bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterizing Longitudinal Antibody Responses in Recovered Individuals Following COVID-19 Infection and Single-Dose Vaccination in British Columbia, Canada: a Prospective Cohort Study
Authors: Olmstead Andrea D. , Nikiforuk Aidan M. , Schwartz Sydney , Márquez Ana Citlali , Valadbeigy Tahereh , Flores Eri , Saran Monika , Goldfarb David M. , Hayden Althea , Masud Shazia , Jassem Agatha N. , Morshed Muhammad , Sekirov Inna
Published: September 2022

Background

Investigating antibody titres in individuals who have been both naturally infected with SARS-CoV-2 and vaccinated can provide insight into antibody dynamics and correlates of protection over time.

Methods

Human coronavirus (HCoV) IgG antibodies were measured longitudinally in a prospective cohort of PCR-confirmed, COVID-19 recovered individuals (k=57) in British Columbia pre- and post-vaccination. SARS-CoV-2 and endemic HCoV antibodies were measured in serum collected between Nov. 2020 and Sept. 2021 (n=341). Primary analysis used a linear mixed-effects model to understand the effect of single dose vaccination on antibody concentrations adjusting for biological sex, age, time from infection and vaccination. Secondary analysis investigated the cumulative incidence of high SARS-CoV-2 anti-spike IgG seroreactivity equal to or greater than 5.5 log10 AU/mL up to 105 days post-vaccination. No re-infections were detected in vaccinated participants, post-vaccination by qRT-PCR performed on self-collected nasopharyngeal specimens.

Results

Bivariate analysis (complete data for 42 participants, 270 samples over 472 days) found SARS-CoV-2 spike and RBD antibodies increased 14-56 days post-vaccination (p<0.001) and vaccination prevented waning (B=1.66 [95%CI: 1.45-3.46]); while decline of nucleocapsid antibodies over time was observed (B=-0.24 [95%CI: -1.2-(−0.12)]). A non-significant trend towards higher spike antibodies against endemic beta-HCoVs was also noted. On average, SARS-CoV-2 anti-spike IgG concentration increased in participants who received one vaccine dose by 2.06 log10 AU/mL (95%CI: 1.45-3.46) adjusting for age, biological sex, and time. Cumulative incidence of high SARS-CoV-2 spike antibodies (>5.5 log10 AU/mL) was 83% greater in vaccinated compared to unvaccinated individuals.

Conclusions

Our study confirms that vaccination post-SARS-CoV-2 infection provides multiple benefits, such as increasing anti-spike IgG titers and preventing decay up to 85 days post-vaccination.
Important anatomical, age-related, and species considerations regarding ocular fibulin-3 (EFEMP1) analysis
Authors: Daniel Steffi , Hulleman John D.
Published: September 2022

Purpose

Fibulin-3 (F3) or EFEMP1 is a secreted extracellular matrix glycoprotein implicated in several ocular diseases. Little is known about the native biology of this protein. Thus, our study aims to determine expression and localization characteristics of F3 utilizing a range of mammalian species as well as F3-associated changes with age.

Methods

Gene expression analyses for fibulins as well as immunohistochemistry for F3 were conducted in ocular tissue from mice, pigs, non-human primates (NHPs), and humans (n = 3-5). Age-based F3 expression study along with changes in ECM remodeling enzymes was also evaluated in mice.

Results

Within the mouse retina, F3 staining was consistent throughout the entirety of the retina (far-periphery, mid-periphery, and central), being enriched in the ganglion cell layer and inner nuclear layer (INL). However, in humans, the F3 staining pattern was quite unique; enriched in the RPE, INL, and outer nuclear layer (ONL) in the peripheral retina, but then shifting to predominantly outer plexiform layer (OPL) staining in the central retina and macula with waning RPE immunoreactivity approaching the fovea. We demonstrate that F3 expression in the mouse retina significantly increases with age, and the levels of extracellular F3 degrading enzymes produced by the RPE and retina (e.g., Mmp2 and Htra1) decrease with age.

Conclusions

These findings demonstrate that F3 has distinct species-dependent as well as ocular region-specific expression and localization patterns. We also show that F3 and ECM enzyme dynamics favor F3 accumulation in the retina and RPE with increasing age.
Red Palm Oil (RPO) May Enhance Chronic Inflammation Through Disturbance in Lipid Metabolism
Authors: Binyameen Ridwan Badmos , Akinola Franklin
Published: September 2022

