bluuebunny/crossref_metadata_2025 huggingface dataset:
N1-methylpseudouridine-incorporated mRNA enhances exogenous protein expression and suppresses immunogenicity in primary human fibroblast-like synoviocytes
Authors: Mokuda Sho , Watanabe Hirofumi , Kohno Hiroki , Ishitoku Michinori , Araki Kei , Hirata Shintaro , Sugiyama Eiji
Published: March 2022

Studies conducted using murine arthritis models have indicated that the use of in vitro-transcribed messenger RNA (IVT mRNA) is an effective therapeutic approach for joint diseases. However, the use of IVT mRNA in human synovial cells has not been widely studied. Recently, the outbreak of the novel coronavirus disease has accelerated the development of innovative mRNA vaccines such as those containing a modified nucleic acid, N1-methylpseudouridine-5′-triphosphate (m1ψ). IVT mRNA is an attractive tool for biological experiments and drug discovery. To verify the protein expression of IVT mRNA in vitro, primary cultured human fibroblast-like synoviocytes (FLS) were transfected with enhanced green fluorescent protein (EGFP) mRNA with or without m1ψ incorporation. EGFP was detected using western blotting and fluorescence microscopy. A multiplex assay was performed to comprehensively understand IVT mRNA-induced immunogenicity. FLS transfected EGFP mRNA containing m1ψ generated higher levels of EGFP than unmodified EGFP mRNA or control RNAs. The multiplex assay of the FLS culture supernatant revealed that concentrations of IL-6, TNF-α, and CXCL10 were upregulated by unmodified EGFP mRNA, whereas they were suppressed by EGFP mRNA with m1ψ. Overall, m1ψ incorporation enhanced protein expression and decreased cytokine expressions in primary cultured FLS. The findings may contribute to arthritis research.
Suppression of transposon mobilization by m6A-mediated RNA sequestration in stress granules
Authors: Fan Wenwen , Wang Ling , Lei Zhen , Chu Jie , Cho Jungnam
Published: March 2022

Transposon is a mobile and ubiquitous DNA that can vastly causes genomic alterations. In plants, it is well documented that transposon mobilization is strongly repressed by DNA methylation; however, the roles of RNA methylation in transposon control remain unknown. Here we suggest that transposon RNA is marked by m6A RNA methylation and is sequestered in stress granule (SG) in m6A-dependent manner. Intriguingly, a SG-localized AtALKBH9B selectively demethylates a heat-activated retroelement Onsen, and thereby releases from spatial confinement allowing for its mobilization. In addition, we show evidence that m6A RNA methylation contributes to transpositional suppression by inhibiting the virus-like particles assembly and extrachromosomal DNA production. In summary, this study unveils a hidden role for m6A in the suppression of transposon mobility and provides an insight into how transposon counteracts the host’s epitranscriptomic control by hitchhiking RNA demethylase.
Wolbachia wAlbB inhibit dengue and Zika infection in the mosquito Aedes aegypti with an Australian background
Authors: Hugo Leon E. , Rašić Gordana , Maynard Andrew J. , Ambrose Luke , Liddington Catherine , Thomas Callum J. E. , Nath Nisa S. , Graham Melissa , Winterford Clay , Wimalasiri-Yapa B. M. C. Randika , Xi Zhiyong , Beebe Nigel W. , Devine Gregor J.
Published: March 2022

Biological control of mosquito vectors using the insect-specific bacteria Wolbachia is an emerging strategy for the management of human arboviral diseases. We recently described the development of a strain of Ae. aegypti infected with the Wolbachia strain wAlbB (referred to as the wAlbB2-F4 strain) through simple backcrossing of wild type Australian mosquitoes with a wAlbB infected Ae. aegypti strain from the USA. Field releases of male wAlbB2-F4 mosquitoes resulted in the successful suppression of a wild population of mosquitoes in the trial sites by exploiting the strains Wolbachia-induced cytoplasmic incompatibility. We now demonstrate that the strain is resistant to infection by dengue and Zika viruses and is genetically similar to endemic Queensland populations. There was a fourfold reduction in the proportion of wAlbB2-F4 mosquitoes that became infected following a blood meal containing dengue 2 virus (16.7%) compared to wild type mosquitoes (69.2%) and a 6-7 fold reduction in the proportion of wAlbB2-F4 mosquitoes producing virus in saliva following a blood meal containing an epidemic strain of Zika virus (8.7% in comparison to 58.3% in wild type mosquitoes). Restriction-site Associated DNA (RAD) sequencing revealed that wAlbB2-F4 mosquitoes have > 98% Australian ancestry, confirming the successful introduction of the wAlbB2 infection into the Australian genomic background through backcrossing. Genotypic and phenotypic analyses showed the wAlbB2-F4 strain retains the insecticide susceptibility phenotype and genotype of the Australian mosquitoes. We demonstrate that the Wolbachia wAlbB2-F4, in addition to being suitable for suppression programs, can be effective in population replacement programs given its high inhibition of virus infection in mosquitoes. The ease at which a target mosquito population can be transfected with wAlbB2, while retaining genotypes and phenotypes of the target population, shows the robustness of this strain as a biocontrol agent against the Ae. aegypti mosquito itself as well as the pathogens it transmits.

