at Muslim millennials aged from 20 to 40 years. Secondly, the variables used in this study are only four variables.

Practical implications

To increase the visiting intention among Muslim millennials to halal tourism destination, the authorities should create and design the concept of halal tourism to attract Muslim millennials by considering the factors in this study. In addition, related parties need to improve halal infrastructure quality to boost halal tourism development. Indonesia is the biggest Muslim country in the world recently, the better promotion and campaign of halal tourism, the more Muslim millennials who are interested to visit halal tourism destination.

Originality/value

This study explores Muslim millennials’ visiting intention to halal tourist attraction in Indonesia. The study combines four important determinants affecting Muslim millennials to visit Lombok as one of the halal tourist attractions in Indonesia. In addition to that, literature explaining visiting intention in the context of prospective Muslim millennial is scarce.
Contribution of machine learning in continuous improvement processes
Authors: Mjimer Imane , Aoula Es-Saadia , Achouyab E.L. Hassan
Published: September 2022

Purpose

The aim of this study is to predict one of the key performance indicators used to improve continually production systems using machine learning techniques known by the ability to teach the machine to perform complex things as opposed to simple statistical methods by giving this machine the historical dataset, according to the kind of machine learning the authors will use, the machine will be able to predict a new output data from the input data given by the user.

Design/methodology/approach

This work is divided into six sections: In the first section, the state of art for OEE, machine learning, and regression models. In the second section, the methodology, followed by an experimental study conducted in an automotive company specialised in the manufacturing of manual transmissions.

Findings

The three models show a very high accuracy (higher than 99%), a comparison between these three models was done using three indicators, namely mean absolute error (MAE) mean square error (mean squared error and mean absolute percentage error which shows that the best model is the least angle followed by Bayesian Ridge and automatic relevance determination regression.

Originality/value

As the authors can see many works were done in the different production systems for prediction, the most relevant works were done to predict a parameter in the production system such as The prediction of part thickness in aluminium hot stamping process with partition temperature control the prediction of CO2 trapping performance the prediction of crop yield the prediction of lean manufacturing in automotive parts industry the contribution of the work will be to use the machine learning techniques to predict the key performance indicator “used to measure manufacturing efficiency” which is the overall equipment effectiveness used in the authors’ case to measure the improvement of the production system.
Althea McNish: Designs without Borders
Authors: Hart Imogen
Published: September 2022

Althea McNish (1924–2020) defies many of art history's borders. Born in Trinidad, McNish trained in London; her work crosses the line between fine and decorative art; and she brings the history of modern pattern design into dialogue with the history of Black British art. Focusing on her textiles of the 1950s and 1960s, this article foregrounds the multivalence of McNish's practice, exploring the productive tensions and possibilities that arise from her work's location at multiple points of intersection. Examining her treatment of colour and line, it demonstrates that McNish's textiles embody in their complex screen‐printed surfaces the composite, multi‐layered character of cultures and identities. The article considers McNish's participation in activism, and argues that her work prefigures the Black British Art Movement of the 1980s and global postmodern appropriations of the decorative by exploiting the subversive power of pattern.
Impact of a collaboration revolving around virtual capacity evaluations
Authors: Factora Ronan , Hashmi Ardeshir Z.
Published: September 2022

Objective

To assess the impact of virtual capacity assessments on access to medical care, community supports, and transitions to higher levels of care.

Study Setting

Virtual capacity evaluations of homebound suspected elder abuse/neglect/financial exploitation victims identified via exclusion criteria and initiated by Cuyahoga County adult protective services (APS) and conducted with Cleveland Clinic Geriatric Medicine.

Study Design

A retrospective chart review was conducted in conjunction with APS using their database to determine the outcomes of individuals who underwent virtual capacity evaluation from May 2020 through September 2021. Variables collected included completion of a statement of expert evaluation, guardianship assignment, offering community services, transfer to a higher level of care, and establishment of primary care.

Data Collection/Extraction

Data were extracted from medical records and the APS database. Outcomes were measured as percentages.

Principal Findings

Fifty‐four individuals underwent evaluation. Statements of expert evaluation were completed in 38 cases (70%). Guardianship was assigned in 28 cases (52%). Community services were offered to 51 (89%). Thirty‐one (57%) remained at home. At baseline, only 23 (43%) were receiving primary care. Post evaluation, 44 (81%) were connected or reconnected to their medical provider.