Several studies have been published on lipid lowering effect of red palm oil (RPO) with little known about health impact of differential dosage. In this study, we examined lipid profile of hyperlipidemia-induced wistar rats fed with varying quantity of RPO supplementation (15ml/kg, 20ml/kg and 25ml/kg feed). A total of 30 male wistar rats were procured and randomly divided into five groups (A, B, C, D and E) with 6 rats in each group. Group C, D and E received 15 ml/kg, 20ml/kg and 25ml/kg of RPO respectively (thoroughly mixed with high fat diet). No force feeding or oral gavage procedures were employed. While rats in group A were fed with standard rat chow, group B animals fed on high fat diet only and neither of the two groups received RPO supplementation. Plasma concentration of total cholesterol (TC), triglycerides (TG), Albumin, low density lipoproteins (LDL-C), high density lipoproteins (HDL-C), and total proteins (TP) were assessed at the end of the experiment that lasted 4 weeks. In addition to the lipid lowering effect observed in RPO supplementation groups (C, D, E) compared to fatty diet fed only (group B) as widely reported in many studies, both the LDL-C and TG appeared to rise with more RPO supplementation. Findings also revealed the lipid lowering effect more pronounced on triglycerides than the low density lipoproteins. TP in group E was significantly higher compared to group A and B (P < 0.05) and RPO supplementation had a tendency to increase plasma TP.
Not getting in too deep: a practical deep learning approach to routine crystallisation image classification
Authors: Milne Jamie , Qian Chen , Hargreaves David , Wang Yinhai , Wilson Julie
Published: September 2022

Using a relatively small training set of ∼16 thousand images from macromolecular crystallisation experiments, we compare classification results obtained with four of the most widely-used convolutional deep-learning network architectures that can be implemented without the need for extensive computational resources. We show that the classifiers have different strengths that can be combined to provide an ensemble classifier achieving a classification accuracy comparable to that obtained by a large consortium initiative. We use eight classes to effectively rank the experimental outcomes, thereby providing detailed information that can be used with routine crystallography experiments to automatically identify crystal formation for drug discovery and pave the way for further exploration of the relationship between crystal formation and crystallisation conditions.

Author summary

X-ray crystallography can provide structural information on the molecules that play important roles in cell function and allow interactions vital for drug design to be elucidated. However, the technique requires the molecules to be crystallised and obtaining sufficiently high-quality crystals can require hundreds of experiments under different conditions. Robots have been designed to perform the microscopic experiments with imaging systems to record the results over time but automated classification of all these images is becoming essential. In this work we compare different classifiers that can be used without the need for vast computational resources and show that an ensemble classifier which combines the different strengths of four deep-learning networks is able to correctly classify the experimental results into one of eight different categories 94% of the time.
Systematic analysis of in-source modifications of primary metabolites during flow-injection time-of-flight mass spectrometry
Authors: Farke Niklas , Schramm Thorben , Verhülsdonk Andreas , Link Hannes
Published: September 2022

Flow-injection mass spectrometry (FI-MS) enables metabolomics studies with a very high sample-throughput. However, FI-MS is prone to in-source modifications of analytes because samples are directly injected into the electrospray ionization source of a mass spectrometer without prior chromatographic separation. Here, we spiked authentic standards of 160 primary metabolites individually into an Escherichia coli metabolite extract and measured the thus derived 160 spike-in samples by FI-MS. Our results demonstrate that FI-MS can capture a wide range of chemically divers analytes within 30 seconds measurement time. However, the data also revealed extensive in-source modifications. Across all 160 spike-in samples, we identified significant increases of 11,013 ion peaks in positive and negative mode combined. To explain these unknown m/z features, we connected them to the m/z feature of the (de-)protonated metabolite using information about mass differences and MS2 spectra. This resulted in networks that explained on average 49 % of all significant features. The networks showed that a single metabolite undergoes compound specific and often sequential in-source modifications like adductions, chemical reactions, and fragmentations. Our results show that FI-MS generates complex MS1 spectra, which leads to an overestimation of significant features, but neutral losses and MS2 spectra explain many of these features.

Highlights

FI-MS enables measurements of chemically divers metabolites.

Extensive in-source modifications during electrospray ionization are detected by FI-MS.

A network approach explains 49 % of all recorded in-source modifications.
Piezo1-mediated spontaneous activity of satellite glia impacts DRG development
Authors: Brandt Jacob P. , Smith Cody J.
Published: September 2022

Spontaneous activity of neural cells is a hallmark of the developing nervous system. It is widely accepted that chemical signals, like neurotransmitters, contribute to spontaneous activity in the nervous system. Here we reveal an additional mechanism of spontaneous activity that is mechanosensitive in the peripheral nervous system (PNS) using intravital imaging of growing dorsal root ganglia (DRG) in zebrafish embryos. GCaMP6s imaging shows that developing DRG satellite glia contain distinct spontaneous Ca2+transients, classified into simultaneous, isolated and microdomains. Longitudinal analysis over days in development demonstrates that as DRG satellite glia become more synchronized, isolated Ca2+transients remain constant. Using a chemical screen, we identify that Ca2+transients in DRG glia are dependent on mechanical properties, which we confirmed using an experimental application of mechanical force. We find that isolated spontaneous Ca2+transients of the glia during development is altered by manipulation of mechanosensitive protein Piezo1, which is expressed in the developing ganglia. In contrast, simultaneous Ca2+transients of DRG satellite glia is not Piezo1-mediated, thus demonstrating that distinct mechanisms mediate subtypes of spontaneous Ca2+transients. Activating Piezo1 eventually impacts the cell abundance of DRG cells and behaviors that are driven by DRG neurons. Together, our results reveal mechanistically distinct subtypes of Ca2+transients in satellite glia and introduce mechanobiology as a critical component of spontaneous activity in the developing peripheral nervous system.
Nirmatrelvir-resistant SARS-CoV-2 is efficiently transmitted in Syrian hamsters
Authors: Abdelnabi Rana , Jochmans Dirk , Donckers Kim , Trüeb Bettina , Ebert Nadine , Weynand Birgit , Thiel Volker , Neyts Johan
Published: September 2022