IMPORTANCE

Epidemics of arthopod-borne virus (arbovirus) diseases affect millions of people and are becoming more frequent and widespread. A successful strategy to control these diseases is by infecting mosquito populations with benign, insect-specific Wolbachia bacteria that render mosquitoes refractory to infection with pathogenic arboviruses. Here we show that a strain of the major mosquito vector Ae. aegypti that was infected with Wolbachia following a simple back-cross mating procedure is refractory to infection with dengue and Zika viruses. Importantly, the genetic background of the strain is equivalent to the target population, which is important for persistence of the strain and regulatory approval.
Identifying competition phenotypes in synthetic biochemical circuits
Authors: Al-Radhawi M. Ali , Del Vecchio Domitilla , Sontag Eduardo D.
Published: March 2022

Synthetic gene circuits require cellular resources, which are often limited. This leads to competition for resources by different genes, which alter a synthetic genetic circuit’s behavior. However, the manner in which competition impacts behavior depends on the identity of the “bottleneck” resource which might be difficult to discern from input-output data. In this paper, we aim at classifying the mathematical structures of resource competition in biochemical circuits. We find that some competition structures can be distinguished by their response to different competitors or resource levels. Specifically, we show that some response curves are always linear, convex, or concave. Furthermore, high levels of certain resources protect the behavior from low competition, while others do not. We also show that competition phenotypes respond differently to various interventions. Such differences can be used to eliminate candidate competition mechanisms when constructing models based on given data. On the other hand, we show that different networks can display mathematically equivalent competition phenotypes.
Fat tails and the need to disclose distribution parameters of qEEG databases
Authors: Wood Guilherme , Willmes Klaus , Koten Jan Willem , Kober Silvia Erika
Published: March 2022

Neurometry (a.k.a. quantitative EEG or qEEG) is a popular method to assess clinically relevant abnormalities in the electroencephalogram. Neurometry is based on norm values for the distribution of specific EEG parameters and believed to show good psychometric properties such as test-retest reliability. Many psychometric properties only hold under the Gaussian distribution and become problematic when distributions are fat-tailed. EEG signals are typically fat-tailed and do not show fast convergence to a Gaussian distribution. To circumvent this property of EEG, log-transformations have frequently, but not always been employed. In Monte Carlo simulations, we investigated the impact of fat-tails (i.e. deviations from Gaussian) on the cut-off criteria and changeability of what in neurometry is termed “abnormal EEG”. Even slight deviations from the Gaussian distribution as measured by skewness and kurtosis lead to large inflation in the number of false positive qEEG findings. The more stringent the cutoff value adopted, the larger the inflation. Moreover, “abnormal EEG” seems to recover spontaneously at rates not compatible with the alleged test-retest reliability of qEEG. Alternative methods should be employed to determine cut-off values for diagnostics purposes, since a large number of false positive results emerge even when slight deviations from the Gaussian distribution are present. We argue that distribution properties of qEEG databases should be disclosed in much more detail by commercial providers to avoid questionable research practices and promote diagnostic transparency. We provide recommendations for the improvement of psychometric properties of existing qEEG databases.
COMMUTE: communication-efficient transfer learning for multi-site risk prediction
Authors: Gu Tian , Lee Phil H , Duan Rui
Published: March 2022

Objectives

We propose a communication-efficient transfer learning approach (COMMUTE) that efficiently and effectively incorporates multi-site healthcare data for training risk prediction models in a target population of interest, accounting for challenges including population heterogeneity and data sharing constraints across sites.

Methods

We first train population-specific source models locally within each institution. Using data from a given target population, COMMUTE learns a calibration term for each source model, which adjusts for potential data heterogeneity through flexible distance-based regularizations. In a centralized setting where multi-site data can be directly pooled, all data are combined to train the target model after calibration. When individual-level data are not shareable in some sites, COMMUTE requests only the locally trained models from these sites, with which, COMMUTE generates heterogeneity-adjusted synthetic data for training the target model. We evaluate COMMUTE via extensive simulation studies and an application to multi-site data from the electronic Medical Records and Genomics (eMERGE) Network to predict extreme obesity.

Results

Simulation studies show that COMMUTE outperforms methods without adjusting for population heterogeneity and methods trained in a single population over a broad spectrum of settings. Using eMERGE data, COMMUTE achieves an area under the receiver operating characteristic curve (AUC) around 0.80, which outperforms other benchmark methods with AUC ranging from 0.51 to 0.70.