Conclusion

Of individuals who underwent our virtual capacity evaluations, most were able to remain at home, offered community services for support, and linked to primary care.
Hexosamine pathway activation improves memory but does not extend lifespan in mice
Authors: Allmeroth Kira , Hartman Matías D. , Purrio Martin , Mesaros Andrea , Denzel Martin S.
Published: September 2022

Glucosamine feeding and genetic activation of the hexosamine biosynthetic pathway (HBP) have been linked to improved protein quality control and lifespan extension. However, as an energy sensor, the HBP has been implicated in tumor progression and diabetes. Given these opposing outcomes, it is imperative to explore the long‐term effects of chronic HBP activation in mammals. Thus, we asked if HBP activation affects metabolism, coordination, memory, and survival in mice. N‐acetyl‐D‐glucosamine (GlcNAc) supplementation in the drinking water had no adverse effect on weight in males but increased weight in young females. Glucose or insulin tolerance was not affected up to 20 months of age. Of note, we observed improved memory in young male mice supplemented with GlcNAc. Survival was not changed by GlcNAc treatment. To assess the effects of genetic HBP activation, we overexpressed the pathway's key enzyme GFAT1 and a constitutively activated mutant form in all mouse tissues. We detected elevated levels of the HBP product UDP‐GlcNAc in mouse brains, but did not find any effects on behavior, memory, or survival. Together, while dietary GlcNAc supplementation did not extend survival in mice, it positively affected memory and is generally well tolerated.
Analysis of alcohol use, consumption of micronutrient and macronutrients, and liver health in the 2017–2018 National Health and Nutrition Examination Survey
Authors: Warner Jeffrey B. , Zirnheld Kara H. , Hu Huirong , Floyd Alison , Kong Maiying , McClain Craig J. , Kirpich Irina A.
Published: September 2022

Background

Alcohol use is a major global healthcare burden that contributes to numerous adverse health outcomes, including liver disease. Many factors influence individual susceptibility to alcohol‐associated diseases, including nutritional factors. The objective of the current study was to examine inter‐relations among alcohol, dietary micronutrients and macronutrient consumption, and liver health by analyzing data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES).

Methods

Based on self‐reported alcohol consumption, NHANES respondents were assigned to one of four categories: never drinkers (lifetime abstainers), non‐drinkers (past‐year abstainers), moderate drinkers (1/2 drinks per day for females/males, respectively), and heavy drinkers (>1/>2 drinks per day for females/males, respectively, and/or frequent binge drinking). Survey‐weighted regression analyses (adjusted for gender, age, race, education, and body mass index) were performed to examine associations between alcohol intake, dietary, and liver health characteristics.

Results

Individuals categorized as heavy drinkers were significantly younger, most often well‐educated males with low incidences of diabetes and other comorbidities. They consumed the most overall calories and various micronutrients, indicating a diet that was not necessarily nutrient poor. Neither moderate nor heavy drinkers had liver steatosis or fibrosis as measured by liver elastography, although heavy drinkers had modestly elevated plasma biomarkers of liver injury, including ALT, AST, and GGT, compared with the other groups.

Conclusions

Our findings suggest that the category of heavy drinkers in the 2017–2018 NHANES consisted of generally healthy individuals with high‐energy intake and no evidence of liver steatosis or fibrosis. However, slightly increased plasma liver markers may indicate a risk of future progression to more advanced stages of liver disease over time in some individuals. Several limitations should be considered when interpreting these data, including the potential misclassification of drinking categories and the lack of standardized cutoff scores for fatty liver as assessed by elastography, among others.
Evaluation and validation of chemotherapy‐specific diarrhoea and histopathology in rats
Authors: Dahlgren David , Rosenqvist Evelina , Hellström Per M. , Nygren Peter , Kullenberg Fredrik , Peters Karsten , Sjöblom Markus , Lennernäs Hans
Published: September 2022

Chemotherapy‐induced mucositis is characterized by diarrhoea and villous atrophy. However, it is not well‐understood why diarrhoea arises, why it only occurs with some chemotherapeutics and how it is related to villus atrophy. The objectives in this study were to determine (i) the relationship between chemotherapy‐induced diarrhoea and villus atrophy and to (ii) establish and validate a rat diarrhoea model with clinically relevant endpoints. Male Wistar Han IGS rats were treated with saline, doxorubicin, idarubicin, methotrexate, 5‐fluorouracil, irinotecan or 5‐fluorouracil+irinotecan. After 72 h, jejunal tissue was taken for morphological, apoptotic and proliferative analyses, and faecal water content and change in body weight were determined. All treatments except methotrexate caused a similar reduction (≈42%) in villus height, but none of them altered mucosal crypt cell proliferation or apoptosis. Doxorubicin, idarubicin, irinotecan and 5‐fluorouracil+irinotecan caused body weight reduction, but only irinotecan and idarubicin caused diarrhoea. No direct correlation between diarrhoea and villus height or body weight loss was observed. Therefore, studies of the mechanisms for chemotherapy‐induced diarrhoea should focus on functional factors. Finally, the irinotecan and idarubicin diarrhoea models established in this study will be useful in developing supportive treatments of this common and serious adverse effect in patients undergoing chemotherapy.
The antecedents and consequences of stereotype threat in Parkinson's disease
Authors: Coundouris Sarah P. , von Hippel Courtney , Lehn Alexander C. , Henry Julie D.
Published: September 2022