The SARS-CoV-2 main protease (3CLpro) is one of the promising therapeutic target for the treatment of COVID-19. Nirmatrelvir is the only the 3CLpro inhibitor authorized for treatment of COVID-19 patients at high risk of hospitalization; other 3Lpro inhibitors are in development. We recently repored on the in vitro selection of a SARS-CoV2 3CLpro (L50F-E166A-L167F; short 3CLprores) virus that is cross-resistant with nirmatrelvir and yet other 3CLpro inhibitors. Here, we demonstrate that the resistant virus replicates efficiently in the lungs of intranassaly infected hamsters and that it causes a lung pathology that is comparable to that caused by the WT virus. Moreover, 3CLprores infected hamsters transmit the virus efficiently to co-housed non-infected contact hamsters. Fortunately, resistance to Nirmatrelvir does not readily develop (in the clinical setting) since the drug has a relatively high barrier to resistance. Yet, as we demonstrate, in case resistant viruses emerge, they may easily spread and impact therapeutic options for others. Therefore, the use of SARS-CoV-2 3CLpro protease inhibitors in combinations with drugs that have a different mechanism of action, may be considered to avoid the development of drug-resistant viruses in the future.
Concordance between male- and female-specific GWAS results helps define underlying genetic architecture of complex traits
Authors: Miller Anna K , Pan Calvin , Bartlett Jacquelaine , Lusis Aldons J , Crawford Dana C , Williams Scott M , Buchner David A
Published: September 2022

A better understanding of genetic architecture will help translate genetic data into improved precision-based medicine and clinical care. Towards this end, we explored the use of sex-stratified analyses for several traits in the Hybrid Mouse Diversity Panel (HMDP) and UK Biobank to better determine trait polygenicity and identify contributing loci. This was accomplished by comparing the direction of allelic effects in males and females in sex-stratified analyses under the hypothesis that loci that are not associated with a trait should have equal chances of trending in the same direction of effect. Instead, we found that even for most alleles that do not meet nominal levels of statistical significance, the direction of effect in the two sexes was highly concordant. Results were consistent with hundreds of loci regulating each mouse trait and thousands of loci regulating each human trait, including traits for which no statistically significant loci were identified using conventional approaches. We also found evidence of likely spurious widespread epistasis. Collectively, these findings demonstrate the importance of stratifying by sex to discover novel associating loci, suggest a new method for identifying biologically rather than statistically significant associations, and caution that widespread marginal effects can lead to phantom epistasis.
Drug-combination wide association studies of cancer
Authors: Lalagkas Panagiotis Nikolaos , Melamed Rachel Dania
Published: September 2022

Background

Combinations of common drugs may, when taken together, have unexpected effects on cancer. It is not feasible to test for all combination drug effects in clinical trials, but in the real world, drugs are frequently taken in combination. Then, there may be undiscovered effects protecting users from cancer–or increasing their risk. By analyzing massive health claims data containing numerous people exposed to drug combinations, we have an opportunity to evaluate the association of drug combinations with cancer risk. Discovering these effects can not only contribute to prevention of cancer, but also suggest new uses for combinations to prevent or treat cancer.

Method

Our approach emulates a randomized trial where one arm would have been assigned to take a particular drug alone, while the other arm takes it together with a second drug. Because discovery of associations from observational data is prone to spurious results due to confounding, we develop strategies to distinguish confounding from biomedically relevant findings.

Results

This tactic allows us to systematically assess effects across over 9,000 drug combinations, on all common cancers. Through multiple sensitivity analyses we identify a robustly supported beneficial drug combination that may synergistically impact lipid levels to reduce risk of cancer.

Conclusions

This study demonstrates the importance of considering confounding factors in drug-wide studies. But, we also show that our method is able to uncover associations with robust support.