Conclusion

COMMUTE improves the risk prediction in the target population and safeguards against negative transfer when some source populations are highly different from the target. In a federated setting, it is highly communication efficient as it only requires each site to share model parameter estimates once, and no iterative communication or higher-order terms are needed.
IsarPipeline: Combining MMseqs2 and PSI-BLAST to Quickly Generate Extensive Protein Sequence Alignment Profiles
Authors: Arab Issar
Published: March 2022

Many of the machine learning (ML) models used in the field of bioinformatics and computational biology to predict either function or structure of proteins rely on the evolutionary information as summarized in multiple-sequence alignments (MSAs) or the resulting position-specific scoring matrices (PSSMs), as generated by PSI-BLAST. The current procedure used in protein structure and function prediction is computationally exhaustive and time-consuming. The main issue relies on the PSI-BLAST software being forced to load the current database of sequences (about 220 GB) in batches and search for similar sequence alignments to a query sequence. This leads to an average runtime of about 40-60 min for a medium-sized (450 Amino Acids) query protein. This average runtime is strictly dependent on the hardware used to run the software. The issue is becoming more problematic since the bio-sequence data pools are increasing in size exponentially over time, hence raising PSI-BLAST runtime as well. A prominent solution claims to speed up the current process by 100 folds. The MMseqs2 method, given enough memory, will load the whole database in memory and apply certain heuristics to retrieve the relevant set of aligned sequences. However, this solution cannot be used directly to generate the final output in the desired PSI-BLAST alignment and PSSM profile data format. In this research project, we analyzed the runtime performance of each tool separately. Furthermore, we built a pipeline that combines both MMseqs2 and PSI-BLAST to obtain a robust, optimized and very fast hybrid alignment tool, faster than PSI-BLAST by two orders of magnitude. It is implemented in C++ and is freely available under the MIT license at https://github.com/issararab/IsarPipeline. The output of our pipeline was evaluated on two previously built predictive models.
Commensal fungi Candida albicans modulates dietary high-fat induced alterations in metabolism, immunity, and gut microbiota
Authors: Peroumal Doureradjou , Sahu Satya Ranjan , Kumari Premlata , Utkalaja Bhabasha , Acharya Narottam
Published: March 2022

Obesity and its associated diseases represent a growing health concern. Despite a strong correlation between gut microbiota and obesity, a limited study is available to suggest the direct involvement of fungus in host physiology. Candida albicans survives as a commensal fungus in the gastrointestinal tract, and its excessive growth causing infections in immune-suppressed individuals is widely accepted. However, any mutualistic relationship that may exist between C. albicans and the host remains outstanding. Here we show that the dietary C. albicans do not cause any noticeable infections, and our metagenomics analyses suggest that it colonizes in the gut and modulates microbiome dynamics which in turn negates the high-fat diet induced uncontrolled body weight gain, metabolic hormonal imbalances, and inflammatory response. Interestingly, adding C. albicans to a non-obesogenic diet stimulates the appetite regulated hormones and helped the mice gain healthy body weight. In concert, our results suggest a mutualism between C. albicans and the host, therefore, contrary to the notion, C. albicans is not always an adversary rather a bonafide admirable companion of the host. Finally, we discuss its potential translational implication as a probiotic especially in obese people or people dependent on high fat calorie intakes to manage obesity and associated complications.
Epigenetic clocks for mice based on age-associated regions that are conserved between mouse strains and human
Authors: Perez-Correa Juan , Tharmapalan Vithurithra , Geiger Hartmut , Wagner Wolfgang
Published: March 2022

Aging of mice can be tracked by DNA methylation changes at specific sites in the genome. In this study, we used the recently released Infinium Mouse Methylation BeadChip to compare such epigenetic modifications in C57BL/6 (B6) and DBA/2J (DBA) mice. We observed marked differences in age-associated DNA methylation in these commonly used inbred mouse strains, indicating that epigenetic clocks for one strain cannot be simply applied to other strains without further verification. In B6 mice age-associated hypomethylation prevailed with focused hypermethylation at CpG islands, whereas in DBA mice CpG islands revealed rather hypomethylation upon aging. Interestingly, the CpGs with highest age-correlation were still overlapping in B6 and DBA mice and included the genesHsf4,Prima1,Aspa, andWnt3a. Notably,Hsf4andPrima1were also top candidates in previous studies based on whole genome deep sequencing approaches. Furthermore,Hsf4,Aspa, andWnt3arevealed highly significant age-associated DNA methylation in the homologous regions in human. Subsequently, we used pyrosequencing of the four relevant regions to establish a targeted epigenetic clock that provided very high correlation with chronological age in independent cohorts of B6 (R2= 0.98) and DBA (R2= 0.91). Taken together, the methylome differs extensively between B6 and DBA mice, while prominent age-associated changes are conserved among these strains and even in humans. Our new targeted epigenetic clock with 4 CpGs provides a versatile tool for other researchers analyzing aging in mice.
Long-read-resolved, ecosystem-wide exploration of nucleotide and structural microdiversity of lake bacterioplankton genomes
Authors: Okazaki Yusuke , Nakano Shin-ichi , Toyoda Atsushi , Tamaki Hideyuki
Published: March 2022