Objective

The aim of this study was to examine what factors make people with Parkinson's disease more susceptible to stereotype threat (i.e., the concern of being evaluated in line with negative group‐based stereotypes) and the clinical consequences of this.

Method

Forty‐nine people with Parkinson's disease completed a measure of stereotype threat, as well as measures that indexed potential antecedents and clinical consequences of stereotype threat.

Results

Younger age and greater communication difficulties emerged as significant predictors of stereotype threat. Higher stereotype threat was also associated with increased emotional distress.

Conclusions

These findings are an important first step in understanding stereotype threat in Parkinson's disease and may help to guide the development of intervention and educational efforts aimed at countering its effects.
Isolation, Loneliness and Aloneness in the Age of Covid‐19: Reflections on Clinical Experiences
Authors: Goldblatt Mark J. , Casado Sastre Casilda M. , Briggs Stephen , Lindner Reinhard
Published: September 2022

The Covid‐19 pandemic brought a heightened fear of death and illness, and increased experiences of isolation, loneliness and aloneness. In this article we describe clinical experiences of psychotherapists in Argentina, the UK and Germany in order to explore how the impacts of the pandemic are variously felt and mediated by inner resources. We explore the capacity to relate internally to good experiences of infancy and a secure internal world, and the risks of loneliness, and interpersonal and intrapsychic withdrawal, that lead to vulnerability in patients and therapists. We contrast instances where psychotherapy in response to increased fears of death, infection and isolation is facilitative of change and growth, with situations where perverse, destructive or defensive relating predominate. We ask if we are witnessing and, through our therapeutic activities, contributing to the emergence of new ways of understanding the internal conflicts of this Covid‐19 age, and tentatively identify some key emerging themes; the capacity for facilitative interactions and change; identifications with the powerful virus; an increase in paranoid anxieties and the potential for a more considerate, ‘care‐full’ way of relating.
Healthy masculinity construction: The influence of race, faith and athletics
Authors: Newman Tarkington J. , McCray Kristy , Lower‐Hoppe Leeann M. , Rockhill Carter , Ingram Donta , Ohanasian Justice , Simmons‐Horton Sherri
Published: September 2022

Due to structural racism, young men living in urban cities—particularly Black and other youth of colour—are at risk for developing hegemonic, toxic masculine identities. However, through a positive youth development approach, sport can be used to promote healthy masculinity. This study explored the importance and meaning of masculinity, as well as influences of masculinity construction among 14 urban male youth who participated in a faith‐based sport program. Findings from semi‐structured interviews highlight the importance of a masculine identity; depict masculinity through key attributes (leadership, persistence, responsibility, confidence, strength) and underscore the intersectional influence of race, faith, athletics and adult role models.
Time‐lagged effects of habitat fragmentation on terrestrial mammals in Madagascar
Authors: Broekman Maarten J. E. , Hilbers Jelle P. , Schipper Aafke M. , Benítez‐López Ana , Santini Luca , Huijbregts Mark A. J.
Published: September 2022