Impact

Searching for combinations of factors impacting cancer is crucial, but these effects can only be systematically discovered through observational data analysis.
A “grappling hook” interaction balances self-assembly and chaperone activity of Nucleophosmin 1
Authors: Saluri Mihkel , Leppert Axel , Gese Genis Valentin , Sahin Cagla , Lama Dilraj , Kaldmäe Margit , Chen Gefei , Elofsson Arne , Allison Timothy M. , Arsenian-Henriksson Marie , Johansson Jan , Lane David P. , Hällberg B. Martin , Landreh Michael
Published: September 2022

How the self-assembly of partially disordered proteins generates functional compartments in the cytoplasm and particularly in the nucleus is poorly understood. Nucleophosmin 1 (NPM1) is an abundant nucleolar protein that forms large oligomers which provide the scaffold for ribosome assembly but also prevent protein aggregation as part of the cellular stress response. Examining the relationship between the self-assembly and chaperone activity of NPM1, we find that oligomerization of full-length NPM1 modulates its ability to retard amyloid formation in vitro. Machine learning and cryo-electron microscopy reveal fuzzy interactions between the disordered region and the C-terminal nucleotide-binding domain that cross-link NPM1 pentamers into oligomers. Ribosomal peptides mediate in a tighter association within the oligomers, reducing their capacity to prevent amyloid formation. We conclude that NPM1 uses a “grappling hook” interaction to form a network-like structure whose chaperone activity is tuned by basic proteins, suggesting a regulatory mechanism for the nucleolar stress response.
Wage equation misrepresents gay wage discrimination: overlooked evidence from Russia
Authors: Alexeev Sergey
Published: September 2022

Purpose

Only data from developed countries were used to estimate the sexual orientation difference in wages. This paper is the first, which aims to identify the wage discrimination of gay men in Russia – a country where institutional discrimination and ignorance against gay men are known to present.

Design/methodology/approach

Gays are identified as men who reported having sex with other men in several waves of the national household survey. A wage equation is used to estimate the gay wage penalty. Extending the wage equation to implement a difference-in-difference design, the paper also evaluates the effect of the gay-propaganda law of 2013 on gay wages.

Findings

No wage discrimination is identified. The law also has no adverse effect on gay wages.

Practical implications

Cross-country comparison and theoretical generalizations are premature, and better identification strategies are needed to understand sexual orientation differences.

Social implications

Policymakers should be aware that in both discriminatory and equitable environments, there may be hidden inequality even if researchers do not detect it.

Originality/value

The findings are implausible and add to existing evidence that gay discrimination measured with wage equation suffers from endogeneity and should be interpreted with caution. Particular caution should be exercised in cross-sectional and time-series comparisons, as a tendency to report the orientation honestly and unobserved confounders vary by location and time.
The impact of perceived organizational support on professional commitment: a moderation of burnout and mediation of well-being
Authors: Ilyas Sehrish , Abid Ghulam , Ashfaq Fouzia
Published: September 2022

Purpose

In today’s challenging world, achieving professional commitment among healthcare workers is becoming the need of time. Drawing on self-determination theory, the current study examines how and under which boundary conditions perceived organizational support affects professional commitment.

Design/methodology/approach

Data was collected from doctors and nurses employed in public and private sector hospitals by employing a split-questionnaire design.

Findings

The authors’ study findings demonstrate that perceived organizational support has a positive and indirect effect on the professional commitment of nurses and doctors via mediating the role of subjective well-being. The authors also found that these findings depend on healthcare workers’ burnout levels. The positive relationship between perceived organizational support and subjective well-being is attenuated by burnout syndrome.

Practical implications

The current study poses implications for policymakers and administrators of healthcare institutions as well as to develop a supportive culture to evoke more professional commitment among healthcare workers. Implications for nursing managers and policymakers are discussed in light of the study findings.

Originality/value

Healthcare institutions are increasingly paying attention to raising the professional commitment of their workforce, especially in the wake of a crisis like the COVID-19 outbreak. The current study will add to the body of literature on nursing management, healthcare studies and organizational psychology in the South Asian context by explaining the relationship between POS and professional commitment, drawing on self-determination theory.
The role of adaptive reuse in historic urban landscapes towards cities of inclusion. The case of acre
Authors: Yarza Pérez Ana Jayone , Verbakel Els
Published: September 2022

Purpose

Cities are facing challenges that dramatically affect their social and physical landscapes, leading to the increase of urban segregation and polarization. One response to these challenges is adaptive reuse, yet, in heterogeneous communities, these adaptations are often a source of conflict, because local actions often lack an integrative approach, leading to further exclusion. In this paper the authors explore the potential of adaptive reuse of urban heritage as a planning tool to support inclusiveness and heterogeneity.

Design/methodology/approach

The city of Acre is used as a case study, where different scenarios for urban heritage are proposed and tested among stakeholders through interviews. These aim to explore how adaptive reuse processes can lead to the inclusion or exclusion of certain groups and how design interventions in historic urban landscapes challenge the way the current disconnected historic and urban layers interact.

Findings

The paper presents the commonalities and differences between the interviewees' perceptions on Acre's functioning, their idea of inclusiveness and other aspects related to urban design. Moreover, it highlights the existing conflicts of interest, value prioritization and the adequacy of the proposed scenarios, serving as a way to verify the accuracy of the scenario building process.