Reconstruction of metagenome-assembled genomes (MAGs) has become a fundamental approach in microbial ecology. However, an MAG is hardly complete and overlooks genomic microdiversity because metagenomic assembly fails to resolve microvariants among closely related genotypes. Aiming at understanding the universal factors that drive or constrain prokaryotic genome diversification, we performed an ecosystem-wide high-resolution metagenomic exploration of microdiversity by combining spatiotemporal (2 depths × 12 samples) sampling from a pelagic freshwater system, MAG reconstruction using long- and short-read metagenomic sequences, and profiling of single nucleotide variants (SNVs) and structural variants (SVs) through mapping of short and long reads to the MAGs, respectively. We reconstructed 575 MAGs, including 29 circular assemblies, providing high-quality reference genomes of freshwater bacterioplankton. Read mapping against these MAGs identified 100–101,781 SNVs/Mb, 0–305 insertions, 0–467 deletions, 0–41 duplications, and 0–6 inversions for each MAG. Nonsynonymous SNVs were accumulated in genes potentially involved in cell surface structural modification to evade phage recognition. Most (80.2%) deletions overlapped with a gene-coding region, and genes of prokaryotic defense systems were most frequently (>8% of the genes) involved in a deletion. Some such deletions exhibited a monthly shift in their allele frequency, suggesting a rapid turnover of genotypes in response to phage predation. MAGs with extremely low microdiversity were either rare or opportunistic bloomers, suggesting that population persistency is key to their genomic diversification. The results lead to the conclusion that prokaryotic genomic diversification is primarily driven by viral load and constrained by a population bottleneck.
A wheat resistosome defines common principles of immune receptor channels
Authors: Förderer Alexander , Li Ertong , Lawson Aaron , Deng Ya-nan , Sun Yue , Logemann Elke , Zhang Xiaoxiao , Wen Jie , Han Zhifu , Chang Junbiao , Chen Yuhang , Schulze-Lefert Paul , Chai Jijie
Published: March 2022

Plant intracellular nucleotide-binding leucine-rich repeat (NLRs) receptors detect pathogen effectors to trigger immune responses. Indirect recognition of a pathogen effector by the dicotyledonous Arabidopsis thaliana coiled-coil (CC) domain containing NLR (CNL) ZAR1 induces the formation of a large hetero-oligomeric protein complex, termed the ZAR1 resistosome, which functions as a calcium channel required for ZAR1-mediated immunity (1–3). Whether the resistosome and channel activities are conserved among plant CNLs remains unknown. We report here a cryogenic electron microscopy (cryo-EM) structure of the wheat CNL Sr35 in complex with the effector AvrSr35 of the wheat stem rust pathogen at 3.0 Å resolution. Direct effector binding to the leucine-rich repeats (LRRs) of Sr35 results in the formation of a pentameric Sr35-AvrSr35 complex, which we designate the Sr35 resistosome. Wheat Sr35 and Arabidopsis ZAR1 resistosomes bear striking structural similarity, including a previously unnoticed arginine cluster in the LRR domain that co-occurs and forms intramolecular interactions with the ‘EDVID’ motif in the CC domain. Electrophysiological measurements show that the Sr35 resistosome exhibits non-selective cation channel activity. These structural insights allowed us to generate novel variants of closely related wheat and barley orphan NLRs that recognize AvrSr35. Our data support the evolutionary conservation of CNL resistosomes in plants and demonstrate proof of principle for structure-based engineering of NLRs for crop improvement.
Cdk1-mediated threonine phosphorylation of Sam68 modulates its RNA binding, alternative splicing activity, and cellular functions
Authors: Malki Idir , Liepina Inara , Kogelnik Nora , Lightfoot Adam , Gonchar Oksana , Watmuff Hollie , Bottrill Andrew , Fry Andrew M. , Dominguez Cyril
Published: March 2022

Sam68 is a member of the STAR family of proteins that directly link signal transduction with post-transcriptional gene regulation. Sam68 controls the alternative splicing of many oncogenic proteins and its role is modulated by post-translational modifications, including serine/threonine phosphorylation, that differ at various stages of the cell cycle. However, the molecular basis and mechanisms of these modulations remain largely unknown. Here, we combined mass spectrometry, NMR spectroscopy, and cell biology techniques to provide a comprehensive post-translational modification (PTM) mapping of Sam68 at different stages of the cell cycle in HEK293 and HCT116 cells. We established that Sam68 is specifically phosphorylated at T33 and T317 by Cdk1, and demonstrated that these phosphorylation events reduce the binding of Sam68 to RNA, control its cellular localization, and reduce its alternative splicing activity, leading to a reduction in the induction of apoptosis and an increase in the proliferation of HCT116 cells.
SUMO4 promotes SUMO deconjugation required for DNA double-strand break repair
Authors: Garvin Alexander J. , Lanz Alexander J. , Starowicz Katarzyna , Ronson George E , Mackintosh Matthew J.W. , Walker Alexandra K. , Aghabi Yara , MacKay Hannah , Densham Ruth M. , Leney Aneika C. , Morris Joanna R.
Published: March 2022

The amplitudes of small-modifier protein signalling through ubiquitin and the Small Ubiquitin-like Modifiers, SUMO1-3, are critical to the correct phasing of DNA repair protein accumulation, activity, and clearance, and for the completion of mammalian DNA double-strand break (DSB) repair. However, how SUMO-conjugate signalling in the response is delineated is poorly understood. At the same time, the role of the non-conjugated SUMO protein, SUMO4, has remained enigmatic. Here we reveal that SUMO4 is required to prevent excessive DNA-damage-induced SUMOylation and deleterious over-accumulation of RAP80. Mechanistically we show SUMO4 acts independently of its conjugation and potentiates SENP1 catalytic activity. These data identify SUMO4 as a SUMO deconjugation component and show SUMO4:SENP1 are critical regulators of DNA-damage-induced SUMO signalling.