Biodiversity is severely threatened by habitat destruction. As a consequence of habitat destruction, the remaining habitat becomes more fragmented. This results in time‐lagged population extirpations in remaining fragments when these are too small to support populations in the long term. If these time‐lagged effects are ignored, the long‐term impacts of habitat loss and fragmentation will be underestimated. We quantified the magnitude of time‐lagged effects of habitat fragmentation for 157 nonvolant terrestrial mammal species in Madagascar, one of the biodiversity hotspots with the highest rates of habitat loss and fragmentation. We refined species’ geographic ranges based on habitat preferences and elevation limits and then estimated which habitat fragments were too small to support a population for at least 100 years given stochastic population fluctuations. We also evaluated whether time‐lagged effects would change the threat status of species according to the International Union for the Conservation of Nature (IUCN) Red List assessment framework. We used allometric relationships to obtain the population parameters required to simulate the population dynamics of each species, and we quantified the consequences of uncertainty in these parameter estimates by repeating the analyses with a range of plausible parameter values. Based on the median outcomes, we found that for 34 species (22% of the 157 species) at least 10% of their current habitat contained unviable populations. Eight species (5%) had a higher threat status when accounting for time‐lagged effects. Based on 0.95‐quantile values, following a precautionary principle, for 108 species (69%) at least 10% of their habitat contained unviable populations, and 51 species (32%) had a higher threat status. Our results highlight the need to preserve continuous habitat and improve connectivity between habitat fragments. Moreover, our findings may help to identify species for which time‐lagged effects are most severe and which may thus benefit the most from conservation actions.
Rare association of absent pulmonary valve syndrome, complete atrioventricular canal defect, double outlet right ventricle, right aortic arch, and aberrant right subclavian artery in a fetal case
Authors: Başar Eviç Zeynep , Doğan Yasemin , Şaşmazel Ahmet , Babaoğlu Kadir
Published: September 2022

Absent pulmonary valve syndrome (APVS) is a rare congenital cardiac anomaly. It is often associated with TOF, but may also be associated with an intact ventricular septum or, more rarely, with tricuspid atresia. It's combination with a complete atrioventricular septal defects and double outlet right ventricle has been reported extremely rare, even in the postnatal period. Herein, we report a 20‐week‐old fetus with a right aortic arch and an aberrant left subclavian artery with this rare combination. We report a case of a 20‐week fetus diagnosed having this rare combination of right aortic arch and aberrant left subclavian artery. The APVS with complete atrioventricular septal defects may represent another type of APVS.
Can molecular genetic techniques improve our understanding of the role the microbial biomass plays in soil aggregation?
Authors: Kaur Rupinder , Page Kathryn L. , Dalal Ram C. , Menzies Neal W. , Dang Yash P.
Published: September 2022

Soil structure plays an integral role in regulating the physical, chemical, and biological functioning of soil systems and is essential for maintaining agricultural productivity. Many studies have investigated soil structure formation and stability. However, the underlying mechanisms behind its formation are still often unclear, including how soil microorganisms regulate this process via the aggregation of soil particles. In this review, we seek to summarise current information regarding how microorganisms influence aggregation and explore whether the application of molecular genetic techniques has potential to increase our understanding in this important area. Specifically, we review current information regarding the exact nature and role of microbially produced soil binding agents (extracellular polymeric substances, glomalin, hydrophobins and chaplins) and how different soil microorganisms (bacteria, archaea, fungi, protists) regulate and influence the production of these substances. Molecular genetic techniques have the capacity to provide new information regarding the genetic make‐up of the soil microbial biomass, which could potentially be related to their function in soil and role in the aggregation of soil particles. However, more work is required to identify the key functional genes important for studying aggregation processes. Techniques better able to study the fine scale distribution of microorganisms and microbial products are also required to fully understand microbial interactions and functioning on a scale relevant to aggregation. Future developments in this area may offer an opportunity to improve our understanding of, and potentially manipulate, soil aggregation for the benefit of soil functioning and environments.
Tobacco smoke exacerbates Filifactor alocis pathogenicity
Authors: Iskander Mina M. Z. , Lamont Gwyneth J. , Tan Jinlian , Pisano Michele , Uriarte Silvia M. , Scott David A.
Published: September 2022

Aim

Filifactor alocis has recently emerged as a periodontal pathobiont that appears to thrive in the oral cavity of smokers. We hypothesized that identification of smoke‐responsive F. alocis genes would provide insight into adaptive strategies and that cigarette smoke would enhance F. alocis pathogenesis in vivo.

Materials and Methods

F. alocis was grown in vitro and cigarette smoke extract‐responsive genes determined by RNAseq. Mice were exposed, or not, to mainstream 1R6F research cigarette smoke and infected with F. alocis, or not, in an acute ligature model of periodontitis. Key clinical, infectious, and immune data were collected.

Results

In culture, F. alocis growth was unaffected by smoke conditioning and only a small number of genes were specifically regulated by smoke exposure. Reduced murine mass, differences in F. alocis‐cognizant antibody production, and altered immune profiles as well as altered alveolar bone loss were all attributable to smoke exposure and/or F. alocis infection in vivo.