Originality/value

Testing an urban design tool related to adaptive reuse of urban heritage in a real and extreme case, based on the guidelines of the Historic Urban Landscape Recommendation; and critically analysing the sources of conflict and value systems to address inclusion in heterogenous settings.
Diaspora diplomacy and modes of engagement: the case of Romanian Diaspora in the UK
Authors: Moise Raluca
Published: September 2022

Purpose

The current study aims to map the existent modes of engagement used by both individual and organisational actors of Romanian diaspora community in the UK to build public legitimacy and social value in the host society. This study focuses on two main questions: (1) What are the forms of engagement by which diaspora members enact their role as diplomats for ethnic diaspora communities? (2) What is the nature of their communication practices that sustain these forms of diasporic engagement?

Design/methodology/approach

This study is based on an analysis of online public documents extracted from different websites, blogs and public social media accounts, complemented by primary data. The research design is a multi-levelled case study.

Findings

The main findings are that Romanian diaspora in the UK develops a specific model of diplomacy, focused on cultural and political forms of engagement. Firstly, equality and belonging are two key dimensions that clearly define this diasporic community diplomatic actions and practices. Secondly, the communication that fosters its networked and associative features has shifted towards a more democratic and strategic model.

Originality/value

This paper has multiple original points. Firstly, it deepens the understanding of diaspora diplomacy, connecting the concept with strategic communication. Secondly, the identification and theorisation of specific forms of engagement of diasporic communities reflects a process which is yet underdeveloped in both types of literature. Findings may be instrumental in providing strategies for relationship building, cultivation and the engagement efforts of the UK institutions regarding immigrant integration.
Indoor environmental quality-based space categorization framework: the case of health-care facilities
Authors: Budaiwi Ismail Mohammed , Mohammed Mohammed Alhaji , Harbi Hammad Ali
Published: September 2022

Purpose

Indoor environmental quality (IEQ) in buildings has an impact on people’s health, productivity and comfort. Maintaining the highest possible IEQ level in complex buildings, such as health care, is difficult due to economic and organizational constraints. This study aims to categorize the vicinities in a typical health-care facility in terms of importance and criticality in relation to the various IEQ factors, as well as to develop an IEQ assessment procedure.

Design/methodology/approach

A comprehensive literature review, established standards and structured interviews with industrial hygiene professionals in health-care settings were used in this study. To test the applicability of the developed IEQ assessment procedure, a pilot study was conducted in an existing health-care facility.

Findings

This study categorized health-care facilities into various vicinities and discovered three respondents group had varying IEQ perceptions (facility managers, environmental health specialists and nurses). According to the findings, indoor air quality is the most important and dominant factor influencing overall IEQ in health-care facilities. The trial application of the framework shows that much work is needed to improve the level of response and readiness of facility management and occupants to allow for the effective use of the developed procedure.

Originality/value

Previous research did not include a detailed categorization of vicinities in health-care buildings based on IEQ requirements. The findings of this study will help to close this knowledge gap and guide facility managers and operators in recognizing the relative importance of different IEQ factors, maintaining functional requirements and identifying priorities when developing maintenance and operational procedures and allocating resources.
The moderating effect of managerial discretion on cross-border knowledge search and the innovation quality of high-tech firms in a global health emergency: evidence from China
Authors: Duan Yunlong , Liu Shuling , MU Chang , Liu Xiangwei , Cheng Edwin , Liu Yongsong
Published: September 2022

Purpose

This study aims to analyze the moderating effect of managerial discretion on the relationship between cross-border knowledge search and the high-tech firms’ innovation quality in a global health emergency and addresses the following issues: the influence mechanism of different types of cross-border knowledge search on the high-tech firms’ innovation quality in a global health emergency; and the moderating role of different dimensions of manager discretion on the above relationship.

Design/methodology/approach

Based on the firms’ strategy selection methods, the authors divided cross-border knowledge search into three aspects, namely, breadth, depth and balance, and analyzed the impact of cross-border knowledge search on the innovation quality of high-tech firms in a global health emergency, taking managerial discretion as the moderating variable, and divided it into position rights, pay rights and operation rights according to the key rights of firms’ strategic management. Furthermore, the authors constructed a theoretical model, and for an analysis sample, the authors collected data from Chinese high-tech firms from 2013 to 2021.

Findings

The empirical results show that there is an inverted U-shaped relationship between cross-border knowledge search breadth, depth and balance and the innovation quality of high-tech firms. The position rights, pay rights and operation rights of managerial discretion have partially significant moderating effects on the relationship between cross-border knowledge search breadth, depth and balance and the high-tech firms’ innovation quality.

Originality/value

Considerable literature has grown around the theme of the impact of knowledge search on the firms’ innovation quality. Nevertheless, only a few studies draw on the combination of global health emergency, cross-border knowledge search and the innovation quality; in particular, no literature has analyzed the relationship between the three from the managerial discretion perspective. Exploring the above relationships has great theoretical value for enriching and improving knowledge management and innovation management theories and provides a theoretical basis and practical support for high-tech firms to face challenges of a global health emergency and to break through the innovation dilemma.
Randomised controlled trial: effects of gluten‐free diet on symptoms and the gut microenvironment in irritable bowel syndrome
Authors: Algera Joost P. , Magnusson Maria K. , Öhman Lena , Störsrud Stine , Simrén Magnus , Törnblom Hans
Published: September 2022

Background

A gluten‐free diet reduces symptoms in some patients with irritable bowel syndrome (IBS) through unclear mechanisms.