Highlights

The roles of the SUMO family members, SUMO1-4, in DSB repair are not redundant.

SUMO4 conjugation is deleterious.

SUMO4 promotes SENP1 catalytic activity.

SUMO4:SENP1 restrict SUMO-signalling and accumulation of the BRCA1-A complex.
Population genetic analysis of Ophidiomyces ophidiicola, the causative agent of snake fungal disease, indicates recent introductions to the USA
Authors: Ladner Jason T. , Palmer Jonathan M. , Ettinger Cassandra L. , Stajich Jason E. , Farrell Terence M. , Glorioso Brad M. , Lawson Becki , Price Steven J. , Stengle Anne G. , Grear Daniel A. , Lorch Jeffrey M.
Published: March 2022

Snake fungal disease (SFD; ophidiomycosis), caused by the pathogen Ophidiomyces ophidiicola (Oo), has been documented in wild snakes in North America and Eurasia, and is considered an emerging disease in the eastern USA. However, a lack of historical disease data has made it challenging to determine whether Oo is a recent arrival to the USA or whether SFD emergence is due to other factors. Here, we examined the genomes of 82 Oo strains to determine the pathogen’s history in the eastern USA. Oo strains from the USA formed a clade (Clade II) distinct from European strains (Clade I), and molecular dating indicated that these clades diverged too recently (∼2,000 years ago) for transcontinental dispersal of Oo to have occurred via natural snake movements across Beringia. A lack of nonrecombinant intermediates between clonal lineages in Clade II indicates that Oo has actually been introduced multiple times to North America from an unsampled source population, and molecular dating indicates that several of these introductions occurred within the last few hundred years. Molecular dating also indicated that the most common Clade II clonal lineages have expanded recently in the USA, with time of most recent common ancestor mean estimates ranging from 1985-2007 CE. The presence of Clade II in captive snakes worldwide demonstrates a potential mechanism of introduction and highlights that additional incursions are likely unless action is taken to reduce the risk of pathogen translocation and spillover into wild snake populations.
Geographical indications' prices and marketing margins: the role of group size, longevity and production decisions
Authors: Bimbo Francesco , Bonanno Alessandro , Viscecchia Rosaria
Published: March 2022

Purpose

Geographical indication (GI) labels aim to improving farmers' and processors' income. This article studies how characteristics related to GI groups and their reputation (e.g. the producer group size, longevity and production decisions) are related to prices at the origin, final (consumption) prices and marketing margins.

Design/methodology/approach

The authors use 8 years of annual data for the Italian Extra Virgin Olive Oil (EVOO) GI market encompassing 46 GI EVOOs. Estimated parameters characterizing the relationship between the GI's group features and prices (at origin and at consumption) are obtained via Three-Stage Least Squares (3SLS).

Findings

Results show that the number of GI operators is related to consumption prices, while is weakly related to prices at the origin. GIs' age is not associated with higher consumption prices, while origin prices are lower for older GIs compared to younger ones. Higher farmers' olive/oil conversion rate is associated with lower origin and consumption prices, whereas the extent of vertical integration is related to higher prices at the origin and a higher share of the marketing margins going to producers.

Originality/value

To the best of their knowledge, the authors offer the first empirical evidence on how structural characteristics and production decisions of a GI group relate to prices and marketing margins.
Give play to strengths or overcome weaknesses? The impact of family involvement on exploitative and exploratory OFDI
Authors: Yang Xuelei , Shang Hangbiao , Li Weining
Published: March 2022

Purpose

This study explores the impact of family ownership and management on exploitative and exploratory outward foreign direct investment (OFDI) in family businesses in emerging economies, as well as the moderating effects of intra-family successions and founder CEOs.

Design/methodology/approach

The authors empirically tested the hypotheses based on the data of Chinese listed manufacturing family enterprises from 2009 to 2018.

Findings

Family ownership does not significantly reduce exploitative OFDI but significantly increases exploratory OFDI. When family offspring have succession intentions, these relationships are strengthened. Additionally, family management is negatively associated with exploitative OFDI and positively associated with exploratory OFDI. Founder CEOs have a positive moderating effect on the relationship between family management and exploitative and exploratory OFDI.

Originality/value

This study is the first attempt to introduce exploitative and exploratory OFDI into the internationalization of family enterprises. The research goes beyond internationalization as a single concept and provides new evidence to solve the controversy about how family involvement affects family firms’ internationalization. On the other hand, the authors respond to the call to understand the impact of family heterogeneity on internationalization by systematically examining the influence of four important family heterogeneity characteristics on family firms’ OFDI choice.
Work site food purchases among healthcare staff: Relationship with healthy eating and opportunities for intervention
Authors: Utter Jennifer , McCray Sally , Denny Simon
Published: March 2022

Aim

The current study describes food‐purchasing behaviours of healthcare staff, determines whether purchasing food at work is associated with overall indicators of healthy eating, and explores opportunities for improving the hospital food environment.

Methods

A secondary analysis of a health and wellbeing survey of healthcare workers (n = 501) in Queensland, Australia. Multiple regression models describe the associations between food purchases and indicators of healthy eating, while controlling for age, gender and work role.