Conclusions

F. alocis is well‐adapted to tobacco‐rich conditions and its pathogenesis is enhanced by tobacco smoke exposure. A smoke‐exposed ligature model of periodontitis shows promise as a tool with which to further unravel mechanisms underlying tobacco‐enhanced, bacteria‐induced disease.
Transdiagnostic profiles of behaviour and communication relate to academic and socioemotional functioning and neural white matter organisation
Authors: Mareva Silvana , Akarca Danyal ,   The CALM Team, Holmes Joni
Published: September 2022

Background

Behavioural and language difficulties co‐occur in multiple neurodevelopmental conditions. Our understanding of these problems has arguably been slowed by an overreliance on study designs that compare diagnostic groups and fail to capture the overlap across different neurodevelopmental disorders and the heterogeneity within them.

Methods

We recruited a large transdiagnostic cohort of children with complex needs (N = 805) to identify distinct subgroups of children with common profiles of behavioural and language strengths and difficulties. We then investigated whether and how these data‐driven groupings could be distinguished from a comparison sample (N = 158) on measures of academic and socioemotional functioning and patterns of global and local white matter connectome organisation. Academic skills were assessed via standardised measures of reading and maths. Socioemotional functioning was captured by the parent‐rated version of the Strengths and Difficulties Questionnaire.

Results

We identified three distinct subgroups of children, each with different levels of difficulties in structural language, pragmatic communication, and hot and cool executive functions. All three subgroups struggled with academic and socioemotional skills relative to the comparison sample, potentially representing three alternative but related developmental pathways to difficulties in these areas. The children with the weakest language skills had the most widespread difficulties with learning, whereas those with more pronounced difficulties with hot executive skills experienced the most severe difficulties in the socioemotional domain. Each data‐driven subgroup could be distinguished from the comparison sample based on both shared and subgroup‐unique patterns of neural white matter organisation. Children with the most pronounced deficits in language, cool executive, or hot executive function were differentiated from the comparison sample by altered connectivity in predominantly thalamocortical, temporal–parietal‐occipital, and frontostriatal circuits, respectively.

Conclusions

These findings advance our understanding of commonly co‐morbid behavioural and language problems and their relationship to behavioural outcomes and neurobiological substrates.
Polygenic risk score and peer victimisation independently predict depressive symptoms in adolescence: results from the Quebec Longitudinal Study of Children Development
Authors: Perret Léa C. , Boivin Michel , Morneau‐Vaillancourt Geneviève , Andlauer Till F.M. , Paquin Stéphane , Langevin Stéphanie , Girard Alain , Turecki Gustavo , O'Donnell Kieran , Tremblay Richard E. , Côté Sylvana M. , Gouin Jean‐Philippe , Ouellet‐Morin Isabelle , Geoffroy Marie‐Claude
Published: September 2022

Background

Peer victimisation has been associated with depressive symptoms during adolescence, however not all peer victimised adolescents will exhibit such symptoms. This study tested whether having a genetic predisposition to developing depression increased the risk of experiencing depressive symptoms in peer victimised youth. To date, no study has explored such gene–environment interaction using a polygenic risk score for depression (PRS‐depression) in the context of peer victimisation and depressive symptoms in adolescence.

Methods

The sample included 748 participants born in 1997/98 from the Quebec Longitudinal Study of Child Development with genotype data and prospectively collected information on peer victimisation (12–13 years) obtained from both self‐ and teacher‐reports, as well as self‐reported depressive symptoms (15–17 years). The PRS‐depression was based on the genome‐wide association meta‐analysis of broad depression by Howard et al. (2019).

Results

Self‐ and teacher‐reported peer victimisation in early adolescence were both associated with depressive symptoms in adolescence (β = 0.34, p < .001; β = 0.14, p = .001 respectively), and this association remained significant when accounting for PRS‐depression (β = 0.33, p < .001; β = 0.13, p = .002 respectively). PRS‐depression was independently associated with depressive symptoms, but there was no significant PRS‐depression by peer victimisation interaction (self‐reported and teacher‐reported). PRS‐depression was correlated with self‐reported, but not teacher‐reported, peer victimisation.

Conclusions

Our findings suggested that a partial measure of an individual's genetic predisposition to depression, as measured by PRS‐depression, and being exposed to peer victimisation (self‐ and teacher‐reported) were independently associated with depressive symptoms in adolescence. Furthermore, PRS‐depression did not exacerbate the risk of depressive symptoms among adolescents who had been peer victimised. Lastly, we found evidence of a gene–environment correlation between PRS‐depression and self‐reported peer victimisation. Future studies are needed to replicate this finding and to further understand the role of genetic predispositions in experiencing depressive symptoms following peer victimisation.