Aims

To assess the effects of gluten‐free versus gluten‐containing diet on symptoms and the gut microenvironment, and to identify predictors of response to the gluten‐free diet in IBS

Methods

Twenty patients with IBS and 18 healthy controls (HC) followed a gluten‐free diet during two 14‐day intervention periods where they sprinkled either gluten (14 g/day) or rice flour powder over their meals. Primary outcomes included effects of the interventions on IBS symptoms (IBS‐SSS) and bowel habits. Secondary outcomes included effects of gluten‐free diet on faecal microbiota and metabolite profile.

Results

IBS symptoms improved during the gluten‐free (p = 0.02), but not the gluten‐containing period, with no difference between the interventions. IBS patients reported fewer loose stools during the gluten‐free intervention (p = 0.01). Patients with IBS and HC presented distinct metabolite profiles based on the effects of the gluten‐free diet (p < 0.001). True responders (reduced IBS‐SSS by ≥50 solely after gluten‐free period) and non‐responders were discriminated based on the effects of the gluten‐free diet on the microbiota (p < 0.01) and metabolite profiles (p < 0.001). The response to the gluten‐free diet could be predicted by the metabolite profile before the intervention (p < 0.001).

Conclusions

A gluten‐free diet may influence symptoms in a subset of patients with IBS, with a particular effect on bowel habits. A gluten‐free diet seems to impact the gut microenvironment. Responsiveness to the gluten‐free diet may be predicted by the metabolite profile. Clinicaltrials.gov: NCT03869359.
Effect of compassion‐focused therapy on self‐criticism and self‐soothing: A meta‐analysis
Authors: Vidal Joana , Soldevilla Joan Miquel
Published: September 2022

Objective

Compassion is oriented towards perceiving and relieving suffering. Hence, its development is beneficial for mental health. Many interventions aimed at cultivating compassion in patients have been empirically supported. This meta‐analysis analyses the effectiveness of compassion‐focused therapy (CFT) in decreasing self‐criticism, a vulnerability factor that has been related to several mental health problems, and in increasing self‐soothing.

Methods

A literature search was conducted in the PsycInfo, Web of Science, Medline and Scopus databases, through which 7 controlled trials (N = 640) and 7 observational studies (N = 207) were retrieved.

Results

The results of the meta‐analysis determine that CFT decreases the level of self‐criticism and increases the ability to experience soothing. The size of the effect varies depending on the design of the study and the subscale of the test used to measure self‐criticism (Forms of Self‐Criticizing/Attacking and Self‐Reassuring Scale).

Conclusions

CFT has proven to be an effective intervention for reducing self‐criticism. However, given that the number of studies is small and that only half of them are controlled trials, the results must be interpreted cautiously. More randomized controlled trials comparing CFT with other therapies are needed to determine the effect of this intervention on self‐criticism with more scientific evidence.
Challenges of vaccination and herd immunity in COVID‐19 and management strategies
Authors: She Jun , Hou Dongni , Chen Cuicui , Bi Jing , Song Yuanlin
Published: September 2022

Coronavirus disease 2019 (COVID‐19), the highly contagious viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has spread worldwide with millions of cases and more than 5 million deaths to date. SARS‐CoV‐2 has caused serious damage all over the world with many countries experiencing the third or the fourth wave of the viral disease outbreaks, mainly due to the emergence of mutant variants. Those who unvaccinated remain most vulnerable to COVID‐19 and its variants. COVID‐19 vaccination, along with prevention strategies, is a critical measure to defense against the disease. COVID‐19 vaccination can reduce the spread of virus and help protect susceptible population. Although herd immunity might not be realized solely by vaccination, COVID‐19 vaccines have been proved to be effective in reducing the risk of severe disease, hospitalization, and even death. It is recommended that people get vaccinated as soon as they are eligible. This review summarizes the recent SARS‐CoV‐2 variants that brought challenges for vaccination and herd immunity and discusses promising management strategies.
Liquid biopsy‐based targeted gene screening highlights tumor cell subtypes in patients with advanced prostate cancer
Authors: Derderian Seta , Vesval Quentin , Wissing Michel D. , Hamel Lucie , Côté Nathalie , Vanhuyse Marie , Ferrario Cristiano , Bladou Franck , Aprikian Armen , Chevalier Simone
Published: September 2022