Results

More than 60% of staff purchased food/drinks at work in the past week, and this was inversely associated with indicators of healthy eating. For example, among those purchasing food/drinks at work on most days, only 18% reported their overall diet as excellent or very good, compared to 50% of those who do not purchase food/drink at work (odds ratio [OR] = 0.24; 95% confidence interval [CI] = [0.12,0.48] in adjusted models). Staff feedback prioritised strategies to make healthy meals more accessible and affordable.

Conclusion

Improvements to the retail food environment in hospitals could have a positive impact on the overall nutritional wellbeing of staff.
Microbial biotechnology to assure national security of supplies of essential resources: energy, food and water, medical reagents, waste disposal and a circular economy
Authors: Timmis Kenneth , Ramos Juan Luis , Verstraete Willy
Published: March 2022

The core responsibility of governments is the security of their citizens, and this means inter alia protecting their safety, nutrition and health. Microbiology and microbial biotechnology have key roles to play in improving supply security of essential resources. In this paper, we discuss the urgent need to fully and immediately exploit existing microbial biotechnologies to maximize supply security of energy, food and medical supplies, and of waste management, and to invest in new research specifically targetting supply security of essential resources.
A quantitative framework to infer the effect of traits, diversity and environment on dispersal and extinction rates from fossils
Authors: Hauffe Torsten , Pires Mathias M. , Quental Tiago B. , Wilke Thomas , Silvestro Daniele
Published: March 2022

Speciation, dispersal and extinction govern the spatial and temporal dynamics of biodiversity. The fossil record offers the opportunity to directly estimate range expansion and contraction via dispersal and extinction, respectively. However, due to the incomplete occurrence record, determining the dynamics of these processes and the biotic and abiotic factors influencing them remains challenging.

The dispersal–extinction–sampling (DES) model infers dispersal and extinction rates from present and past geographical ranges of taxa while accounting for the incompleteness of the fossil record via jointly estimated sampling rates. Here, we expand the DES framework to a new suite of models that (a) incorporate heterogeneity in fossil sampling across taxa, (b) reconstruct diversity trajectories through time and across regions, and (c) link rates of range evolution with biotic and abiotic covariates. These models integrate the effects of competitive interaction, traits and environmental change on dispersal and extinction while controlling for phylogenetic effects through higher level taxonomy.

We validate our framework through simulations and find that likelihood‐based model testing has the power to discriminate among models with or without biotic and abiotic effects on dispersal and extinction. Among the tested models, we found that trait‐dependent models yielded the most accurate parameter estimates. We then assess the factors influencing geographical range evolution for Eurasian and North American terrestrial carnivores. We identify substantial variation in the fossil sampling rates of carnivore genera and find that global cooling increased their extinction risk while their dispersal rate varied among families and increased with larger body size.

The expanded suite of DES models for fossil biogeography is a powerful tool to test hypotheses about the factors influencing geographical range evolution using fossil data.
Clozapine and COVID‐19 Vaccination: Effects on blood levels and leukocytes. An observational cohort study
Authors: Veerman Selene R. T. , Moscou Timo , Bogers Jan P. A. M. , Cohen Dan , Schulte Peter F. J.
Published: March 2022

Objective

To investigate the safety of COVID‐19 vaccination in patients on clozapine as regards plasma clozapine concentration and haematological parameters.

Methods

We conducted a multicentre observational cohort study from 22 February 2021 to 2 September 2021. Primary outcomes were clinically relevant increase in clozapine blood levels (>100 μg/L increase compared to baseline) and clozapine alert levels (>1000 μg/L). Secondary outcomes were granulocytopenia, leukocytopenia and lymphocytopenia. Outcomes were measured approximately 5 days after the first and (where applicable) second dose of COVID‐19 vaccine.

Results

This study included 139 patients. Compared to baseline, clozapine blood levels increased significantly (ES = 0.28, p = 0.003) after the second vaccination. Clinically relevant increases in clozapine blood levels occurred in 20/92 patients (22%) and in 16/56 patients (29%) during the first and second phases, respectively. Clozapine alert levels developed in one patient (1%) following the first dose and in three patients (5%) after the second dose. In both phases, changes in white blood cells (WBC) were limited to mild granulocytopenia (3% and 5%), moderate granulocytopenia (1% and 0%) and leukocytopenia (2% and 3%) without cause for extra monitoring according to the guideline.

Conclusion

In general, as regards WBC counts COVID‐19 vaccination seems to be safe in patients with SMI. Changes in WBC had no clinical implications. Psychoeducation on the symptoms of clozapine intoxication is recommended, especially in patients with clozapine blood levels approaching the upper limit of the therapeutic range. Increase in the C‐reactive protein (CRP) level can signal inflammation rapidly and help to prevent clozapine intoxication following vaccination.
Influence of mental health professionals’ attitudes and personality traits on decision‐making around coercion: Results from an experimental quantitative survey using case vignettes
Authors: Efkemann Simone Agnes , Scholten Matthé , Bottlender Ronald , Juckel Georg , Gather Jakov
Published: March 2022

Objective

Research on coercion in mental healthcare has recently shifted to the investigation of subjective aspects, both on the side of the people with mental disorders affected and the staff members involved. In this context, the role of personality traits and attitudes of staff members in decision‐making around coercion is increasingly being assessed. This study aimed to examine the role of staff attitudes towards coercion and staff members’ personality traits in decision‐making around coercion in an experimental setting.

Methods

We assessed the attitudes towards coercion and (general) personality traits of mental health professionals in psychiatric hospitals with a quantitative survey. Furthermore, we developed case vignettes representing cases in a ‘grey zone’ and included them in the survey to assess staff members’ decisions about coercion in specific situations.

Results

A general approving attitude towards coercion significantly influenced decisions around coercion in individual cases—resulting in a more likely approval of applying coercion in the cases described in the vignettes. Personality traits did not seem to be relevant in this regard.

Conclusion

Strategies to reduce coercion in mental healthcare institutions should focus more on the role of staff attitudes and encourage staff members to reflect on them critically.
Telehealth for gynaecology outpatients during the COVID‐19 pandemic: Patient and clinician experiences
Authors: Mclaughlin Emma Jane , Ellett Lenore Caroline , Readman Emma , Mooney Samantha
Published: March 2022

Background

The COVID‐19 pandemic has necessitated alterations in provision of health care and how patients access it. Telehealth has replaced traditional face‐to‐face outpatient clinics in an unprecedented manner. This study aimed to assess overall patient and clinician satisfaction with telehealth consultations, to establish acceptability of telehealth during pandemic and non‐pandemic times, and document feedback.

Materials and Methods

A prospective observational study involving women presenting to a general gynaecology outpatient department was performed. Women who attended for consultation between 13 July and 4 September 2020 were invited to participate in a questionnaire following their telehealth appointment. Clinicians consulting in the outpatient department were invited to complete a questionnaire at the end of the eight‐week study period. Satisfaction, utility and acceptability data were obtained using visual analogue scales (VAS).

Results

Twenty‐six out of 56 (46.4%) clinicians and 124/870 (14.3%) patients completed the questionnaire. Patients who responded were older and more likely to have been born in Australia than women who did not (P = 0.0355 and P = 0.005, respectively). Overall patient satisfaction with telehealth was high (median VAS (interquartile range), 8.6 (5.6–9.8)). More women found telehealth to be acceptable during a pandemic than afterward (8.9 vs 6.6, P < 0.0001). Clinicians were less satisfied with telehealth than patients (7.1 vs 8.6, P = 0.02); however, most would be happy to continue using telehealth in non‐pandemic times (7.0 (6.2–9.8)).

Conclusion

Telehealth consultations allow provision of gynaecological care at a time when reducing risk of infection to patients and staff is paramount. Telehealth gynaecology consultations are efficient and convenient without significant detriment to patient or clinician satisfaction.
Peche problems
Authors: PEREZ JUSTIN
Published: March 2022

As declarations of a possible “end of AIDS” emerged during the epidemic's fourth decade, some HIV‐prevention efforts shifted to address social conditions and individual dispositions among the populations most affected. In Peru, where HIV was concentrated among transgender women and gay men, health science positioned transactional sex as one site of intervention. Gay and transgender communities themselves circulated stories that dramatized transactional sex. Set against the backdrop of Peru's armed conflict (1980–2000), these stories pivoted on peches—the small gifts given to incentivize sexual and romantic relationships—and reflected a shared moral imaginary linked to the context of postconflict society. Interpreting transactional sex like a peche illuminates the moral dimensions of the category and suggests that the technical project of achieving an “end of AIDS” future is also imaginative and moralizing. Peches thus offer an interpretive approach to the persistent tensions between local and globalized categories, in relation to both HIV/AIDS and more broadly to other contexts. [sexuality, transactional sex, HIV/AIDS, end of AIDS, gay, transgender, morality, Peru]
Multilevel musculo‐fascial defect magnetic resonance study of female pelvic floor: retrospective case control study in women with pelvic floor dysfunction after the first vaginal delivery
Authors: Krcmar Michal , Horcicka Lukas , Nemec Martin , Hanulikova Petra , Feyereisl Jaroslav , Krofta Ladislav
Published: March 2022

Introduction

Magnetic resonance imaging (MRI) provides a detailed display of the pelvic floor structures responsible for normal pelvic floor anatomy. The aim of the study is to assess the appearance of musculo‐fascial defects in women with pelvic floor dysfunction following first vaginal delivery.

Material and methods

Analysis of axial T3 (Tesla 3) MRI scans from a case control study of symptomatic (n = 149) and asymptomatic (n = 60) women after first vaginal delivery. Presence and severity of pelvic organ support and attachment system defects in three axial pelvic planes were assessed.

Results

In the symptomatic group, major muscular defects were found in 67.1% (for pubovisceral muscle complex) and 87.9% (for iliococcygeal muscle). Only 6.7% of major pubovisceral and 35.0% of major iliococcygeal defects were identified in the controls (p = 0.000). Prolapse patients had an odds ratio (OR) of 22.1 (95% CI 8.94–54.67) to have major pubovisceral muscle complex defect and OR of 4.9 (95% CI 1.51–15.71) to have major iliococcygeal muscle defect. Fascial defects were found in 60.4% and 83.2% the symptomatic group, respectively. Those with prolapse had an OR of 29.1 (95% CI 9.77–86.31) to have facial defect at the level of pubovisceral muscle complex and an OR of 16.9 (95% CI 7.62–37.69) to have fascial defect at the level of iliococcygeal muscle. Uterosacral ligaments detachment was associated with prolapse with an OR of 10.1 (95% CI 4.01–25.29). For the model based on combination on all MRI markers, the area under the receiver operating characteristic curve is 0.921.