Prostate cancer (PCa) clinical heterogeneity underscores tumor heterogeneity, which may be best defined by cell subtypes. To test if cell subtypes contributing to progression can be assessed noninvasively, we investigated whether 14 genes representing luminal, neuroendocrine, and stem cells are detectable in whole blood RNA of patients with advanced PCa. For each gene, reverse transcription quantitative polymerase chain reaction assays were first validated using RNA from PCa cell lines, and their traceability in blood was assessed in cell spiking experiments. These were next tested in blood RNA of 40 advanced PCa cases and 40 healthy controls. Expression in controls, which was low or negative, was used to define stringent thresholds for gene overexpression in patients to account for normal variation in white blood cells. Thirty‐five of 40 patients overexpressed at least one gene. Patients with more genes overexpressed had a higher risk of death (hazard ratio 1.42, range 1.12–1.77). Progression on androgen receptor inhibitors was associated with overexpression of stem (odds ratio [OR] 7.74, range 1.68–35.61) and neuroendocrine (OR 13.10, range 1.24–142.34) genes, while luminal genes were associated with taxanes (OR 2.7, range 1.07–6.82). Analyses in PCa transcriptomic datasets revealed that this gene panel was most prominent in metastases of advanced disease, with diversity among patients. Collectively, these findings support the contribution of the prostate cell subtypes to disease progression. Cell‐subtype specific genes are traceable in blood RNA of patients with advanced PCa and are associated with clinically relevant end points. This opens the door to minimally invasive liquid biopsies for better management of this deadly disease.
Publicly subsidised smoking cessation medicines in times of COVID‐19 in Australia: An interrupted time series analysis
Authors: Baliunas Dolly , Gartner Coral , Hollingworth Samantha A. , Sullivan Clair , Comans Tracy , Pole Jason D.
Published: September 2022

Introduction

In Australia, the available published literature demonstrated a spike in dispensed prescription medicines after the onset of the COVID‐19 pandemic that subsequently returned to expected levels. Smoking cessation medicines may not follow this pattern because quit attempts are influenced by a range of factors. Knowledge of whether dispensing of these medicines has changed since the pandemic is lacking. We explored the change in dispensing of publicly subsidised smoking cessation medicines since the pandemic.

Methods

Australia's universal health‐care system provides access to government‐subsidised medicines via the Pharmaceutical Benefits Scheme and records of dispensed medicines are publicly available on a nationally aggregated level. We retrieved Pharmaceutical Benefits Scheme data from January 2016 to January 2021. We used interrupted time series modelling to quantify the impact of COVID‐19 on dispensing of nicotine replacement therapy (NRT) patches, varenicline and all smoking cessation treatments combined separately.

Results

After an initial spike in medicines at the onset of the pandemic, the monthly rate of prescriptions dispensed for varenicline was predominantly within predicted ranges, while that of NRT patches was predominantly below predicted ranges.

Discussion and Conclusions

There has been a differential change in the number of subsidised smoking cessation medicines supplied in Australia since the COVID‐19 pandemic, with varenicline prescriptions largely within, and NRT patches largely lower than, expected ranges. The reasons for the apparent change in dispensing of subsidised smoking cessation medicines are unclear.
“Spread too thin”: Parents' experiences of burnout during COVID‐19 in Australia
Authors: Wiemer Samira , Clarkson Larissa
Published: September 2022

Objective

We aimed to investigate parental burnout (PB) within an Australian context during COVID‐19.

Background

Little is known about how the increase in the parental burden created by COVID‐19 restrictions has affected parents and whether this has resulted in increased PB.

Method

A mixed‐methods approach examined PB in a sample of Australian parents (N = 403) during COVID‐19. Regression analyses were conducted to identify predictors of PB, and multivariate analysis of covariance (MANCOVA) was used to compare PB scores to scores collected prior to COVID‐19. Thematic analysis was used to understand the qualitative experience of parenting during lockdowns.

Results

PB scores obtained during COVID‐19 were significantly higher than pre–COVID‐19, and prevalence of PB almost doubled. Age of the parent was the most significant predictor of PB, although gender of the parent, average age of children, and number of children were also predictors on the PB subscales. Qualitatively, parents reported increased stress and a loss of coping mechanisms during lockdown, and this commonly led to negative outcomes.

Conclusion

Results suggest that parents struggled to cope with the additional responsibilities and the reductions to resources created by COVID‐19 restrictions.

Implications

These findings support researchers globally who call for interventions that support parents during periods of COVID‐19 restrictions.
Effect of absorbed power and dopant content on densification during rapid microwave sintering of Bi2O3‐doped ZnO
Authors: Egorov Sergei V. , Eremeev Anatoly G. , Kholoptsev Vladislav V. , Plotnikov Ivan V. , Rybakov Kirill I. , Sorokin Andrei A. , Rostokina Elena Ye. , Balabanov Stanislav S.
Published: September 2022

ZnO samples with an addition of 0, 0.035, 0.1, and 0.35 mol.% Bi2O3were microwave sintered at heating rates 10 and 50°C/min to a maximum temperature of 1200°C with zero hold time. The densification curves obtained by optical dilatometry have been studied in their dependence on the dopant concentration and the heating rate. Direct volumetric absorption of microwave radiation resulted in a 50–60°C shift of the densification curves toward low temperatures compared to susceptor‐assisted heating. An analysis of the effect of the volumetrically absorbed microwave power on the formation of grain‐boundary phases that facilitate densification is presented.
Collateralized Loan Obligations: A Primer
Authors: Martin John , Sayrak Akin
Published: September 2022

In recent years, collateralized loan obligations, or CLOs, have become the largest nonbank lender in the U.S. This added source of financing, which lies outside the purview of banking regulation, has given rise to the concept of a “shadow banking system.” And the lack of transparency and regulatory oversight of CLOs and shadow banking have led to concern that this growing market might contribute to a financial crisis similar to the GFC of 2007‐2008, which was triggered by the securitization of subprime mortgages.

The authors provide a first look at CLOs and their distinctive features as a securitization vehicle that allowed them not only to weather the 2007‐2008 financial crisis but to thrive in the post‐GFC world. Though the collateral performance of CLOs suffered during GFC, their recovery was faster and stronger than that of mortgage‐backed CDOs. Furthermore, the return performance of CLO tranches has in general also been superior to the returns from the comparable leveraged loans upon which CLOs are based—though there are difficulties in measuring returns for CLO tranches since transaction prices are not public information, especially in the case of the equity tranche.

After describing their remarkable growth, the authors focus on two fundamental risks posed by CLOs. The first risk relates to the reliability of credit ratings—though it's important to note that the extensive due diligence behind leverage loans versus mortgage loans effectively reduces CLO investors' reliance on the rating agencies. The second risk relates to the systematic risk borne by the CLO investors, which is lower than that of MBS if only by virtue of the fact that CLOs are based on shorter‐term floating rate instruments than 30‐year mortgages. More important, what happens in most MBS, CLO managers can actively manage their loan portfolios in the secondary markets, and effective and active management of collateral works to limit both default risk and the possible effects of systemic shocks.
Do You Really Know Your Cost of Capital?
Authors: Keloharju Matti , Linnainmaa Juhani , Nyberg Peter
Published: September 2022

We argue that the cost of equity capital varies much less across firms than previously thought. We find that expected return differences across stocks are short term in nature and become empirically indistinguishable from zero in five years. When we aggregate expected returns over longer periods of time, our results translate into 99% of the firms having their cost of equity within 1% of the market‐wide average. The amount of variation in the cost of capital implied by these results is of the order of one‐fifth or perhaps only of one‐tenth of the variation in firms' discount rates indicated by surveys. Our results suggest that high‐risk firms apply much higher, and low‐risk firms much lower, discount rates than they should.

Why do differences in firms' cost of equity capital converge in just a few years? This is because the differences in firm characteristics translating into cost of equity differences vanish over time. For example, competition in the product market makes it hard for profitable firms to maintain their edge, allowing less profitable firms to catch up. As a result, firms representing different levels of risk can, over time, be expected to become more like one another. Some differences in firm characteristics, such as in the ratio of the book and market value of equity, can also stem from the mispricing of stocks. Financial markets are arguably more efficient than product markets, so potential differences in mispricing can be expected to converge even faster than differences in firm characteristics.
A Message from the Editor
Authors: Chew Don
Published: September 2022

In what might be called the first principle of modern corporate finance, the primary source and main driver of a company's long‐run value is said to be its strategy and what finance academics refer as the corporate investment decision—in brief, what corporate managers choose to do with the capital their investors have entrusted them with. Having committed themselves to a strategy and business plan, and figured out the amount of capital required to carry out the plan, the managers are then assumed to address the financing decision: What's our targeted capital structure? Should it be mostly equity, with few (visible) strings attached; or should it include large amounts of debt, with its contractually fixed and obligatory payments of interest and principal?
Quality assessment of consumer‐facing websites on sodium reduction
Authors: Hussain Tasfia , Ahmedna Taha , Marklund Matti , Appel Lawrence J. , Henry Megan E.
Published: September 2022

The purpose of this paper is to evaluate the quality of information and guidance on dietary sodium reduction available on consumer‐facing websites. Google Trends was used to identify the five most‐used search terms related to dietary sodium reduction. For each term, websites on the first two pages were collected (n = 18–20). Of 93 websites collected, 24 were excluded due to defective links, duplicate websites, or not being consumer‐focused. The remaining 69 websites were evaluated using a novel instrument, JHU‐SALT, that includes 14 questions on topics related to salt reduction. The questions are grouped into three domains (“information,” “guidance,” and “accuracy”). For each question, websites were scored using a 3‐step ordinal scale (“topic not addressed,” “topic somewhat addressed,” or “topic addressed adequately”). Only three of 14 JHU‐SALT questions were addressed adequately by a majority of websites. Many websites provided information on the adverse health effects of a high sodium diet (74%, n = 51) or mentioned intake recommendations (64%, n = 44). Information on fundamental concepts was largely missing. The majority of websites (80%, n = 55) provided information on lifestyle strategies to reduce blood pressure, but most did not provide guidance to help implement those strategies. While missing information was common, misinformation was uncommon. The DISCERN questionnaire was utilized as well. Consumers seeking information and guidance on dietary sodium reduction will find that most available websites provide accurate but limited information, and insufficient guidance on how to lower sodium intake. Websites that provide both relevant information and guidance are needed to help consumers effectively reduce dietary sodium.