Conclusions

This study provides comprehensive data about first vaginal delivery‐induced changes in the levator ani muscle and endopelvic fascial attachment system. These changes are seen also in asymptomatic controls, but they are significantly less expressed.
Age, income and sleep duration were associated with outcomes in children participating in weight management
Authors: Kjetså Ingrid , Halvorsen Peder Andreas , Kokkvoll Ane Sofie
Published: March 2022

Aim

To explore associations between baseline factors and weight‐related outcomes among participants enrolled in a paediatric obesity trial.

Methods

We included children aged 6–12 years participating in a 2‐year multidisciplinary family programme who attended a postintervention follow‐up 36 months from baseline (n = 62). Outcome measures were change in body mass index standard deviation score (BMI SDS), reduction in BMI SDS ≥0.25 and change in waist circumference (WC). Independent variables included in linear and logistic regression models were age, sex, household income, parents' education, sleep duration, screen time and physical activity.

Results

Altogether, 26 children (42%) attained a reduction of BMI SDS ≥0.25. Higher family income and longer sleep duration were associated with greater change in BMI SDS (−0.05 per 100.000 NOK, p = 0.02, and −0.24 per hour, p = 0.02, respectively). Higher age was associated with greater change in WC (−2.1 cm per year, p = 0.01) but lower odds of attaining a reduction in BMI SDS ≥0.25 (OR per year 0.70, p = 0.04). There was a borderline statistically significant trend towards greater increase in WC with longer daily screen time (p = 0.05).

Conclusion

Age, family income and sleep duration at baseline were associated with weight‐related outcomes 1‐year postintervention.
Carvedilol versus endoscopic band ligation for secondary prophylaxis of variceal bleeding—long‐term follow‐up of a randomised control trial
Authors: Dunne Philip D. J. , Young David , Chuah Cher Shiong , Hayes Peter C. , Tripathi Dhiraj , Leithead Joanna , Smith Lyn A. , Gaya Daniel R. , Forrest Ewan , Stanley Adrian J.
Published: March 2022

Background and Aims

Carvedilol reduces rates of variceal bleeding and rebleeding by lowering portal pressure. However, an associated pleiotropic survival benefit has been proposed. We aimed to assess long‐term survival in a cohort of patients previously randomised to receive either carvedilol or endoscopic band ligation (EBL) following oesophageal variceal bleeding (OVB).

Methods

The index study randomised 64 cirrhotic patients with OVB between 2006 and 2011 to receive either carvedilol or EBL. Follow‐up was undertaken to April 2020 by review of electronic patient records. The primary outcome was survival. Other outcomes including variceal rebleeding and liver decompensation events were compared.

Results

26 out of 33 participants received carvedilol in the follow‐up period and 28 out of 31 attended regular EBL sessions. The median number of follow‐up days for all patients recruited was 1459 (SE = 281.74). On the intention to treat analysis, there was a trend towards improved survival in the carvedilol group (p = 0.09). On per‐protocol analysis, carvedilol use was associated with improved long‐term survival (p = 0.005, HR 3.083, 95% CI 1.397–6.809), fewer liver‐related deaths (0% vs 22.57%, p = 0.013, OR ∞, 95%CI 1.565–∞) and fewer admissions with decompensated liver disease (12% vs 64.29%, p = 0.0002, OR 13.2, 95% CI 3.026–47.23) compared to the EBL group. There was no statistically significant difference in variceal rebleeding rates.

Conclusion

Following OVB in cirrhotic patients, carvedilol use is associated with survival benefit, fewer liver‐related deaths and fewer hospital admissions with decompensated liver disease. Further studies are needed to validate this finding.
Left thoracoscopic surgery in the prone position for a bronchogenic cyst localized to the lower thoracic esophagus: A case report
Authors: Imai Takeharu , Yamada Makoto , Nakashima Takuya , Namiki Kenji , Ukai Jyunko , Horaguchi Takeshi , Matsumoto Keita , Tanahashi Toshiyuki , Yawata Kazunori , Marui Tsutomu , Sasaki Yoshiyuki
Published: March 2022

A 60‐year‐old woman with an abnormality discovered during a chest X‐ray was referred to the authors' hospital for diagnosis and treatment. Upon enhanced computed tomography (CT), endoscopic ultrasonography, and magnetic resonance imaging, a tumor on the left side of the lower thoracic esophagus was detected. We diagnosed mediastinum cyst. One year after the first visit, a CT examination confirmed an increase in lesion size. Therefore, surgery was performed using a left thoracoscopic approach in the prone position. Before surgery, 3D models were used for simulation. Excision was performed without leakage of the contents. The histopathological diagnosis was a bronchogenic cyst. The left thoracoscopic surgery in the prone position is an uncommon approach but is useful for resecting tumors in the left side of the lower mediastinum. The authors were well‐prepared and able to perform safe and reliable surgery.